Glycemic Control in the Hospitalized Patient
Glycemic Control
in the Hospitalized Patient
A Comprehensive Clinical Guide
Edited by
Lillian F. Lien, MD
Medical Director, Duke Inpatient Diabetes Management,
Department of Medicine, Division of Endocrinology, Metabolism, and Nutrition,
Duke University Medical Center, Durham, North Carolina
Mary E. Cox, MD, MHS
Department of Medicine, Division of Endocrinology, Metabolism, and Nutrition,
Duke University Medical Center, Durham, North Carolina
Mark N. Feinglos, MD, CM
Professor of Medicine, Chief, Division of Endocrinology, Metabolism,
and Nutrition, Duke University Medical Center, Durham, North Carolina
Leonor Corsino, MD, MHS
Instructor of Medicine, Department of Medicine, Division of Endocrinology,
Metabolism, and Nutrition, Duke University Medical Center, Durham,
North Carolina
Foreword by
Guillermo Umpierrez, MD, FACP, FACE
Professor of Medicine, Emory University School of Medicine
123
Editors
Lillian F. Lien, MD
Division of Endocrinology,
Metabolism, and Nutrition
Department of Medicine
Duke University Medical Center Box 2956
Durham, NC 27710, USA
[email protected]
Mark N. Feinglos, MD, CM
Division of Endocrinology,
Metabolism, and Nutrition
Department of Medicine
Duke University Medical Center
Baker House Trent Drive
Durham, NC 27710, USA
[email protected]
Mary E. Cox, MD, MHS
Division of Endocrinology,
Metabolism, and Nutrition
Department of Medicine
Duke University Medical Center
Durham, NC 27710, USA
[email protected]
Leonor Corsino, MD, MHS
Division of Endocrinology,
Metabolism, and Nutrition
Department of Medicine
Duke University Medical Center Box 3921
Durham, NC 27710, USA
[email protected]
ISBN 978-1-60761-005-2
e-ISBN 978-1-60761-006-9
DOI 10.1007/978-1-60761-006-9
Springer New York Dordrecht Heidelberg London
Library of Congress Control Number: 2010935296
© Springer Science+Business Media, LLC 2011
All rights reserved. This work may not be translated or copied in whole or in part without the written
permission of the publisher (Springer Science+Business Media, LLC, 233 Spring Street, New York,
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The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are
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While the advice and information in this book are believed to be true and accurate at the date of going
to press, neither the authors nor the editors nor the publisher can accept any legal responsibility for
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respect to the material contained herein.
Printed on acid-free paper
Springer is part of Springer Science+Business Media (www.springer.com)
Disclaimer
The views expressed in this book are those of the authors and do not necessarily
represent the views of Duke University and the Durham Veterans Affairs Medical
Center.
This book contains information intended as an educational aid. This book is not
intended as medical advice for individual patients or conditions. The suggestions
in this book do not substitute for a medical exam and do not replace the need for
evaluation and judgment of medical professionals. Although the authors have done
their best to ensure full integrity of the work, the publisher, editors, and authors do
not assume any risk for the use of suggestions contained within this book. Please
inform us of any inaccuracies so they may be corrected in future editions.
v
To my mom and dad, Mei-fong W. Lien and
Stephen Lien, for love and great wisdom:
you are my inspiration. In loving memory of
Sheue Lin Wang.
-Lillian F. Lien, MD
To my husband, Bryan, and to Mom and
Dad, for your love and support.
-Mary E. Cox, MD MHS
To my mother and husband, Luz Maria and
Carlos, for their unconditional support; in
memory of my father, Damian, who battled
diabetes for over 30 years.
-Leonor Corsino, MD MHS
Foreword
I am pleased to write the foreword for the first edition of this book entitled Glycemic
Control in the Hospitalized Patient. The text is written by a group of expert healthcare providers at Duke University Medical Center who have extensive experience
in the management of hospitalized individuals with hyperglycemia. The experience
of the authors is highly valuable as they come from an institution that was one of
the earliest to develop an inpatient Diabetes Management Service. In this book, the
reader will find detailed and focused guidance for the management of hyperglycemia
and hypoglycemia in situations which are unique to the inpatient setting, such as
enteral and parenteral nutrition, intravenous insulin, and insulin pumps. This book
should be useful for providers at all levels, from medical students, to interns and
residents, and our endocrine fellows and other colleagues. I believe that the reader
will find this text useful in achieving the ultimate goal of providing high quality care
for all patients in the hospital.
Atlanta, GA
Guillermo Umpierrez
ix
Preface
Rationale for Inpatient Management of Hyperglycemia
The number of people with diabetes mellitus continues to increase at an alarming
rate. It is estimated that the number of individuals diagnosed with diabetes worldwide will be approximately 366 million by the year 2030. With this rapidly growing
group of people diagnosed with diabetes, it is not surprising that the proportion
of individuals admitted to the hospital with diabetes as a comorbidity is elevated
as well. Additionally, a significant number of patients without a prior diagnosis of
diabetes will develop hyperglycemia during hospitalization.
In recent years, there has been an evolution in the management of hospitalized
patients with hyperglycemia. Inconsistent clinical trial results urged experts in the
field to reconsider the targets of control warranted in hospitalized patients. However,
despite some of the existent controversy generated by these clinical trial results,
most experts agree that hyperglycemia in the hospitalized patient cannot be ignored
and that appropriate management continues to be critical.
One of the major issues addressed during the controversy was the potential deleterious effect of tight glycemic control (80–110 mg/dL [4.4–6.1 mmol/L]) in both
critically and noncritically ill patients and those at risk for hypoglycemia. Based on
the fact that some of these studies failed to demonstrate significant improvement in
mortality in the intensive care unit patient and some showed a possible increase, it
is clear that the controversy continues and glycemic targets should be reconsidered
in order to avoid potential patient harm. However, it is our hope, and the hope of
many experts in the field, that patients admitted to the hospital with a history of diabetes and those with newly developed hyperglycemia will be carefully monitored
and treated.
The most recent consensus statement on this topic from the American Diabetes
Association and the American Association of Clinical Endocrinologists addressed
the current evidence both against and in favor of glycemic control in hospitalized patients and recommended that therapy should be initiated in critically ill
patients with persistent hyperglycemia, starting with a threshold of no greater than
180 mg/dL (10 mmol/L) and, once insulin is started, therapy should target a glucose
range of 140–180 mg/dL (7.8–10 mmol/L). For noncritically ill patients, the glucose
xi
xii
Preface
target should generally be a fasting glucose of less than 140 mg/dL (7.8 mmol/L)
and random glucose of less than 180 mg/dL (10 mmol/L), providing that these goals
can be achieved safely.
The goal of this book is to provide a very useful and practical resource for healthcare providers who treat hyperglycemia in the inpatient setting. The authors have
included a practical approach to different scenarios that occur while treating patients
with hyperglycemia, such as patients receiving enteral nutrition. Additionally, the
book serves as a comprehensive guide to all aspects of inpatient glycemic control,
such as the initiation of insulin, treatment of hypoglycemia, and the transition of
care to the outpatient setting. The ultimate goal of the contributors is to improve
the quality of care and quality of life of our patients with diabetes and those with
hyperglycemia in the inpatient setting.
Finally, the editors would like to acknowledge Dr Corsino for her idea of writing
a book that provides guidance to healthcare providers taking care of patients with
hyperglycemia in the inpatient setting and for making this book a reality. In addition,
the editors would like to thank our contributors for their hard work and for their
continued efforts to improve the care of patients with diabetes.
Durham, NC
Lillian F. Lien
Mary E. Cox
Mark N. Feinglos
Leonor Corsino
Special Acknowledgments
We wish to give special thanks to the following individuals, who provided particular
assistance to the editors and authors in the preparation of this book:
From our publishers, we especially thank Richard Lansing for his assistance and
for believing in our project, as well as Robin Weisberg, style editor, for her excellent
work.
From Duke University Medical Center, we thank Mary Jane Stillwagon and
the Duke Hospital Glycemic Safety Committee, as well as Melanie Mabrey,
Sarah Gauger, Ellen Davis, Daniel Feinglos, and Mark Feinglos for expertise and
friendship.
We also wish to acknowledge individuals from Abbott, Michelle L Zendah and
Linda A Murray, as well as Nestle, Marilyn Cook and Sally Crush, who assisted us
with permissions to use their material.
Finally, we thank our colleagues and patients for their insights and strength.
xiii
Contents
1 Physiology of Diabetes Mellitus and Types of Insulin . . . . . . . .
Bryan C. Batch, Mary E. Cox, and Lillian F. Lien
2 Subcutaneous Insulin: A Guide for Dosing Regimens
in the Hospital . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Karen Barnard, Bryan C. Batch, and Lillian F. Lien
3 IV Insulin Infusions: How to Use an “Insulin Drip” . . . . . . . . .
Melanie E. Mabrey and Lillian F. Lien
4 Laboratory Testing in Hospitalized Patients
with Diabetes Mellitus . . . . . . . . . . . . . . . . . . . . . . . . .
Karen Barnard and Mary E. Cox
5 Inpatient Diabetes Education: Realistic and Evidence-Based . . . .
Ellen D. Davis, Anne T. Nettles, and Ashley Leak
6 Hyperglycemic Emergencies: Diabetic Ketoacidosis
and Hyperosmolar Hyperglycemic State . . . . . . . . . . . . . . .
Leonor Corsino and Lekshmi T. Nair
1
7
17
29
41
51
7 Medical Nutrition Therapy in the Hospital . . . . . . . . . . . . . .
Sarah Gauger
63
8 Insulin Pumps and Glucose Sensors in the Hospital . . . . . . . . .
Sarah Gauger
67
9 Non-insulin Antidiabetic Medications
in the Inpatient Setting . . . . . . . . . . . . . . . . . . . . . . . . .
Jennifer V. Rowell, Lekshmi T. Nair, and Mary E. Cox
77
10
Hypoglycemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Melanie E. Mabrey, Mary E. Cox, and Lillian F. Lien
91
11
Transitioning to Outpatient Care . . . . . . . . . . . . . . . . . . .
Beatrice D. Hong and Ellen D. Davis
101
xv
xvi
12
Contents
Management of Hyperglycemia Associated with Enteral
and Parenteral Nutrition . . . . . . . . . . . . . . . . . . . . . . . .
Sarah Gauger
113
13
When to Consult Endocrinology . . . . . . . . . . . . . . . . . . .
Beatrice D. Hong
119
14
Frequently Asked Questions . . . . . . . . . . . . . . . . . . . . . .
Mary E. Cox and Matthew J. Crowley
121
Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
139
Contributors
Karen Barnard Division of Endocrinology, Metabolism, and Nutrition,
Department of Medicine, Duke University Medical Center, Durham, NC 27710,
USA; Department of Veterans Affairs, Durham, NC 27707, USA,
[email protected]
Bryan C. Batch Division of Endocrinology, Metabolism, and Nutrition,
Department of Medicine, Duke University Medical Center, Durham, NC 27710,
USA; Department of Veterans Affairs, Durham, NC 27707, USA,
[email protected]
Leonor Corsino Division of Endocrinology, Metabolism, and Nutrition,
Department of Medicine, Duke University Medical Center, Durham, NC 27710,
USA,
[email protected]
Mary E. Cox Division of Endocrinology, Metabolism, and Nutrition, Department
of Medicine, Duke University Medical Center, Durham, NC 27710, USA,
[email protected]
Matthew J. Crowley Division of Endocrinology, Metabolism, and Nutrition,
Department of Medicine, Duke University Medical Center, Durham, NC 27710,
USA,
[email protected]
Ellen D. Davis Department of Advanced Clinical Practice, Duke University
Hospital, Durham, NC 27710, USA; Duke University School of Nursing, Durham,
NC 27710, USA,
[email protected]
Sarah Gauger Duke Inpatient Diabetes Management, Duke University Medical
Center, Durham, NC 27710, USA,
[email protected]
Beatrice D. Hong Division of Endocrinology, Metabolism and Nutrition,
Department of Medicine, Duke University Medical Center, Durham, NC 27710,
USA,
[email protected]
Ashley Leak Accelerated BSN Program, Duke University School of Nursing,
John A. Hartford Building Academic Geriatric Nursing Capacity (BAGNC)
xvii
xviii
Contributors
Scholar, 2009–2011, Durham, NC, USA; UNC-Chapel Hill School of Nursing,
Durham, NC, USA,
[email protected]
Lillian F. Lien Division of Endocrinology, Metabolism, and Nutrition, Department
of Medicine, Durham, NC 27710, USA; Duke Inpatient Diabetes Management,
Duke University Medical Center, Durham, NC 27710, USA,
[email protected]
Melanie E. Mabrey Duke Inpatient Diabetes Management, Department of
Advanced Clinical Practice, Duke University Hospital, Durham, NC, USA; Duke
University Schools of Nursing and Medicine, Duke University Medical Center,
Durham, NC, USA,
[email protected]
Lekshmi T. Nair Division of Endocrinology, Metabolism, and Nutrition,
Department of Medicine, Duke University Medical Center, Durham, NC 27710,
USA,
[email protected]
Anne T. Nettles Diabetes CareWorks, Wayzata, MN, USA,
[email protected]
Jennifer V. Rowell Division of Endocrinology, Metabolism, and Nutrition,
Department of Medicine, Duke University Medical Center, Durham, NC 27710,
USA,
[email protected]
Chapter 1
Physiology of Diabetes Mellitus
and Types of Insulin
Bryan C. Batch, Mary E. Cox, and Lillian F. Lien
Keywords Type 1 diabetes · Type 2 diabetes · MODY · Insulin resisR
R
) · Glulisine insulin
) · Lispro insulin (Humalog
tance · Aspart insulin (Novolog
R
R
R
(Apidra ) · Regular insulin (Humulin · Novolin ) · NPH insulin · Detemir
R
R
)
) · Glargine insulin (Lantus
insulin (Levemir
Prevalence
In 2008, the Centers for Disease Control and Prevention (CDC) estimated that 24
million people in the United States had diabetes mellitus, constituting nearly 8% of
the population. The CDC further estimated that 57 million individuals were affected
by prediabetes, and approximately 10% of those with prediabetes will progress
to diabetes each year. Because of this large population of individuals who now
have and who will have diabetes in the near future, it is important for providers to
have a basic understanding of diabetes pathophysiology and to thoughtfully pursue
appropriate diagnoses.
The American Diabetes Association (ADA) has defined diagnostic criteria for
diabetes and prediabetes (Table 1.1).
Pathophysiology
Glucose homeostasis is a balance of many factors, including insulin release from
the pancreas, central and peripheral insulin utilization, and endogenous production
and exogenous intake of glucose. Both insulin release and insulin utilization are,
in turn, modulated by many cytokines and hormones. When either insulin release
is insufficient or insulin utilization is incomplete (i.e., insulin resistance), diabetes
mellitus is the result.
B.C. Batch (B)
Division of Endocrinology, Metabolism, and Nutrition, Department of Medicine, Duke University
Medical Center, Durham, NC 27710, USA; Department of Veterans Affairs, Durham, NC
27707, USA
e-mail:
[email protected]
L.F. Lien et al. (eds.), Glycemic Control in the Hospitalized Patient,
C Springer Science+Business Media, LLC 2011
DOI 10.1007/978-1-60761-006-9_1,
1
2
B.C. Batch et al.
Table 1.1 American Diabetes Association diagnostic criteria for prediabetes and diabetes
Diagnosis
Diagnostic test
Prediabetes: impaired fasting
glucosea
Prediabetes: impaired glucose
tolerancea
Diabetes
Fasting plasma glucose of 100–125 mg/dL (5.5–6.9 mmol/L)
75-g OGTT 2-h plasma glucose of 140–199 mg/dL
(7.7–11 mmol/L)
Fasting plasma glucose ≥126 mg/dL (7 mmol/L)
Or
Random plasma glucose ≥200 mg/dL (≥11.1 mmol/L) with
symptoms of diabetes (polyuria, polydipsia, unexplained
weight loss)
Or
75-g OGTT 2-h plasma glucose ≥200 mg/dL
(≥ 11.1 mmol/L)
Or
A1c ≥6.5%
OGTT, oral glucose tolerance test
a There is no formal A
1C cut-off point that defines the category of prediabetes, but values between
5.7 and 6.5% suggest patients who are “at risk”
There are two main forms of diabetes, types 1 and 2 (Table 1.2). Although the
clinical results of hyperglycemia and related complications are similar among the
types of diabetes, establishment of a clinical distinction is important to guide appropriate management. This being said, it is important to recognize that it may not
always be possible to classify patients firmly as having “either” type 1 or type 2,
Table 1.2 Characteristics of type 1 and type 2 diabetesa
Characteristic
Type 1 diabetes
Type 2 diabetes
Age at onset
Symptoms at diagnosis
Cause of diabetes
Young; typically <40 years of age
Polyuria, polydipsia, weight loss;
patients typically are ill at the
time of presentation
Pancreatic destruction
Weight
Family history
Presence of antibodies
Acute complications
Normal
~10%
Present in 90%
DKA
C-peptide or endogenous
insulin level
Low
Adult
May be detected on routine
screening or present with
symptoms
Insulin resistance in
combination with β-cell
dysfunction
Overweight or obese
>90%
Uncommon
Hyperosmolar nonketotic
hyperglycemia; DKA is rare
Normal or high
DKA, diabetic ketoacidosis
a For each characteristic of disease, there may be exceptions. The distinction between type 1 and
type 2 diabetes must be made based on a compilation of all of the clinical evidence rather than
with any single characteristic
1
Physiology of Diabetes Mellitus and Types of Insulin
3
given the reality that diabetes mellitus actually encompasses a group of heterogeneous disorders. Here, we discuss the basic underlying pathophysiology and clinical
characteristics of the two major types of diabetes, as well as a hereditary form of
diabetes called maturity onset diabetes of the young (MODY).
Type 1 Diabetes
Type 1 diabetes presents with an absolute deficit of pancreatic insulin production
due to T cell-mediated destruction of the β-cells. Additionally, autoantibodies have
been detected in up to 90% of patients with immune-mediated diabetes. The stimulus for this autoimmune destruction is not well understood. Type 1 diabetes results
in an absolute insulin deficiency and must be treated with exogenous insulin.
Individuals with type 1 diabetes often are affected from a young age, although
there is a subset of patients who present with immune-mediated diabetes at an older
age. This is called latent autoimmune diabetes of the adult (LADA). All patients
with type 1 diabetes are at risk for the acute complication of diabetic ketoacidosis, as
described in Chapter 6. Other characteristics of the disease can be seen in Table 1.2.
Diseases that result in destruction of the pancreas from nonimmune causes,
such as pancreatectomy, pancreatitis, and cystic fibrosis, will result in a similar
insulin deficiency and require treatment with insulin. Many of these patients have
additional problems with glucose homeostasis and will require management by an
endocrinologist.
Type 2 Diabetes
Type 2 diabetes has a complex physiology involving many processes that, together,
lead to hyperglycemia and its associated complications. Individuals with type 2
diabetes often are overweight or obese, and caloric excess is a key precipitant.
This contributes to excess adiposity and insulin resistance. However, adiposity and
peripheral insulin resistance are not the only factors; β-cell dysfunction appears
to play a pivotal role as well. Prevention and treatment of type 2 diabetes must
be directed at both pathologic components: preservation of β-cell function and
improvement in insulin resistance. This therapy leans heavily toward lifestyle modification via healthy eating and exercise, and it comes to incorporate many types of
medical therapies as well.
MODY
MODY is an uncommon, autosomal dominant form of diabetes, sometimes referred
to as “monogenic” diabetes. There are various forms of MODY, which vary in severity from manageable with diet to completely dependent on insulin. The pathologic
deficit is at the level of insulin secretion, although some amount of insulin secretion often is maintained. It is important to distinguish MODY from other types of
diabetes, as the hyperglycemia in patients with MODY often responds very well to
4
B.C. Batch et al.
sulfonylurea medications. Individuals who are suspected to have MODY should be
referred to an endocrinologist for assessment and counseling.
Types of Exogenous Insulin
The most common treatment for hyperglycemia in the inpatient setting is the
administration of subcutaneous insulin. The insulin formulations available today far
exceed what was available even a decade ago. Although this variety of formulations
enables providers to individualize therapy for each patient’s unique needs, it also
creates opportunity for confusion. Inpatient providers must be attentive to details
of their patients’ regimens to avoid medication errors. The insulins are categorized
according to their durations of action: rapid-, short-, intermediate-, and long-acting
(Table 1.3).
Table 1.3 Types of insulin
Insulin type
Onset of action
Time to peak
Duration
Administration
Lispro
R
(Humalog
)
Aspart
R
)
(Novolog
Glulisine
R
(Apidra
)
Regular
R
(Humulin
,
R
Novolin
)
NPH
Glargine
R
(Lantus
)
1–2 h
30 min
1–2 h
short-acting
intermediate- long-acting
acting
1–2 h
2–4 h
4–10 h
No peak
3–5 h
4–8 h (subcu- 12–20 h
~24 h
taneous)
Without regard
30–60 min
≤15 min before 30–60 min
before meals before meals to meals;
meals or
usually at
or at
immediately
bedtime
bedtime
after meals
15–30 min
rapid-acting
Detemir
R
(Levemir
)
~1 h
long-acting
No/little peak
Up to 24 h
Without regard
to meals;
daily to
twice per
day
R
R
),
), Aspart (Novolog
Rapid-Acting Insulin: Lispro (Humalog
R
and Glulisine (Apidra )
The rapid-acting insulin formulations, also called analog insulins, are characterized
by a rapid onset (15–30 min), rapid peak (1–2 h), and limited duration (3–5 h).
Because of the rapid onset of action, these insulin formulations must be accompanied by food. Specifically, they should be administered no more than 15 min prior
to meals or, in the case of uncertain food intake, they can be given immediately after
meals. If a patient is temporarily fasting, then the rapid-acting insulin should not be
given.
1
Physiology of Diabetes Mellitus and Types of Insulin
5
R
R
)
, Humulin
Short-Acting Insulin: Regular (Novolin
Like the rapid-acting insulins, regular insulin typically is given for prandial coverage. A basal-prandial insulin regimen containing regular insulin usually consists of
regular insulin injected with each meal (breakfast, lunch, and supper), accompanied
by an injection of neutral protamine hagedorn (NPH) insulin at bedtime.
Regular insulin must be given 30 min before meals and can be expected to reach
its peak activity approximately 2–4 h later. Its duration of action lasts 4–8 h. Regular
insulin has the advantage of being inexpensive, and it can be mixed in a syringe
with NPH insulin if patients require concomitant administration. However, some
patients and providers find that it is inconvenient to administer insulin 30 min prior
to mealtime. Additionally, use of regular insulin leads to a slightly greater risk
for hypoglycemia than use of the newer insulin analogs. For these reasons, some
providers are moving away from its use for prandial coverage.
Intermediate-Acting Insulin: Neutral Protamine Hagedorn
NPH insulin is considered an intermediate-acting insulin, with a prolonged duration
of action over 12–20 h. It has an onset of action time of 1–2 h, and a peak action time
of 4–10 h. NPH insulin commonly is given for basal coverage, either at bedtime,
in the morning, or at both times. It also can be combined with regular insulin for a
mixed preparation. Like regular insulin, NPH insulin is fairly inexpensive, and it can
be mixed with regular insulin. The disadvantage of NPH insulin is that its delayed
peak may cause hypoglycemia. For this reason, some providers prefer to replace
NPH with one of the newer long-acting insulins.
Mixture of Regular and NPH Insulin
This combination typically is not recommended in the hospital and should be continued only if the patient is stable on this regimen at home and when other factors,
such as diet, activity level, and scheduled procedures, have been considered. When
mixing regular and NPH insulin, the regular insulin must be drawn into the syringe
first, so that contamination of the regular insulin with NPH insulin will not occur.
This contamination could alter the kinetics of the regular insulin. There are a variety
of available premixed insulin formulations (Table 1.4), but we do not recommend
their routine use in the hospital.
Table 1.4 Premixed insulin formulations
Combination insulins
Long-acting component
Short-acting component
R
70/30TM or
Humulin
R
70/30TM
Novolin
R
NovoLog Mix
70/30TM
R
Humalog Mix 75/25TM
70% NPH
30% regular
70% aspart-protamine suspension
75% lispro-protamine suspension
30% aspart
25% lispro
6
B.C. Batch et al.
R
) and Detemir
Long-Acting (Basal) Insulin: Glargine (Lantus
R
)
(Levemir
Glargine and detemir insulins are unique basal insulin formulations that have little
to no true peak. Their duration of action is up to 24 h. These insulins have the advantage of provision of “smooth” basal coverage, reducing the risk for hypoglycemia
that can be seen with insulins that peak. However, some patients will experience a
peak effect with these formulations, and glucoses should be monitored regularly as
with use of all insulins. It should be noted that long-acting insulins cannot be mixed
in a syringe with other insulins.
For more information on how to properly dose and administer the various insulins
discussed above, see Chapter 2: Subcutaneous Insulin and Chapter 11: Transition to
Outpatient Care.
Bibliography
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Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of
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Chapter 2
Subcutaneous Insulin: A Guide for Dosing
Regimens in the Hospital
Karen Barnard, Bryan C. Batch, and Lillian F. Lien
Keywords Basal-bolus insulin · Prandial insulin · Basal insulin · Correction dose
insulin · Total daily dose of insulin
Basal-Bolus Insulin
Insulin continues to be the preferred method for the management of hyperglycemia
in the inpatient setting. It can be titrated easily, does not have a ceiling dose, and can
be administered intravenously and subcutaneously. Details of IV insulin, including
the transition from IV to subcutaneous, are discussed in Chapter 3: IV Insulin. In
this chapter, we focus on subcutaneous insulin regimens.
Many patients who require subcutaneous insulin in the hospital will already have
a diagnosis of diabetes; some will have been on insulin prior to admission. However,
some nondiabetic patients may develop hyperglycemia as well. For all inpatients
with hyperglycemia, we recommend a proactive insulin regimen that includes two
components: (1) basal insulin, to cover basal insulin needs (mainly due to hepatic
glucose production) and (2) bolus (or prandial) insulin, to cover any forms of caloric
intake—meals, enteral feedings, or total parenteral nutrition (TPN). This strategy
is referred to as basal-bolus insulin. For patients with type 1 diabetes, the basalbolus insulin strategy is optimal, and these patients should always receive basal
insulin, even during periods of fasting. Patients with type 1 diabetes require exogenous insulin to prevent the production of ketones and the subsequent development
of diabetic ketoacidosis (DKA). For patients with type 2 diabetes also, the basalbolus insulin strategy is preferred; however, the insulin requirement may decrease
over periods of prolonged fasting. Current evidence supports the basal-bolus regimen as more effective, easier to design and adjust, better for blood glucose control,
and lower risk for hypoglycemia than alternative strategies.
K. Barnard (B)
Department of Medicine, Division of Endocrinology, Metabolism, and Nutrition, Duke University
Medical Center, Durham, NC 27710, USA
e-mail:
[email protected]
L.F. Lien et al. (eds.), Glycemic Control in the Hospitalized Patient,
C Springer Science+Business Media, LLC 2011
DOI 10.1007/978-1-60761-006-9_2,
7
8
K. Barnard et al.
An optional insulin regimen component is the correctional insulin scale (socalled sliding scale). The scale is used before meals along with the bolus insulin
to correct hyperglycemia. The correctional insulin scale should not be used alone
for patients with diabetes; this reactive strategy will not be effective to prevent
hyperglycemia or inpatient complications such as hypoglycemia.
Special Care Situations
Subcutaneous insulin may not always be appropriate for patients in the intensive
care unit, particularly those with severe sepsis, requiring vasopressors, with acute
hepatic failure, or with severe hypoalbuminemia. In these patients IV insulin may
be a better choice. An endocrinology consultant can assist with decision making in
situations such as these.
Key Points: Basal-Bolus Insulin
• Insulin strategy: Basal + bolus + correctional insulin scale (optimal insulin
regimen)
• Correctional insulin scale: avoid using as only insulin regimen. It is only good
for patients who are at risk for hyperglycemia, but who do not currently have
hyperglycemia.
• Patients with type 1 diabetes always require basal insulin, even if they are not
eating.
Transition from Outpatient to Inpatient Care
A patient’s outpatient regimen may not be appropriate in the inpatient setting for a
variety of reasons.
• Stress can either increase or decrease a patient’s insulin requirements.
• Nutrition in the hospital may be different from that at home (i.e., carbohydrate
content, total calories, periods of fasting, etc., may be different).
• Medical conditions, such as hypotension, vasopressor use, edema, acute renal
failure, surgical procedures, may alter insulin requirements.
• The insulin dose at home may not have provided adequate control.
• For patients who use premixed (2 shots/day) insulin products, such as 70/30
R
Mix 70/30) and 50/50 (Humulin 50/50; Humalog
(Humulin 70/30; Novolog
Mix 50/50) at home: These components are not easily titrated in the inpatient
setting. We recommend transition to a basal-bolus insulin regimen while these
patients are hospitalized.
• Patients who have no prior diagnosis of diabetes, but who are at risk for developing hyperglycemia in the hospital (such as those receiving glucocorticoids or
other medications, or TPN or enteral nutrition [EN]), should have their glucose
closely monitored. If a patient develops consistent hyperglycemia, scheduled
basal-bolus insulin should be initiated.
2
Subcutaneous Insulin: A Guide for Dosing Regimens in the Hospital
9
Glucose Monitoring
How Often to Monitor?
The frequency of monitoring will depend on the patient’s nutrition pattern and
insulin regimen.
• Patients eating scheduled meals should be monitored before meals, at bedtime,
and, for some, at 3 AM. The 3 AM level can aid in interpretation of an elevated fasting glucose; potential causes include the “dawn phenomenon” and the
“Somogyi effect,” a rebound rise in blood glucose after hypoglycemia. Once
glucoses are stable overnight, the 3 AM check can be discontinued.
• Patients receiving enteral feeding in boluses should be monitored prior to each
bolus while the insulin regimen is still being adjusted. Once the insulin dose is
stable, monitoring every 6 h is usually sufficient.
• If a patient has symptoms that could be consistent with hyper- or hypoglycemia,
the glucose should be checked immediately, even if it is not a prescribed
monitoring time.
Blood Glucose Targets
Over the last several years, the optimal glycemic target for the hospitalized patient
with hyperglycemia has been the focus of significant discussion and controversy.
However, it is reasonable to pursue the following as a straightforward set of goals
that can be used in the treatment of most inpatients:
• Pre-meal blood glucose less than 140 mg/dL (7.8 mmol/L)
• Random blood glucose of less than 180 mg/dL (10.0 mmol/L)
• Recent discussions of glycemic control have emphasized the importance of individualizing targets. The selection of a more or less stringent target will depend
on the patient’s history of previous glucose control and current medical status
(e.g., less stringent in patients with terminal illness and those with history of
hypoglycemia unawareness).
Choosing an Insulin Regimen
The calculations recommended in this chapter are estimates and are meant to be
a starting point. Always use clinical judgment, and make adjustments based on
glucose readings obtained over the subsequent 24 h.
Obtain Baseline Information
Subjective: Type of diabetes, new or established, home medications (insulin and
non-insulin), total daily dose (TDD) of insulin at home, hypoglycemia frequency,
and symptoms.
10
K. Barnard et al.
Objective: Age, weight, height, body mass index (BMI), previous hemoglobin
A 1 C (if available), glomerular filtration rate (GFR), liver function tests, nutritional
status in the hospital, use of new medications such as glucocorticoids.
Calculate the Total Daily Insulin Dose
General Considerations
As discussed earlier in this chapter, multiple factors can affect the insulin regimen
of a hospitalized patient. Although the degree of glycemic control optimal for the
hospitalized patient is still debated, there is no debate regarding the importance of
avoiding hypoglycemia. Insulin dosages can be rapidly and easily titrated upward,
so it is reasonable to start near the low end of an estimated dose calculation and to
ensure that necessary adjustments are made promptly. For patients with GFR less
than 60 (stage III or higher chronic kidney disease (CKD), as well as those with
acute renal failure), see the section on renal impairment below.
• For patients with type 1 diabetes, the total daily insulin dosage can be estimated
at 0.3–0.5 units/kg/day. Patients with type 1 diabetes often are quite sensitive to
insulin; thus, it is reasonable to start on the low end.
• For patients with type 2 diabetes, the total daily insulin dosage can start at 0.3–
0.7 units/kg/day. Patients with type 2 diabetes have varying degrees of insulin
resistance, so a patient who is new to insulin, with uncertain needs, may benefit
from a relatively low dose to start. However, some patients may require more
than 1 unit/kg/day. If there is uncertainty about the level of insulin resistance, it
is simple and safe to start with a TDD of 0.5 units/kg/day.
Scenarios and Examples
Scenario 1: Patient with Hyperglycemia (With or Without Diabetes)
Who Is New to Insulin
The patient is new to insulin, so it is reasonable to start with a TDD of
0.3 units/kg/day. However, a higher TDD may be implemented in certain cases.
0.1 units/kg/day can be added to the TDD for the presence of each of the following:
• The patient has type 2 diabetes and is less than 70 years old.
• The patient has evidence of difficult control; that is, he or she takes at least
three oral agents at home, or the hemoglobin A1C is greater than 8%, or he
or she reports fasting glucoses greater than 200 mg/dL (11.0 mmol/L) prior to
admission.
• The patient has a BMI greater than 35 kg/m2 .
For example, a 40-year-old patient with type 2 diabetes who has never used
insulin, whose preadmission A1C is 9%, and whose BMI is 36 kg/m2 , could
reasonably be given a TDD of 0.6 units/kg/day.
2
Subcutaneous Insulin: A Guide for Dosing Regimens in the Hospital
11
Scenario 2: Patient with Type 2 Diabetes, on Known Dosages
of Insulin at Home
The first step is to determine the patient’s true TDD. Consistency of usage is an
important component of the history. Does the patient always take the prescribed
dosage, or does he or she make modifications? How often does he or she miss an
insulin dose?
In order to determine the safety of the patient’s reported TDD, it is helpful to
calculate a weight-adjusted TDD based on units per kilogram per day. For example,
a patient has type 2 diabetes and normally takes 40 units of insulin per day. He
weighs 80 kg. His weight-based TDD is 40 units/80 kg/day, or 0.5 units/kg/day.
This is reasonable and likely to be safe for a patient with type 2 diabetes. Based
on this calculation, it is reasonable to continue with the patient’s home TDD in the
hospital. If the dose seems too high, a smaller dose can be used initially, with prompt
increases as deemed necessary from monitored glucose values.
A list of situations for which the insulin dose can be modified is found in
Table 2.1.
Table 2.1 Situations warranting cautious modification of home total daily dose of insulina
Situation
Modification
Type 1 diabetes and uncontrolled glucoses (A1C >8%) or
fasting glucoses >200 mg/dL (11 mmol/L)
Type 2 diabetes and uncontrolled glucoses (A1C >8%) or
fasting glucoses >200 mg/dL (11 mmol/L)
Patient is ABOUT TO BEGIN corticosteroids (newly
prescribed for the inpatient stay)
Patient reports hypoglycemia unawareness
Hypoglycemia within the past 24 h: Glucose 50–70 mg/dL
(2.8–3.9 mmol/L)
Hypoglycemia within the past 24 h: Glucose <50 mg/dL
(2.8 mmol/L)
↑home TDD by 10%
↑ home TDD by 20%
↑ home TDD by 20%
↓ home TDD by 20%b
↓ home TDD by 30%b
↓ home TDD by 40%b
TDD, total daily dose
a These recommendations are based on the algorithm developed by the Duke University Medical
Center Glycemic Safety Committee
b Always consider making further adjustments if the patient continues to develop hypoglycemia
despite changes
Scenario 3: Patient with Type 2 Diabetes Who Is Not Using Insulin
and Is Not Hyperglycemic in the Hospital
This situation can occur in patients with type 2 diabetes who are overnourished
at home but who are admitted after periods of fasting, as in gastrointestinal illnesses, or who have had moderate weight loss related to illness or other factors.
Patients who are not hyperglycemic can be followed with glucose monitoring alone,
at least four times daily, usually before meals and at bedtime. However, a scheduled insulin regimen must be added if glucoses rise above the target ranges. It is
12
K. Barnard et al.
not appropriate to follow hyperglycemia with only a correctional insulin scale; this
retroactive approach does not effectively prevent future hyperglycemic episodes and
will increase the risk for hypoglycemia.
Insulin for Patients with Renal Impairment
For patients with renal impairment, it often is necessary to decrease the TDD
depending on the stage of kidney failure due in large part to changes in insulin
clearance (Table 2.2). This applies to patients with both chronic and acute renal failure, although patients with improving renal function after acute failure may have
increasing insulin requirements. As always, prompt adjustments should be made
according to monitored glucoses.
Table 2.2 Renal impairment warranting cautious modification of total daily dosea
Situation
Modification
Patient on insulin at home, no history of hypoglycemia,
and stable CKD stage I and II (GFR >40 mL/min per
BSA 1.73 m2 )
CKD stage III (GFR 30–39 mL/min per BSA 1.73 m2 )
CKD stage IV (GFR 15–29 mL/min per BSA 1.73 m2 )
CKD stage V (GFR 15 mL/min per BSA 1.73 m2 ) or
ESRD or acute renal injury
None: May use home TDD
↓ home TDD by 30%
↓home TDD by 50%
↓home TDD by 60%
BSA, body surface area; CKD, chronic kidney disease; ESRD, end-stage renal disease; GFR,
glomerular filtration rate; TDD, total daily dose
a These recommendations are based on the algorithm developed by the Duke University Medical
Center Glycemic Safety Committee
Insulin for Patients Taking Glucocorticoids
For patients taking glucocorticoids, it is recommended by some diabetologists that
R
R
) insulin be used in order to adjust for the
, Humulin R
regular (Novolin R
delayed increase in prandial glucose that may be seen in this scenario. In patients
taking glucocorticoids, the fasting glucose may be minimally increased, with a substantially more exaggerated increase in postprandial glucose. Occasionally, patients
without a previous diagnosis of diabetes might require only prandial insulin. As
with other patients with hyperglycemia, the insulin dose should be based on the
patient’s weight, calorie consumption, meal time, and other associated factors that
might be affecting glycemic levels (e.g., the patient’s status following major surgical
intervention).
Distribution of the Total Daily Dose
Most experts agree that a basal-bolus insulin regimen is the best approach for
patients requiring intensive insulin treatment. The variable timing of nutrition,
2
Subcutaneous Insulin: A Guide for Dosing Regimens in the Hospital
13
medications, and procedures in the hospital makes premixed and split-mix insulin
regimens unreliable and dangerous. Basal-bolus insulin regimens will be different for patients who are eating regular, discrete meals than for those who have
continuous nutrition (through EN or TPN routes) and those who are fasting.
The Patient Who Is Eating Discrete Meals
A basal-bolus regimen for this patient can be accomplished in two ways: (1) a
R
R
]), for
] or detemir [Levemir
long-acting peakless insulin (i.e., glargine [Lantus
R
the basal component with a rapid-acting insulin (i.e., aspart [Novolog ], lispro
R
R
]) at mealtime, or (2) an intermediate-acting
], or glulisine [apidra
[Humalog
insulin (i.e., NPH [Neutral Protamine Hagedorn]) at bedtime with a short-acting
R
or Humulin R]) at mealtime.
insulin (i.e., regular [Novolin R
Long-Acting Insulin (Glargine[Lantus] or Detemir[Levemir]), with
Rapid-Acting Insulin (Aspart[Novolog], Lispro[Humalog],
or Glulisine[Apidra])
Long-acting insulin serves as the entire basal component; 50% of the TDD usually
is administered as one or two long-acting insulin injections over 24 h. (If this component is greater than 50 units, it is advisable to give it as two injections to maximize
absorption). This can be done at the same time or divided into morning and evening
doses, according to the physician and patient preferences. The remaining 50% of
the dose is divided into three mealtime injections of rapid-acting insulin such that
approximately 17% is administered at each meal. It should be noted that this equal
distribution of mealtime doses must be adjusted subsequently based on glucose levels; it is rare for a patient to consume equal amounts of carbohydrates for each meal
of the day. If the patient skips a meal, rapid-acting insulin should not be given.
Although a basal insulin such as glargine or detemir can be given at any time of
the day, it is commonly given at bedtime, in part to prevent the mistake of mixing it
with a short- or rapid-acting insulin.
Intermediate-Acting Insulin (NPH[Neutral Protamine Hagedorn]),
and Short-Acting Insulin (Regular [Novolin R or Humulin R])
In this strategy, the basal and bolus components are not distinctly divided into separate insulins. Thus, the role of each insulin is not as intuitive as with the long- and
rapid-acting insulins. Nonetheless, the strategy is simple. Here, 25% of the TDD is
administered as short-acting (regular) insulin before each of the three meals. The
remaining 25% is administered as intermediate-acting (NPH) insulin at bedtime.
An important feature of this type of plan is that, unlike the long- and rapid-acting
insulin plan, mealtime insulin must be given even when a meal is omitted or reduced.
This is because the mealtime insulin covers part of the basal-insulin requirement.
When a patient is fasting, the “mealtime” insulin dose should be reduced by half,
14
K. Barnard et al.
and the full bedtime dose should be continued unchanged (see below). Additionally,
it is important to consider proper timing of the short-acting insulin in relation to
meals. The most challenging aspect of this regimen in the inpatient setting is to
ensure the delivery of short-acting insulin 30–45 min before a meal, for optimal
efficacy.
NPH insulin has a significant peak, albeit fairly broad, which means it has a
bolus component as well. Therefore, in some people, it may be helpful when given
in the morning, to help cover lunch, and given at bedtime to help with the dawn
hepatic glucose output surge. However, for patients who are fasting and who do not
exhibit this dawn phenomenon, the dose of evening NPH must be reduced to prevent
hypoglycemia. Furthermore, NPH insulin is not recommended for daytime use for
patients who are fasting, as the midday peak may result in hypoglycemia.
The Patient Who Is Not Eating
The general principal in this situation is to continue the basal component while
removing the bolus component. For the long- and rapid-acting insulin strategy
described above, the long-acting insulin can be continued at the usual dose and time.
The rapid-acting insulin is not given. When used at an appropriate dose, basal insulin
should not cause fasting hypo- or hyperglycemia. However, for patients who will
have prolonged periods of fasting or whose basal dose is unknown, administration
of a long-acting basal insulin may increase the risk for prolonged hypoglycemia, and
use is not recommended. These patients can be transitioned to a regimen of regular
insulin every 6 h, as below. For the intermediate- and short-acting insulin regimen,
the regimen can be changed in two ways. If the period of fasting is short-term, the
existing regimen can be continued, with administration of half doses of the regular
insulin at mealtimes. Alternatively, for patients who are not eating for an extended
period of time, short-acting (regular) insulin may be given every 6 h without any
intermediate-acting (NPH) insulin. In this second strategy, there will still be a small
peak in the insulin activity, but it prevents hyperglycemia similar to longer-acting
basal insulin, without the danger of prolonged hypoglycemia.
Patients with type 1 diabetes should always receive basal insulin, even if they are
not eating, to prevent development of DKA. If necessary, IV dextrose (D5) may be
given to support blood glucose during this time.
Correctional Insulin Scale
The correctional insulin scale is a tool designed to correct unpredictable hyperglycemia so that a patient’s scheduled insulin regimen can be effective. It should not
be used alone. Importantly, correctional insulin is given as a rapid- or short-acting
insulin along with bolus insulin (depending on the patient’s scheduled insulin type);
it should never be given at bedtime.
Although many institutions have a “standard” correctional insulin scale, it is better to calculate an individualized scale to avoid under- or overtreatment. A quick
and easy estimation for the scale increment is to use 5% of the TDD of insulin. For
2
Subcutaneous Insulin: A Guide for Dosing Regimens in the Hospital
15
Table 2.3 Example of correctional insulin scale
Glucose
Correctional insulin dosea
150 mg/dL (8.0 mmol/L)
150–200 mg/dL (8.0–11.0 mmol/L)
201–250 mg/dL (11.1–13.8 mmol/L)
251–300 mg/dL (13.9–16.6 mmol/L)
>300 mg/dL (>16.6 mmol/L)
None
3 units
6 units
9 units
12 units
a In some patients it might be too aggressive to start a correctional insulin scale
at 150 mg/dL (8.0 mmol/L); e.g. a patient with hypoglycemia unawareness
example, if a patient has a TDD of 60, then 5% of 60 units is 3 units. Thus, the scale
is designed with 3-unit increments as shown in Table 2.3.
Key Points: Choosing an Insulin Regimen
• All of the calculations shown here are estimates. Each patient will have a unique
response to insulin, which will vary with inpatient circumstances. Thus, it is critical to reassess the regimen daily and adjust promptly. If this becomes challenging,
an endocrine consultant can assist.
• Calculate a weight-based TDD of insulin for a starting point, or use the home
TDD, if it appears reasonable.
• Make modifications based on age, type of diabetes, concern for hypoglycemia,
use of non-insulin antidiabetic agents, renal function, and concomitant glucocorticoid use.
• Divide into basal and bolus components and, if desired, add a correctional insulin
scale.
Bibliography
American Diabetes Association. Diabetes care executive summary from the American Diabetes
Association. Standards of medical care in diabetes 2009. Diabetes Care. 2009;32(suppl 1):
S6–S12.
Campbell KB, Braithwaite S. Hospital management of hyperglycemia. Clin Diabetes.
2004;22(2):81–88.
Clement S, Braithwaite SS, Magee MF, et al. Management of diabetes and hyperglycemia in
hospitals. Diabetes Care. 2004; 27(2):553–591.
Hamann A, Matthaei S, Rosak C, Silvestre L for the HOE901/4007 Study Group. A randomized clinical trial comparing breakfast, dinner, or bedtime administration of insulin glargine in
patients with type 1 diabetes. Diabetes Care. 2003; 26(6):1738–1744.
Hirsch I, Pauw D, Brunzell J. Inpatient management of adults with diabetes. Diabetes Care. 1995;
18(6):870–878.
Inzucchi SE. Management of hyperglycemia in the hospital setting. N Engl J Med. 2006;
355(18):1903–1911.
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Kitabchi A, Freirea A, Umpierrez G. Evidence for strict inpatient blood glucose control: time to
revise glycemic goals in hospitalized patients. Metabolism. 2008; 57(1):116–120.
Levetan C, Magee M. Hospital management of diabetes. Endocrinol Metab Clin N Am. 2000;
29(4):745–770.
Lien LF, Bethel MA, Feinglos MN. In-hospital management of type 2 diabetes mellitus. Med Clin
N Am. 2004;88(4):1085–1105, xii.
Moghissi ES, Korytkowski MT, DiNardo M. American Association of Clinical Endocrinologist
and American Diabetes Association consensus statement on inpatient glycemic control. Endocr
Pract. 2009;15(4):1–17.
Nathan D. Insulin treatment of type 2 diabetes mellitus. In: Prote D, Sherwin R, Baron A, eds.
Ellenberg and Rifkin’s Diabetes Mellitus. 6th ed. New York, NY: McGraw-Hill; 2003:515–522.
NICE-SUGAR Study Investigators. Intensive versus conventional glucose control in critically ill
patients. N Engl J Med. 2009;360(13):1283–1297.
Trence DL. Management of patients on chronic glucocorticoid therapy: an endocrine perspective.
Prim Care. 2003;30(3):593–605.
Umpierrez GE, Andres P, Smiley D, et al. Randomized study of basal-bolus insulin therapy in
the inpatient management of patients with type 2 diabetes (Rabbit 2 trial). Diabetes Care.
2007;30(9):2181–2186.
Umpierrez GE, Palacio A, Smiley D. Sliding scale insulin dose: myth or insanity. Am J Med.
2007;120(7):563–567 (Review).
Wesorick D, O’Malley C, Rushakoff R, Larsen K, Magee M. Management of diabetes and hyperglycemia in the hospital: a practical guide to subcutaneous insulin use in the non-critically ill,
adult patient. J Hosp Med. 2008;3(suppl 5):S17–S28.
Wittlin S, Woehrle H, Gerich J. Insulin pharmacokinetics. In: Leahy J, Cefalu W, eds. Insulin
Therapy. New York, NY: Marcel Dekker; 2002:73–85.
Chapter 3
IV Insulin Infusions: How to Use
an “Insulin Drip”
Melanie E. Mabrey and Lillian F. Lien
Keywords IV insulin · Diabetic ketoacidosis · Hyperosmolar nonketotic
hyperglycemia
Appropriate Scenarios for Use
Several clinical scenarios mandate the use of an IV insulin infusion (often informally referred to as an “insulin drip”). Any inpatient with diabetic ketoacidosis
(DKA) requires an IV insulin infusion for proper management; simply continuing
subcutaneous injections is not the standard of care in the hospital. Also, a patient
with hyperosmolar nonketotic hyperglycemia should be initially managed with IV
insulin. Indeed, any critically ill patient with persistent hyperglycemia for 24 h is
a candidate for an IV insulin infusion, particularly if the hyperglycemia lingers
despite increasing doses of subcutaneous insulin. Many surgical units now consider
IV insulin to be the standard of care in patients with diabetes during the perioperative period, based on the data that glycemic control decreases the risk for infection
and improves morbidity and mortality in the surgical patient. Common indications
for uses of IV insulin can be found in Table 3.1.
NOTE: A single dose of IV insulin as a bolus is only appropriate in two settings:
when starting an insulin infusion and for temporary treatment of hyperkalemia. It is
almost never sufficient to give a bolus of IV insulin without simultaneously starting
an IV insulin infusion. The half-life of IV insulin is only minutes; once given, the
insulin will be cleared within 20 minutes in patients with normal renal function.
This rapid clearance is the reason that an IV bolus alone is not effective.
Key Points: Scenarios for Use
• Use IV insulin for a patient with DKA or hyperosmolar nonketotic hyperglycemia, and consider it for any acutely ill patient (Table 3.1).
M.E. Mabrey (B)
Duke Inpatient Diabetes Management, Department of Advanced Clinical Practice, Duke University
Hospital, Durham, NC, USA; Duke University Schools of Nursing and Medicine, Duke University
Medical Center, Durham, NC, USA
e-mail:
[email protected]
L.F. Lien et al. (eds.), Glycemic Control in the Hospitalized Patient,
C Springer Science+Business Media, LLC 2011
DOI 10.1007/978-1-60761-006-9_3,
17
18
M.E. Mabrey and L.F. Lien
• Apart from emergent hyperkalemia treatment, never use a single IV insulin bolus
without simultaneously starting an IV insulin infusion.
• IV insulin has a very short half-life.
Table 3.1 Common indications for the uses of IV insulin
•
•
•
•
•
•
•
•
•
•
Diabetic ketoacidosis
Hyperosmolar nonketotic hyperglycemia
Persistent hyperglycemia, uncontrolled by subcutaneous insulin
Myocardial infarction
Dose finding in patients with glycemic lability
Hyperglycemia in high-dose corticosteroids
Labor and delivery
Peri- and postoperative glycemic management
Temporary, severe hyperglycemia induced by acute illness
Temporary, severe hyperglycemia induced by medications (i.e., glucocorticoids)
Starting the IV Insulin Infusion
IV insulin infusions are dosed in units per hour, based on weight in kilograms
(see Table 3.2). Regular insulin is the type most commonly prescribed for IV use.
Although there are anecdotal reports of rapid-acting types of insulin given via this
route, the efficacy and safety of these newer insulins in this setting are not well
studied.
Table 3.2 Initial IV insulin infusion rate calculations
Patient
Initial infusion rate
Bolus dose
DKA
0.1 units/kg/h
Any setting other than DKA
0.025 units/kg/h
0.1 units/kg given as a single
bolus prior to starting the
IV infusion (ADULTS
only)
May provide a 0.025 units/kg
single bolus when starting
the IV insulin
Bedside glucose monitoring should be performed hourly for the patient on IV
insulin until stable. Once blood glucoses have been stable for four consecutive
hours, some providers may allow some leniency in monitoring (i.e., glucose checks
every 2 h) but the default should always be hourly monitoring in an unstable patient.
Insulin is a major regulator of potassium via the sodium-potassium pump. Prior
to initiating IV insulin, the patient’s potassium level must be assessed. IV insulin
should not be started without treatment of the potassium if the level is less than
3.3 mEq/L. On the other hand, for hyperkalemic patients, IV insulin will assist with
transport of potassium into the cell. For details on the management of electrolytes
in DKA, see Chapter 6: Hyperglycemic Emergencies.
3
IV Insulin Infusions: How to Use an “Insulin Drip”
19
Adjusting the IV Insulin Infusion Rates
A number of protocols have been developed to assist with titration of IV insulin
infusion rates, and most hospitals have a preferred order set. We favor an insulin
infusion nomogram that takes into account the patient’s insulin-sensitivity level.
One way to achieve this is to adjust the insulin infusion according to the rate of
change of glucose level from hour to hour. A multiplication factor can be used to
assist with titration: An example of this type of protocol is the Lien-Spratt IV insulin
nomogram used throughout Duke University Hospital (Fig. 3.1). Implementation
of this nomogram was found to significantly reduce errors in the delivery of IV
insulin, which also reduced episodes of persistent hyperglycemia in critical care
patients.
Other IV insulin protocols account for differences in patients’ insulin sensitivities by using a choice format (with the appropriate algorithm chosen according
to level of sensitivity). In any case, a safe general goal for treatment of hyperglycemia with IV insulin is an hourly decrease in blood glucose of approximately
50–75 mg/dL (2.7–4.1 mmol/L). Overall, the choice of protocol is less important than ensuring that a single method of titrating IV insulin is used throughout
the institution and that providers and staff are all educated on how to properly adhere to the protocol to promote safety. If there is uncertainty about the
method at the institution, the charge nurse on the patient’s nursing unit should be
consulted.
Despite the effectiveness of IV insulin protocols for most patients, it is worth
noting that there are patients for whom no protocol is perfect. An example is the
highly insulin-resistant patient, who may require large volumes of IV insulin (e.g.,
>20 units/h). Similarly, the highly insulin-sensitive patient, particularly those with
renal failure and type 1 diabetes, may require very small volumes of insulin. This
type of patient will require the attention of an experienced provider (rather than a
protocol alone), and when an endocrinology consultation is available, it should be
requested.
Key Points: Implementation of IV Insulin
• Start the infusion at a weight-based dose rate (Table 3.2).
• Titrate the dose according to the institution’s protocol (Fig. 3.1), including
frequent glucose monitoring.
Special Scenario: IV Insulin in the Patient Who Is Eating
If the patient is ready to start eating regular food but still requires an insulin infusion,
the IV insulin infusion will cover basal insulin needs, but will generally not be
effective for the patient’s prandial hyperglycemia. Thus, a reasonable strategy is to
20
M.E. Mabrey and L.F. Lien
Fig. 3.1 (continued)
continue the IV infusion of regular insulin as before, titrated per the usual protocol,
while also adding low-dose rapid-acting insulin given subcutaneously at each meal.
Orders for this patient may appear as follows:
R
R
) insulin. Titrate according to
or Humulin R
• Infuse IV regular (Novolin R
nomogram, using data from hourly blood glucose monitoring.
3
IV Insulin Infusions: How to Use an “Insulin Drip”
21
Fig. 3.1 Duke University Hospital: Lien-Spratt IV insulin nomogram. Source: Lien et al. (2005).
Reproduced with permission from Endocrine Practice and the American Association of Clinical
Endocrinologists
22
M.E. Mabrey and L.F. Lien
R
R
• Give 6 units1 of lispro (Humalog
), or glulisine
) or aspart (Novolog
R
(Apidra ) insulin subcutaneously three times/day before meals only. Hold if
patient is NPO (nothing by mouth).
Transitioning to Subcutaneous Insulin
The first important step is determining when it is safe to transition the patient from
an IV to a subcutaneous insulin regimen. The patient may be ready for the transition
if the following are in place:
• Stable blood glucoses between 140 and 180 mg/dL (7.7–10 mmol/L) for at least
4–6 h consecutively
• Normal anion gap
• Resolution of acidosis
• Stable clinical status
• Not on vasopressors
• Stable nutrition plan or patient is eating
Once a patient stabilizes insulin requirements may change dramatically, and it
is prudent to monitor the glucose levels frequently, particularly when transitioning
from IV to subcutaneous insulin.
Transitioning from IV to Subcutaneous Insulin
in the NPO Patient
In the NPO patient, the conversion is fairly straightforward; it is reasonable to
assume that the IV insulin infusion has accounted for the patient’s basal needs.
Step 1: Calculate the 24-h IV insulin requirement. In other words, how much IV
insulin does the patient need to maintain control over 24 h? Keep in mind that it may
be necessary to estimate an average infusion rate based on a shorter period of time
(such as between midnight and 6 AM) if the glucoses were the most stable during
that period (Table 3.3).
Table 3.3 Insulin infusion rate example
Time
2100
Glucose (mg/dL)
Insulin rate (units/h)
300
200
110
130
140
126
130
128
135
140
4.0
2.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1 The
2200
2300
MN
0100
0200
0300
0400
0500
0600
dose estimate for the subcutaneous rapid-acting insulin with meals should be fairly conservative, as many patients may be just beginning to resume food intake in this scenario. In general,
we would recommend a dose of no more than 0.1 units/kg/day subcutaneously with each meal.
3
IV Insulin Infusions: How to Use an “Insulin Drip”
23
• Since the patient has had stable glucoses from midnight to 6 AM, this is a good
time period to use for the calculation.
• During this time, the IV insulin infusion rate was 1 unit/h.
• Extrapolated to a 24-h period, 24 h × 1 unit/h = 24 units.
• Thus, the 24-h IV insulin requirement is 24 units.
Step 2: Calculate a total daily dose (TDD) of subcutaneous insulin. Typically,
this will be a fraction of the 24-h IV insulin requirement. A safe estimate is 80% of
the 24-h IV insulin requirement as the new TDD for subcutaneous insulin.
Example Continued
• Calculate 80% of 24 units = 19.2. For simplicity, round to 20 units.
• Therefore, the TDD of subcutaneous insulin will be 20 units.
Step 3: Decide how to distribute the subcutaneous insulin throughout the day.
Because the patient is still NPO, a simple and safe regimen will be once-daily basal
R
R
]) particularly in patients with a
] or detemir [Levemir
insulin (glargine [Lantus
known history of diabetes.
Example Continued
The TDD of subcutaneous insulin is estimated at 20 units.
• For the patient with a known history of diabetes, a simple and safe regimen will
be once-daily basal insulin. Thus, the patient would receive 20 units of basal
R
R
]) given subcutaneously once
] or detemir [Levemir
insulin (glargine [Lantus
daily.
• For the patient without a history of diabetes, or when the provider is concerned
about a potential reduction in insulin requirements over the next 24 h, the TDD
is best divided into four injections of short-acting insulin:
• 20 units/4 = 5 units per injection.
• Thus, the 4-injection subcutaneous regimen should be
R
R
) insulin subcutaneously every 6 h.
or Humulin R
5 units regular (Novolin R
Transitioning from IV to Subcutaneous Insulin in the Patient
Already Eating
Option 1: Transition to Long-acting Basal and Rapid-acting Prandial Insulin
The goal in this situation is to create a basal–bolus (4-injection) subcutaneous
insulin regimen, mimicking physiologic insulin production, using
R
R
), or glulisine
) or aspart (Novolog
• Rapid-acting insulin lispro (Humalog
R
(apidra ) subcutaneously three times a day with meals, and
24
M.E. Mabrey and L.F. Lien
R
R
• Long-acting insulin (glargine [Lantus
]) subcutaneously
] or detemir [Levemir
at bedtime.
Because the patient is already eating, he or she should already be on a combination of IV insulin for basal needs and rapid-acting subcutaneous insulin at each
meal for prandial needs, as in the section above on administration of IV insulin to
the patient who is eating.
Step 1: Prandial Insulin
• If the rapid-acting subcutaneous insulin already begun was adjusted
appropriately, then this can simply be continued three times a day with
meals.
• Example: If the patient already is receiving 6 units of rapid-acting subcutaneous insulin three times a day before meals, this regimen should be
continued.
Step 2: Basal Insulin
• Calculate the 24-h IV insulin requirement in the same manner as described
in the NPO section.
• Again, use only 80% of this 24-h IV insulin requirement as the subcutaneous basal dose.
EXAMPLE
• Patient with a 24-h IV insulin requirement of 24 units.
• Calculate 80% of 24 units = 19.2. For simplicity, round to 20 units.
• Therefore, the basal dose of subcutaneous insulin will be 20 units.
Step 3: The above steps should complete the basal–bolus regimen.
• EXAMPLE: Final orders should read as follows:
• 6 units of rapid-acting insulin subcutaneously three times a day with meals
• 20 units of long-acting insulin subcutaneously at bedtime.
A word of caution: The above simple transition is appropriate if the IV insulin
is truly only covering basal needs. If there is any concern that the IV insulin may
also be covering prandial needs, then the first step is to titrate up the prandial subcutaneous insulin accordingly, and lower the IV requirement, before attempting a
transition.
3
IV Insulin Infusions: How to Use an “Insulin Drip”
25
Transitioning from IV to Subcutaneous Insulin in the Patient
Already Eating
Option 2: Transition to Regular and NPH Subcutaneous Insulin
The goal in this situation is to create an intensive basal–bolus (4-injection)
subcutaneous insulin regimen using the following:
• Regular insulin subcutaneously three times a day before meals, and
• NPH insulin subcutaneously at bedtime.
Because the patient is already eating, he or she should be on a combination of
IV insulin for basal needs and rapid-acting subcutaneous insulin at each meal for
prandial needs, as in the section above on IV Insulin in the patient who is eating.
Step 1: Prandial Insulin
• If the rapid-acting subcutaneous insulin already begun was adjusted
appropriately, this can simply be added up to determine the total prandial
dose.
• EXAMPLE: The patient already receiving 6 units of rapid-acting subcutaneous insulin three times a day before meals is receiving a total of 18
units of prandial insulin.
Step 2: Basal Insulin
• Calculate the 24-h IV insulin requirement in the same manner as described
in the NPO section.
• Again, use only 80% of this 24-h IV insulin requirement as the subcutaneous basal dose.
EXAMPLE
• Patient with a 24-h IV insulin requirement of 24 units.
• Calculate 80% of 24 units = 19.2. For simplicity, round to 20 units.
• Therefore, the basal dose of subcutaneous insulin will be 20 units.
Step 3: Total the TDD of insulin
• EXAMPLE: From above, if the patient has a prandial subcutaneous
insulin requirement of 18 units plus a basal subcutaneous insulin requirement of 20 units, he or she will need 38 units as the TDD for subcutaneous
insulin.
Step 4: Redistribute the TDD as regular and NPH subcutaneous insulin
• 25% of the TDD ( 1/4 TDD) is administered as regular insulin before
breakfast, before lunch, and before dinner.
26
M.E. Mabrey and L.F. Lien
• 25% of the TDD (1/4 TDD) is administered as NPH insulin before
bedtime.
EXAMPLE: The above calculation showed a TDD of 38 units of subcutaneous
insulin. Therefore, 1/4 TDD = 9.5 rounded to 10 units.
• Final orders should read as below:
•
•
10 units regular insulin subcutaneously three times daily with meals.
10 units NPH insulin subcutaneously at bedtime.
Overlap of IV Insulin Discontinuation and Subcutaneous
Insulin Initiation
The first subcutaneous insulin dose should be administered at least 1 h before stopping the IV insulin infusion. This is particularly critical for patients with impaired
insulin secretion as in type 1 diabetes or long-standing type 2 diabetes. This is
important because all subcutaneous insulin has a time to onset that is longer than
the half-life of the IV insulin (<10 min). Failure to allow for overlap in the IV and
subcutaneous insulin can result in rapid development of hyperglycemia. Thus, the
subcutaneous insulin should be given as follows:
• 1 h before discontinuation of IV insulin when using regular or rapid-acting
subcutaneous insulin.
• 3–6 h before discontinuing IV insulin when using intermediate or long-acting
subcutaneous insulin.
Bibliography
Bode BW, Braithwaite SS, Steed DR, Davidson PC. Intravenous insulin infusion therapy: indications, methods, and transition to subcutaneous insulin therapy. Endocr Pract. 2004;10(suppl
2):71–80.
Brown G, Dodek P. Intravenous insulin nomogram improves blood glucose control in the critically
ill. Crit Care Med. 2001;29(9):1714–1719.
Clement S, Braithwaite S, Magee M, et al. Management of diabetes and hyperglycemia in hospitals.
Diabetes Care. 2004;27(2):553–591.
Davis ED, Harwood K, Midgett L, Mabrey M, Lien LF. Implementation of a new intravenous
insulin method on intermediate-care units in hospitalized patients. Diabetes Educ. 2005;31(6):
818–821, 823.
Furnary AP, Gao G, Grunkemeier GL, et al. Continuous insulin infusion reduces mortality in
patients with diabetes undergoing coronary artery bypass grafting. J Thorac Cardiovasc Surg.
2003; 125(5):1007–1021.
Furnary AP, Zerr KJ, Grunkemeier GL, Starr A. Continuous insulin infusion reduces the incidence of deep sternal wound infection in diabetic patients after cardiac surgical procedures.
Ann Thorac Surg. 1999;67(2):352–362.
Goldberg PA, Siegel MD, Sherwin RS, et al. Implementation of a safe and effective insulin infusion
protocol in a medical intensive care unit. Diabetes Care. 2004;27(2):461–467.
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IV Insulin Infusions: How to Use an “Insulin Drip”
27
Henderson KE, Baranski TJ, Bickel PE, Clutter WE, McGill JB, eds. The Washington Manual
Endocrinology Subspecialty Consult. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins;
2009.
Krinsley JS. Effect of an intensive glucose management protocol on the mortality of critically ill
adult patients. Mayo Clin Proc. 2004;79(8):992–1000.
Lien L, Bethel MA, Feinglos M. In-hospital management of type 2 diabetes mellitus. Med Clin
North Am. 2004;88(4):1085–1105.
Lien LF, Spratt SE, Woods Z, Osborne K, Feinglos MN. Optimizing hospital use of intravenous
insulin: improved hyperglycemic management and error reduction with a new nomogram.
Endocr Pract. 2005;11(4):240–253.
Malmberg K, Ryden L, Efendic S, et al. Randomized trial of insulin-glucose infusion followed by
subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI
Study): effects on mortality at 1 year. J Am Coll Cardiol. 1995;26(1):57–65.
Markovitz LJ, Wiechmann RJ, Harris N, et al. Description and evaluation of a glycemic
management protocol for patients with diabetes undergoing heart surgery. Endocr Pract.
2002;8(1):10–18.
Moghissi ES, Korytkowski MT, DiNardo M, et al. American Association of Clinical
Endocrinologists and American Diabetes Association consensus statement on inpatient
glycemic control. Endocr Pract. 2009;15(4):353–369.
Nazer LH, Chow SL, Moghissi ES. Insulin infusion protocols for critically ill patients: a highlight
of differences and similarities. Endocr Pract, 2007;13(2):137–146.
Trence DL, Kelly JL, Hirsch IB. The rationale and management of hyperglycemia for inpatients
with cardiovascular disease: time for change. J Clin Endocrinol Metab. 2003;88(6):2430–2437.
Umpierrez GE, Jones S, Smiley D, et al. Insulin analogs versus human insulin in the treatment of patients with diabetic ketoacidosis: a randomized controlled trial. Diabetes Care.
2009;32(7):1164–1169.
Van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in the critically ill patient.
N Engl J Med. 2001;345(19):1359–1367.
Zerr KJ, Furnary AP, Grunkemeier GL, Bookin S, Kanhere V, Starr A. Glucose control lowers the risk of wound infection in diabetics after open heart operation. Ann Thorac Surg.
1997;63(2):356–361.
Chapter 4
Laboratory Testing in Hospitalized Patients
with Diabetes Mellitus
Karen Barnard and Mary E. Cox
Keywords Random plasma glucose · Fasting plasma glucose · Oral glucose tolerance test · Point-of-care glucose test (POCT) · Hemoglobin A1C
· Fructosamine · Insulin · Pro-insulin · C-peptide · Autoantibody · Ketone · Urine
microalbumin · Lipid panel · High sensitivity CRP (hsCRP)
Many of the laboratory tests routinely ordered for patients with diabetes mellitus in
the outpatient setting are of more limited use in the hospitalized patient. However,
the hospital is certainly a place for opportunistic diabetes diagnosis, and laboratory
monitoring for effects of therapy is essential. The laboratory tests that are most
useful for management of an inpatient with diabetes are discussed in this chapter
(Table 4.1).
Glucose-Based Tests
Plasma Glucose
Plasma glucose is obtained by venipuncture and is conveniently assayed with
other components of the basic metabolic panel. In order to avoid falsely low
readings, plasma glucose samples must be processed promptly. In the hospital, uses of plasma glucose include the following: (1) provision of support to a
new diabetes diagnosis, (2) monitoring effectiveness of therapy in patients for
whom point-of-care glucose testing (POCT) is unreliable, and (3) confirmation
of an extreme POCT glucose value obtained from a portable glucose meter. The
following sections review diabetes screening and diagnostic testing, as well as
POCT.
K. Barnard (B)
Division of Endocrinology, Metabolism, and Nutrition, Department of Medicine, Duke University
Medical Center, Durham, NC 27710, USA; Department of Veterans Affairs, Durham, NC
27707, USA
e-mail:
[email protected]
L.F. Lien et al. (eds.), Glycemic Control in the Hospitalized Patient,
C Springer Science+Business Media, LLC 2011
DOI 10.1007/978-1-60761-006-9_4,
29
Table 4.1 Laboratory tests for inpatient diabetes assessment
30
Test
Recommended for
routine inpatient use
Plasma glucose
Yes
Point-of-care glucose
Urinary glucose
A1C
Yes
No
Yes
Point-of-care A1C
No
Fructosamine
No
Markers of endogenous
insulin (C-peptide,
pro-insulin)
Insulin
No
No
Hypoglycemia evaluation
Autoantibody markers
Serum ketones
Urine ketones
Urine microalbumin
No
Yes, if DKA suspected
Yes, if DKA suspected
No
Lipid panel
Yes
hsCRP
No
Support of diagnosis of type 1 diabetes
Support of diagnosis of DKA
Support of diagnosis of DKA
Diagnosis of diabetic nephropathy (>1 positive
measurement)
Cardiovascular risk stratification and monitoring of
lipid-lowering therapy
Cardiovascular risk stratification
Inpatient use
Limitations to use
Opportunistic or intentional diabetes diagnosis;
Limited for diabetes diagnosis because of
confirmation of extreme point-of-care glucose levels
propensity toward circumstantial variability;
sample requires prompt processing
Routine monitoring of glucose-lowering therapy
May be inaccurate at extreme glucose levels
Not recommended
Not recommended
Evidence-based monitoring of glucose-lowering
Hospitalized patients may have reasons for
therapy; diabetes diagnosis
inaccuracy
Not recommended
Similar inaccuracy as for central laboratory A1C ;
may measure slightly higher A1C values and
may have additional intra- and interindividual
variability
Estimate overall effects of glucose-lowering therapy for Little evidence correlating fructosamine level to
patients in whom A1C is unreliable
complications and outcomes; highly variable
Hypoglycemia evaluation; limited use for diagnosis of Can be unreliable in hyperglycemic emergencies
type 1 diabetes
and early type 1 diabetes
Unreliable in most hospitalized patients,
particularly those with infectious and
inflammatory conditions
K. Barnard and M.E. Cox
DKA, diabetic ketoacidosis; hsCRP, high-sensitivity C-reactive protein
Not a reliable measure of endogenous insulin
production and has high inter- and
intraindividual variation
Expensive and often unnecessary
May be falsely negative
May be positive in conditions other than DKA
Multiple causes of microalbuminuria other than
diabetic nephropathy
May have falsely low levels in acute illness
4
Laboratory Testing in Hospitalized Patients with Diabetes Mellitus
31
Diabetes Screening and Diagnosis
The screening and diagnostic criteria for diabetes are the same for inpatients as for
outpatients, although all glucose-based tests share a fundamental flaw when used
in the hospital: patient glucose levels can change considerably under the conditions
of dietary alteration, physiologic stress, and disrupted sleep that often accompany
hospital visits. Furthermore, there is no finite physiologic threshold for any diabetes diagnostic test at which normality ends and diabetes begins. All patients with
risk factors for type 2 diabetes, even those with test parameters below the diagnostic thresholds, should be given appropriate education about nutrition, exercise, and
weight loss. Results close to the diagnostic thresholds should be confirmed once the
patient is stable and, preferably, an outpatient.
There are three categories of plasma glucose-based tests for screening and diagnosis of diabetes: (1) random plasma glucose (RPG), (2) fasting plasma glucose
(FPG), and (3) oral glucose tolerance test (OGTT), discussed here in the context of
a 75-g glucose load.
Random Plasma Glucose
The RPG is the most conveniently obtained, usually along with routine basic
metabolic panels. The commonly held RPG threshold for diagnosis of diabetes is
200 mg/dL or greater (≥11.1 mmol/L), along with symptoms of polyuria, polydipsia, and unexplained weight loss. An RPG of 140–199 mg/dL (7.7–11 mmol/L)
is suggestive of prediabetes. Based on diagnosis by OGTT, an RPG 200 mg/dL
or greater (≥11.1 mmol/L) is insensitive but has a specificity approaching 100%,
which, in the setting of symptoms, is unlikely to lead to a false-positive diagnosis. One must use caution, however, when diagnosing diabetes based on the RPG
level given its propensity to change as a patient’s circumstances do. Elevated levels
should always be confirmed.
Fasting Plasma Glucose
The FPG test is a simple plasma glucose measurement obtained after at least 8 h of
fasting (usually an overnight fast), which can be accomplished under supervision in
the hospital. It has been the American Diabetes Association’s (ADA) test of choice
for diagnosis of both prediabetes (FPG 100–125 mg/dL [5.5–6.9 mmol/L]) and diabetes (FPG ≥126 [≥7 mmol/L]). Although the intraindividual stability is fair, FPG
should be confirmed on a second occasion or with a second test to avoid false results.
Oral Glucose Tolerance Test
The 75-g OGTT currently is considered the worldwide gold standard for diabetes
diagnosis. The 2-h post-load glucose level diagnostic for prediabetes is 140–
199 mg/dL (7.7–11 mmol/L), and the level diagnostic for diabetes is ≥ at least
32
K. Barnard and M.E. Cox
200 mg/dL (≥11.1 mmol/L). OGTT is the only way to formally diagnose impaired
glucose tolerance (IGT), which represents the fundamental pathophysiologic defect
in type 2 diabetes (i.e., the inability to respond to insulin release). In the hospital,
OGTT also has obvious practical downsides, such as the required 8-h fast before
testing, commitment of nursing staff, and the length of the test itself.
POCT Glucose
POCT glucose, or capillary glucose, is measured by a portable glucose meter and
measures whole blood glucose. POCT is used frequently in the hospital because of
ease of use and rapidity of results. POCT glucose measurements are increasingly
used to make point-of-care decisions about therapy. In general, use of these meters
is reasonable; however, there are important limitations.
• POCT glucose is less reliable than plasma glucose when measuring extreme
values, that is, less than 60 mg/dL (3.3 mmol/L) and greater than 500 mg/dL
(27.7 mmol/L). Glucose levels in these ranges should be confirmed with plasma
glucose.
• POCT glucose can differ by 10–15% from plasma glucose; the direction and
magnitude of this difference varies among meters.
• Caution should be used in patients on peritoneal dialysis or in those receiving therapeutic immunoglobulin preparations. Many POCT testing kits employ
the chemical glucose dehydrogenase pyrroloquinoline quinone (GDH-PQQ) to
quantify glucose. GDH-PQQ reacts with several nonglucose sugars, including maltose, galactose, and xylose, which are found in peritoneal dialysis
solutions and therapeutic immunoglobulin preparations. Use of these testing
kits in combination with use of products containing nonglucose sugars can
result in a falsely elevated POCT glucose value. The US Food and Drug
Administration (FDA) has released a Public Health Notification that provides a
list of GDH-PQQ glucose test strips; this can be accessed at http://www.fda.gov/
MedicalDevices/Safety/AlertsandNotices/PublicHealthNotifications/. In cases
where it is not possible to avoid test strips that contain GDH-PQQ, errors can
be avoided by use of plasma glucose. This is particularly important for elevated
glucose values or those that are inconsistent with a patient’s history or glucose
pattern.
• Hematocrit level can affect the precision of POCT glucose: A low hematocrit can
result in a falsely high glucose reading, whereas a high hematocrit can result in a
falsely low reading. These readings should be confirmed with plasma glucose.
Urinary Glucose
Urinary glucose is a semi-quantitative measurement of glycosuria, which represents
hyperglycemia above the renal threshold, that is, plasma glucose around 180 mg/dL
(10 mmol/L) in many patients. The renal threshold can differ significantly with the
4
Laboratory Testing in Hospitalized Patients with Diabetes Mellitus
33
duration of a patient’s diabetes as well as average glucose levels. Prior to the advent
of widely available portable glucose meters, urinary glucose was used for home
monitoring. Currently, urinary glucose rarely is used for outpatients, and it is not
useful for hospitalized patients.
Glycated Proteins: Hemoglobin A1C and Fructosamine
Hemoglobin A1C
The A1C is a measure of glycosylation of the hemoglobin molecule, which occurs as
a nonenzymatic process over time. In patients with diabetes, glycosylation rates rise,
reflecting the increased ambient blood glucose levels. Because the average lifetime
of a red blood cell is approximately 120 days, the A1C measurement reflects average
glucose concentration for that period of time, although weighted toward more recent
trends. The relationship between the A1C value and estimated average glucose has
been prospectively investigated and can be defined by the following equation: average glucose (mg/dL) = 28.7 × A1C – 46.7. Alternatively, a calculator is available at
http://professional.diabetes.org/eAG.
The A1C is the gold standard for assessment of glycemic control, with the ADA
targeting A1C levels below 7% as the therapeutic goal for most patients. As of 2010,
the A1C has been recommended by the International Expert Committee for screening and diagnostic purposes, with a level of at least 6.5% diagnostic of diabetes. A
level of 5.7–6.5% represents “at risk” for diabetes, although this is not the same as
a diagnosis of prediabetes made by a glucose-based test.
The A1C is a useful test in hospitalized patients, both for diagnostic purposes and
to gather objective information about recent glycemic control. Exceptions include
patients who have cause for inaccurate A1C (as below), as well as those who have
an outpatient A1C value documented in the prior 30 days.
Conditions Causing Inaccurate A1C Readings
A longstanding concern about use of A1C was the lack of standardization among
various methods at different institutions. However, the A1C assay methods have
now been largely standardized; most laboratories now use the high-performance
liquid chromatographic technique. The following conditions are some of the more
common causes of inaccurate A1C ; other, rarer conditions also may affect the
measurement.
• Recent blood transfusion: dilutes the patient’s red cells with those of the donor
and will give a falsely low A1C .
• Anemia, including hemolytic anemia, symptomatic β-thalassemia, and sickle cell
anemia: Any condition that results in an overall increased rate of red cell turnover
can result in a falsely low A1C . Conversely, iron deficiency anemia or other
34
K. Barnard and M.E. Cox
conditions that result in a decreased rate of red cell production can result in a
falsely elevated A1C .
• Pregnancy: In early pregnancy, fetal red cell production can lower the A1C
level. Later in pregnancy, increased red cell turnover lowers the normal range
for A1C .
• Splenectomy: the resulting decreased red cell destruction can result in higher A1C
levels.
Point-of-Care A1C
Point-of-care A1C measurement is performed using a capillary blood sample. In an
office-based setting, its use has been observed to result in more frequent intensification of diabetes regimens as well as small but significant improvements in A1C
of 0.1–0.5%. Point-of-care A1C testing (via the DCA 2000 model) appears to measure slightly different values than from plasma A1C testing, although by no more
than 0.5%. There may also be slightly more intra- and interindividual variability.
Newer POC instruments are now available, and although more studies are needed to
confirm reliability with standardized assays, the POC method seems promising for
convenient monitoring of glucose control in outpatients. There are no data for use
of point-of-care A1C testing in the inpatient setting, and its use is not recommended
currently.
Fructosamine
Fructosamine is a glycated serum protein that is formed as the result of a reaction
between glucose and albumin. Its serum concentration also can be used to estimate
glycemia, and there is generally a good correlation between serum fructosamine
and A1C . However, routine clinical use of fructosamine is limited by several factors. First, fructosamine only reflects glycemia for the prior 2–3 weeks, as opposed
to A1C , which reflects 2–3 months. Second, fructosamine can show considerable
variability, even within a single patient, which makes successive measurements
more difficult to interpret. Finally, fructosamine level correlates with serum albumin
level, and appropriate adjustments must be made for patients with hypoalbuminemia. Overall, the clinical utility of fructosamine is limited, and use in the inpatient
setting is not recommended.
Insulin, Pro-insulin, and C-Peptide
Insulin production in the β-cell is a multistep process. Its direct precursor is
a molecule called pro-insulin, which is comprised of two components: (1) the
future insulin molecule, and (2) 31 amino acids of the “connecting peptide,” or
4
Laboratory Testing in Hospitalized Patients with Diabetes Mellitus
35
C-peptide. During the final phase of production, insulin is cleaved from the Cpeptide, and both are packaged into secretory granules for release into circulation.
Pro-insulin and C-peptide are not thought to play a significant independent role in
glucose homeostasis, but they are useful as plasma markers of endogenous insulin
production.
Likewise, insulin precursor measurements are not useful for evaluation of inpatients with diabetes. The C-peptide level can be useful in diabetic patients who are
relatively stable on treatment; in this setting, the C-peptide value, in combination
with history, physical examination, and antibody levels, can be used to make the distinction between type 1 and type 2 diabetes. In acute illness, however, insulin and
insulin precursor measurements often are inaccurate. In patients presenting with
severe hyperglycemia, a low C-peptide level may represent either a true absence
of endogenous insulin, as in type 1 diabetes, or the physiologic result of hyperglycemia and glucose toxicity in type 2 diabetes. Conversely, a normal level may
be present in a patient with insulin resistance and type 2 diabetes or in a patient
with early type 1 diabetes in the honeymoon phase (i.e., that has not yet had full
destruction of pancreatic β-cells). Use of the C-peptide level as a guide for initial
therapy in patients with type 2 diabetes has not been shown to lead to better glycemic
control.
Markers of endogenous insulin production are useful in hospitalized patients
who are undergoing evaluation for fasting hypoglycemia, which should be done
in collaboration with an endocrinology consultant.
Insulin measurement sometimes is undertaken as a measure of insulin resistance.
However, this generally is thought to be unreliable because of high inter- and intraindividual variability. Research studies often use a measure called the homeostatic
model assessment (HOMA) for β-cell function or insulin resistance, but this is not
useful for inpatient management.
Autoantibody Markers
Type 1 diabetes is an autoimmune disease, characterized by T cell-mediated destruction of the pancreatic β-cell. Autoantibodies have been detected in up to 90% of
patients with immune-mediated diabetes. There are three categories of autoantibodies: (1) antibodies to insulin, (2) antibodies to the islet cell and its antigens
(glutamate decarboxylase 65 [GAD], tyrosine phosphatase-related proteins islet
antigen 2 [IA-2A/ICA 512], and IA-2β) and (3) antibodies to the insulin secretory apparatus. The zinc transporter antibody ZnT8 was recently identified as an
autoantigen in this group.
Autoantibody testing to evaluate for type 1 diabetes is relatively specific but
somewhat insensitive, partly because the levels may decline over time in patients
with longstanding disease. Furthermore, autoantibody testing is expensive and,
in most cases, does not add information beyond the clinical impressions of the
provider. Overall, the presence of autoantibodies is supportive, but not required,
for a diagnosis of type 1 diabetes mellitus.
36
K. Barnard and M.E. Cox
Ketones
Serum Ketones
Production of ketone bodies is a normal response to the body’s shortage of glucose during starvation, and is meant to provide an alternate source of fuel via free
fatty acids. Insulin deficiency and subsequent perceived shortage of glucose, as in
diabetic ketoacidosis (DKA), provokes lipolysis, producing free fatty acids. The
fatty acids are then transferred to the liver, where they are oxidized to become
ketone bodies. In DKA, the ketone β-hydroxybutyrate increases to a great extent,
disproportionately to the other ketones, acetone and acetoacetate.
The test strips for measurement of serum ketones do not capture
β-hydroxybutyrate, but they strongly capture acetoacetate and acetone. Despite the
physiologic predominance of β-hydroxybutyrate, this method usually is sufficient
for ketone detection during DKA. However, occasional serum ketone tests may be
read as negative even in the presence of true DKA. A specific β-hydroxybutyrate
level is available in some laboratories, but it is rarely necessary to confirm the diagnosis. To avoid confusion, serum ketone levels should be ordered in combination
with electrolytes, arterial blood gas, and other appropriate laboratory assessments
and should be interpreted in the context of the clinical presentation. Further information about diagnosis and management of DKA can be found in Chapter 6:
Hyperglycemic Emergencies.
During treatment with insulin and fluids, β-hydroxybutyrate is oxidized to acetoacetate and acetone, which can result in persistent elevation of measured serum
ketone levels, despite obvious clinical improvement. For this reason, serial serum
ketone measurements are not recommended for routine monitoring during DKA
management.
Urine Ketones
The urine ketone measurement represents a semi-quantitative level of acetone and
acetoacetate, with a positive test indicating ketoacidosis. The primary advantage of
the urine measurement over the serum measurement is that it will be positive prior
to presence of measurable ketones in the serum. Therefore, it is a quick and easy
way to screen for DKA in patients with hyperglycemia. However, as with other
laboratory tests in diabetes, the presence of urine ketones alone is not definitive and
must be interpreted in the context of the overall clinical picture, serum electrolytes,
anion gap, and serum ketone measurement.
Urine Microalbumin
The urine microalbumin measurement represents small but abnormal amounts of
albuminuria, present in early stages of diabetic nephropathy, prior to the development of frank proteinuria and nephrotic syndrome (Table 4.2). Additionally, the
4
Laboratory Testing in Hospitalized Patients with Diabetes Mellitus
37
Table 4.2 American Diabetes Association definitions for levels of albuminuria in patients with
diabetes
Volume of albumin excretion
Normal
Microalbuminuria
Clinical albuminuria
mg/24 h
mcg/min
mcg/mg of creatinine
<30
30–300
>300
<20
20–200
>200
<30
30–300
>300
presence of microalbuminuria in patients with diabetes is a predictor of ischemic
cardiovascular (CV) events related to the development of atherosclerosis.
Urine microalbumin is not specific to diabetic nephropathy; in fact, there are
multiple causes for albuminuria in a hospitalized patient. Because microalbuminuria
related to other causes can be transient, it is best to assess urine microalbumin in
outpatients who are in stable condition. Even in the outpatient setting, the ADA
recommends confirmation of multiple measurements over a period of months before
making the diagnosis of diabetic nephropathy. If microalbuminuria is identified, it
is important to consider other possible causes, such as
•
•
•
•
•
•
•
Urinary tract infection
Severe hyperglycemia
Acute febrile illness
Heart failure
Hypertension
Strenuous exercise in the last 24 h
Pregnancy
Cardiovascular Risk Assessment
Lipid Profile
Serum lipid levels are a well-characterized component of cardiovascular (CV) risk,
and their measurement is useful both for risk prediction and assessment of the effectiveness of a patient’s lipid-lowering therapy. The ADA recommends an annual
screening fasting lipid profile for all patients with type 2 diabetes. Furthermore, the
National Cholesterol Education Program Adult Treatment Panel (ATP) III suggested
use of statins and dietary therapy in all patients with diabetes, even for those without known CV disease (CVD), because of their poor prognosis once CVD becomes
manifest. Therapeutic goals are based on ATP III recommendations for levels of
low-density lipoprotein (LDL); these have gained support from more recent data,
including the Heart Protection Study (HPS). For patients with diabetes and without known CVD, the risk for future events is roughly equivalent to those in the
opposite situation—without diabetes but with history of CVD. HPS data for this
population support the ATP-III recommended LDL goal of no more than 100 mg/dL
38
K. Barnard and M.E. Cox
(2.5 mmol/L). Patients with both diabetes and history of CVD are at very high
risk for future cardiac events and, in the HPS, obtained the greatest benefit from
lipid-lowering therapy with statins. For these patients, it is reasonable to attempt to
achieve a very low LDL level of 70 mg/dL (1.8 mmol/L) or less.
Although lipid panels frequently are ordered for patients in the hospital and can
be useful, their reliability is limited; conditions such as acute myocardial infarction
and systemic inflammation may cause falsely low readings.
High-Sensitivity C-Reactive Protein (hsCRP)
C-reactive protein (CRP) is an acute-phase inflammatory protein that is released
from hepatocytes in response to acute injury, infection, or other inflammatory
stimuli. An increase in total CRP is expected in association with many conditions requiring hospitalization. Increased CRP can be seen on a subtle level in
diseases with long-term, low-grade inflammation, such as atherosclerotic disease.
Traditional CRP assays have had limited analytical sensitivity, with a minimum
detectable level of 0.5–1 mg/dL, and were not useful for evaluating these slight
levels of inflammation. However, new high-sensitivity assays, like the rate nephelometry method, can detect CRP concentrations as low as 0.02 mg/dL. These
high-sensitivity CRP (hsCRP) assays have become widely available for clinical use.
This availability, combined with the short half-life (about 18 h), the stability of CRP
in serum (lasts up to 3 days at room temperature), and evidence for its correlation
with atherosclerotic disease have made this a popular test for CV risk stratification.
Furthermore, in patients with type 2 diabetes, there may be an independent association between hsCRP levels greater than 0.3 mg/dL and risk for death from CVD.
Finally, data from the JUPITER (Justification for the Use of Statins in Prevention:
an Interventional Trial Evaluating Rosuvastatin) trial suggests that use of rosuvastatin in patients with normal LDL cholesterol but elevated hsCRP may provide CV
risk protection. For these reasons, hsCRP may be a useful test in the outpatient setting; however, the utility of this test in hospitalized patients, especially those with
infection or inflammation from other conditions, is limited.
Bibliography
American Diabetes Association. Standards of medical care in diabetes—2010. Diabetes Care.
2010;33(suppl 1):S11–S61.
Beaser RS. Joslin’s Diabetes Deskbook. A Guide for Primary Care Providers. 2nd ed. Boston, MA:
Joslin Diabetes Center; 2008.
Bingley PJ. Clinical applications of diabetes antibody testing. J Clin Endocrinol Metab.
2010;95(1):25–33.
Camacho P, Gharib H, Sizemore G. Evidence-Based Endocrinology. 2nd ed. Philadelphia, PA:
Lippincott Williams & Wilkins; 2007.
Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the
Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care.
1997;20(7):1183–1197.
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults.
Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP)
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Laboratory Testing in Hospitalized Patients with Diabetes Mellitus
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Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults
(Adult Treatment Panel III). JAMA. 2001;285(19):2486–2497.
Grundy SM, Cleeman JI, Bairey Merz CM, et al. for the Coordinating Committee of the
National Cholesterol Education Program. Implications of recent clinical trials for the
National Cholesterol Education Program Adult Treatment Panel III Guidelines. Circulation.
2004;110(2):227–239.
Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial.
Lancet. 2002;360(9326):7–22.
International Expert Committee. International Expert Committee report on the role of the A1C
assay in the diagnosis of diabetes. Diabetes Care. 2009;32(12):1–8.
Karon BS, Griesmann L, Scott R, et al. Evaluation of the impact of hematocrit and other
interference on the accuracy of hospital-based glucose meters. Diabetes Technol Ther.,
2008;10(2):111–120.
Khan AI, Vasquez Y, Gray J, Wians FH Jr, Kroll MH. The variability of results between pointof-care testing glucose meters and the central laboratory analyzer. Arch Pathol Lab Med.
2006;130(10):1527–1537.
Khosla N, Sarafidis PA, Bakris GL. Microalbuminuria. Clin Lab Med. 2006;26(3):635–653.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model
assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin
concentrations in man. Diabetologia. 1985;28(7):412–419.
Miller CD, Barnes CS, Phillips LS, Ziemer DC, Gallina DL, Cook CB, et al. Rapid A1c availability improves clinical decision-making in an urban primary care clinic. Diabetes Care.
2003;26(4):1158–1163.
Nathan DM, Kuenen J, Borg R, Zheng H, Schoenfeld D, Heine RJ, A1c-Derived Average Glucose
Study Group. Translating the A1C assay into estimated average glucose values. Diabetes Care.
2008;31(8):1473–1478.
National Glycated Hemoglobin Standardization Project. http://www.ngsp.org/prog/index.html.
Accessed May 10, 2009.
Ridker PM, Danielson E, Fonseca FA, JUPITER Study Group. Rosuvastatin to prevent vascular
events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359(21):2195–
2207.
Sacks DB, Bruns DE, Goldstein DE, et al. Guidelines and recommendations for laboratory analysis
in the diagnosis and management of diabetes mellitus. Clin Chem. 2002;48(3):436–472.
Soinio M, Marniemi J, Laakso M, et al. High-sensitivity C-reactive protein and coronary heart
disease mortality in patients with type 2 diabetes. A 7-year follow-up study. Diabetes Care.
2006;29(2):329–333.
Tamborlane WV, Kollman C, Steffes MW, Ruedy KJ, Dongyuan X, Beck RW, et al. The Diabetes
Research in Children Network Study Group. Comparison of fingerstick hemoglobin A1c levels
assayed by DCA 2000 with the DCCT/EDIC central laboratory assay: results of a Diabetes
Research in Children Network (DirecNet) Study. Pediatr Diabetes, 2005;6(1):13–16.
Wilson AM, Ryan MC, Boyle AJ. The novel role of C-reactive protein in cardiovascular disease:
Risk marker or pathogen. Int J Cardiol. 2006;106(3):291–297.
Chapter 5
Inpatient Diabetes Education: Realistic
and Evidence-Based
Ellen D. Davis, Anne T. Nettles, and Ashley Leak
Keywords Diabetes education · Diabetes self-care · Patient-centered approach ·
Empathetic listening · Multidisciplinary teamwork · Teachable moment
Hospitalization can present an opportunity to address unique urgent learning needs.
Although some would argue that the hospital is a poor setting for patient education, this does not have to be the case. Brief targeted diabetes education is readily
available, and take-home materials can reinforce instruction. Given the sheer volume of inpatients with diabetes, dedicated resources for their care and education are
essential.
Inpatients with well-controlled diabetes sometimes find hospitalization a loss
of personal control filled with challenges. Other inpatients may never have
been able to achieve good blood glucose control, and still others may not
even know that they have diabetes. Recent studies have shown that providers
have a tendency to neglect diabetes and hyperglycemia in the hospital, which
leads to missed opportunities for teaching. In this chapter, we discuss these
opportunities and how providers can best equip individuals for self-care after
discharge.
Understanding Diabetes Education
Why Do Patients Need Diabetes Education?
Self-care education results in the following:
• An improvement in the patient’s ability to problem-solve at home.
• Better glycemic control.
• Improved quality of life.
E.D. Davis (B)
Department of Advanced Clinical Practice, Duke University Hospital, Durham, NC 27710, USA;
Duke University School of Nursing, Durham, NC 27710, USA
e-mail:
[email protected]
L.F. Lien et al. (eds.), Glycemic Control in the Hospitalized Patient,
C Springer Science+Business Media, LLC 2011
DOI 10.1007/978-1-60761-006-9_5,
41
42
E.D. Davis et al.
Why Do Patients Need Diabetes Education in the Hospital?
It is often the case that patients are not well informed about diabetes self-care
because comprehensive outpatient diabetes education may not be convenient or even
available to them.
What Factors Interfere with Inpatient Diabetes Education?
There are a variety of factors that interfere with effective inpatient diabetes education. In the busy inpatient setting, patients may not be interested or engaged in
educational efforts, physical condition, literacy, numeracy, culture, mental health,
and finances influence knowledge, learning, and self-care possibilities. Additionally,
there are many misconceptions about diabetes, at both the provider and patient
levels. Provider misconceptions include the following:
• Diabetes care and education are only outpatient issues.
• Every adverse patient outcome is a result of poor self-care.
• When people get diabetes, they do not mind suddenly making major lifestyle
changes.
• Scare tactics motivate patients to make lifestyle changes. “If you don’t do what I
(the ‘expert’) say, you’ll go blind or have your feet amputated.”
• Handouts about diabetes and a few “discharge orders” are all that patients need.
• Physicians don’t have time to effectively support their patients.
• When providers use the word “stress,” patients know what it means. Although
providers usually are referring to physiological stress, patients interpret this term
as meaning that they are doing something wrong by not handling their emotional
stress well.
• Diabetes self-care is the only thing patients have on their minds.
Patient misconceptions include
• Chronic complications are inevitable, so self-care is a waste of time.
• “Pills worked before, so I shouldn’t need insulin.”
• “I’m ‘guilty’ of bringing this on myself.” (“My spirits are low and I can’t do all
of these things they want me to do.”)
• “Needing insulin is a sign that I, and the treatment, have ‘failed’.”
• “I have to deprive myself by eating ‘diabetic food’.”
• “I will be hungry all the time.”
• “It’s all about not eating ‘sugar’ and about eating ‘special foods’.”
There are specific tactics clinicians can use when dealing with patient misconceptions, while also effectively imparting information:
5
Inpatient Diabetes Education: Realistic and Evidence-Based
43
• Use nonjudgmental language.
• Avoid negative words:
• Noncompliant. The use of noncompliant is believed by diabetes education
experts to negatively affect patient outcomes.
• Failure (i.e., “diet failure” or “oral agent failure”). Progression to need for oral
medication or insulin may be viewed by the patient as a personal failure or serious character flaw. People are not motivated when they perceive themselves as
failures, and people do not act on both negative and positive associations at
the same time.
• Bad blood sugars. Use “safe” or “unsafe.”
• Sliding scale insulin. Many patients infer, “Don’t take insulin unless your
blood sugar is high.” When describing correction bolus or supplements
for scheduled insulin, point out the difference and probable need for later,
proactive scheduled insulin adjustments.
• Use patient-centered approaches. Starting with the patient’s agenda produces
the best outcomes. For example, if the patient is concerned about nocturnal
hypoglycemia, start by collaboratively discussing prevention, recognition, and
treatment of hypoglycemia.
• This type of lifestyle coaching, as part of a larger lifestyle intervention,
resulted in improved glycemic levels in the Diabetes Prevention Program
(DPP, 2002) and all ensuing community-based trials of lifestyle interventions. The Diabetes Control and Complication Trial (DCCT, 1994) also
produced outstanding glycemic results with significantly decreased complications through patient-centered education with individualized problem
solving.
• Elicit patient candor through empathetic listening. If possible, sit down and establish direct eye contact with the patient. Acknowledge the patient’s individual
concerns. (Patients are not interested in “diabetes,” but in their own lives.)
• Ask specific but open-ended questions rather than lecturing. Evidence shows that
this takes less time than repeatedly listing what every person “should” do.
• “What are you most worried about when it comes to taking care of your diabetes?” The answer may reflect cultural misunderstandings that may be dealt
with easily, like, “I can’t afford ‘diabetic’ food.”
• Rather than saying, “Follow this list of instructions,” ask, “What one thing
will you do differently when you go home or until your next outpatient visit?”
• “On a scale of 1–10, how would you rate the way you eat for your diabetes?”
“What one thing could you do when you go home to make that upward move
you mentioned?”
• Rather than say, “Get more exercise,” ask, “At what time of day could you take
a walk and with whom?”
• Asking, “Do you have any questions?” after provider-centered care seldom
elicits information that helps provider improve patient outcomes.
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E.D. Davis et al.
• Provide up-to-date resources: on-demand patient educational TV, written materials, translation services, patient teaching by staff nurses, diabetes resource nurses
or champions, and clinical nurse specialists. Many hospitals have resources like
these; find out what is available to you, and use it!
Key Points: Education Strategy
• Human beings change one behavior at a time.
• Asking good questions and listening are keys to all patient interaction.
• People respond more positively to compliments for what they are doing well
rather than to criticism or lectures on what is needed for improvements.
• “Covering the material” and “rules are rules” patient education approaches do not
improve glycemic control or quality of life or reduce costs for systems.
• Behavioral change strategies (like those listed above) work better than lectures
and “should” talk. No one feels upbeat enough to make continuous major lifestyle
changes when feeling judged, blamed, guilty, or terrified of the future.
• A good first question to ask patients is “What have you heard about taking care
of diabetes?”
The Content of Diabetes Education
The American Diabetes Association (ADA) 2010 Standards of Medical Care
suggest that a smooth transition to home be ensured by anticipation of the postdischarge regimen, effects of the current illness on glycemic control, and, for those
with hyperglycemia only, follow-up diagnostic testing for diabetes. There is comprehensive ADA diabetes education curricula designed for outpatients, but in the
hospital, the ADA prefers a more focused, “survival skills” approach. Two useful
education constructs, which are described in detail below, are the following: (1)
The American Association of Diabetes Educators (AADE) AADE7TM Self-Care
Behaviors and (2) a synthesis of The Joint Commission, AADE, ADA, and other
groups’ published pre-discharge assessment and education content.
AADE7TM Self-Care Behaviors
The AADE believes that behavior change can be most successfully achieved when
patients follow seven self-care behaviors:
1. Healthy eating today means healthy foods in reasonable portions to meet weight
and nutrition goals. Individual strategies for eating less, if overweight, and eating breakfast daily are top counseling priorities. If the patient is taking insulin,
spreading the carbohydrate foods across the day requires extra attention. Referral
for nutrition counseling is appropriate at discharge if needed.
2. Being active is the same for patients with diabetes as for the general public:
Patients should aim for at least 150 min of physical exercise a week, like walking,
each day with resistance training three times/week. Main point: Get started.
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Inpatient Diabetes Education: Realistic and Evidence-Based
45
3. Glucose monitoring is a frequent occurrence for hospitalized patients. Bedside
glucose testing poses a “teachable moment” for staff nurses. (See section, “What
Can Nurses Do?”)
4. Medications may change from oral agents to insulin while the patient is in the
hospital. Although this can alarm some patients, many are relieved to find that
injections are not as bad as they had feared. Insulin initiation can be explained as
merely a reliable way to rapidly control glucose during acute illness. In helping
patients deal with taking insulin at home, ask them about their concerns, and then
provide information. When insulin is new, prevention, recognition, and treatment
of hypoglycemia must be discussed.
5. Problem solving is a common method learned by healthcare professionals, and
is rarely formally familiar to patients. When they learn to address self-care problems systematically and objectively, they can be more successful. It is helpful to
explain this approach as a 6-step process.
1.
2.
3.
4.
5.
6.
Identify the problem objectively and specifically.
Consider a variety of possible strategies to address the problem.
Consider the pros and cons of each strategy.
Pick the best strategy.
Try it, and evaluate how it is working.
If the problem is not solved, identify barriers and try to reduce them or try
another strategy.
More than 99% of patient outcomes are the result of patient problem solving
at home. Some problems have no solutions; for example, the disease will
not be cured. For unsolvable problems, patients need to use enhanced coping
mechanisms (below).
6. Reducing risks includes regular screening for complications and comorbidities.
Patients should be advised that there are a variety of ways to understand how
diabetes affects the body, including the hemoglobin A1C level, foot examination,
urine microalbumin screening, dilated eye exams, and dental exams. Patients can
discuss these screening tests with their outpatient provider.
7. Healthy coping is essential in daily diabetes life; it is about decision making and
performing self-care. Self-care is challenging for most people because diabetes
care involves daily disruptions of the usual. Interestingly, social support has been
found to be one of the most helpful self-care strategies. Providers should routinely assess sources of support and provide information about other resources
in the community. A wide variety of coping tactics have been used, such as relaxation, guided imagery, humor, music, and exercise. The strategies are different
for different people.
Synthesis of Published Recommendations for Assessments
and Education during Discharge Planning
• Assess current practice of self-care and provide needed information on basic
diabetes self-management skills for newly diagnosed patients and others with
46
•
•
•
•
•
•
•
E.D. Davis et al.
changes in the regimen, using focused, short sessions. Does the patient require
outpatient diabetes self-management education?
Does the patient prepare his or her own meals? Discuss consistent eating patterns.
Advise the patient to avoid concentrated sugar foods until he or she has ongoing
counseling by a diabetes educator on how to do so safely.
Can the patient perform self-monitoring of blood glucose at a reasonable frequency? List resources for home blood glucose monitoring and sharing of results
with the healthcare provider. Can the patient teach-back (verbalize what he or she
understood) that sharing home testing numbers results in improved medical care?
If relevant, the patient should do a demonstration at least once.
Can the patient take his or her diabetes medications or insulin accurately? The
patient should demonstrate drawing up and self-administering insulin at least
once or twice. Is there a family member who can assist with tasks that the patient
cannot perform? Is a home health nurse needed to facilitate transition to the
home?
Explore possibilities for individualized exercise.
Provide information on prevention, symptoms, and treatment of hypoglycemia.
Provide information on hyperglycemia and “Sick Day Rules,” since not understanding that insulin is needed with hyperglycemia even if unable to eat, causes
many hospitalizations.
Help patients understand who and when to call for help and specific arrangements for follow-up, including appointments for outpatient diabetes education
in hospitals, physicians’ offices, communities, churches, senior centers, health
departments, and others.
Every Patient Is Unique
Consider the following scenarios:
• A 30-year-old man with type 1 diabetes admitted with diabetic ketoacidosis:
Information should focus on the diabetic crisis and any deficient self-care skills.
• A 20-year-old woman with a hemoglobin A1C of 11%, who has not been
informed about the consequences of an unplanned pregnancy and diabetes, needs
preconceptual diabetes counseling first.
Who Are the Educators?
Inpatient education requires multidisciplinary teamwork. Patients learn about
chronic disease management at each encounter with healthcare providers. Providing
patient-centered education and support cannot be delayed until the discharge day! It
must be effectively implemented, starting with an admission assessment.
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Inpatient Diabetes Education: Realistic and Evidence-Based
47
Role of Physician and Other Providers
• Diagnosis and medical decision making.
• Communication with other providers.
• Use teachable moments with patients each day. For example, when seeing a
patient with diabetes who is drinking fruit juice and eating pancakes for breakfast, use this as an opportunity to talk about the effect of carbohydrates on glucose
levels, realizing that appropriate carbohydrate foods are needed. Realize that
patients may be afraid to eat and may make choices based on out-of-date admonishments, like, “Don’t eat sugar.” When a patient asks how often to test, listen,
reflect and collaboratively design an achievable plan, like staggered or paired
testing.
• When a patient needs to start on daily insulin for home use and says he or she
is strongly opposed to doing so, the provider can say, “Will you tell us more
about your thinking regarding taking insulin at home?” Then, empathetically help
patients look at risk–benefit issues. After this nonjudgmental discussion, usually
patients decide that home insulin is a beneficial, achievable part of their future,
and perhaps, short-term, self-care.
• When talking with patients about home blood glucose testing, remember that
their particular insurance coverage of the strips used for testing is the main factor
in choice of meter and frequency of testing.
Role of Staff Nurse
• Assess and supplement the basic knowledge and skills of people with diabetes.
Listen, explain, and teach discharge recommendations.
• If registered nurses do glucose monitoring, they can assess the patient’s use of
self-monitoring of blood glucose, the frequency of home testing, and strategy for
sharing of results with the outpatient provider. During individualized education,
discuss meaningful home testing; for example, staggered time schedules can be
cost effective. A second strategy is to test once a day in a “pair,” like before and
after exercise or before and 2 h after a meal.
• Inpatient-type education also can be provided in emergency departments.
Outpatient education referral is essential.
• Assess sources of social support and provide information about other resources
in the community.
• If a hospital is closely linked to an ADA- or AADE-recognized outpatient education program, inpatient and outpatient nurses can collaborate, document on
the same educational forms, and share teaching responsibilities to enhance the
patient’s experience and eliminate duplication.
Role of the Certified Diabetes Educator (CDE), Nurse, and Dietician
• The role of the CDE in the inpatient setting is to serve as a resource and role
model for other healthcare professionals.
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E.D. Davis et al.
• The CDE also can provide direct patient education for patients with complex
medical problems.
Training and Support for Healthcare Providers Engaged
in Diabetes Inpatient Education
Training is needed for providers to educate inpatients with diabetes. Numerous
approaches can be useful: publications, unit-based classes, mentoring, online
programs, rounds with diabetes care providers, clinical nurse specialists and
discharge planners, and individual unit diabetes nurse champions.
Key Points: Inpatient Diabetes Education
• Acknowledge that all healthcare providers support and educate patients toward
better outcomes.
• Listen to the patient and collaborate to develop a plan.
• Address the most crucial education concepts and practices, including healthy
diet, activity plan, medication administration, blood glucose monitoring, and
sharing of results, hypoglycemia, hyperglycemia, and managing minor illness,
emergency care, and plans for follow-up.
• Practice behavioral change strategies, like motivational Interviewing, which take
less healthcare provider-time and produce improved outcomes.
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Spectr. 2008;21:268–271.
Nettles AT. Patient education in the hospital. Diabetes Spectr. 2005;18(1):44–48.
Parkin C, Hinnen D, Campbell K, Geil P, Tetrick D, Polonsky W. Effective use of paired testing in
type 2 diabetes: practical applications in clinical practice. Diabetes Educ. 2009;35(6):915–927.
Rollnick S, Miller W, Butler C. Motivational Interviewing in Health Care: Helping Patients
Change Behavior. New York, NY: Guilford Press; 2008.
Turek P, Mueller M, Egede L. Estimating physician effects on glycemic control in the treatment of diabetes: methods, effects sizes, and implications for treatment policy. Diabetes Care.
2008;31(5):869–873.
Urbanski P, Wolf A, Herman WH. Cost-effectiveness of diabetes education. J Am Diet Assoc.
2008;108(suppl 4):S6–S11.
Welch G, Rose G, Ernst D. Motivational interviewing and diabetes: what is it, how is it used, and
does it work? Diabetes Spectr. 2006;19:5–11.
Chapter 6
Hyperglycemic Emergencies:
Diabetic Ketoacidosis and Hyperosmolar
Hyperglycemic State
Leonor Corsino and Lekshmi T. Nair
Keywords Diabetic ketoacidosis · Hyperosmolar nonketotic hyperglycemia ·
Counterregulatory hormones · Ketosis · Acidosis · IV insulin
Diabetic Ketoacidosis
Diabetic ketoacidosis (DKA) is a serious acute complication of type 1 diabetes
mellitus and, less commonly, type 2 diabetes mellitus. DKA continues to be an
important cause of morbidity and mortality in individuals with diabetes, despite significant advances in the treatment of DKA. With prompt and appropriate treatment,
the mortality is rated between 5–20%, but this increases substantially with aging
and the presence of concomitant severe illness.
Case Presentation
A 32-year-old woman presented to the emergency department complaining of nausea, vomiting, and abdominal pain for the last 24 h.1 According to the patient,
she was in her usual state of health until 1 week prior to presentation when she
developed a cough with chills and fevers. Over the next few days, her condition
progressed to include nausea, vomiting, and mid-epigastric pain. She denied any
prior medical conditions and stated that she had always been healthy. Upon arrival
at the emergency department, she was an alert and oriented, young, obese, black
woman. Her blood pressure was 116/73 mmHg, pulse was 114 beats/min, respiratory rate was 20 breaths/min, and temperature was 100◦ F. Pertinent physical exam
findings were decreased breath sounds in the right lower lung and mid-epigastric
tenderness.
L. Corsino (B)
Division of Endocrinology, Metabolism, and Nutrition, Department of Medicine, Duke University
Medical Center, Durham, NC 27710, USA
e-mail:
[email protected]
1 The
case presented above does not represent a real patient. It was created as an educational aid.
L.F. Lien et al. (eds.), Glycemic Control in the Hospitalized Patient,
C Springer Science+Business Media, LLC 2011
DOI 10.1007/978-1-60761-006-9_6,
51
52
L. Corsino and L.T. Nair
Biochemical evaluation showed the following:
Sodium: 135 mmol/L [reference: 135–145 mmol/L]
Potassium: 4 mmol/L [3.5–5.0 mmol/L]
Chloride: 110 mmol/L [98–108 mmol/L]
Bicarbonate: 9 mmol/L [21–30 mmol/L]
Blood urea nitrogen (BUN): 35 mg/dL [7–20 mg/dL]
Creatinine: 1 mg/dL [0.6–1.3 mg/dL]
Blood glucose: 550 mg/dL [70–140 mg/dL]
Blood glucose in mmol/L: (30.5 mmol/L [3.8–7.7 mmol/L])
• Serum osmolality: 313 mOsm/L [277–293 mOsm/L]
• Arterial blood gas: pH: 7.1 [7.35–7.45]
• Urine ketones: positive [negative]
•
•
•
•
•
•
•
Chest radiography demonstrated right lower lobe pneumonia.
The patient was diagnosed with new-onset diabetes presenting with DKA and
right lower lobe pneumonia.
Pathogenesis
DKA is caused by a reduced concentration of circulating insulin with a corresponding increase in counterregulatory hormones, such as glucagon, catecholamines,
cortisol, and growth hormone (Fig. 6.1).
Clinical Presentation and Manifestations
Clinical presentation and manifestations include the following:
•
•
•
•
•
•
•
•
•
•
•
Polyuria (increased urination)
Polydipsia (increased thirst)
Fatigue
Weight loss
Nausea and vomiting
Abdominal pain, which can resemble an acute abdomen or pancreatitis
Vital sign abnormalities: tachycardia, tachypnea, hypotension, normo- or
hypothermia
Dry mucous membranes and reduced skin turgor
Kussmaul breathing (deep and labored breathing pattern often associated with
severe metabolic acidosis)
Mental status changes, including coma
“Fruity” breath odor, which represents acetone
It should be noted that some patients might present with DKA without prior
symptoms or history of diabetes. Also, it is important to understand that DKA per
6
Hyperglycemic Emergencies
53
Fig. 6.1 Simplified pathophysiology of diabetic ketoacidosis
se does not cause fever, so the presence of fever may be a clue to the pathogenesis/
precipitating event.
Precipitants
Among precipitants of DKA are
•
•
•
•
•
•
Infection (the most common)
New-onset diabetes
Discontinuation of or inadequate insulin regimen
Cerebrovascular accidents
Myocardial infarction
Alcohol abuse
54
L. Corsino and L.T. Nair
• Pancreatitis
• Trauma
• Medications (corticosteroids, thiazides, sympathomimetics such as dobutamine
and terbutaline)
• Drugs (cocaine)
• Pregnancy
• Psychological problems complicated by eating disorders
Differential Diagnosis
It is critical to remember that most of the information needed to differentiate DKA
from other diagnoses will come from a good clinical history.
• Starvation ketosis and alcoholic ketoacidosis: will present with mildly elevated
blood glucose (rarely > 200 mg/dL [11.1 mmol/L]) to hypoglycemia; bicarbonate
usually not lower than 18 mEq/L.
• Lactic acidosis: Because lactic acidosis is more common in patients with diabetes
than in nondiabetic persons and because elevated lactic acid levels may occur in
severely volume contracted patients it should always be measured on admission;
ketones will not be present.
• Ingestion of drugs (salicylate, methanol, ethylene glycol, isoniazid, and paraldehyde) – these ingestions can be detected on specific drug screens; ethylene
glycol can be suggested by the presence of calcium oxalate crystals in the urine;
paraldehyde ingestion is indicated by the strong odor on the breath.
• Chronic or acute kidney failure with severe uremia – differentiate by history and
biochemical testing.
• There are some case reports of patients with acromegaly presenting with DKA.
Certainly, patients with diabetes also can be affected with the above disorders.
These conditions are not mutually exclusive with DKA, and complete evaluation
should be conducted in patients who are at risk for multiple-etiology metabolic
disturbances.
Evaluation
Urgent evaluation should include the following:
• History and physical examination. The history should focus on possible precipitating factors. Almost 20% of patients presenting to the emergency department
with DKA have no previous diagnosis of diabetes.
• Biochemical testing should include plasma glucose, BUN/creatinine, serum
and urine ketones, electrolytes (with calculated anion gap), plasma osmolality,
urinalysis, complete cell count with differential.
• Chest X- ray, urine, sputum, and blood cultures should also be obtained.
6
Hyperglycemic Emergencies
55
• Calculated anion gap (AG):
• AG = [Na+ ] – ([Cl– ] + [HCO3 – ])
• Normal range: 9–12 mmol/L.
• Calculated total plasma osmolality:
• Total plasma osmolality = 2 [Na+ (mmol/L)] + [Glucose (mg/dL)/18] + [BUN
(mg/dL)/2.8].
• Normal: 290 ± 5 mOsm/L (this number might have a different range based on
each laboratory’s reference values).
• Arterial blood gas to evaluate for acidosis.
• Electrocardiogram with attention to signs of hyperkalemia or acute myocardial
infarction.
Laboratory Findings
Confirmation of DKA will be completed by presence of anion-gap metabolic acidosis and positive serum and/or urine ketones. Blood glucose almost always will be
elevated as well; however, in the case of chronic starvation, blood glucose level may
be normal and up to 10% of patients with DKA might present with so-called “euglycemic DKA”. Occasionally, serum ketones are read as low or negative because
ketone strips, using the nitroprusside reagent, only detect acetoacetate and acetone, while the ketone β(beta) -hydroxybutyrate predominates in DKA. A β (beta)
-hydroxybutyrate level is available in some laboratories, but it rarely is necessary to
confirm the diagnosis.
Once DKA is confirmed, the patient should be evaluated for precipitating factors.
Hemoglobin A1C may be useful to differentiate between poorly controlled or undiagnosed diabetes and an acute event in an otherwise well-controlled patient. Many
patients with DKA present with leukocytosis. This is usually proportional to the
blood ketone concentrations and might not be indicative of infection. Also, patients
with DKA might have elevated lipase, amylase, and liver enzymes. Physicians must
always remember that a good clinical history is the key to determine if this is due to
pancreatitis or an elevation related to DKA.
Management
Treatment goals include the following:
• Decrease plasma glucose and osmolality by giving IV insulin.
• Increase circulatory volume and perfusion by giving IV fluids.
• Correct electrolyte imbalances. Hyponatremia often will correct with routine
management, but potassium and bicarbonate may need to be replaced. In some
cases, replacement of phosphorus, calcium, and magnesium may also be required
(see section on electrolytes).
• Clear serum and urine ketones.
• Treat precipitating events.
56
L. Corsino and L.T. Nair
In many cases, intensive care unit (ICU)-level monitoring will be required
because of the necessary frequency of monitoring.
Insulin
Prior to initiation of insulin therapy, hypokalemia (less than 3.3 mmol/L) must be
treated as detailed under Electrolytes.
Although there are prospective, randomized trial data that support the use of
subcutaneous insulin analogs for treatment of uncomplicated DKA, regular insulin
given intravenously is still the treatment of choice in the majority of cases.
IV regular insulin is given as follows:
• Therapy should begin with a bolus dose of 0.1–0.15 units/kg of regular IV insulin.
• Along with the bolus dose, a continuous IV insulin infusion is initiated at a rate
of 0.1 units/kg/h.
• The goal is an hourly decrease in blood glucose of approximately 50–75 mg/dL
(2.75–4.12 mmol/L). Many institutions have an automatic protocol for infusion
adjustment based on monitoring results and other parameters. One method for
adjustment of the infusion rate can be found in Chapter 3: IV Insulin.
• While the patient is on IV insulin, capillary glucose should be monitored hourly.
(Many institutions require ICU status for this intensity of patient care.)
• Continue IV insulin until the patient is stable. The American Diabetes
Association (ADA) defines criteria for DKA resolution as glucose less than
200 mg/dL (11.1 mmol/L), and two of the following: serum bicarbonate greater
than or equal to 15 mEq/L, a venous pH greater than 7.3, and a calculated
anion gap less than or equal to 12 mEq/L. If the glucose reaches 200 mg/dL
(11.1 mmol/L) or less, but the bicarbonate and pH are not at goal, 5% dextrose
should be given to prevent hypoglycemia while the insulin infusion is continued.
Once the criteria for resolution of DKA are met, a transition to subcutaneous
insulin can be undertaken. The infusion and subcutaneous insulin should overlap for
a length of time appropriate to the peak of absorption of the subcutaneous insulin.
For the rapid-acting insulins, the overlap should be at least 1 h. If only a long-acting
R
R
) is given, the overlap should
) or detemir (Levemir
insulin like glargine (Lantus
be at least 4 h.
IV Fluids
On average, patients with DKA have a total water deficit of approximately 6 L. The
first step is to determine the patient’s hydration status by calculation of the precise
water deficit using the formula:
water deficit (L) = [0.6 (men) or 0.5 (women) or 0.45 (elderly)]
×lean body weight (kg) × [(plasma [Na + ] − 140)/140].
6
Hyperglycemic Emergencies
57
Normal saline is the IV fluid of choice for most adults, and a rate of 1 L/h is
generally a reasonable starting point. However, a slower, more cautious approach is
recommended for patients with impaired ability to manage their volume status, such
as those with chronic renal insufficiency and congestive heart failure.
After 2 h of IV fluid administration, the sodium level should be evaluated. If the
sodium level has not returned to normal (i.e., is still low), normal saline should be
continued, and sodium reevaluated after an additional 2 h. Once the sodium level has
returned to normal, the IV fluid should be changed to half-normal saline (0.45%) at
a rate appropriate for continued volume repletion.
IV fluid management and electrolyte monitoring are done concomitantly with
glucose and insulin management. When the blood glucose reaches 200 mg/dL
(11.1 mmol/L) or less, addition of 5% dextrose to the IV fluids is warranted.
Electrolytes
Electrolytes should be monitored every 2 h during aggressive fluid and insulin
administration. Once the patient is stabilized, monitoring frequency can be
decreased to every 4 h. This should be continued for at least the first 24 h.
Potassium
If the potassium is low (<3.3 mEq/L), insulin should be held, and potassium chloride
should be initiated intravenously (with IV fluids if desired), at 20–30 mEq/h, until
potassium is more than 3.3 mEq/L.
Patients with initial potassium levels in the reference range frequently also
require supplementation once insulin is begun. Although plasma potassium is maintained in the normal range, there is a total body deficit of potassium. Insulin
provokes movement of potassium from the plasma into the cells, which can result
in a decreased plasma potassium level once treatment is initiated.
If the initial potassium level is high, the patient’s potassium should be monitored,
every 2 h, without specific treatment. It is likely that the level will decrease with
insulin and fluid administration.
Sodium
The initial sodium level often is low. This phenomenon does not represent true
hyponatremia and will typically resolve with treatment of the hyperglycemia.
Bicarbonate
Bicarbonate administration is controversial, particularly in patients who have
impaired respiratory function. However, it should be considered in patients who
have severe acidosis (i.e., pH less than 6.9).
If pH is less than 6.9, dilute bicarbonate (NaHCO3 ) with 100 mmol in 400
mL of water with 20 mEq of potassium chloride (KCl) and infuse over a period
58
L. Corsino and L.T. Nair
of approximately 2 h. Monitor bicarbonate every 2 h and repeat bicarbonate
replacement until pH is greater than or equal to 7.0
Phosphate
Unless hypophosphatemia is severe (phosphate <1 mg/dL [< 0.32 mmol/L]) and
the patient has cardiac dysfunction, anemia, or respiratory depression, phosphate
is not administered. Phosphate administration in this setting can lead to severe
hypocalcemia.
Key Points: DKA
• Potassium should be checked BEFORE initiation of IV insulin and frequently
thereafter. Replacement should be given immediately if the level is low.
• IV regular insulin should be started promptly.
• Aggressive IV fluids are indicated as long as the patient can tolerate them; (use
caution in chronic renal insufficiency and congestive heart failure).
• Monitor electrolytes: replace potassium; follow sodium and adjust IV fluids
accordingly; and be judicious with bicarbonate replacement.
• Frequent glucose monitoring, with appropriate treatment adjustments.
• At least 1 h of overlap should be allowed between the first subcutaneous insulin
injection and the cessation of IV insulin.
• Patients with diabetes mellitus type 1 can be in DKA even with blood glucose
below 200 mg/dL (11.1 mmol/L)
• Patients with diabetes mellitus type 2 also can present with DKA, especially
blacks and Hispanics/Latinos.
Hyperosmolar Hyperglycemic State
Hyperosmolar hyperglycemic state (HHS), also called hyperosmolar nonketotic
hyperglycemia (HONK or HNKH), is a serious acute complication of diabetes.
HHS is under diagnosed, despite its high mortality rate of approximately 11%.
It is seen almost exclusively in patients with type 2 diabetes, and is more common in the elderly. The severe hyperglycemia seen in HHS results from decreased
peripheral insulin effect (either from deficiency or resistance) combined with an
increased counterregulatory hormone effect, and it is further compounded by volume depletion. The hyperglycemia results in glycosuria, which leads to dehydration
and depletion of electrolytes.
Once a hyperglycemic emergency is diagnosed, the next step is to differentiate
HHS from DKA. The major difference between the two disorders is the presence
of insulin and its metabolic effects. Unlike DKA, HHS is a condition in which
enough insulin is present to avoid release of fatty acids and subsequent ketoacidosis.
Because of this and because HHS can present after long periods of hyperglycemia
in patients with less efficient renal glucose excretion, the patients can present with
very high glucose levels, sometimes greater than 1,000 mg/dL (55.5 mmol/L).
6
Hyperglycemic Emergencies
59
Clinical Presentation and Manifestations
The clinical presentation and manifestations of HHS include the following:
•
•
•
•
•
•
•
Polyuria
Polydipsia
Weight loss
Fatigue
Slow, insidious onset of days to weeks
Central nervous system effects, such as altered mental status or seizures
Signs of volume depletion
•
•
•
•
Decreased skin turgor
Tachycardia
Hypotension
Low urine output
Differential Diagnosis
DKA will present with lower blood glucose. Compared with DKA, HHS usually has
a blood glucose greater than 600 mg/dL (33.3 mmol/L); arterial pH usually is greater
than 7.30; serum bicarbonate (NaHCO3 ) is greater than 18 mEq/L; and ketones
are usually less. Other disease entities to consider will depend on the presenting
symptoms.
Precipitants
Precipitants of HHS include the following:
•
•
•
•
•
•
•
New diagnosis of diabetes
Nonadherence to medications or inadequate use of prescribed medications
Infection
Myocardial infarction
Cerebroavascular accident
Drugs
Pancreatitis
Evaluation
Evaluation of the patient should include the following:
• Plasma glucose.
• Complete metabolic panel, with electrolytes, bicarbonate, BUN, and creatinine.
Calculation of the anion gap can be helpful in distinguishing HHS from DKA;
however, patients with HHS will not always have a normal anion gap. An elevated
60
•
•
•
•
•
L. Corsino and L.T. Nair
anion gap may also be related to ingested substances, uremia, or lactic acidosis,
and examination for these factors in appropriate patients, in addition to ketones,
is an important component of the evaluation.
Serum osmolality.
Urine ketones.
Serum ketones.
Arterial blood gas.
Echocardiogram, cardiac biomarkers, chest x-ray, and urine and blood cultures
may be appropriate to evaluate for precipitants and sequelae, depending on the
patient’s presenting symptoms and comorbidities.
Laboratory Findings
Laboratory findings usually will show severe hyperglycemia and hyperosmolality,
with serum osmolality greater than 320 mOsm/L. Serum bicarbonate, anion gap, and
pH typically are normal, although acidosis can result from coexisting conditions,
particularly if the patient is having seizures related to the hyperosmolality.
The patient may have hyponatremia, which often is artifactual. Osmotic pressure related to the high glucose level forces water into the vascular space, causing a
dilutional hyponatremia, or “pseudohyponatremia.” Furthermore, the high glucose
can increase triglyceride levels, which can displace sodium in the plasma assay.
Serum sodium level can be corrected mathematically with the following equation:
Measured sodium +(((Serum glucose − 100)/100) × 1.6). (However, some laboratories will report the corrected sodium.) Pseudohyponatremia should correct with
resolution of the hyperglycemia.
Hyperkalemia can result from lack of insulin effect at the potassium channels in
the cell membranes, causing a shift of potassium to the extracellular space. (This
problem is compounded in DKA because of the combined effects of inadequate
insulin and acidemia.) These patients frequently have low total body potassium and
will develop hypokalemia as the hyperglycemia is corrected.
Management
In brief, the following elements should be included. Detailed descriptions of each
component follow.
•
•
•
•
•
IV fluids
IV insulin
Electrolyte correction and maintenance
Vigilance
Treatment of precipitating factor
6
Hyperglycemic Emergencies
61
IV Fluids
Patients with HHS are severely dehydrated, and aggressive IV hydration is indicated. First, intravascular volume should be restored, usually with normal saline
(0.9% NaCl) at 15–20 mL/kg/h, or about 1–1.5 L/h. Generally, it is necessary to
maintain this rate for at least 1 h. As always, IV fluid administration requires caution
in patients with impaired volume status, such as those with chronic renal insufficiency or congestive heart failure. After the first hour, the patient’s volume status
should be re-assessed: blood pressure, pulse rate, skin turgor, and urine output, along
with evaluation of blood electrolytes and glucose.
Once the patient is hemodynamically stable and volume replete, half-normal
saline (0.45% NaCl) can replace the 0.9% NaCl. The 0.45% NaCl should be continued at a reduced rate, such as 100–250 mL/h, as long as the patient remains
hyperglycemic. In HHS, once the serum glucose reaches 300 mg/dL (16.6 mmol/L),
5% dextrose (D5) should be added to the 0.45% NaCl.
Insulin
IV insulin is used because of its rapid onset and facility for titration. (More discussion of titration methods is provided in Chapter 3: IV Insulin.) It is ideal to continue
the insulin infusion until mental status has returned to normal, hyperosmolarity and
hyperglycemia have resolved, and the patient is able to eat.
Electrolytes
Sodium
Sodium will normalize with IV fluid and insulin administration and resolution of
the hyperglycemia.
Potassium
This may be elevated at presentation but will decrease with treatment with IV fluids and insulin. If initial potassium is below 3.3 mEq/L, insulin should be held
and 20–30 mEq/h of potassium should be given until the potassium level is above
3.3 mEq/L. Patients with potassium levels between 3.3 and 5.2 mEq/L should
receive 20–30 mEq of potassium in each liter of IV fluid. Finally, patients with
potassium levels greater than 5.2 mEq/L won’t need potassium supplementation initially, but the potassium level must be monitored every 2 h because of the anticipated
decline in potassium with insulin therapy.
Phosphate
Phosphate can decrease with insulin treatment. As in the case of DKA, unless
hypophosphatemia is severe, phosphate administration is not routinely given;
62
L. Corsino and L.T. Nair
phosphate administration has been associated with development of hypocalcemia
and hypomagnesemia. Although phosphate supplementation is not indicated for routine use, serum phosphate levels should be monitored to avoid cardiac, hematologic,
or muscular complications.
Vigilance
Patients with HHS often require intensive monitoring and care, and an ICU setting
is most appropriate. However, some institutions have intermediate care units that
are equipped and have the trained personnel to manage patients with HHS. Vital
signs, mental status, and hydration status should be monitored every 1–2 h while
the patient is unstable and every 2–4 h for the first 24 h. Capillary glucose should
be monitored hourly while the patient is on IV insulin, and electrolytes, creatinine,
and serum osmolality should be checked every 2–4 h.
Key Points: HHS
• When hyperglycemic emergency is suspected, evaluation should be done immediately.
• Fluid administration is critical; volume status should be closely monitored.
• IV insulin infusion.
• Electrolyte management.
• Monitor the glucose frequently and adjust treatment as appropriate.
Bibliography
Henderson KE, Baranski TJ, Bickel PE, Clutter WE, McGill JB, eds. The Washington Manual of
Endocrinology Subspecialty Consult. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins;
2009.
Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with
diabetes: a consensus statement from the American Diabetes Association. Diabetes Care.
2009;32(7):1335–1343.
Lien LF, Spratt SE, Woods Z, Osborne K, Feinglos MN. Optimizing hospital use of intravenous
insulin: improved hyperglycemic management and error reduction with a new nomogram.
Endocr Pract. 2005;11(4):240–253.
Chapter 7
Medical Nutrition Therapy in the Hospital
Sarah Gauger
Keywords Carbohydrate counting · Carbohydrate serving · Nutrition counseling
Medical nutrition therapy (MNT) is an integral component of diabetes management and of diabetes self-management education. It is usually best provided in an
outpatient and home setting; however, a hospital admission provides an excellent
opportunity to review, reinforce, and educate both the patient and family regarding
appropriate dietary choices.
The American Diabetes Association (ADA) does not endorse any single meal
plan or strict pattern of macronutrient composition. Instead, the organization recommends a dietary plan that includes carbohydrates from foods like fruits, low-fat
milk, legumes, whole grains, and vegetables. Additionally, an important component of nutrition for patients with diabetes includes monitoring carbohydrates by
carbohydrate counting and carbohydrate exchanges. In general, approximately 45–
60 g of carbohydrates per meal can be the goal. Also, the use of low-glycemic
index carbohydrates might provide moderate additional benefits. The ADA recommends that saturated fat intake should be limited to less than 7% of the total calories
and that trans-fat intake should be minimized. Additionally, patients with diabetes
should be encouraged to consume foods containing significant amounts of fiber,
and to limit the consumption of alcohol to moderate amounts (no more than one
drink/day for women and two or less for men). Finally, it is critical that any MNT
be individualized and that a multidisciplinary approach is used.
Goals of MNT in the Hospital
• Support medical therapy with the aim to attain and maintain glucose control.
• Provide adequate calories throughout illness and early recovery.
• Address individual preferences based on personal, cultural, religious, and ethnic
background.
S. Gauger (B)
Duke Inpatient Diabetes Management, Duke University Medical Center, Durham, NC 27710, USA
e-mail:
[email protected]
L.F. Lien et al. (eds.), Glycemic Control in the Hospitalized Patient,
C Springer Science+Business Media, LLC 2011
DOI 10.1007/978-1-60761-006-9_7,
63
64
S. Gauger
What Is a Carbohydrate Serving?
One “carbohydrate serving” is the same as 15 g of carbohydrate. Historically, diabetic patients counted servings as a form of carbohydrate counting, but it is now
more common for patients to use grams for calculation of an insulin dose. Many
hospitals still report carbohydrate servings rather than grams with their menus and
food service, and some patients find this confusing. Examples of a carbohydrate
serving: 4 oz fruit juice or regular soda, 1 slice of bread, 1 pint of milk, 1 small
fresh fruit, such as a plum or small apple, 1/3 cup of cooked rice/pasta, 1/2 cup
mashed potatoes, or 3 glucose tablets.
What Can Be Done in the Hospital?
Nutrition Consult
A nutrition consult can be invaluable for inpatient nutrition education and advice,
particularly for patients who are being treated with insulin or with modified diets.
However, all patients with diabetes can benefit from nutrition counseling, and this
should be undertaken if it is available.
Patients taking insulin. Many of these patients, specifically those using a continuous subcutaneous insulin infusion (CSII; see Chapter 8), will need to count
carbohydrates in order to determine their mealtime (bolus) insulin dosages.
Patients receiving modified diets. Patients who are receiving a “liquid diet,” (in
other words, a diet consisting of liquids which are often low in protein but high
in carbohydrates) may experience disproportionate hyperglycemia, because simple
sugars often comprise the entire calorie content of these liquids. Usually, use of
a liquid diet is temporary, but some patients will need extra counseling about this
issue.
Supervised Calorie Counting
Calorie counting in the hospital usually is ordered to assess for undernutrition in
patients who have reasons for inadequate intake. Additional therapy can be given
for patients who are not meeting their caloric needs. (Caloric need for the average
hospitalized patient is 25–35 kcal/kg.) Calorie counting also can be valuable for
patients who overeat. These patients often are best served by self-monitoring calorie
intake with food diaries. This task also can be translated to home monitoring.
Assess for Related Comorbidities
It is important to recognize that a diabetic patient may have comorbidities that
will have an impact on nutrition and nutritional goals. Some of these comorbidities
include the following:
7
Medical Nutrition Therapy in the Hospital
65
• Gastroparesis: Because of slow gastric emptying, patients should eat smaller,
more frequents meals; avoid late evening snacks and high-fat foods; avoid
caffeine, alcohol, and tobacco; eat slower; and eat a diet lower in fiber.
• Celiac disease (more common in association with type 1 diabetes).
• Dental disease: Will impact the dietary plan; patients with severe disease or no
dentures might limit their diet to liquids and soft foods.
• Cystic fibrosis (CF)-related diabetes: Caloric restriction is never an appropriate way to control glucose in these patients. Patients with CF require nutrition
in order to maintain their weight and for survival; high-fat meals usually are
recommended.
Discharge Planning
Any dietary instructions given during the patient’s hospital stay should be reinforced prior to discharge; this can include carbohydrate counting, food diaries, or
elimination of certain high-carbohydrate products like sugar-sweetened beverages.
Patients who require further education or follow-up can be referred for outpatient
diabetes and nutrition counseling. Additionally, some patients do well with simple
mnemonics like these:
• “Rule of Thumb”
•
•
•
•
Size of Thumb = 1 ounce of cheese or meat
Size of Fist = 1 cup of fruit or 1 medium whole raw fruit
Size of Fingertip = Approximately 1 teaspoon
Size of One Cupped Hand = 1–2 ounces of dry goods like nuts, cereal, etc.
• “Plate Method” (http://platemethod.com)
•
•
•
•
Fill one-half of plate with nonstarchy vegetables
Fill one-fourth of plate with starch source
Fill one-fourth of plate with protein source
Use fruit and milk sources for mealtime deserts
Conclusion
MNT is primarily an outpatient strategy and therefore can often end up being overlooked during a busy hospitalization. Nonetheless, it is a critical component of
diabetes management, and the inpatient stay provides a unique opportunity to educate patients. MNT can be particularly useful for those patients who have little
understanding of how their nutrition relates to glycemic control. Specific teaching topics for inpatient use include calorie counting and portion sizes. Finally, an
inpatient nutrition consult may be requested when this resource is available.
66
S. Gauger
Key Points: MNT in the Hospital
• Although the majority of MNT is directed at outpatients, it is important not to
overlook the hospitalization as a teachable moment.
• Strategies for MNT in the inpatient setting include nutrition consultation and
supervised calorie and carbohydrate counting.
• Discharge planning should include a review of inpatient information as well as a
personalized nutrition plan for home.
Bibliography
American Diabetes Association. Diabetes nutrition recommendations for health care institutions.
Diabetes Care. 2004;27(supp 1):S55–S57.
American Diabetes Association. Nutrition recommendations and interventions for diabetes. A
position statement of the American Diabetes Association. Diabetes Care. 2008;31(supp 1):
S61–S78.
American Diabetes Association. Standards of medical care in diabetes. Diabetes Care.
2009;32(supp 1):S13–S61.
Goody CM, Drago L. Using cultural competence constructs to understand food practices and
provide diabetes care and education. Diabetes Spectr. 2009;22(1):43–47.
Idaho Plate Method. http://platemethod.com. Accessed January 19, 2010.
McKnight KA, Carter L. From trays to tube feedings: overcoming the challenges of hospital
nutrition and glycemic control. Diabetes Spectr. 2008;21(4):233–240.
Parrish CR, Pastors JG. Nutrition FYI: nutritional management of gastroparesis in people with
diabetes. Diabetes Spectr. 2007;20(4):231–238.
Swift CS, Boucher JL. Nutrition care for hospitalized individuals with diabetes. Diabetes Spectr.
2005;18(1):34–38.
Swift CS. Nutrition FYI: nutrition trends: implications for diabetes health care professionals.
Diabetes Spectr. 2009;22(1):23–25.
Wilson DC, Kalnins D, Steward C, et al. Challenges in the dietary treatment of cystic fibrosis
related diabetes mellitus. Clin Nutr. 2000;19(2):87–93.
Chapter 8
Insulin Pumps and Glucose Sensors
in the Hospital
Sarah Gauger
Keywords Insulin pump · Continuous subcutaneous insulin infusion (CSII) · Target
blood glucose range · Active insulin time · Insulin to carbohydrate ratio · Basal
rate · Insulin sensitivity factor · Inpatient diabetes self-management · Bolus
wizard · Continuous glucose monitoring · Glucose sensor
Understanding the Insulin Pump
An insulin pump is a small mechanical device that, through a flexible catheter,
delivers insulin via a patient’s subcutaneous tissue. The pump supplies a continuous infusion of insulin (continuous subcutaneous insulin infusion [CSII]). CSII is
standard of care in the management of type 1 diabetes and also can be used for management of type 2 diabetes. CSII provides tremendous flexibility for patients but
also requires a thorough understanding of the hardware as well as proven ability to
perform diabetes self-care.
R
), lispro
In most cases, a rapid-acting insulin, such as aspart (Novolog
R
R
(Humalog ), or glulisine (Apidra ), is used in the pump. Even though only one
type of insulin is used, it functions as both the basal and bolus components. The
basal insulin component is continuously infused at a programmed hourly rate, such
as 0.5 units/h. (Note: Most patients will have multiple different basal rates throughout the day.) The bolus insulin component is infused at discrete times, usually
with meals, and the user can direct its administration on an as-needed basis. The
calculation of the insulin bolus dose is determined by a number of programmed
factors:
• Target blood glucose range. Recommended ranges may differ according to
the time of day (i.e., fasting, mealtime, regular exercise times); most pumps
accommodate multiple target glucose ranges.
S. Gauger (B)
Duke Inpatient Diabetes Management, Duke University Medical Center, Durham, NC 27710, USA
e-mail:
[email protected]
L.F. Lien et al. (eds.), Glycemic Control in the Hospitalized Patient,
C Springer Science+Business Media, LLC 2011
DOI 10.1007/978-1-60761-006-9_8,
67
68
S. Gauger
• Active insulin time. Active insulin time is a feature that allows for the pump to
factor in amounts of insulin that remain from a previous bolus. This helps to avoid
“insulin stacking.” The default setting usually is 5 hours, and this rarely needs to
be adjusted.
• Insulin to carbohydrate ratio. This is the amount of insulin needed to cover a specific amount of carbohydrate. It is written as a ratio, with 1:15 as a representation
of 1 unit per 15 g of carbohydrate.
• Insulin sensitivity factor (ISF). The ISF represents the decrease in plasma glucose
that occurs with 1 unit of insulin. For example, an ISF of 50 indicates that 1 unit
of insulin will decrease the glucose by 50 mg/dL (2.7 mmol/L).
The physician or provider should predetermine these factors. The bolus calculator also incorporates the current blood glucose level and the anticipated
carbohydrate content of the meal, which are entered by the user at the time of the
bolus.
When admitting a patient who is wearing an insulin pump, the provider should
review the settings and document them in the medical record. Because understanding the pump settings is an important part of treatment and safety in the hospital, it
may be necessary to consult an endocrinologist for help.
Who Can Continue CSII in the Hospital?
Patients who are eligible to continue CSII should meet the following criteria: they
should be (1) fully alert with normal mental status, (2) physically able to selfmanage, and (3) equipped with extra infusion sets and other necessary supplies.
If there is any concern about mental status, such as fatigue or use of narcotic medications, CSII should be discontinued. Patients must have their own supplies, as
even major academic hospitals do not stock supplies for insulin pumps. There are
multiple types of pumps, and their use is not common enough to justify the cost of
keeping supplies in the hospital.
Hospitalization is not the time for initiation of CSII, even though this question
may arise during the hospital stay. Initiation of CSII requires intensive education and
training that must occur over a series of outpatient appointments. Patients who are
eligible and appropriate for use of CSII can be referred for outpatient consultation
with a pump educator.
When Must Insulin Pumps Be Removed?
Insulin pumps should be removed during the following procedures:
• X-rays
• Computed tomography scans
• Magnetic resonance imaging scans
8
Insulin Pumps and Glucose Sensors in the Hospital
69
• Any other exposure to radiation
• Surgical procedures
The infusion set and tubing may remain in place during radiation exposure;
however the pump itself must be removed.
Appropriate Documentation of Settings
There are several important pieces of data that must be obtained in order to properly
care for a patient who will remain on CSII during the hospitalization. It also is
important to document these data in the medical record so that all providers can be
aware of the settings and other pertinent information. The following information, at
a minimum, is needed to write appropriate inpatient pump self-management orders.
•
•
•
•
•
•
•
•
Make and model of the pump
Type of insulin
Basal rates
Insulin to carbohydrate ratio
ISF
Time and amount of the most recent bolus
Date of the most recent infusion set change
What is the “off-pump plan?” (Many patients using CSII will have a predetermined subcutaneous insulin regimen to be used in the case of pump failure. This
regimen is a good starting point for creation of an inpatient subcutaneous insulin
regimen if needed).
Example: Pump Self-Management Orders
• [Patient name] will self-administer insulin through his/her [make/model] insulin
pump.
• Basal rate: At 0000 infuse [type] insulin at 1.1 units/h; then at 0300 change to 1.2
units/h; then at 0600 change to 1.1 units/h; then at 1600 change to 1.3 units/h;
then at 2100 change to 0.9 units/h.
• Use the bolus wizard for bolus insulin with meals, with 1 unit of [type] insulin
for every 15 g of carbohydrates.
• Use the bolus wizard to give correctional insulin, with a sensitivity factor of 50
(or give 1 unit insulin for every 50 mg/dL [2.7 mmol/L] of blood glucose over
200 mg/dL [11.1 mmol/L]).
• Change infusion set every 3 days, with first change today.
• The insulin pump, but not the infusion set, must be removed for all imaging
procedures.
• Blood glucose monitoring before meals, at bedtime, and per patient request. For
glucose less than 60 mg/dL (<3.3. mmol/L), treat hypoglycemia immediately,
suspend the pump temporarily, and call endocrinology for assistance. For glucose
70
S. Gauger
greater than 250 mg/dL (>13.8 mmol/L), also call for assistance. Record all blood
glucoses and bolused insulin doses on the nurses’ medication administration
record.
Troubleshooting
Hyperglycemia
The following problems can occur with the infusion set:
•
•
•
•
•
•
•
•
•
The tubing is not primed.
There is air in the tubing.
There is no insulin in the cannula.
The infusion set is not connected to the cartridge or syringe.
The infusion set is not connected to the patient.
There is a leak in the infusion set.
The cannula is dislodged or kinked.
The infusion set has been in too long (>3 days).
There are signs of infection (i.e., redness, discomfort, or bleeding) at the
insertion site.
The following are possible problems with the pump itself:
(Many pumps have alarms that may provide insight when there is a problem.)
•
•
•
•
The insulin cartridge is empty.
The time and date on the pump are incorrect.
The pump is not correctly programmed.
The patient forgot to administer the most recent bolus.
The following are possible problems with the insulin:
• The insulin is expired or inactive (inactive insulin may appear cloudy or
clumped).
• The insulin has been in a warm location or at room temperature for too long.
• The insulin in the cartridge is more than 3 days old.
There always is the possibility that the insulin dosage may need to be adjusted.
Hypoglycemia
Hypoglycemia should be treated promptly before causes are considered. The insulin
administration via the pump should be suspended for at least 20 minutes, and
15–30 g of carbohydrates administered. Once the glucose is greater than 90 mg/dL,
insulin administration may be resumed.
8
Insulin Pumps and Glucose Sensors in the Hospital
71
Insulin dose errors may occur if the bolus is too large, which may be a result of
miscounted carbohydrates, inaccurate carbohydrate ratio, or other improper settings;
or if the basal rate is too high.
Situational causes may include the following:
• Unanticipated fasting
• Increase in activity level, as with initiation of physical therapy or a general
increase in time out of bed
• New medications
• Increased insulin absorption, which may happen in patients with improvement in
edematous conditions
• Onset of menses
Prevention of Hypoglycemia
In order to prevent hypoglycemia, insulin doses, including both basal and bolus,
should be reduced for patients who develop acute renal failure, hepatic failure, or
other conditions that can change insulin metabolism. (A complete list can be found
in Chapter 14: FAQ.) If a patient is anticipated to have rapidly changing insulin
needs throughout the hospital stay, it is advisable to switch to subcutaneous insulin
injections or an IV insulin infusion.
The patient’s blood glucose should be monitored 6–8 times/day or more often if
the patient has variable or increasing physical activity level.
Accurate carbohydrate counting is important for appropriate bolus dosing. For
patients who find this difficult, a nutrition consult may be helpful.
Once a mealtime bolus is given, a corresponding carbohydrate load must be
given. If a patient is inconsistent about eating meals because of nausea or any other
reason, the mealtime bolus can be delivered at the end of the meal. If the patient has
been given a bolus and is then unable to eat, IV dextrose should be given to prevent
hypoglycemia.
Pump Site Reactions
Site Infection
Infection at the pump or sensor site is the most common complication associated
with pump therapy and also is the most common reason for discontinuation of pump
therapy; (in addition, please see below for more details on sensors). These infections
can be rapidly progressive and must be treated immediately.
To treat, the infected infusion sets must be removed and discarded, and a new
set should be placed at a site distant from the infection. Antibiotic therapy for
subcutaneous infection, with consideration of resistant organisms, should be given
promptly. Incision and drainage is sometimes but not always necessary; this can be
determined on a case-by-case basis.
72
S. Gauger
Patients with recurrent infusion site abscesses should be observed for proper
insertion technique, which includes washing the area with an antibacterial soap,
an antibacterial solution, or an antiseptic wipe, and letting it dry before inserting the
infusion set.
Allergic Reactions
Allergic reactions may occur at infusion sites and usually are the result of adhesives
or components of the infusion set needles. This most commonly occurs soon after
initiation of CSII but may occur later if supply products are changed. Because pump
supplies are not stocked in the hospital, no alternative supplies will be available.
Thus, a patient in this situation will need subcutaneous insulin injections until he or
she can see the outpatient provider to discuss options.
Transition to Subcutaneous Insulin
Conversion to subcutaneous or IV insulin often is necessary in the inpatient setting.
We recommend discontinuation of CSII in the following situations:
• Patient is unable to self-manage (as determined by the patient or the provider).
• The pump malfunctions.
• A hyperglycemic emergency, such as diabetic ketoacidosis or hyperosmolar
nonketotic hyperglycemia occurs.
• Patient has a critical illness.
• Patient experiences prolonged periods of fasting.
• Patient is in the perioperative period, particularly for organ transplantation.
• Total parenteral nutrition is being given to the patient.
• Glucocorticoids are being initiated.
• Patient has had a stroke.
• Patient is undergoing labor and delivery.
• Patient needs serial imaging procedures or radiation treatments.
• Other illnesses requiring prompt glucose control that are better managed with IV
infusion.
The determination of route, subcutaneous versus IV, should be handled on a caseby-case basis. IV insulin infusions may be more appropriate for rapidly changing
conditions or insulin needs, as well as when true insulin requirements are unclear.
For more information on IV insulin, see Chapter 3: IV Insulin Infusions.
For subcutaneous insulin, the dose determination strategy is similar to that
of other subcutaneous insulin regimens, which are described in Chapter 2:
Subcutaneous Insulin. However, there are some differences. We describe two strategies here: the first for a patient who is eating discrete meals, the second for a patient
who is fasting.
8
Insulin Pumps and Glucose Sensors in the Hospital
73
Patient Eating Discrete Meals
If the patient has an off-pump plan, this is a good place to start. If the patient does
not have an off-pump plan or has changing insulin requirements, the insulin dosages
can be calculated based on the patient’s weight (as in Chapter 2) or estimated from
the pump settings. When using the pump settings to estimate, the basal and bolus
doses are calculated separately rather than as percentages of the total daily dose.
To calculate a new basal dose, it is useful to first determine the ongoing daily
basal dose from the pump; most pumps report this. This basal dose can be given
R
) or
as one or two basal injections with long-acting insulin, like glargine (Lantus
R
detemir (Levemir ). If there have been episodes of hypoglycemia with the ongoing
CSII, the basal dose should be decreased. Also, it takes several hours for long-acting
insulin to reach active levels, so patients may need additional insulin before the
long-acting insulin takes effect.
To calculate the mealtime dose, the carbohydrate to insulin ratio setting can be
used. If the patient is in a condition to continue counting carbohydrates, the same
carbohydrate ratio can be used for rapid-acting subcutaneous insulin. If the patient
is unable to count carbohydrates, use the insulin to carbohydrate ratio and an estimated consistent carbohydrate content of 60 g/meal to determine the mealtime dose.
For example, if the insulin to carbohydrate ratio is 1 unit/10 g carbohydrate (1:10),
the patient should be given approximately 6 units of rapid-acting insulin per meal
(1 unit/10 g × 60 g = 6 units). If a patient is not eating well, this dose can be reduced.
A correctional insulin scale can be created using the sensitivity factor from the
pump. The ISF represents the amount of glucose reduction for each unit of insulin
given. For example, a sensitivity of 50 implies that 1 unit of insulin will decrease
the glucose by 50 mg/dL. A correctional insulin scale for a patient with a sensitivity factor of 50 would be in increments of 1 extra unit per 50 mg/dL greater than
150 mg/dL. Alternatively, 5% of the total daily dose of scheduled insulin can be
used (as described in Chapter 2).
If a patient is getting nutrition enterally or parenterally, refer to the insulin
strategy in Chapter 12: Enteral and Parenteral Nutrition.
Patient Is Fasting
Again, if the patient has an off-pump plan, this is a good place to start. Otherwise, a
basal dose can be calculated by acquisition of the ongoing daily basal rate from the
pump. This basal rate can be translated directly as the total basal dose into one or
two doses of long-acting insulin. Alternatively, it could be divided into four doses
of regular insulin, given every 6 hours. Just as for patients who are eating, if there
has been hypoglycemia while on CSII and fasting, the basal dose should be reduced
before administered subcutaneously.
Continuous Glucose Monitoring
Continuous glucose monitoring (CGM) is performed by a device called a glucose
sensor, which is inserted and worn separately from an insulin pump. The sensor
74
S. Gauger
measures interstitial blood glucose levels in rapid succession to create glucose
trends. It tracks glucose levels 24 hours a day, observing trends and alarming at prespecified levels of hyper- and hypoglycemia. Typically, CGM is used by patients
with diabetes who have hypoglycemia unawareness or who are pregnant, although
many other patients can use it as well. The results of the Juvenile Diabetes Research
Foundation trial suggest that CGM improves glycemic control without increasing
hypoglycemia in patients older than age 25 years. Sensors may be worn in the arm
or abdomen and, depending on the model, can remain in place for 3–7 days. CGM
is not a substitute for glucose monitoring with a glucose meter; glucose meter readings are necessary for confirmation and calibration of the CGM device and should
be continued multiple times daily.
Interpreting CGM Results
It is important to focus on the speed and direction of the glucose trend rather than the
discrete numbers reported by the CGM. Patients with trends toward hypoglycemia
and hyperglycemia can be treated accordingly.
Acknowledgment Special thanks to Jan Nicollerat, MSN, ACNS-BC, CDE, the director of Duke
University’s Adult Diabetes Education Program, who contributed time, resources, and wisdom
during the composition of this chapter.
Bibliography
2009 Resource Guide. Diabetes Forecast. 62(1). http://www.forecast.diabetes.org/
january-2009. Accessed January 2009.
AACE Diabetes Mellitus Clinical Practice Guidelines Task Force. American Association of
Clinical Endocrinologists medical guidelines for clinical practice for the management of
diabetes mellitus. Endocr Pract. 2007;13(suppl 1):3–68.
American Diabetes Association. Position statement: continuous subcutaneous insulin infusion.
Diabetes Care. 2004;27(suppl 1):S110.
Animas Corporation. My insulin pump workbook. http://www.animascorp.com/
sites/default/files/pdf/Workbook.pdf. Accessed December 3, 2009.
Burge MR, Mitchell S, Sawyer A, Schade DS. Continuous glucose monitoring: the future of
diabetes management. Diabetes Spectr. 2008;21(2):112–119.
Farkas-Hirsch R, Levandoski LA. Implementation of continuous subcutaneous insulin infusion
therapy: an overview. Diabetes Educ. 1988;14(5):401–406.
Lenhard MJ, Reeves GD. Continuous subcutaneous insulin infusion: a comprehensive review of
insulin pump therapy. Arch Intern Med. 2001;161(19):2293–2300.
Medtronic MiniMed, Inc. Getting Started Guide to CGM Training. Northridge, CA: Medtronic
Diabetes; 2007.
Parkin, C. Insulin pumps and infections. Diabetes Forecast. 2008;61(1). http://www.
forecast.diabetes.org/magazine/ask-experts/insulin-pumps-and-infection. Accessed January
2009.
Pickup J, Keen H. Continuous subcutaneous insulin infusion at 25 years. Diabetes Care.
2002;25(3):593–597.
8
Insulin Pumps and Glucose Sensors in the Hospital
75
The Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group.
Continuous glucose monitoring and intensive treatment of type 1 diabetes. N Engl J Med.
2008;359(14):1464–1476.
Weissber-Benchell J, Antisdel-Lomadlio J, Seshadri R. Insulin pump therapy: a meta-analysis.
Diabetes Care. 2003;26(4):1079–1087.
Chapter 9
Non-insulin Antidiabetic Medications
in the Inpatient Setting
Jennifer V. Rowell, Lekshmi T. Nair, and Mary E. Cox
R
Keywords Acarbose (Precose) · Bromocriptine mesylate (Cycloset
) · Exenatide
R
R
R
(Byetta ) · Glimeperide (Amaryl ) · Glipizide (Glucotrol ) · Glyburide
R
R
R
) · Metformin
) · Liraglutide (Victoza
· Micronase
(Diaβeta
R
R
R
) · Pramlintide
(Glucophage ) · Nateglinide (Starlix ) · Pioglitazone (Actos
R
R
(Symlin ) · Repaglinide (Prandin ) · Rosiglitazone (Avandia R ) · Saxagliptin
R
R
)
) · Sitagliptin (Januvia
(Onglyza
Oral and injectable non-insulin antidiabetic medications are important components
of outpatient management of type 2 diabetes. They are effective and safe for plasma
glucose. However, even when patients have good glycemic control at home on
these medications, it is essential to evaluate their safety and utility for the management of inpatient hyperglycemia. Factors that govern glucose stability are variable
for inpatients: diet and physical activity level, planned and unplanned procedures,
acute/critical illness, and unexpected complications. Furthermore, antidiabetic medications typically are evaluated for efficacy in trials of outpatients who use the
medications over a period of weeks or months. Most of these medications will not
effectively lower glucose when used acutely in the hospital, and therefore should
not be prescribed with this intent. In order to determine whether continuation of
oral agents is appropriate, the provider must carefully consider the patient’s anticipated length of stay and hospital course. This chapter briefly discusses the reported
outpatient efficacies, including risk for hypoglycemia and other safety concerns
(Tables 9.1 and 9.2).
J.V. Rowell (B)
Division of Endocrinology, Metabolism, and Nutrition, Department of Medicine, Duke University
Medical Center, Durham, NC 27710, USA
e-mail:
[email protected]
L.F. Lien et al. (eds.), Glycemic Control in the Hospitalized Patient,
C Springer Science+Business Media, LLC 2011
DOI 10.1007/978-1-60761-006-9_9,
77
78
Table 9.1 Drug summary
Risk for
Common
hypoglycemiaa adverse effects
Metformin
R
(Glucophage
,
Glucophage
R
XR
)
1.5–2
No
Pioglitazone
R
(Actos
)
Rosiglitazone
R
(Avandia
)
1.5
No
1.5
No
Glipizide
R
)
(Glucotrol
1–2
Yes
Glyburidec
R
,
(Diaβeta
R
Micronase
)
1–2
Yes
Glimeperide
R
)
(Amaryl
1–2
Yes
Drug
Contra-indicationsb Renal dosing
Weight
Loss
Not for use in
Abnormal CrCl,
GI (nausea,
creatinine >1.5 in patients with
vomiting,
abnormal CrCl
men, >1.4 in
diarrhea,
abdominal pain) women. Acute or
chronic metabolic
acidosis
Edema
Symptomatic CHF No dose adjustGain
ment necessary
Gain
Edema, possible Symptomatic CHF No dose adjustment necessary
association
with myocardial
ischemia
Gain
Limited data
Type 1 diabetes,
GI (nausea,
DKA
available; ↑ risk
vomiting,
for hypoglycemia
diarrhea,
abdominal pain)
Gain
Limited data
Type 1 diabetes,
GI (nausea,
available; ↑ risk
DKA, patients
vomiting,
for hypoglycemia
treated with
diarrhea,
abdominal pain) bosentan
Gain
Limited data
Type 1 diabetes,
GI (nausea,
available; ↑risk
DKA, severe
vomiting,
for hypoglycemia
hepatic
diarrhea,
abdominal pain) dysfunction
Dosing
Route of
administration
500–1,000 mg b.i.d. Oral
XR form:
500–2,000 mg
with evening meal
15–45 mg/day
Oral
4–8 mg/day
Oral
5 mg/day to 15 mg Oral
b.i.d. (with meals)
1.25–20 mg/day
Oral
1–4 mg/day
Oral
J.V. Rowell et al.
A1c
lowering
(%)
9
A1c
lowering
(%)
Risk for
Common
hypoglycemiaa adverse effects
Repaglinide
R
)
(Prandin
0.5–1
Yes
Type 1 diabetes,
GI (nausea,
DKA
vomiting,
diarrhea,
abdominal pain)
Nateglinide
R
(Starlix
)
0.5–1
Yes
Acarbose
R
(Precose
)
0.5–1
No
Dizziness,
elevated liver
enzymes
GI (diarrhea,
flatulence,
abdominal
discomfort)
Exenatide
R
(Byetta
)
1–2
No
Liraglutide
R
(Victoza
)
1–2
No
Drug
Contra-indicationsb Renal dosing
Type 1 diabetes,
DKA
Weight
Full dose for CrCl Gain
≥40 mL/min,
half dose for CrCl
20–40 mL/min.
Not studied in
patients with CrCl
<20 mL/min
No dose adjustment Gain
necessary
Data not available; Neutral
Type 1 diabetes,
use not
DKA, hepatic
cirrhosis, chronic recommended
intestinal
diseases
GI (nausea,
(See section on
Not recommended Loss
vomiting,
safety in text)
for CrCl <30
diarrhea,
mL/min, consider
abdominal pain)
5-mcg dose for
CrCl 30–50
mL/min
Personal or family No dose adjustment; Loss
GI (nausea,
limited experience
history of MTC
vomiting,
in patients with
or MEN 2
diarrhea,
abnormal renal
dyspepsia,
function
constipation)
Dosing
A1c <8% or drug
naïve –
0.5–4 mg/meal
A1c >8% –
1–4 mg/meal
Route of
administration
Oral
60–120 mg given Oral
1–30 min before
meals
25–100 mg given Oral
with the first bite
of meals
5–10 mcg b.i.d., 1 h Subcutaneous
before meals
0.6 mg/days for 1
week, then
1.2 mg/dayd
Non-insulin Antidiabetic Medications in the Inpatient Setting
Table 9.1 (continued)
Subcutaneous
79
A1c
lowering
(%)
Common
Risk for
hypoglycemiaa adverse effects
Sitagliptin
R
(Januvia
)
0.5–1
No
Rare
Saxagliptin
R
(Onglyza
)
0.5–1
No
Rare
Pramlintide
R
(Symlin
)
0.5–1
No
GI (nausea, loss
of appetite),
headache
Bromocriptine
mesylate
R
(Cycloset
)
0.5
No
GI (nausea),
somnolence,
psychosis,
orthostatic
hypotension,
dizziness
Drug
Contra-indicationsb Renal dosing
80
Table 9.1 (continued)
Weight
Neutral
50 mg/day dose
None except
for CrCl 30–50
history of
mL/min,
hypersensitivity
25 mg/days dose
for CrCl <30
mL/min
None
2.5 mg/days dose Neutral
for CrCl <50
mL/min
No dose reduction Loss
Confirmed
for CrCl >20
gastroparesis,
mL/min; untested
hypoglycemia
in CrCl <20
unawareness
mL/min
No data available
Syncopal
migraines,
lactating women
Neutral
Dosing
Route of
administration
100 mg/day
Oral
5 mg/day
Oral
Subcutaneous
Type 1 diabetes:
15–60 mcg t.i.d.
with meals; type 2
diabetes: 60–120
mcg t.i.d. with
meals
Oral
0.8–4.8 mg/day,
taken within 2 h
of waking in the
morning, with
food
J.V. Rowell et al.
b.i.d., twice daily; CHF, congestive heart failure; CrCl, creatinine clearance; DKA, diabetic ketoacidosis; GI, gastrointestinal; MEN 2B, Multiple Endocrine
Neoplasia syndrome type 2; MTC, medullary thyroid cancer; t.i.d., three times daily; XR, extended release
a Risk for hypoglycemia increases with addition of antidiabetic medications. Patients who are at high risk for hypoglycemia include those who are elderly,
debilitated, or malnourished
b Each medication is contraindicated for use in patients with hypersensitivity
c Glynase PresTabs have different dose recommendations and are not discussed here
d May increase to 1.8 mg/days if not at goal on 1.2 mg/day
9
Non-insulin Antidiabetic Medications in the Inpatient Setting
81
Table 9.2 Non-insulin antidiabetic medications and toxicities
Medication
Toxicities seen in overdose
Half-life h
Dialyzable
Metformin
R
,
(Glucophage
R
,
Glucophage XR
R
Fortamet ,
R
Riomet
,
R a
)
Glumetza
R
Piogiltazone (Actos
)
Rosiglitazone
R
(Avandia
)
R
,
Glipizide (Glucotrol
R
Glucotrol XL
)
R
Glyburide (Diabeta
,
R
Micronase
)
R
)
Glimepiride (Amaryl
R
Repaglinide (Prandin
)
Nausea, vomiting, diarrhea, pancreatitis,
severe lactic acidosis, hypothermia,
hypotension, tachypnea, tachycardia.
Hypoglycemia is usually only seen in
conjunction with other symptoms
6, XR 8–12
Yes
Edema, anemia, myalgia, hepatotoxicity
Edema, congestive heart failure, myocardial
ischemia, angina, cholestatic hepatitis
Hypoglycemia, nausea, diarrhea, headache,
dizziness
Hypoglycemia, nausea
16–24
3–4
No
No
Hypoglycemia, nausea
Hypoglycemia, tachycardia, coma, seizures,
confusion, metabolic acidosis
R
Nateglinide (Starlix
) Hypoglycemia, tachycardia, coma, seizures,
confusion, metabolic acidosis
R
Acarbose (Precose
)
Abdominal pain, diarrhea, flatulence
R
Exenatide (Byetta
)
Nausea, vomiting, diarrhea, anxiety,
hypoglycemia; pancreatitis, renal failure
R
) Severe nausea, vomiting
Liraglutide (Victoza
R
)
Hypoglycemia, headache
Sitagliptin (Januvia
R
) No dose-related clinical adverse reactions
Saxagliptin (Onglyza
R
) Severe nausea, vomiting, diarrhea,
Pramlintide (Symlin
vasodilation, dizziness
Bromocriptine mesylate Nausea, vomiting, constipation, diaphoresis,
R
(Cycloset
)
dizziness, pallor, severe hypotension,
malaise, confusion, lethargy, drowsiness,
delusions, hallucinations, and repetitive
yawning
2–4, XL 6–12 No
10
No
5–9
1
No
No
1.5
Yes
2
2.4
No
No
13
12.4
2.5–3.1
0.8
No
Yes
Yes
No
6
No
XR, extended release
R
R
a Fortamet
and Glumetza
are extended-release preparations
Biguanides
R
R
, Glucophage XR
)
Metformin (Glucophage
Mechanism and Efficacy
Metformin improves glucose tolerance by decreasing hepatic glucose production, decreasing intestinal absorption of glucose, and increasing peripheral glucose
uptake and utilization. The clinical efficacy of metformin is dependent on the
amount of insulin resistance that is present; a typical reduction in A1C is about
1.5–1.8%.
82
J.V. Rowell et al.
Safety
For outpatients, the major adverse effect of metformin is its propensity to cause
gastrointestinal (GI) symptoms, particularly diarrhea. However, for inpatients, the
major concern is the risk for lactic acidosis. Compared with a previous biguanide
phenformin, which is no longer on the market, the incidence of lactic acidosis with
metformin is rare. However, it is life threatening, and, thus, use of metformin should
be avoided in patients at risk. These include the following:
• Renal failure, acute or chronic: Creatinine level greater than 1.5 mg/dL in men or
1.4 mg/dL in women, or abnormal creatinine clearance. Because aging is associated with reduced renal function, absolute creatinine levels may not be reflective
of abnormal creatinine clearance in elderly patients
• Liver dysfunction
• Acute or chronic metabolic acidosis
• Cardiac disease, including congestive heart failure (CHF; acute or chronic under
drug treatment), myocardial infarction, cardiovascular collapse
• History of alcohol abuse
• Severe infection
• Hypoxia from any cause
Metformin does not increase risk for hypoglycemia when used alone, although
it may increase the risk for hypoglycemia when combined with other antidiabetic
medications, including insulin. Elderly, debilitated, and malnourished patients are
particularly susceptible to hypoglycemia.
Inpatient Considerations
Most providers choose to discontinue metformin during hospitalization because of
the safety issues above. If metformin is continued, its use should be avoided at
least 48 h before and after imaging procedures with iodinated contrast or surgical
procedures. The same is true for concomitant use of medications that are known
to affect renal function. Metformin may be restarted once renal function has been
reevaluated and found to be normal.
Thiazolidinediones
R
R
), Rosiglitazone (Avandia
)
Pioglitazone (Actos
Mechanism and Efficacy
Thiazolidinedione (TZD) medications share a common mechanism, which is to
decrease peripheral insulin resistance in muscle and adipose tissues as well as inhibit
hepatic gluconeogenesis. Specifically, these compounds are agonists for peroxisome proliferator–activated-receptor-γ (PPARγ), which modulates transcription of
a number of insulin-responsive genes.
9
Non-insulin Antidiabetic Medications in the Inpatient Setting
83
As with metformin, the efficacy of TZD therapy differs depending on an
individual patient’s insulin resistance. However, a typical A1C reduction is approximately 1.5%.
Safety
The most common adverse effect of the TZD class is an increase in fluid retention, which can worsen peripheral edema and CHF. Patients with symptomatic CHF
should not use TZDs.
The first member of the TZD class, troglitazone, was withdrawn from the market because of rare but serious hepatotoxicity. The newer agents, pioglitazone and
rosiglitazone, do not appear to share this adverse effect. However, hepatic monitoring is recommended for patients at initiation of these medications, and periodically
thereafter, as rare patients have been noted to have hepatic enzyme elevations greater
than three times the upper limit of normal.
TZDs have not been found to cause hypoglycemia when used independently but
may be associated with hypoglycemia when combined with other agents like insulin
or sulfonylureas.
In a meta-analysis of 42 clinical studies, rosiglitazone, as compared with placebo,
was found to be associated with an increased risk for myocardial ischemic events
(Nissen and Wolski, 2007). To date, further study has not confirmed or excluded this
risk. Available data on pioglitazone has not confirmed a similar risk. Rosiglitazone
should be used with caution in patients who have high risk for coronary artery
disease.
Inpatient Considerations
TZD’s generally are safe for continuation during hospitalization, as long as the
patient continues with a regular diet, and none of the safety concerns listed above
apply. It should be noted that TZDs are ineffective for acute management of
hyperglycemia because the time to steady state is about 6 weeks.
Sulfonylureas
R
R
), Glyburide
), Glimepiride (Amaryl
Glipizide (Glucotrol
R
R
R
(Diaßeta , Glynase PresTabs , Micronase )
Mechanism and Efficacy
The sulfonylureas are the traditional insulin secretagogues. They work by influencing closure of an adenosine triphosphate (ATP)-dependent potassium channel on
the β(beta)-cell membrane. This channel closure results in a series of effects that
culminate in insulin release. Notably, release of insulin in response to sulfonylurea
administration is not related to blood glucose level. Treatment with a sulfonylurea
drug can be expected to lower the A1C by 1–2%.
84
J.V. Rowell et al.
Safety
The most common adverse reaction to sulfonylurea drugs is GI disturbance, such as
nausea and diarrhea or constipation. The most common serious reaction with these
medications is hypoglycemia; all sulfonylurea drugs are capable of producing severe
hypoglycemia. (Table 9.3).
Table 9.3 Risk factors for hypoglycemia
Adrenal or pituitary insufficiency
Advanced age
Alcohol ingestion
Hepatic insufficiency
Malnourishment or low calorie intake
Multiple glucose-lowering drugs
Renal insufficiency
Severe or prolonged exercise
The package insert for sulfonylurea drugs contains a warning regarding the
results of the University Group Diabetes Program (Diabetes, 1970), that administration of sulfonylureas is associated with increased cardiovascular mortality, as
compared with treatment with diet alone or diet plus insulin. This association
remains controversial.
Inpatient Considerations
The most important inpatient consideration with sulfonylureas is the potential for
hypoglycemia, particularly in patients with acute or chronic renal dysfunction.
Because hospitalized patients are at particular risk for hypoglycemia, sulfonylureas
must be used with caution.
Meglitinides
R
R
)
), Nateglinide (Starlix
Repaglinide (Prandin
Mechanism and Efficacy
Although the meglitinides are chemically unrelated to the traditional insulin secretagogues, their mechanism of action is similar. The meglitinides also function to
close the ATP-dependent potassium channels in the β-cell membrane, resulting in a
number of events that culminate in insulin secretion. A typical A1C reduction for a
meglitinide medication is approximately 0.5–1%.
Safety
As with the sulfonylureas, meglitinide-induced insulin secretion is not related to
plasma glucose levels, and hypoglycemia can result from its administration. Its use
should be avoided in patients who are not eating or who are at risk for hypoglycemia
9
Non-insulin Antidiabetic Medications in the Inpatient Setting
85
(Table 9.3). Other adverse effects of meglitinides are similar to those of sulfonylureas, and are primarily gastrointestinal. Repaglinide appears to be safe if slowly
up-titrated in patients with impaired hepatic function, but nateglinide has not been
studied in this population.
Inpatient Considerations
The most important inpatient consideration for meglitinides is the potential for
hypoglycemia. For this reason, as with the sulfonylureas, the meglitinides should
be used with caution in hospitalized patients.
α (alpha)-Glucosidase Inhibitor
R
)
Acarbose (Precose
Mechanism and Efficacy
The anti-hyperglycemic effect of acarbose results from inhibition of disaccharide
cleavage in the small intestine, which delays carbohydrate absorption. This effect
results in a decrease in postprandial hyperglycemia. A typical AC reduction with
acarbose is 0.5–1%. It is important to note that the mechanism of acarbose is
uniquely effective for patients who are eating and will not lower glucose levels in
patients who are fasting. Its efficacy is also related to the amount of carbohydrate in
the diet.
Safety
The most common adverse effects with acarbose are gastrointestinal: diarrhea, flatulence, and abdominal discomfort. These may decrease in severity over weeks of
treatment. However, because of these actions, this drug is contraindicated in patients
with chronic intestinal diseases. Also, there have been reports of patients with
elevated transaminases while taking acarbose, and its use is not recommended in
patients with cirrhosis. Acarbose does not cause hypoglycemia as mono-therapy.
Because acarbose inhibits disaccharide cleavage, orally administered disaccharides
such as sucrose can not be used to treat hypoglycemia when acarbose has been
administered. Orally administered glucose tablets or glucose gel, as well as other
non-oral methods of hypoglycemia treatment, should be effective.
Inpatient Considerations
As above, acarbose is uniquely effective in patients who are eating regular meals
with significant portions of carbohydrate. For this reason, it is infrequently used in
the inpatient setting, given the propensity for missed meals.
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J.V. Rowell et al.
Glucagon-Like Peptide-1 Analogs
R
R
Exenatide (Byetta
)
), Liraglutide (Victoza
Mechanism and Efficacy
Exenatide and liraglutide exert their actions by mimicking endogenous glucagonlike peptide (GLP)-1; in fact, liraglutide shares 97% homology with human GLP-1.
The effects of GLP-1 receptor agonism are to increase glucose-dependent pancreatic
insulin secretion, suppress glucagon secretion, decrease the rate of gastric emptying,
and induce central appetite suppression. These effects are dependent on the plasma
glucose level and will not occur if glucose levels are below 65 mg/dL. Exenatide
is typically effective for lowering A1C by 1–2%, and liraglutide has shown similar
efficacy.
Safety
GI adverse effects are common, primarily with nausea and vomiting. GI effects may
be more pronounced in patients with diabetic gastroparesis. In such patients, caution
should be used. Because of the glucose-dependent mechanism, hypoglycemia does
not occur when exenatide is used as mono-therapy.
Based on postmarketing data, exenatide has been associated with episodes of
pancreatitis. In preclinical trials, liraglutide was also associated with a slightly
increased risk of pancreatitis over placebo. Although this risk has not been confirmed to be greater than that with other antidiabetic medications on subsequent
retrospective analysis, it currently is recommended that the GLP-1 analogs be
avoided in patients with a history of pancreatitis, and that the drugs be discontinued immediately in patients who develop signs or symptoms of pancreatitis while
using exenatide or liraglutide.
Liraglutide causes development of medullary thyroid carcinoma at clinically relevant exposures in rat and mouse models. It has not conclusively been found to have
this effect on humans; however, it is prudent to avoid its use in patients with family
or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia
syndrome type 2B.
Inpatient Considerations
Neither of these medications causes hypoglycemia when used as mono-therapy.
Exenatide is given in relation to meals, and this is likely to be a problem in the
inpatient setting. Liraglutide is not given in relation to meals and may be easier to
administer in the hospital. However, there are no data as to whether one may be
substituted for the other. Because of the effects on gastric emptying, use of GLP1 analogs may interfere with absorption of oral contraceptive pills and antibiotics;
they should be given 2 h before or after administration of exenatide or liraglutide. In
general, there is only limited experience with the use of these agents in the inpatient
setting.
9
Non-insulin Antidiabetic Medications in the Inpatient Setting
87
Dipeptidyl Peptidase-4 Inhibitors
R
R
Sitagliptin (Januvia
)
), Saxagliptin (Onglyza
Mechanism and Efficacy
Dipeptidyl peptidase (DPP)-4 inhibitors increase GLP-1 levels by inhibiting the
enzyme responsible for endogenous GLP-1 metabolism. The increase in endogenous GLP-1 results in an increase in glucose-dependent pancreatic insulin secretion.
However, other effects of GLP-1 analogs, such as satiety, are not as evident with the
DPP-4 inhibitor medications. Anticipated improvements in A1C are in the order of
0.5–1%.
Safety
The DPP-4 inhibitors are relatively free from common adverse effects. Because
of the glucose-dependent mechanism of action, risk for hypoglycemia is low. As
for GLP-1 agonists, there have been postmarketing reports that associate use of
DPP-4 inhibitors with episodes of pancreatitis. Follow-up retrospective data has not
confirmed this association, but it is still reasonable to avoid these medications for
patients who have a history of pancreatitis. Finally, a history of hypersensitivity is a
contraindication for these agents.
Inpatient Considerations
The DPP-4 inhibitors have few side effects, do not cause hypoglycemia, and do not
need to be administered in relation to meals. However, it should be noted that they
may not effectively treat acute hyperglycemia, which still is best addressed with use
of insulin.
Amylin Analog
R
)
Pramlintide (Symlin
Mechanism and Efficacy
Pramlintide exerts its action by mimicking the physiologic effects of amylin (i.e.,
to suppress postprandial glucagon secretion, delay gastric emptying, and influence
satiety via effects on the central nervous system). These combined effects result in
a reduced postprandial glucose excursion. Pramlintide can be expected to lower the
A1C by 0.5–1%. Pramlintide is unique among the non-insulin antidiabetic agents
because it also has been found to be effective in patients with type 1 diabetes.
Safety
Pramlintide’s most common adverse effects are nausea, loss of appetite, and
headache. When used alone, it does not increase risk for hypoglycemia. It should
88
J.V. Rowell et al.
be noted that, although pramlintide and prandial insulin can be administered at the
same time, they should not be given in the same syringe.
Inpatient Considerations
Pramlintide may be continued along with prandial insulin for patients who are eating
meals in the hospital. However, it should be held whenever meals are held. Like the
other non-insulin antidiabetic drugs, it is unlikely to be as effective as insulin at
treatment of acute hyperglycemia.
Dopamine Agonist
R
)
Bromocriptine Mesylate (Cycloset
Mechanism and Efficacy
Bromocriptine mesylate is a dopamine agonist that is indicated for treatment of
prolactinoma and Parkinson’s disease. It recently achieved an FDA indication for
treatment of type 2 diabetes as well. The mechanism of glucose lowering is not well
understood but is thought to be a central signaling phenomenon. It can be expected
to lower A1C by approximately 0.5%.
Safety
GI side effects, primarily nausea, are common with bromocriptine. At higher doses
than those prescribed for diabetes therapy, central effects have been noted, including
somnolence, orthostatic hypotension, dizziness, and psychosis. It is not recommended to use bromocriptine for patients with low blood pressure or psychotic
disorders. Furthermore, fibrotic complications, such as retroperitoneal fibrosis and
pulmonary fibrosis, have been noted with other formulations of bromocriptine. Risk
for hypoglycemia with bromocriptine is low.
Inpatient Considerations
Because bromocriptine’s mechanism of action on lowering glucose is not well
understood, and because there is little experience with it for this indication, it is
not recommended to use bromocriptine in hospitalized patients.
Non-insulin Antidiabetic Medications
and Cardiovascular Health
Historically, the antidiabetic medications had been presumed to improve cardiovascular health by way of improving glycemic control. However, in recent years, this
has come into question, and the FDA has required that prescribing information for
these drugs explicitly state whether the drug has been associated with improved
cardiovascular outcomes. Data on specific drugs remain controversial, and more
9
Non-insulin Antidiabetic Medications in the Inpatient Setting
89
research needs to be done in this area. For now, these drugs should not be prescribed
for the explicit purpose of cardiovascular protection.
Key Points
• Non-insulin antidiabetic agents are quite useful for outpatient management, but
have limited use in the inpatient setting for reasons described here.
• Acute intervention with insulin is the safest and most rapid means for achieving
glycemic control in the hospital.
Bibliography
Actos [Prescribing Information]. Deerfield, IL: Takeda Pharmaceuticals America, Inc.; 2008.
Ahmad SR, Swann J. Exenatide and rare adverse events: letter to the editor. N Engl J Med.
2008;358(18):1970–1971.
Amaryl [package insert]. Bridgewater, NJ: Sanofi-aventis; 2009.
Avandia [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; 2008.
Byetta [prescribing information]. San Diege, CA: Amylin Pharmaceuticals; 2009.
Cycloset [prescribing information]. Tiverton, RI: VeroScience, LLP; 2009.
Diaβeta [package insert]. Bridgewater, NJ: Sanofi-aventis US, LLC; 2009.
Donner TW, Flammer KM. Diabetes management in the hospital. Med Clin North Am.
2008;92(2):407–425, ix–x.
Drucker DJ. The incretin system: glucagon-like peptide-1 receptor agonist and dipeptidyl
peptidase-4 inhibitors in type 2 diabetes. Lancet. 2006;368:1696–1702.
Edelman SV, Caballero L. Amylin replacement therapy in patients with type I diabetes. Diabetes
Educ. 2006;32(3):119S–127S.
Edelman SV, Darsow T, Frias JP. Pramlintide in the treatment of diabetes. J Clin Pract.
2006;60(12):1647–1653.
Gallwitz B. Exenatide in type 2 diabetes: treatment effects in clinical studies and animal study data.
J Clin Pract. 2006;60(12):1654–1661.
Glucophage and Glucophage XR [package insert]. Princeton, NJ: Bristol-Myers Squibb Company;
2006.
Glucotrol [package insert]. New York, NY: Pfizer; 2009.
Glumetza [package insert]. Menlo Park, CA: Depomed, Inc; 2006.
Januvia [prescribing information]. White House Station, NJ: Merck, 2006.
Kruger DF, Martin CL, Sadler CE. New insights into glucose regulation. Diabetes Educ.
2006;32(2):221–228.
Lien LF, Bethel MA, Feinglos MN. In-hospital management of type 2 diabetes mellitus. Med Clin
North Am. 2004;88(4):1085–1105, xii.
Martin C. The physiology of amylin and insulin: maintaining the balance between glucose
secretion and glucose uptake. Diabetes Educ. 2006;32(3):101S–104S.
McMahon GT. State-of-the-art diabetes care: where we’ve been, where we are, and where we’re
going. Adv Stud Med. 2005;5:S912–S918.
Mikhail NE. Is exenatide a useful addition to diabetes therapy? Endocr Prac. 2006;12(3):307–314.
Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from
cardiovascular causes. N Engl J Med. 2007;356(24):2457–2471.
Odegard PS, Setter SM, Iitz JL. Update in the pharmacologic treatment of diabetes mellitus: focus
on pramlintide and exenatide. Diabetes Educ. 2006;32(5):693–712.
Onglyza [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2009.
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Owen SK. Amylin replacement therapy in patients with insulin-requiring type 2 diabetes. Diabetes
Educ. 2006;32(3):105S–110S.
Prandin [package insert]. Princeton, NJ: Novo Nordisk; 2006.
Precose [prescribing information]. Wayne, NJ: Bayer HealthCare Pharmaceuticals; 2008.
Saudek CD. Assessing new options for the treatment of diabetes: a review for practicing clinicians.
Adv Stud Med. 2005;5:S910–S911.
Starlix [prescribing information]. Stein, Switzerland: Novartis Pharma Stein AG; 2008.
Symlin [prescribing information]. San Diego, CA: Amylin Pharmaceuticals; 2008.
Umpierrez GE, Palacio A, Smiley D. Sliding scale insulin use: myth or insanity? Am J Med.
2007;120(7):563–567.
Victoza [prescribing information]. Bagsvaerd, Denmark: Novo Nordisk A/S, 2010.
Chapter 10
Hypoglycemia
Melanie E. Mabrey, Mary E. Cox, and Lillian F. Lien
Keywords Hypoglycemia · Glucagon · Gluconeogenesis · Neuroglycopenic ·
Whipple’s triad · Counterregulatory hormones · Hypoglycemia unawareness · 50%
dextrose (D50) · Glucose monitoring
Hypoglycemia is the primary limiting factor for achieving optimal glucose control
for patients both in and out of the hospital. Certainly, concerns about hypoglycemia
are warranted given the acute danger of hypoglycemia as well as the potential
for long-term sequelae. Although diabetes may be only one of many comorbidities for patients admitted to the hospital, practical measures can be taken that will
prompt recognition and treatment if hypoglycemia occurs. This chapter addresses
three components of inpatient diabetes management with respect to hypoglycemia:
recognition, treatment, and prevention.
Recognition of Hypoglycemia
Because the human body preferentially uses glucose as fuel, there are several complementary protective mechanisms in response to low circulating blood glucose
levels. In the early phase of hypoglycemia, pancreatic alpha cells respond by releasing glucagon. Glucagon stimulates hepatocytes to break down stored glycogen,
releasing glucose, while also activating hepatic gluconeogenesis. These mechanisms
often suffice to raise blood glucose to normal levels, although glucagon response
may decline with longstanding disease, particularly in patients with type 1 diabetes. In prolonged hypoglycemia, as in patients who have taken a disproportionate
amount of insulin, or for those who are malnourished and have low hepatic glucose
stores, other counterregulatory mechanisms are triggered: release of epinephrine,
norepinephrine, growth hormone, and cortisol. These counterregulatory hormones
M.E. Mabrey (B)
Duke Inpatient Diabetes Management, Department of Advanced Clinical Practice, Duke University
Hospital, Durham, NC, USA; Duke University Schools of Nursing and Medicine, Duke University
Medical Center, Durham, NC, USA
e-mail:
[email protected]
L.F. Lien et al. (eds.), Glycemic Control in the Hospitalized Patient,
C Springer Science+Business Media, LLC 2011
DOI 10.1007/978-1-60761-006-9_10,
91
92
M.E. Mabrey et al.
can raise blood glucose and also result in detectable symptoms and signs, termed
neurogenic or autonomic symptoms of hypoglycemia. Other symptoms, due directly
to the brain’s deprivation of glucose, are termed neuroglycopenic.
The diagnosis of true hypoglycemia only can be confirmed in patients for whom
the three components of Whipple’s triad are observed: (1) signs or symptoms of
hypoglycemia, (2) low blood glucose level, and (3) resolution of signs and symptoms with normalization of the blood glucose level. However, it is important to
recognize that symptoms of hypoglycemia vary from patient to patient. Some
patients will have a complete absence of symptoms, termed hypoglycemia unawareness; this is not rare and has many possible causes (Table 10.1). Some patients
present with typical neurogenic/autonomic symptoms, which may include tremor,
diaphoresis, nervousness or anxiety, and palpitations. Others may experience neuroglycopenic symptoms such as dizziness, sleepiness, weakness, and confusion.
Some patients will experience hunger or a change in vision. Yet others will demonstrate extreme changes in behavior which may vary from inappropriate laughter, to
belligerence or violence, to complete loss of consciousness or seizure.
Table 10.1 Causes of hypoglycemia unawareness
•
•
•
•
•
•
Recent history of frequent hypoglycemia
Rapid decline in blood glucose
Alcohol consumption
Use of medications like β (beta) -blockers, which may blunt symptoms
Long duration of diabetes
Significant stress or depression
When a patient exhibits signs or symptoms that are suspected to be related to
hypoglycemia, the blood glucose level must be checked immediately. Point-ofcare glucose testing is usually employed so that appropriate treatment can ensue
promptly. Hypoglycemia must be considered for any patient who is treated with
insulin or other anti-hyperglycemic medication; in the hospital, “insulin reactions”
are the cause of almost all hypoglycemic events. Hypoglycemia is defined in patients
treated with these medications as a blood glucose level of less than 70 mg/dL.
(Some nondiabetic patients, particularly young women, can have normal blood glucose levels much lower than 70 mg/dL after periods of fasting. These patients are
typically asymptomatic.) Once hypoglycemia is identified, treatment should begin
immediately (Table 10.2).
Treatment of Hypoglycemia
The treatment for all hypoglycemic events is administration of glucose. The route
and amount of administration will depend on the glucose level as well as the
patient’s level of consciousness and available access (Table 10.2 and Fig. 10.1).
Consider the “rule of 15s:” 15 g of carbohydrate will raise the glucose about
15 mg/dL in about 15 min. Obviously the “rule of 15s” is just a starting point,
and frequent monitoring is required until the blood glucose is observed to return to
normal.
10
Hypoglycemia
93
Table 10.2 Steps to confirm and treat hypoglycemia
1
2
3
4
5
6
7
8
Repeat the glucose measurement right away to confirm—repeat point-of-care testing
glucose can be done quickly, and plasma glucose can be sent for confirmation if desired
Determine the patient’s access route
When treating a patient for whom oral intake is safe, administer 15 g of carbohydrate orally
If hypoglycemic coma or seizure occur, immediately administer one ampule of 50%
dextrose (D50) intravenously and continue close patient monitoring
After treatment, glucose measurement should be repeated in 15–20 min. If the blood
glucose is still less than 70 mg/dL (3.8 mmol/L), re-treat. Repeat the process until
glucose is greater than 70 mg/dL (3.8 mmol/L)
If the glucose remains less than 70 mg/dL (3.8 mmol/L) after three treatments, consider a
continuous 5 or 10% dextrose IV infusion
Determine the cause of the hypoglycemic episode and whether insulin or other medications
need to be adjusted
Continue subsequent glucose monitoring to ensure that the patient does not have rebound
hyperglycemia after the occurrence or treatment of hypoglycaemia
Source: Duke University Hospital Glycemic Safety Committee, courtesy of Mary Jane Stillwagon,
BSN, RN
Patients who are able to take glucose by mouth should consume 15 g of simple
carbohydrates, often in the form of three to four glucose tablets, a tube of glucose
gel, or 4 ounces of juice or regular soda. Patients with profoundly low blood glucose
(i.e., <40 mg/dL) may require at least 30 or 45 g of carbohydrates for normalization.
For patients who are unable to take oral glucose but who have an IV in place, concentrated IV 50% dextrose (D50) is the preferred treatment. D50 comes in ampules
of 50 mL, or 25 g dextrose. A starting point for D50 dosing is to give a half ampule,
or 25 mL (12.5 g), of D50 by IV push, to treat hypoglycemia in the range of 41–
69 mg/dL. A whole ampule is given for blood glucose less than 40 mg/dL. D50 also
can be given through a feeding tube when mixed with equal parts of water.
If it is not feasible to give glucose by mouth, and the patient does not have a
feeding tube or an IV, 1 mg of glucagon given by intramuscular injection is the
necessary treatment. Glucagon may cause vomiting, so it is a choice of last resort,
and appropriate precautions should be taken to prevent aspiration if the patient is
unconscious. Glucagon may not be effective in patients who are malnourished and
have low hepatic glycogen stores, so a route of access for D50 should be pursued
promptly.
Once glucose (dextrose) has been given, the patient’s glucose should be monitored until the level is observed to be above 70 mg/dL. If the episode of
hypoglycemia occurs between meals, an additional form of glucose along with protein should be given (i.e., peanut butter and crackers, milk, half a sandwich, or
cheese and crackers). If the hypoglycemia is observed just before mealtime, the
regular meal and mealtime insulin can be given once the blood glucose has stabilized. Once an episode of hypoglycemia has been observed and treated, appropriate
steps should be taken to determine the etiology and direct future prevention.
It is worth noting that the patient may continue to experience mild symptoms
even after the blood glucose level has risen. Reassurance can be helpful, concurrent
with close monitoring. Certainly, resolution of symptoms will make the patient more
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M.E. Mabrey et al.
Fig. 10.1 Hypoglycemia algorithm. Decision about therapy should be based on the patient’s
mental status and access routes, using the least invasive method available. Abbreviations: D50,
50% dextrose; IV, intravenous; IM, intramuscular. ∗ If a patient does not have access, this should
be discussed promptly with the care team. Source: Duke University Hospital Glycemic Safety
Committee, courtesy of Mary Jane Stillwagon, BSN, RN
comfortable, but it also is important to avoid giving carbohydrates in an amount that
greatly exceeds that required to normalize glucose. Extra food items, together with
the counterregulatory hormone response, can lead to severe rebound hyperglycemia.
Prevention of Hypoglycemia
Prevention of hypoglycemia in the hospital must be a priority, while keeping in
balance the need for appropriate blood glucose control. There are three components
of hypoglycemia prevention: (1) appropriate insulin or medication dosages, adjusted
for conditions that increase risk for hypoglycemia; (2) appropriate blood glucose
targets; and (3) appropriate blood glucose monitoring frequency.
10
Hypoglycemia
95
Appropriate Insulin or Medication Dosages
A strategy for choosing a starting dose schedule for insulin is detailed in Chapter 2:
Subcutaneous Insulin. To avoid hypoglycemia, it is important to reevaluate the dosing schedule at least once a day. There are two common scenarios for which insulin
doses should be decreased: episodes of hypoglycemia and change in nutrition status
or temporary fasting (i.e., nothing by mouth [NPO] status).
Any Episode of Hypoglycemia
With episodes of hypoglycemia, insulin reduction often is appropriate, but complete discontinuation is rarely indicated, even with the immediately subsequent
dose. Counterregulatory hormones as well as hypoglycemia treatments often cause
hyperglycemia.
Change in Nutrition Status, or Temporary Fasting (i.e., NPO Status)
In the hospital, NPO status is implemented most commonly prior to procedures
or operations. Generally, oral anti-hyperglycemic medications are held only on the
morning of the procedure and can be restarted once eating resumes. Metformin,
however, should be held at least 48 h prior to scheduled procedures, and it should
be held for at least 48 h after. (Further information on non-insulin medications can
be found in Chapter 9: Alternatives to Insulin.) Periprocedural insulin management
should incorporate continuation of basal insulin and a pause in prandial insulin, as
shown in Table 10.3.
Patients receiving enteral or parenteral nutrition may have unexpected interruptions in feeding. When interruptions occur after full-dose scheduled insulin has been
given, the risk for hypoglycemia is high. To prevent hypoglycemia in this setting,
Duke Hospital now uses the algorithm given in Fig. 10.2.
Other reasons to decrease insulin might include the following:
•
•
•
•
•
•
•
Downward blood glucose trend
Acute renal failure
Acute hepatic failure
Severe sepsis or shock
Increased physical activity
Taper of steroid dosage
Improvement in infectious illness
Appropriate Glucose Targets
The diabetes field is rich with discussion regarding optimal glycemic targets. The
challenge in the inpatient setting is to prevent hyperglycemia and its known complications (postoperative infection rate increase, morbidity, and mortality), while also
avoiding hypoglycemia and its associated risks. Although the issue requires further
96
M.E. Mabrey et al.
Table 10.3 Insulin adjustments to prevent hypoglycemia when a patient is not eating prior to a
procedure or operation
Type of insulin
Action: night before procedure Action: morning of procedure
Regular insulin
R
R
, Novolin R
• Humulin R
R
• ReliOn R
Give full dose with evening
meal or as scheduled. If the
evening meal is not given,
give half dose at the
scheduled time
Give full dose at bedtime
NPH insulin
R
R
• Humulin N
, Novolin N
R
• ReliOn N
Premixed insulin
R
• Humulin
70/30TM
R
70/30TM
• Novolin
R
75/25TM
• Humalog
R
70/30TM
• Novolog
Rapid-acting insulin
R
• Aspart (Novolog
)
R
)
• Glulisine (Apidra
R
)
• Lispro (Humalog
Long-acting insulin
R
)
• Glargine (Lantus
R
)
• Detemir (Levemir
Continuous subcutaneous
insulin infusion (CSII)
Give half dose at the scheduled
time
If a patient has scheduled AM
NPH insulin, give half dose
at the scheduled time
Give half dose at the scheduled
time
Give full dose with evening
meal or as scheduled. If the
evening meal is not given,
give half dose at the
scheduled time
Give full dose with evening
Do not give
meal. If the evening meal is
not given, do not give the
insulin
Same as the night before
If the regimen includes
long-acting insulin and
rapid-acting insulin, give full
dose at bedtime or as
scheduled
If the regimen includes
long-acting insulin and oral
medications or long-acting
insulin alone, give half dose
Continue current settings
Consult patient’s diabetes care
provider
research, it is reasonable to pursue pre-meal blood glucose less than 140 mg/dL
(7.8 mmol/L), in conjunction with random blood glucose of less than 180 mg/dL
(10.0 mmol/L) as straightforward goals that can apply to most inpatients.
These glucose target ranges are appropriate for “most” patients, but the choice of
glucose target range requires clinical judgment as well. For example, patients with
low risk for hypoglycemia, such as those taking only metformin, may have a target
range of 80–120 mg/dL. Conversely, those of advanced age or with hypoglycemia
unawareness may have goal glucose levels closer to 200 mg/dL. It is appropriate to
make this determination for each individual patient and document the target range
in the patient’s record so that all providers are working toward the same end.
Appropriate Glucose Monitoring Frequency
The frequency of monitoring is usually determined by the insulin-dosing schedule, with a minimum of four point-of-care glucose tests in 24 h. Typically, blood
10
Hypoglycemia
97
Fig. 10.2 Algorithm for administration of dextrose 10% (D10) while a patient’s enteral feeding is
held. Abbreviations: BG, blood glucose; d/c, discontinuation; sq, subcutaneous; TF, tube feeding;
HO, house officer. Source: Duke University Hospital Glycemic Safety Committee, courtesy of
Mary Jane Stillwagon, BSN, RN
98
M.E. Mabrey et al.
glucose monitoring takes place just prior to insulin administration, so that appropriate correctional insulin also may be given. Additional overnight monitoring,
at around 3 AM , can be useful to determine whether undetected hypoglycemia is
occurring overnight. Monitoring may be required more frequently in patients whose
insulin requirements are changing, who are pregnant, or in patients to whom insulin
has been given and feeding is unexpectedly interrupted. Furthermore, monitoring
should occur immediately any time hypoglycemia is suspected.
Some patients have increased risk for development of hypoglycemia. Risk factors
include the following:
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
High doses of insulin
Hypoglycemia unawareness
Renal failure
History of erratic blood glucose
History of pancreatic disorders
Advanced age
Hepatic failure
Heart failure
Change in nutritional status, such as temporary NPO or change in rate or pattern
of enteral or parenteral nutrition
Adrenal insufficiency, chronic glucocorticoid use, or glucocorticoids in tapering
dosages
Severe sepsis, shock, or multiorgan failure
Malignancy or catabolic state
Malabsorption
Improvement in states of physiologic stress and resultant decrease in insulin
resistance
Increased physical activity
Thyroid dysfunction
Key Points: Hypoglycemia
• The official diagnosis of hypoglycemia is the presence of Whipple’s Triad.
• In the hospital, a practical cut-off for hypoglycemia is blood glucose less than
70 mg/dL.
• Symptoms of hypoglycemia vary, so it is important to have a high index of
suspicion and monitor glucose with any unusual symptoms or behavior.
• For hypoglycemia treatment, remember the “rule of 15s”: 15 g of glucose will
raise the blood glucose about 15 mg/dL in about 15 min.
• Treatment options in order of preference are (1) oral glucose (15 g), (2) D50 by
IV or feeding tube, and (3) intramuscular glucagon (last resort).
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Hypoglycemia
99
• An ounce of prevention is worth a pound of cure. Insulin regimens must
be adjusted frequently in response to blood glucose levels and targets, with
consideration for changes in status that can increase hypoglycemia risk.
Bibliography
American Diabetes Association: Diabetes Care Executive Summary from the American Diabetes
Association. Standards of medical care in diabetes 2009. Diabetes Care. 2009;32(suppl 1):
S6–S12.
Ashraf W, Wong DT, Ronayne M, Williams D. Guidelines for preoperative administration of
patients home medications. J Perianesth Nurs. 2004;19(4):228–233.
Braithwaite S, Buie M, Thompson C, et al. Hospital hypoglycemia: not only treatment but also
prevention. Endocr Pract. 2004;10(suppl 2):S89–S99.
Cryer P, Axelrod L, Grossman A, et al. Evaluation and management of adult hypoglycemic disorders: an endocrine society practice guideline. J Clin Endocrinol Metab. 2009;94(3):709–728.
Fischer KF, Lees JA, Newman JH. Hypoglycemia in hospitalized patients: causes and outcomes.
N Engl J Med. 1986;315(20):1245–1250.
Kitabchia A, Freire A, Umpierrez G. Evidence for strict inpatient blood glucose control: time to
revise glycemic goals in hospitalized patients. Metab Clin Exp. 2008;57(1):116–120.
Lien LF, Bethel MA, Feinglos MN. In-hospital management of type 2 diabetes mellitus. Med Clin
N Am. 2004;88(4):1085–1105.
Moghissi ES, Korytkowski MT, DiNardo M. American Association of Clinical Endocrinologist
and American Diabetes Association consensus statement on inpatient glycemic control. Endocr
Pract. 2009;15(4):1–17.
NICE-SUGAR Study Investigators. Intensive versus conventional glucose control in critically ill
patients. N Eng J Med. 2009;360(13):1283–1297.
Skyler JS, Bergenstal R, Bonow RO, et al. Intensive glycemic control and the prevention of
cardiovascular events: implications of the ACCORD, ADVANCE, and VA Diabetes trials.
A position statement of the American Diabetes Association and a scientific statement of the
American College of Cardiology Foundation and the American Heart Association. Diabetes
Care. 2009;32(1):187–192.
Chapter 11
Transitioning to Outpatient Care
Beatrice D. Hong and Ellen D. Davis
Keywords Insulin teaching · Discharge regimen · Diabetes education · Target
glucose range
Orchestrating a smooth transition to outpatient care is critical for all patients with
hyperglycemia in the inpatient setting. There are many factors to consider in preparing patients for discharge. Patients need to feel comfortable with the discharge
regimen; this requires both appropriate prescriptions for medications and supplies,
along with patient education (Fig. 11.1).
Medication Regimen
Most patients with diabetes will be on insulin in the hospital, even if they take
oral medications at home. Additionally, postoperative patients who did not have a
previous diagnosis of diabetes may develop hyperglycemia and then require insulin
during the admission and at discharge.
When prescribing new insulin therapy, remember to consider the following:
• Is the patient capable and willing to inject insulin at home? If not, is there a family
member or caretaker who is willing to take on this responsibility?
• Will home health be necessary temporarily for follow-up education?
Consider continuation of insulin in the following patients:
Postoperative patients. Insulin is the treatment of choice in postoperative patients
to allow optimal healing and reduce the risk of infections. Data supports particular
use to prevent mediastinitis in patients who have undergone coronary artery bypass
graft and other types of thoracic surgery.
B.D. Hong (B)
Division of Endocrinology, Metabolism, and Nutrition, Department of Medicine, Duke University
Medical Center, Durham, NC 27710, USA
e-mail:
[email protected]
L.F. Lien et al. (eds.), Glycemic Control in the Hospitalized Patient,
C Springer Science+Business Media, LLC 2011
DOI 10.1007/978-1-60761-006-9_11,
101
102
B.D. Hong and E.D. Davis
Fig. 11.1 Checklist for discharge
Large doses of insulin. Patients who require large amounts of insulin in the hospital, i.e., greater than 40 units daily, will most likely need to be discharged on
insulin.
Contraindications to non-insulin antidiabetic medications. Patients who have preexisting or newly developed contraindications to the use of non-insulin antidiabetic
medications will require insulin. Some contraindications include decreased renal
function, impaired liver function, pancreatitis, or congestive heart failure. A complete list of non-insulin antidiabetic medications and respective contraindications is
found in Chapter 9: Non-insulin therapy.
Insulin Teaching
Often, staff nurses are able to teach patients how to manage their insulin. Some
hospitals also offer special classes. Certified Diabetes Educators (CDE), when available, can assist with teaching complex regimens or patients with unique needs.
Patients should have supervised, hands-on practice with injection of insulin and
should be able to demonstrate proper technique prior to discharge. With appropriate
advance notice, staff nurses can direct patients to self-administer scheduled insulin
doses. Patients also should be able to demonstrate proper needle disposal.
Choice of Discharge Regimen
A complete guide to insulin regimens is found in Chapter 2: Subcutaneous insulin
(Table 11.1). Commonly used discharge regimens are described below.
Premixed insulin regimen. The premixed insulin regimen is a two-injection daily
regimen. There are various available formulations of premixed insulin; each incorporates an intermediate-acting insulin with either a short- or rapid-acting insulin.
This regimen is an attractive option for patients who have very stable day-to-day
activities and meals. However, this is a very limited population of patients. When
used improperly, patients can have frequent hyper- and hypoglycemia.
11
Regimen
Example
Non-insulin
medication
Some consider oral to be an Many contraindications; may Patients with type 2 diabetes
who refuse insulin or who
easier administration route; not give adequate glucose
have low insulin
control; rarely useful for
less frequent monitoring
requirements. Consider on
patients with type 1
required
case-by-case basis
diabetes
R
Humulin
70/30TM twice daily
Twice daily dosing
Inflexible component ratios Limited population; requires
R
70/30TM twice daily
Novolin
make titration difficult. Not significant education on
R
NovoLog
rigidity (and potential
appropriate for patients
MIX 70/30TM twice daily
R
danger) of regimen, and the
with inconsistent eating.
Humalog
MIX 75/25TM twice daily
need to eat 3 meals at exact
May have more fasting
times each day, with a
hyperglycemia and more
standard carbohydrate
frequent hypoglycemia
amount
No short-acting coverage for Limited population. Consider
Improved flexibility over
Regular and NPH insulin (mixed),
this regimen in patients
the noon meal. May see
premixed insulins because
injected before breakfast
who are willing to mix
fasting hyperglycemia and
individual components can
+
insulin but who are not
more frequent
be titrated
Regular and NPH insulin (mixed),
willing to give more than
hypoglycemia
injected before supper
two daily injections
No short-acting coverage for Limited population. Consider
Regular and NPH insulin before breakfast Improved flexibility over
this regimen in patients
the noon meal. Still not as
premixed insulins because
(mixed in a single syringe)
who are willing to mix
precise titration as the
individual components can
+
insulin but who are not
basal-bolus regimen
be titrated
Regular insulin before supper
willing to give more than
+
three daily injections
NPH at bedtime
Premixed insulin
Two-injection
split-mix insulin
Three-injection
split-mix insulin
A detailed list is found in Chapter 9:
Non-insulin antidiabetic medication
Pros
Cons
Treatment niche
Transitioning to Outpatient Care
Table 11.1 Discharge regimens
103
104
Table 11.1 (continued)
Regimen
Example
Basal-bolus insulin
R
], The most flexible and
Rapid-acting insulin (lispro [Humalog
R
aspart [Novolog
], glulisine
“physiologic” insulin
R
]) at mealtimes
[Apidra
regimen
With
R
Long-acting insulin (glargine [Lantus
],
R
detemir [Levemir
]) at bedtime
Or
Regular insulin at mealtimes
And
NPH at bedtime
Details of CSII can be found in Chapter 8
: insulin pumps
Cons
Treatment niche
Four or more daily injections Should be recommended for
and frequent monitoring
most patients who require
insulin; intensive education
is required
Not appropriate for new start
in the hospital
B.D. Hong and E.D. Davis
Continuous
subcutaneous
insulin infusion
(CSII)
Pros
11
Transitioning to Outpatient Care
105
Split-mix insulin regimen. The split-mix insulin regimen is a less intensive but
reasonable alternative to the basal-bolus regimen described below. It can involve
two or three injections daily and typically incorporates intermediate and short-acting
insulins (Table 11.1). The advantage of the split-mix regimen is improved flexibility
over premixed regimens, low cost, and fewer daily injections than the gold-standard
basal-bolus regimen. However, it requires that patients eat meals consistently, and
patients need to be willing and able to mix insulins for administration.
Basal-bolus insulin regimen. A basal-bolus insulin regimen usually is the best
choice for both optimal glycemic control and prevention of hypoglycemia. This type
of regimen often incorporates one or two injections of long-acting insulin, such as
R
R
), paired with mealtime injections of a
) or detemir (Levemir
glargine (Lantus
R
R
), or glulisine
), lispro (Humalog
rapid-acting insulin, such as aspart (Novolog
R
(Apidra ). These types of insulin are favored because they allow for flexibility
of schedule; however they are expensive for patients who do not have insurance
coverage for medication. An alternative plan incorporates use of regular insulin at
mealtimes and NPH insulin at bedtime. These insulins are less expensive, but the
timing of dose administration is more rigid. Appropriate use of either of these regimens requires that the patient be capable of administration of four or five insulin
injections each day, as well as frequent monitoring.
In addition to any of the choices above, the patient can also be taught to use a
correctional insulin scale, sometimes referred to as a “sliding scale.” (NOTE: The
correctional insulin scale is a reasonable tool when used in addition to the scheduled
regimens above, but it should be not be used alone.) Consider a correctional insulin
scale for patients who have a good understanding of insulin use and who need frequent adjustments in mealtime insulin dose. It is used at mealtime only and not at
bedtime or in the middle of the night. For patients who are new to insulin or who are
having difficulty internalizing the basics of self-management, a correctional insulin
scale can be confusing and dangerous. (More information on the advantages and disadvantages of a correctional insulin scale can be found in Chapter 2: Subcutaneous
Insulin.)
Upon returning home, patients’ insulin requirements are likely to change with
changes in activity level and diet. Communication and follow-up are critical
elements of good diabetes care.
Glucose Monitoring Post-discharge and Reporting Results
All patients should have personalized instructions for the glucose monitoring strategy. Objectives of home testing are improved glycemic control and improved quality
of life. Behaviors have the best chance of implementation with creation of an
individualized plan.
For patients who are using insulin, the recommendation is typically for glucose
monitoring four times daily, i.e., with meals and at bedtime. For patients on oral or
other non-insulin medications, monitoring frequency may be less often but should
not be less than daily. Some patients will need to monitor overnight (3 AM glucoses
106
B.D. Hong and E.D. Davis
occasionally. Pregnant patients and those on continuous subcutaneous insulin infusions (CSII, “insulin pumps,” Chapter 8) will need monitoring as often as six or
eight times daily. In patients for whom cost or motivation is an issue, staggered
monitoring may be appropriate. In this scenario, the patient tests once or twice a
day, at varying times. By the end of a week, the patient will have captured readings
from all important data points. For selected patients, use of this strategy can result
in more data collection than an “all or none approach.”
For a patient to be invested in ongoing testing, he or she needs to understand
individual, short-term, measurable benefits. Asking patients to “test in pairs” can be
effective. For example, a patient on rapid-acting insulin at mealtime can implement
testing before and 2 h after a meal, or before and after exercise. This helps to reveal
causality and can strengthen motivation.
Target Glucose Ranges
• Fasting and preprandial blood glucoses between 70 and 140 mg/dL.
• Postprandial blood glucoses < 180 mg/dL.
• For patients who are elderly or who have frequent problems with hypoglycemia,
targets may not be as strict. Conversely, pregnant patients have tighter targets. An
individual approach is critical, and outpatient follow-up is essential.
Recording and Reporting
Patients need to understand the importance of the patient-provided glucose data to
outpatient providers. They should be encouraged to keep a written blood glucose
log. Many meter kits come with a logbook; alternatively, these can be bought separately, self-made, acquired on the internet, or even graphed on the computer if
desired. Depending on the clinical situation, patients may also want to include monitoring of insulin doses, carbohydrate counting, or recording of food and exercise,
at least for short term or periodically.
Hypo- and Hyperglycemia
Basic instructions about hypoglycemia management are always appropriate, even
for patients who are experienced with insulin and diabetes self-management. It
is often helpful to provide specific parameters for when to call a provider for
help for either hypo- or hyperglycemia, as in the sample discharge instructions in
Fig. 11.2. Some patients may be able to adjust insulin based on home monitoring,
and appropriate instructions should be given in this situation as well.
Prescriptions
At the time of discharge, patients should have an updated supply at home, or be
given prescriptions, for the following items (Fig. 11.3):
11
Transitioning to Outpatient Care
107
Diabetes Discharge Instructions
Blood Glucose Testing - Test blood sugar before every meal and at bedtime or on your
provider’s recommended schedule. Record the glucose readings, and take this record with you
to your doctor appointments.
Take your insulin as follows:
[Fill in type of insulin______] XX units with breakfast
[Fill in type of insulin______] XX units with lunch
[Fill in type of insulin______] XX units with dinner
[Fill in type of insulin______] XX units at bedtime.
Correctional insulin scale:
If your blood sugar is greater than 150 before a meal, you will need to take some extra rapidacting insulin with your dose. Use correction insulin only at meal times. Do not add extra to
your bedtime dose of long-acting insulin.
For Blood Sugar (mg/dL),
Take an additional
151 – 200
XX units of [Fill in type of insulin______]
201 – 250
XX units of [Fill in type of insulin______]
251 – 300
XX units of [Fill in type of insulin______]
301 – 350
XX units of [Fill in type of insulin______]
351 – 400
XX units of [Fill in type of insulin______]
Over 400
XX units of [Fill in type of insulin______]
AND CALL YOUR DOCTOR
Hypoglycemia instructions: If your blood sugar is less than 70 mg/dL (3.8 mmol/L), treat with
one of the following options: Take 3 glucose tablets, drink a ½ cup of juice or ½ can of regular
soda. Recheck blood sugar in 30 minutes. Call your doctor or emergency medical services if
you still have trouble getting the blood sugar to come up to 70 mg/dL or higher.
If hypoglycemia occurs when it is longer than 1 hour until your next regularly-scheduled meal or
snack, follow the treatment with a mixed protein and carbohydrate food, like peanut butter and
crackers.
Fig. 11.2 Sample discharge handout
108
B.D. Hong and E.D. Davis
If your blood sugar is below 80 mg/dL (4.4 mmol/L), take only ½ of the usual dose of insulin.
If you are asked not to eat or drink anything before a procedure or test, do not take rapid-acting
insulin (lispro [Humalog®], aspart [Novolog®], or glulisine [Apidra®]) until you are eating again.
Do take your full dose of long-acting insulin (glargine [Lantus®], detemir [Levemir®]).
If you see a pattern that a lot of your blood sugars are less than 80 mg/dL (4.4 mmol/L) or
greater than 200 mg/dL (11.1 mmol/L), call your doctor. Your doctor may want to change your
insulin prescription.
Your follow-up appointment with Dr.XXX is on XXX date at XXX time.
If you have any questions before you see your doctor, you may call XXX-XXX-XXXX.
Fig. 11.2 (continued)
Medications
• Oral or non-insulin medications if appropriate
• Insulin
• A vial contains 1,000 units; one vial is approximately enough for 30
units/day for 30 days.
• All pens contain 300 units; pens come in boxes of 5.
• Insulin vials and pens should be replaced 1 month after being opened,
even if they are not empty. Current bottles or pens may be kept at room
temperature (above 32◦ F and below 86◦ F). Unopened insulin should be
refrigerated.
• Glucose tablets or gel.
• Glucose tablets are inexpensive, portable, and available over the counter.
Three tablets contain approximately 12–15 g of carbohydrate, which
is an appropriate starting point for the management of a conscious
hypoglycemic episode. Patients can be instructed on the rule of “15s.”
Consume 15 g of carbohydrate, wait 15 min, retest, and re-treat with 15 g,
if needed.
• Other treatments for conscious hypoglycemia may also be recommended
(i.e., 1/2 cup regular soda, 1/2 cup fruit juice).
• Glucagon kit, if appropriate. For proper use, the patient must live with, or
near, someone who is comfortable emergently administering glucagon for
unconscious hypoglycemia.
11
Transitioning to Outpatient Care
109
Fig. 11.3 Sample prescriptions
Supplies
• Glucose meter: often referred to as a “glucometer,” or, more specifically,
“glucose testing device” (Fig. 11.3).
• Lancets: come in boxes of 100.
• Test strips: come in containers of 50 or 100. Sufficient test strips should
be prescribed to ensure availability for regular testing and in case of
emergencies.
• All manufacturers and current literature recommend using warm water and
soap for easier, less painful testing with lower incidence of infection. Many
hospitals also do this. There are no definitive rules for when to use alcohol
on fingers when testing.
110
B.D. Hong and E.D. Davis
• Alternate site testing (forearms and palms) generally has lower reliability than finger testing. Information about this is available on websites like
www.diabetesforecast.org and can be provided at the provider’s discretion.
When writing prescriptions, be sure to include diagnosis codes, which are
required for insurance coverage (Fig. 11.3).
Diabetes medications and supplies may be expensive. This should be considered
when choosing a regimen for discharge. The following are some tips to help patients
use their money wisely.
• There is no generic insulin. Regular and NPH are the least expensive insulins
at retail price. Many of the newer insulins may be available through company
financial assistance programs.
• Glucose meters are often free or inexpensive, but test strips are expensive. Large
chain stores may have supplies at discounted prices. Choice of brand of testing
supplies is influenced by specific insurance coverage, including Medicaid.
• Advance discussion about cost of testing supplies and cost-effective testing
regimens may lessen the impact of cost as a barrier to self-management.
Behavior Recommendations
Medical nutrition therapy (MNT). All patients with diabetes should receive individualized MNT as needed to achieve treatment goals. A thorough discussion of this
topic can be found in Chapter 7: Medical Nutrition Therapy.
Exercise. Patients should be encouraged to engage in at least 150 min of
moderate-intensity aerobic exercise per week unless exercise is contraindicated. Use
of exercise prescriptions and individualized plans can be helpful.
Follow-Up Appointments
Follow-up appointments should be made within 1–2 weeks of the discharge date for
patients with a new diagnosis of diabetes, with recurrent episodes of hypo- or hyperglycemia during the admission, or with major changes to the outpatient diabetes
regimen.
Follow-up with an endocrinologist may also be appropriate, particularly in the
following situations:
• The patient was seen by an endocrinologist while admitted, and specific followup is recommended.
• The patient starts a new basal-bolus insulin regimen.
• The patient has type 1 diabetes.
• The patient has frequent hypoglycemia or hypoglycemia unawareness.
11
Transitioning to Outpatient Care
111
Other Referrals to Consider
• Outpatient diabetes education
• Nutrition
• Diabetes support and education groups. The local American Diabetes Association
(ADA) branch can provide information about these. Additionally, patients
may want to utilize local community resources through their doctor’s offices,
churches, senior centers, etc.
Sample Discharge Instructions
Given the complexity of discharge instructions for patients with diabetes, we recommend providing a handout with personalized diabetes discharge instructions
(Fig. 11.2). The handout will serve as a useful reference when diabetes self-care
questions arise after discharge. The handout also will help the patient and family to
focus on the key elements of diabetes management and to separate these issues from
the myriad of general discharge instructions that patients are given when they leave
the hospital.
Bibliography
American Association of Diabetes Educators (AADE). Inpatient position statement.
http://www.diabeteseducator.org/ProfessionalResources. Accessed April 9, 2009.
American Diabetes Association. Diabetes care executive summary from the American Diabetes
Association. Standards of medical care in diabetes 2010. Diabetes Care. 2010;(supp 1):S6–S12.
Anderson RM, Funnell MM, Burkhart N, Gillard ML, Nwankwo R. 101 Tips for Behavior Change
in Diabetes Education. Alexandria, VA: American Diabetes Association; 2002.
Boinpally T, Jovanovic L. Management of type 2 diabetes and gestational diabetes in pregnancy.
Mt Sinai J Med. 2009;76(3):269–280.
Clement S, Braithwaite SS, Magee MF, et al. Management of diabetes and hyperglycemia in
hospitals. Diabetes Care. 2004;27(2):553–591.
Davis E, Midgett L, Gourley C. Teach less, teach better at every opportunity. Diabetes Educ.
1994;20(3):236–240.
Leak A, Davis ED, Mabrey M, Houchin L. Diabetes self management and patient
education in hospitalized oncology patients. Clin J Oncol Nurs. 2009;13(2):
205–210.
Lien LF, Bethel MA, Feinglos MN. In-hospital management of type 2 diabetes mellitus. Med Clin
N Am. 2004;88(4):1085–1105.
Moghissi ES, Korytkowski MT, DiNardo M. American Association of Clinical Endocrinologist
and American Diabetes Association consensus statement on inpatient glycemic control. Endocr
Pract. 2009;15(4):1–17.
Chapter 12
Management of Hyperglycemia Associated
with Enteral and Parenteral Nutrition
Sarah Gauger
Keywords Enteral nutrition · Parenteral nutrition (TPN) · Continuous feeding ·
Bolus feeding · 10% dextrose (D10)
Understanding Enteral Nutrition
Enteral nutrition, also known as “tube feeding,” is necessary for patients who cannot
eat but who have an intact gastrointestinal system. This may be attributed to a variety of conditions, including altered mental status, inability to swallow, and risk for
aspiration. Hyperglycemia is common after the initiation of enteral nutrition in both
diabetic and nondiabetic patients because the formulas are designed to be calorically dense. Furthermore, they often are delivered continuously throughout the day
rather than as discrete meals. Because the choice of formula for an individual patient
incorporates a variety of factors (protein, fat, and carbohydrate content, along with
micronutrients), resultant hyperglycemia generally is most appropriately managed
by matching subcutaneous insulin injections to the patient’s needs rather than by
changing the formula to correct hyperglycemia.
When treating hyperglycemia related to enteral feeding, it is important to clarify
the following three elements with the ordering provider:
1. Is the feeding continuous, bolus, or nocturnal?
2. Is it anticipated that the patient will begin eating while still on the enteral
feeding?
3. What type of enteral feeding formula is being used? (Table 12.1).
There are several low-carbohydrate formulas designed for patients who have
problems with hyperglycemia. For patients with persistent hyperglycemia despite
use of insulin, or for those who develop erratic hypoglycemia, a nutrition consult
S. Gauger (B)
Duke Inpatient Diabetes Management, Duke University Medical Center, Durham, NC 27710, USA
e-mail:
[email protected]
L.F. Lien et al. (eds.), Glycemic Control in the Hospitalized Patient,
C Springer Science+Business Media, LLC 2011
DOI 10.1007/978-1-60761-006-9_12,
113
114
S. Gauger
Table 12.1 Enteral feeding formulas
Osmolite 1 Cal©
Cal/mL
Carbohydrate
source
1.06
1.2
1.5
Corn maltodextrin, Corn maltodextrin, Maltodextrin,
sugar
corn syrup
corn syrup
solids, scFOS
solids
143.9
169.4
170
Carbohydrate
(g/L)
Carbohydrate
(% Cal)
Fiber (g/L)
R
54.3
−
Jevity 1.2 Cal ©
R
1.5
Isosource
Cal
Product name
R
Novasource
renal
2.0
Corn syrup,
fructose
200
52.5
44
40
18.0
8
−
R
Isosource and Novasource are registered trademarks of Société des Produits Nestlé S.A.,
Vevey, Switzerland
© 2010 Abbott Laboratories. Used with permission
may be helpful to explore alternative formula solutions. Switching to a lowcarbohydrate formula may not completely resolve the hyperglycemia, but it may
improve the ease of insulin management.
Hyperglycemia Management
Hyperglycemia related to enteral feeding must be managed with insulin. Creation
of a regimen can be tricky because of the unusual nutrition timing. A simple way to
begin is to calculate a starting total daily dose of insulin. This can then be divided
into appropriately timed insulin injections in accordance with the nutrition pattern
(Table 12.2).
Steps for determination of a total daily dose can be found in Chapter 2:
Subcutaneous Insulin. The following information must be gathered in order to make
a proper dose calculation:
• Does the patient have previously diagnosed diabetes? If yes, which type?
• What medications for diabetes does the patient take at home? Has this been
effective in lowering the A1C to the patient’s treatment goal, or are changes
necessary?
• Has there been hypoglycemia in the past 24 hours?
In order to determine the timing and dosages of insulin, the following information
must be obtained (Table 12.2):
• If the patient is already receiving subcutaneous insulin injections, at what time
are the injections being given?
• Does the timing of the insulin injections match the timing of administration of
the enteral feeding?
12
Table 12.2 Insulin regimens for enteral feeding
Continuous feeding
Bolus feeding – every 3 h
Bolus feeding – every 4 h
Nocturnal feeding (e.g.,
1800–0600)
Same
Regular insulin in 4 divided
doses. The doses are
administered every 6 h over
each 24-h period
Same
Regular insulin every 6 h,
given 30 min before
alternating tube-feed
boluses
Other notes
At least every 6 h
115
An alternative strategy is to
give a long-acting insulin
once daily and rapid-acting
insulin with each bolus,
although this frequency of
injection and monitoring is
not as convenient
This is not the preferred timing strategy for tube feeding because it makes coordination with insulin difficult. Consider
changing to every 3-h boluses if possible
We describe the 1800–0600
Glucose monitoring should
1800 (or the start of feeding): Insulin at 1800 and 2100 as
pattern because these
occur prior to
for patients with diabetes is
regular insulin
feeding times correspond
administration of insulin at
usually sufficient. Rarely,
2100: NPH insulin, and
with usual insulin
1800 and 2100. Monitoring
daytime coverage is also
consider an additional
administration times
at 0300, 0600, and 1200
needed
small dose of regular
will detect other potentially
insulin for those who have
abnormal glucoses. (Once
overnight hyperglycemia
a regimen is established,
Between 0600 and 1800
the 0300 check can be
(daytime hours), when
discontinued.)
feeding is suspended, some
patients will require low
doses of regular insulin,
given at 0600 and 1200, to
prevent hyperglycemia
With each dose of insulin.
(Consider more frequent
monitoring early on, i.e.,
with each bolus, to assess
for hypoglycemia.)
Management of Hyperglycemia Associated with Enteral and Parenteral Nutrition
Enteral feeding regimen
Subcutaneous insulin strategy
Subcutaneous insulin strategy for patients without known
diabetes
Blood Glucose Monitoring
for patients with diabetes
116
Table 12.2 (continued)
Enteral feeding regimen
Subcutaneous insulin strategy
Subcutaneous insulin strategy for patients without known
diabetes
Blood Glucose Monitoring
for patients with diabetes
Nocturnal feeding + eating
Similar to nocturnal feeding
above. Additional regular
insulin is usually needed
with meals
Same
With meals, at bedtime, and
at 0300
Total parenteral nutrition
Regular insulin every 6 h
Or
For selected patients,
long-acting insulin once
daily
Regular insulin every 6 h as
needed
Every 6 h
Other notes
In this case the 0600 blood
glucose check and the
insulin dose may need to
be moved to 0800 to
correspond more closely
with the morning meal
Insulin is often added to the
TPN bag, so some patients
will not need additional
subcutaneous insulin
S. Gauger
12
Management of Hyperglycemia Associated with Enteral and Parenteral Nutrition
117
• If not, then adjustments must be made so that the insulin and feeding times
match. For example, if the patient is only receiving nocturnal feedings, then
the amount of insulin injected during the daytime should be minimal, to avoid
hypoglycemia.
• For patients receiving bolus feedings, the timing of the insulin injections and
the food boluses should be coordinated. For example, if boluses are being
given every 3 hours, insulin injections could be given with every other bolus,
which would then consist of insulin every 6 hours.
• While the administration rate of a patient’s continuous enteral nutrition is increasing toward a goal rate, the carbohydrate load will also be increasing. Thus, insulin
doses will need to follow.
Hypoglycemia Management in Enteral Feeding
Hypoglycemia always is a concern for patients receiving insulin with enteral feedings. Feedings can be interrupted at any time due to problems with position or
function of the tube or because feeding is paused in preparation for procedures.
The most common reason for hypoglycemia with enteral feeding is an unexpected interruption in feeding. Hypoglycemia can be treated acutely by conventional
methods (see Chapter 10: Hypoglycemia). In order to prevent recurrent hypoglycemia in this situation, the patient will need prolonged carbohydrate support for
the active life of the insulin that was given. If feeding cannot be reinitiated promptly,
it is recommended to begin a low-dose infusion of IV dextrose (D10) until feeding
is restarted or until the insulin is no longer active (see Chapter 10: Hypoglycemia,
Fig. 10.3). Frequent monitoring (hourly) will determine whether more acute hypoglycemia management or carbohydrate support is needed. If hypoglycemia is not
the result of a food interruption, insulin dosages should be decreased; a 10–20%
reduction is reasonable.
Because hypoglycemia is common in patients receiving enteral feeding, it is
advisable to take measures for prevention. At our institution, we employ the
following standard orders:
• Give half of the scheduled dose of regular insulin when feeding is interrupted.
• Patients with type 2 diabetes may have a decreased insulin requirement with
prolonged fasting, and other patients may have a low nutritional insulin
requirement relative to their basal needs. In those patients, even smaller doses
of insulin may be given during periods of interrupted feeding. In fact, some
patients with type 2 diabetes may not require any insulin during periods of
fasting.
• Patients with type 1 diabetes always should be given insulin and should be
supported with IV dextrose if necessary in order to enable administration of
insulin.
118
S. Gauger
• Administer IV D5 or D10 as soon as any unexpected interruption of enteral
feeding occurs (see Chapter 10: Hypoglycemia, Fig. 10.3).
A few patients may require administration of long-acting basal insulin during
their time on enteral or parenteral nutrition. In these patients, it is important for
that insulin to cover only the patient’s basal needs and not the nutrition. With use
of long-acting insulin, there is a high risk for profound hypoglycemia associated
with unplanned discontinuation of the nutrition source. For this reason, we generally
prefer shorter-acting insulins (Table 12.2).
Total Parenteral Nutrition
Total parenteral nutrition (TPN) delivers a nutritional source intravenously to
patients who cannot be fed through the digestive system. Common reasons for use
include bowel obstruction, pancreatitis, or Crohn’s disease. Patients who develop
hyperglycemia while on TPN can be managed similarly to patients on continuous enteral feeding. However, this should be done in close contact with the
nutrition team, as some TPN preparations contain insulin. If the patient has additional basal and correctional insulin needs, subcutaneous or IV insulin can be
used. Some patients are given simultaneous TPN and enteral or oral nutrition. For
these patients, non-TPN nutritional needs should be covered with subcutaneous
insulin.
In general, TPN contains 100–200 g of dextrose per bag, along with 5–20 units
of regular insulin for patients with diabetes. The exact amount is determined by the
nutrition team or the ordering provider and often is based on the estimate of 1 unit
of insulin per 10 g of carbohydrate. Over time, the dextrose concentration of the
formula is increased, and the insulin also is increased. It is not recommended to use
more than 100 units of insulin per bag.
Blood glucose monitoring should be performed at least every 6 hours on all
patients initiated on TPN. If there is no elevation in blood glucoses within the
first 72 hours in a nondiabetic patient, it may be reasonable to discontinue monitoring. For patients who are diabetic or continue to demonstrate hyperglycemia on
TPN, routine monitoring should be continued, and the patient’s insulin needs can be
covered with standing doses of regular insulin.
Bibliography
Clement S, Braithwaite SS, Magee MF, et al. Management of diabetes and hyperglycemia in
hospitals. Diabetes Care. 2004;27(2):553–591.
Department of Nutrition Services, Duke University Hospital. Adult Enteral Nutrition Formulary
2009–2011. Durham, NC: Duke University Hospital; 2009.
Elia M, Ceriello A, Laube H, Sinclair AJ, Engfer M, Stratton RJ. Enteral nutritional support and use
of diabetes-specific formulas for patients with diabetes. Diabetes Care. 2005;28(9):2267–2279.
McKnight KA, Carter L. From trays to tube feedings: overcoming the challenges of hospital
nutrition and glycemic control. Diabetes Spectr. 2008;21(4):233–240.
Chapter 13
When to Consult Endocrinology
Beatrice D. Hong
Keywords Endocrinology consult
Hyperglycemia is common among hospitalized patients, and improved glycemic
control has been shown to improve clinical outcomes such as infection risk and
hospital length of stay (LOS). Improved glycemic control can be facilitated through
a diabetes care team or general endocrinology consultation. One retrospective study
examined the effect of diabetes team consultation on the outcome LOS, and the
investigators reported a 56% shorter LOS among those patients who were seen by a
diabetes team versus those who had no consultation.
An inpatient endocrinology consult team can assist the primary team in the diagnosis and management of hyperglycemic disorders, with the goal of optimizing
patient care and, ideally, patient satisfaction as well. There are many reasons to consult endocrinology. Some situations in which an endocrinology consultation should
be considered are as follows:
• Whenever there is a question about a patient’s diabetes management.
• Patients with newly diagnosed diabetes mellitus of any type.
• Patients on multiple daily injections, multiple types of insulin, or large doses of
insulin at home.
• Patients with type 1 diabetes mellitus.
• Patients who are pregnant.
• Patients with poor glycemic control.
• Patients with persistent hyper- or hypoglycemia, or those whose blood glucose
levels fluctuate in the inpatient setting.
• Patients on continuous subcutaneous insulin infusion.
• Patients with corticosteroid-induced hyperglycemia, particularly those who have
had organ transplantation.
B.D. Hong (B)
Division of Endocrinology, Metabolism, and Nutrition, Department of Medicine, Duke University
Medical Center, Durham, NC 27710, USA
e-mail:
[email protected]
L.F. Lien et al. (eds.), Glycemic Control in the Hospitalized Patient,
C Springer Science+Business Media, LLC 2011
DOI 10.1007/978-1-60761-006-9_13,
119
120
B.D. Hong
• Patients with chronic renal insufficiency, including those on hemodialysis or
peritoneal dialysis.
• Patients on an IV insulin infusion, including postoperative patients.
• Patients with other types of diabetes: cystic fibrosis-related diabetes, pancreoprivic diabetes (patients with their pancreas destroyed by medical condition or
surgically removed), maturity onset diabetes of the young (MODY), or latent
autoimmune diabetes in adults (LADA).
• Patients with hypoglycemia unawareness.
• Patients with complicated nutrition regimens, including those on enteral or
parenteral nutrition.
Bibliography
Furnary A, Gao G, Grunkemeier G, et al. Continuous insulin infusion reduces mortality in
patients with diabetes undergoing coronary artery bypass grafting. J Thorac Cardiovasc Surg
2003;125(5):1007–1021.
Furnary A, Wu Y, Bookin S. Effect of hyperglycemia and continuous intravenous insulin infusions on outcomes of cardiac surgical procedures: the Portland Diabetic Project. Endocr Pract.
2004;10(suppl 2):21–33.
Levetan C, Salas J, Wilets I. Impact of endocrine and diabetes team consultation on hospital length
of stay for patients with diabetes. Am J Med. 1995;99:22–28.
Lien L, Bethel M, Feinglos M. In-hospital management of type 2 diabetes mellitus. Med Clin N
Am. 2004;88(4):1085–1105.
Chapter 14
Frequently Asked Questions
Mary E. Cox and Matthew J. Crowley
Keywords Hypoglycemia · Basal insulin · Prandial insulin · Plasma glucose ·
Point-of-care glucose · Correction dose insulin · Non-insulin antidiabetic
medication · Abnormal glucose measurement
Many questions come through the diabetes management service pager at our institution. This chapter discusses some frequently asked questions and recommended
strategies for management of common situations. This discussion provides focused
recommendations; further details about many topics can be found in their respective
chapters.
Definitions
• Plasma glucose: Glucose can be measured in plasma and used to diagnose diabetes. In the hospital, plasma glucose measurements often are used to confirm a
reading obtained by a point-of-care glucose meter. Plasma testing is generally the
most reliable option for measuring blood glucose.
• Point-of-care glucose monitoring: A point-of-care glucose meter, also known as
a glucometer or capillary glucose monitor, can be used to measure whole blood
glucose. Point-of-care testing (POCT) often is used in the hospital to make realtime decisions about therapy. In general, the accuracy of these meters is good, and
they are calibrated to reflect the plasma glucose; however, they may be limited at
particularly high or low glucose levels.
• Hypoglycemia: Hypoglycemia typically is defined as plasma or blood glucose
less than 70 mg/dL (3.8 mmol/L); in our institution, a documented glucose
below this level automatically activates an inpatient “hypoglycemia protocol,”
with instructions to verify the measurement and administer 50% dextrose (D50)
as indicated. Of note, some patients without diabetes, especially young women,
may have normal fasting glucose levels below 60 mg/dL (3.3 mmol/L). This is
M.E. Cox (B)
Division of Endocrinology, Metabolism, and Nutrition, Department of Medicine, Duke University
Medical Center, Durham, NC 27710, USA
e-mail:
[email protected]
L.F. Lien et al. (eds.), Glycemic Control in the Hospitalized Patient,
C Springer Science+Business Media, LLC 2011
DOI 10.1007/978-1-60761-006-9_14,
121
122
•
•
•
•
M.E. Cox and M.J. Crowley
not likely to be the case for most inpatients with diabetes, and any glucose below
70 mg/dL (3.8 mmol/L) in the hospital setting requires immediate attention.
Basal insulin: This is a long- or intermediate-acting insulin given to control
blood glucose in the fasting state. Examples include the long-acting insulins
R
R
) and the intermediate-acting insulin
) or detemir (Levemir
glargine (Lantus
R
R
NPH (Humulin -NPH, Novolin N). Basal insulin also can be provided via
R
) or
continuous subcutaneous insulin infusion (CSII) using aspart (Novolog
R
lispro (Humalog ).
Prandial insulin: This is a short- or rapid-acting insulin given before or with
meals to control rises in blood glucose that result from carbohydrate ingestion.
Timing of prandial insulin administration is dependent on the timing of carbohydrate exposure. Carbohydrate sources include oral intake, other enteral nutrition,
R
R
R, Humulin
and total parenteral nutrition (TPN). Regular insulin (Novolin
R) is the most common short-acting type; because onset of activity occurs at
approximately 30 min after injection, regular insulin should be given 30 min
R
), lispro
before a meal. Available rapid-acting insulins include aspart (Novolog
R
R
(Humalog ), and glulisine (Apidra ); onset of activity occurs at approximately
5–15 min after injection, so these insulins can be given with or just after meals.
Prandial insulin is sometimes referred to as “bolus” insulin.
Correction dose insulin: This short- or rapid-acting insulin is given in addition to
scheduled insulin for the purpose of correcting hyperglycemia.
Non-insulin antidiabetic medications: These medications include oral and
injectable medications other than insulin.
Abnormal Glucose Measurements
How Do I Manage Hypoglycemia in Hospitalized Patients?
If a hypoglycemic patient exhibits severe neuroglycopenic symptoms such as altered
mental status, coma, or seizure, immediately administer 1 ampule of D50 intravenously and provide appropriate symptomatic treatment and frequent glucose
monitoring. For all asymptomatic patients or patients with less severe symptoms
such as tremor, palpitations, anxiety, sweating, hunger, or paresthesias, proceed with
the following steps for confirmation and treatment:
1. Repeat the glucose measurement for confirmation. A repeat POCT glucose can
be done quickly, but sometimes it also is useful to obtain a plasma glucose measurement, particularly in patients who are asymptomatic. Some patients do have
true hypoglycemia without symptoms, so treatment should not be delayed while
waiting for a confirmatory plasma measurement.
2. Determine the patient’s access route for glucose administration. The oral route
is preferred if the patient is awake and alert. Glucose also can be administered
intravenously, intramuscularly, and through an endotracheal tube. If no access is
available, give 1 mg glucagon intramuscularly (last resort).
14
Frequently Asked Questions
123
Fig. 14.1 Hypoglycemia algorithm. Decision about therapy should be based on the patient’s
mental status and access routes, using the least invasive method available. D50, 50% dextrose;
IV, intravenous; IM, intramuscular. ∗ If a patient does not have access, this should be discussed
promptly with the care team. Source: Duke University Hospital Glycemic Safety Committee,
courtesy of Mary Jane Stillwagon, BSN, RN
3. Treat the hypoglycemia (Fig. 14.1). Consider the “rule of 15s.” Fifteen grams
of oral carbohydrate will raise the blood glucose approximately 15 mg/dL in
approximately 15 min. Of note, the glucose may continue to rise after the first
15 min by as much as 40 mg/dL. Accordingly, when treating a patient for whom
oral intake is safe, start treatment with administration of 15 g of carbohydrate
by mouth, understanding that the individual patient’s response may vary. Oral
options that provide 15 g of carbohydrates include
• 4 oz fruit juice or regular soda (1/2 cup).
• 1 packet of glucose gel
• 3–4 glucose tablets
124
M.E. Cox and M.J. Crowley
Foods with high glucose content (as opposed to fructose or other simple sugars) are preferred. Foods with high fat content, such as ice cream or peanut
butter, will not raise blood glucose as quickly because fat slows glucose
absorption.
Some patients will continue to experience symptoms of tremor, headache,
nausea, sweating, and food craving for 20–30 min after effective treatment.
Reassurance can be helpful, concurrent with close monitoring. Resolution
of symptoms is an important treatment goal, but it is important to remember that excessive amounts of carbohydrate can lead to severe rebound
hyperglycemia.
4. Measure POCT glucose again 15–20 min after initial treatment. If the blood
glucose level remains below 70 mg/dL (3.8 mmol/L), return to the algorithm
and re-treat. Repeat the process until the glucose level is greater than 70 mg/dL
(3.8 mmol/L).
5. If the blood glucose remains less than 70 mg/dL (3.8 mmo/L) after three
treatments, consider a continuous infusion of 10% dextrose (D10).
6. Consider the differential diagnosis for in-hospital hypoglycemia (Table 14.1) and
give special consideration to insulin and other medications. Adjustments to the
patient’s insulin likely will be required.
7. Once hypoglycemia is resolved, consider giving the patient a snack with mixed
carbohydrate, fat, and protein content, such as peanut butter or cheese with crackers, to maintain normoglycemia until the insulin or hypoglycemic medication is
metabolized.
8. Continue subsequent glucose monitoring. After an episode of hypoglycemia, it
is prudent to increase the monitoring frequency until stability is assured.
Table 14.1 Causes of hypoglycemia in the hospitalized patient
• Acute or intermittent hypoglycemia
o Excessive basal or prandial insulin doses
o Acute renal failure
o Acute hepatic failure
o Infection
o NPO status or change in nutrition pattern
o Changing dosages of corticosteroids
o Shock
• Persistent hypoglycemia
o Malignancy
o Alimentary disease
o Adrenal insufficiency
o Pregnancy
o Burns
NPO, nothing by mouth
14
Frequently Asked Questions
125
How Do I Manage Hyperglycemia in Hospitalized Patients?
Hyperglycemia is a frequent finding in hospitalized patients. There are a number of
different causes (Table 14.2). Confirmation and treatment differ somewhat between
patients who have a previous diagnosis of diabetes and those who do not.
Table 14.2 Causes of hyperglycemia in the hospitalized patient
Diabetes mellitus (diagnosed or previously undiagnosed)
Postoperative stress
Infection
Other inflammatory states (e.g., myocardial infarction)
Medication side effects (e.g., corticosteroids, calcineurin inhibitors, atypical
antipsychotic agents)
• Enteral or parenteral nutrition
• Vasopressor administration
• Continuous veno-venous hemodialysis
•
•
•
•
•
Patients Previously Diagnosed with Diabetes
The first step for management of patients with diabetes is a careful disease history, which should include the type of diabetes, the date and circumstances of the
diagnosis, prior management, and importantly, the patient’s current home diabetes
medication regimen. Once this has been ascertained, the next step is to determine
whether the home regimen should be continued during the hospital stay. To aid this
decision making, it usually is helpful to obtain a hemoglobin A1C as a measure of
recent glycemic control (see Chapter 4: Laboratory Testing), as well as history of
recent medication self-adjustments and adherence.
If the patient is taking non-insulin antidiabetic medications at home, it is generally prudent to replace them with scheduled insulin while the patient is in the
hospital (see Chapter 9: Non-insulin Antidiabetic Medications). Many individuals
already using scheduled insulin prior to admission will require adjustments while in
the hospital (see Chapter 2: Subcutaneous Insulin).
When calculating subcutaneous insulin dosing in the hospital, a general rule is to
use the following formula:
Weight (kg) × X units/kg = Total daily dose(units)
In this formula, X = 0.3–0.5 units/kg for patients with type 1 diabetes and X =
0.5–1.0 units/kg for patients with type 2 diabetes. Lower units per kilogram values
should be used for patients who are sensitive to insulin and higher values should be
used for insulin-resistant patients (see Chapter 2: Subcutaneous Insulin). If uncertainty exists about a patient’s level of insulin resistance, a general recommendation
is to start with a lower total daily dose (TDD) and then to promptly adjust according
to subsequent POCT glucose levels.
126
M.E. Cox and M.J. Crowley
Although correction dose insulin alone sometimes is used to treat mild or intermittent hyperglycemia, this practice should be discouraged, as scheduled insulin is
known to maintain normoglycemia more effectively.
Patients Not Previously Diagnosed with Diabetes
The first step in this situation should be to confirm that the patient has not been
diagnosed with diabetes mellitus. If the patient does have known diabetes, document
this in the chart and proceed with treatment as per the previous section.
If the hyperglycemic patient has not been previously diagnosed with diabetes, the
next step should be to determine a scheduled insulin regimen. Although correction
dose insulin, sometimes referred to as “sliding scale insulin,” alone is sometimes
implemented in this situation, this practice should be discouraged. The American
Diabetes Association recommends use of correction dose insulin only when given
in addition to a scheduled insulin regimen, as the preferred method of addressing unexpected hyperglycemia. Scheduled insulin is preferred for the following
reasons:
• Correction dose insulin alone is less effective than a scheduled insulin regimen
in controlling hyperglycemia and decreasing hospital length of stay.
• Correction dose insulin alone does not prevent hyperglycemia.
• Correction dose insulin alone can lead to erratic glycemic control with episodes
of hyperglycemia alternating with hypoglycemia.
Newly diagnosed patients with diabetes, patients who have had surgery, patients
starting hyperglycemia-inducing medications, and patients with medication changes
all may require continuation of insulin or other diabetes medications at hospital
discharge. For these patients, inpatient education is crucial and should be arranged
prior to discharge (see Chapter 11: Transition to Outpatient Care).
What if My Patient Has Severe Hyperglycemia
(Glucose >400 mg/dL [>22.2 mmol/L])?
As with other POCT glucose abnormalities, it is useful to confirm an initial measurement with another POCT measurement or a plasma glucose level. If the glucose
is truly elevated, assess for diabetic ketoacidosis (DKA). A simple, rapid screening
test for ketoacidosis is a semi-quantitative urine ketone measurement on a routine
urinalysis. If urine ketones are present, confirmatory testing should be ordered: basic
metabolic panel, calculated anion gap, serum ketone level, and other appropriate
testing (see Chapter 6: Hyperglycemic Emergencies). If DKA is present, initiation
of an IV insulin infusion and other acute management is indicated.
For a patient with severe hyperglycemia without DKA, it is reasonable to treat
with an insulin infusion, as this strategy will rapidly and accurately correct the
hyperglycemia. In many hospitals, intensive monitoring and/or IV insulin infusion
14
Frequently Asked Questions
127
may require placement in an intermediate or intensive care unit. Indications for IV
insulin infusion are discussed in detail in Chapter 3.
If an insulin infusion is felt not to be indicated, subcutaneous insulin should be
used to correct the hyperglycemia in one of two ways, depending on whether the
patient is able to eat. In both cases, a scheduled basal insulin dose should be provided. In patients for whom eating is not contraindicated, the first option is to give
short- or rapid-acting insulin along with a mixed macronutrient snack or meal. If
eating is contraindicated, the second option is to cautiously give short- or rapidacting insulin without food. With the latter option, the patient’s glucose should be
checked every 30–60 min after insulin administration in order to assure that the glucose does not decrease more rapidly or to a greater degree than desired. Additional
insulin should not necessarily be given in response to these follow-up glucose levels.
Like all drugs, insulins have distinct half-lives, approximately 4–5 h for rapid-acting
analogs. Repeat dosing at intervals shorter than this can cause a phenomenon called
“insulin stacking,” which can lead to hypoglycemia and should be avoided. If the
glucose is not decreasing as expected on repeat monitoring, use of IV insulin should
be reconsidered. A correction dose insulin scale can be a useful adjunct to scheduled
subcutaneous insulin.
What if My Patient’s POCT and Plasma Glucose Readings Don’t
Agree?
As with all laboratory tests, plasma glucose and POCT are not without error.
For plasma glucose testing, expected error is approximately 20–40 mg/dL (1.1–
2.2 mmol/L), and the expected error for POCT is even greater, particularly at
extremes of blood glucose. Furthermore, glucose levels fluctuate within individuals over time, so levels that are not drawn simultaneously can differ. However,
sometimes differences between plasma and point-of-care glucose values cannot
be explained by error or time fluctuation. The following sections discuss possible
explanations for true differences between POCT and plasma glucose testing.
POCT Glucose Is Lower Than Plasma Glucose
Falsely low point-of-care glucose values usually result from inaccurate measurement due to either provider or patient factors such as the following:
• Incorrect use of meter, including inadequate meter calibration, use of expired or
incorrect test strip, poor technique in performing finger prick or applying blood
to test strip
• Situations that cause decreased blood flow to the fingertips, such as Raynaud’s
phenomenon and vasopressor use
• Thickened skin, as for patients with scleroderma or calciphylaxis
128
M.E. Cox and M.J. Crowley
Falsely elevated plasma glucoses also can occur in the following situations:
•
•
•
•
•
•
Low hematocrit
Hyperbilirubinemia
Severe lipemia
Shock and dehydration (may either lower or elevate result)
Hypoxia (may either lower or elevate result)
Drugs: acetaminophen overdose, ascorbic acid, dopamine, fluorescein, mannitol,
and salicylates (may either lower or elevate result)
POCT Glucose Is Higher Than Plasma Glucose
Falsely elevated POCT glucose may occur due to the following:
• Caution should be used in patients on peritoneal dialysis or in those receiving therapeutic immunoglobulin preparations. Many POCT testing kits employ
the chemical glucose dehydrogenase pyrroloquinoline quinone (GDH-PQQ) to
quantify glucose. GDH-PQQ reacts with several non-glucose sugars, including maltose, galactose, and xylose, which are found in peritoneal dialysis
solutions and therapeutic immunoglobulin preparations. Use of these testing
kits in combination with use of products containing non-glucose sugars can
result in a falsely elevated POCT glucose value. The US Food and Drug
Administration (FDA) has released a Public Health Notification that provides a
list of GDH-PQQ glucose test strips; this can be accessed at http://www.fda.gov/
MedicalDevices/Safety/AlertsandNotices/PublicHealthNotifications/. In cases
where it is not possible to avoid test strips that contain GDH-PQQ, errors can
be avoided by use of plasma glucose. This is particularly important for elevated
glucose values or those that are inconsistent with a patient’s history or glucose
pattern.
• Hematocrit level can affect the precision of POCT glucose (see Chapter 4: Lab
Testing).
Falsely low plasma glucose may be due to the following:
• Capture of an accurate serum glucose value depends on the prompt processing of
the sample, as glycolysis continues to occur in collected blood. This is a problem particularly in patients with elevated white cell counts; in these patients, the
glucose can drop quite quickly in the tube. In refrigerated specimens with the
preservative lithium heparin, significant changes in measured glucose should not
occur before 8 h. However, this time is shortened when specimens sit at room
temperature.
• High hematocrit
• Shock and dehydration (may either lower or elevate result)
• Hypoxia (may either lower or elevate result)
14
Frequently Asked Questions
129
• Drugs: acetaminophen overdose, ascorbic acid, dopamine, fluorescein, mannitol,
and salicylates (may either lower or elevate result)
Medication Timing and Administration
Incorrect use of insulin and oral diabetes medications is a common source of medication error in hospitalized patients. In order to prescribe these medications safely, it
is important to become acquainted with the pharmacokinetics of each type of insulin
and appropriate indications for in-hospital use of non-insulin antidiabetic medications (see Chapter 1, 2, and 9). The following are common questions regarding
diabetes medication timing and administration:
What if My Patient’s Diabetes Medication Is Not on My Hospital’s
Formulary?
In general, if a non-insulin medication is not on a hospital’s formulary, it is appropriate to discontinue that agent during the hospital stay and initiate scheduled insulin.
Patients taking insulin at home also often require regimen modifications or substitutions (Table 14.3). This is especially true for patients who use premixed insulin
preparations, such as 70/30 insulin. Because use of premixed insulin requires stable
food intake, patients using these insulins will usually benefit from transition to a
basal/prandial regimen while in the hospital where food intake is often erratic (see
Chapter 2: Subcutaneous Insulin)
Table 14.3 Insulin half-lives and substitutions
Insulin
Approximate half-life, h
Options for substitution
R
)
Aspart (Novolog
R
Lispro (Humalog
)
R
Glulisine (Apidra
)
R
Regular (Novolin
R,
R
Humulin
R)
R
NPH (Novolin
N,
R
Humulin N)
R
)
Detemir (Levemir
R
Glargine (Lantus )
2–4
2–4
2–4
4–6
10–14
Lispro, glulisine
Aspart, glulisine
Aspart, lispro
Aspart, lispro, or glulisine,
with caution
Detemir, with caution
16–20
24
NPH or glargine
Detemir
R
R
and Humulin
What Is the Difference Between Humalog
R
R
Insulins?
and Novolin
or Novolog
R
R
Humulin
and Novolin
are brand names that refer to several different insulin
R
R
NPH
Regular and Humulin
preparations. For example, there are Humulin
R
R
R
insulins, as well as Novolin Regular and Novolin NPH insulins. Humalog
130
M.E. Cox and M.J. Crowley
R
are also brand names. Each corresponds to a single rapid-acting
and Novolog
insulin analog, insulin lispro and insulin aspart, respectively.
It is important to note that many premixed insulin preparations carry the same
brand names as the insulin preparations just listed, along with a number to indicate
R
R
Mix 75/25TM and Novolog
the component percentages. For example, Humalog
R
R
R
TM
Mix 70/30
are not the same as Humalog and Novolog . Humalog Mix
R
), along with 75% lispro protamine, an
75/25TM contains 25% lispro (Humalog
R
R
TM
), along
NPH equivalent. Novolog Mix 70/30 contains 30% aspart (Novolog
with 70% aspart protamine, an NPH equivalent.
What if My Patient Wants to Manage His or Her Diabetes
in the Hospital?
There are some situations where patient self-management of diabetes is appropriate
in the hospital. This often includes patients on continuous subcutaneous insulin infusion (CSII) as described in detail in Chapter 8: Insulin Pumps and Glucose Sensors
in the Hospital. Prerequisite patient characteristics for successful self-management
should include the following:
• Motivated to self-manage
• Stable level of consciousness (usually excludes patients undergoing surgical
procedures until they are stable postoperatively)
• Stable insulin requirement
• History of successfully managing diabetes at home
• Availability of necessary equipment in the hospital
When considering allowing in-hospital self-management, providers should
review hospital policy and follow patient glucose levels and insulin administration
closely.
My Patient Received a Full Dose of an Antidiabetic Medication,
But Now Is Not Eating (or Enteral Feeds Have Been Held).
What Should I Do?
Patient status can fluctuate rapidly during a hospitalization, and nutritional status
may change at any time. Not infrequently, changes in nutritional status occur after a
dose of insulin or non-insulin medication intended to cover a meal or enteral feeding
has already been administered. Risk for hypoglycemia increases significantly in this
situation, and action must be taken to prevent dangerous decreases in blood glucose:
• Blood glucose, patient symptoms, and vital signs should be closely monitored.
• POCT should be performed every 30–60 min for the duration of the medication’s
half-life.
14
Frequently Asked Questions
131
• Patients should be advised to alert the nursing staff if any symptoms of
hypoglycemia develop.
• Hypoglycemia should be treated accordingly per hospital protocol or the algorithm in Fig. 14.1.
• If the procedure cannot be delayed, it is appropriate to administer D10 (our institution utilizes an IV D10 protocol. See Chapter 10: Hypoglycemia, Fig. 10.2).
• Appropriate supervision should be ensured if patients are leaving the unit for a
test or procedure before the risk for hypoglycemia has subsided.
Unexpected interruption of nutrition is the primary reason why non-insulin medications usually should be replaced by insulin at the time of hospitalization. Insulin
has more predictable pharmacokinetics in hospitalized patients and is more easily
adjusted to prevent hypoglycemia in these circumstances.
What if My Patient’s Nutrition Regimen Changes?
Circumstances often necessitate changes in nutrition plans for hospitalized patients.
For example, patients may be changed from oral intake to enteral feeding, or from
continuous enteral feeding to nocturnal feeding with oral intake during the day. This
scenario always calls for a review of insulin dosing (see Chapter 12: Enteral and
Parenteral Nutrition).
• Calculate your patient’s TDD of insulin.
• Redistribute the TDD as appropriate for the new nutrition pattern, using basal and
prandial insulin as indicated.
• It may be reasonable to continue the basal insulin dose, while redistributing
prandial doses to cover the new feeding pattern.
My Patient Missed a Dose of a Diabetes Medication.
Should It Be Given Late?
Insulin
When an insulin dose is missed or delayed, it is important to consider the insulin
type when deciding whether to administer the medication after the scheduled time.
• Basal insulin generally can be given up to a few hours late without grave consequence. Remember to consider the late administration time when analyzing the
patient’s blood glucose control the next day.
• Prandial insulin must be given with food, except in certain situations (see the
section on the patient with severe hyperglycemia). If a patient has taken a meal
without receiving scheduled insulin and more than 90 min have passed, it is best
to defer prandial insulin until the next meal. It may be necessary to give correctional insulin along with the next scheduled prandial dose. If a patient with type
1 diabetes misses a prandial insulin dose, ensure that the patient has received
132
M.E. Cox and M.J. Crowley
appropriate basal insulin; these patients must have exogenous insulin active at all
times in order to avoid DKA.
Non-insulin Antidiabetic Medications
For oral antidiabetic agents that are given without relation to food intake, such
as biguanides or sulfonylureas, a short delay in administration is relatively inconsequential. These medications may be given safely up to a few hours after their
intended administration time. The same is not true for medications that are intended
R
R
),
), nateglinide (Starlix
to be given before meals, such as repaglinide (Prandin
R
and exenatide (Byetta ). These medications should be treated like prandial insulin.
For these medications, missed doses should not be given late, but should be administered at the next scheduled dose time. (See Chapter 9: Non-insulin Antidiabetic
Medications.)
What if My Patient Has Overdosed on a Diabetes Medication?
Patients sometimes present to the hospital following an intentional or unintentional overdose of insulin or other antidiabetic medication. The most common
toxicity associated with this situation is hypoglycemia. (Chapter 9: Table 9.2: Noninsulin Antidiabetic Medications and Toxicities.) When managing a patient who has
overdosed on a diabetes medication, consider the following:
• Treatment of overdose-induced hypoglycemia is generally symptomatic and supportive. However, if hypoglycemia is severe, action should be taken without delay
(see Chapter 10: Hypoglycemia).
• Blood glucose should be monitored every 30–60 min for as long as the medication is active.
• Advise the patient to alert staff if he or she should experience symptoms of
hypoglycemia such as sweating, palpitations, or tremor.
• Nurses should monitor for changes in mental status and vital signs.
Should I Give a Dose of Insulin or Non-insulin Antidiabetic
Medication When . . .?
The Glucose Is in the Lower End of the Normal Range
As stated previously, hospitalized patients with diabetes or sustained hyperglycemia
should receive scheduled insulin. Scheduled insulin regimens are designed to maintain normoglycemia and prevent hyperglycemia, not solely to treat blood glucose
values that are already high. Thus, a normal blood sugar, even if in the lower end of
the normal range, is not a valid reason to hold an insulin dose. If a patient exhibits a
persistent pattern of blood glucose values below the desired range, the entire insulin
regimen should be reviewed and adjusted appropriately. A blood glucose value that
is truly low should result in omission or adjustment of the scheduled insulin dose.
14
Frequently Asked Questions
133
The Patient Is Not Eating in Anticipation of a Test or Procedure
Non-insulin antidiabetic medications should be discontinued when a patient is not
eating. If a patient is on a basal/bolus insulin regimen, basal insulin should be continued while the patient is not eating. If prandial (bolus) coverage is provided by
rapid-acting insulin, it should be held while the patient is not eating. If prandial coverage is provided by short-acting insulin, such as regular insulin, the dose may need
to be cut in half rather than held (see Chapter 10: Hypoglycemia, Table 14.2).
If a patient receiving continuous enteral tube feedings is treated with subcutaneous regular insulin every 6 h, then half of the regular insulin dose should be given,
as the regular insulin provides both basal and prandial coverage under this regimen
(Chapter 12: Enteral and Parenteral Nutrition).
The Insulin Dose Seems Like Too Much or Not Enough
Any time a scheduled insulin dose or insulin regimen doesn’t seem to “make sense,”
it is reasonable to pause and reconsider. Think about the factors that affect a patient’s
insulin requirement, including weight, insulin sensitivity, age, comorbidities, and so
on. A quick assessment of the effectiveness of previous insulin doses can be an
excellent guide for whether an insulin dose is appropriate. If this is not available,
recalculate the patient’s weight-based dose as described in the previous section on
hyperglycemia.
What Is U-500 Insulin?
Nearly all insulin preparations are sold in a standard concentration: 1 mL of solution
contains 100 units of insulin (100 units/mL). This is known as “U-100” insulin.
R
R) that
“U-500” insulin is an alternative preparation of regular insulin (Humulin
contains 500 units/mL rather than the standard 100 units/mL. Many hospitals do not
permit the use of U-500 insulin because of the risk for medication error, and we
recommend consultation with an endocrinologist before considering its use.
Hardware Malfunction
“Hardware” refers to tubes and catheters used for food and medication administration. It is important to be familiar with some of the most common malfunctions that
can affect diabetes management.
What if an IV Insulin Infusion Is Not Lowering
the Blood Glucose as Expected?
An apparently ineffective insulin infusion may result from problems with any part of
the infusion apparatus, from an infiltrated IV catheter to an empty insulin reservoir.
Review the following steps:
134
M.E. Cox and M.J. Crowley
• Check to assure that the IV catheter has not been infiltrated.
• Check tubing for leaks and faulty connections.
• Check the insulin reservoir to assure that it is not empty or connected to the
wrong tubing. It may be necessary to request a new insulin reservoir from the
pharmacy, as occasionally medication bags may be incorrectly labeled or contain
an incorrect substance.
• Check to assure that the pump is plugged in and that the rate is set appropriately.
If all of these items are functioning correctly, continue to follow the insulin
infusion protocol, and discuss the case with an endocrinologist. Extreme insulin
resistance states can sometimes be refractory to even high-dose IV insulin, and this
situation is best managed with endocrinology assistance.
My Patient’s Feeding Tube Is Clogged and Enteral Nutrition
Is Being Interrupted. What Should I Do About the Insulin?
Insulin management in this situation depends on the prescribed insulin regimen:
• If the patient is on a basal/bolus insulin regimen, the basal insulin component can
be continued while the patient is not receiving enteral nutrition. The bolus insulin
should be discontinued.
• If a patient receiving continuous enteral tube feedings is treated with subcutaneous regular insulin every 6 h, half of the regular insulin dose should be given, as
the regular insulin provides both basal and prandial coverage under this regimen.
• Our institution uses an IV D10 infusion protocol when enteral feedings
are discontinued unexpectedly after insulin has been given (see Chapter 10:
Hypoglycemia, Fig. 10.2).
What if My Patient’s Insulin Pump Malfunctions in the Hospital?
The inpatient strategy for this situation is simple: The CSII should be discontinued and the insulin pump removed, and scheduled subcutaneous insulin should be
initiated. The patient or patient’s family should call the help number on the back
of the pump before discharge so that equipment problems can be corrected. This
ensures that CSII can be restarted in a timely manner. To safely convert a patient
from an insulin pump to an appropriate subcutaneous insulin regimen, use the CSII
parameters as a guide (see Chapter 8: Insulin Pumps, for a detailed discussion):
• The total daily basal insulin dose from pump can be given as a single long-acting
insulin dose. It takes several hours for long-acting insulins like glargine and levemir to take effect, so ensure that the patient has adequate insulin coverage in the
meantime.
• The insulin-to-carbohydrate ratio from the insulin pump can be converted to
a short- or rapid-acting prandial insulin injection. The patient should count
carbohydrates as with CSII to determine an appropriate dose.
14
Frequently Asked Questions
135
• The patient’s insulin sensitivity factor (ISF) can be converted to correctional
insulin. The ISF represents the decrease in plasma glucose that occurs with 1 unit
of insulin. For example, an ISF of 50 indicates that 1 unit of insulin will decrease
the glucose by 50 mg/dL (2.7 mmol/L). Correctional insulin for this patient with
an ISF of 50 would be a scale of 1 additional unit for each 50 mg/dL (2.7 mmol/L)
greater than 150 mg/dL (98.3 mmol/L). Alternatively, 5% of the TDD of scheduled insulin can be used as the increment for the correctional insulin scale (see
Chapter 2: Subcutaneous Insulin).
Special Situations
What if My Pregnant Patient with Diabetes Goes into Labor?
The process of labor and delivery presents a challenge to maintenance of blood glucose control. The following points should be kept in mind when caring for patients
with diabetes entering labor:
• If the patient has type 1 diabetes, consider an IV insulin infusion, and call an
endocrinologist for help.
• In patients with type 2 or gestational diabetes, insulin requirements generally decrease during and immediately following labor. Consider an IV insulin
infusion; if using subcutaneous insulin, be ready to decrease doses accordingly.
• Insulin decreases are usually required for peripartum patients with type 1
diabetes, as well. In these patients, balance the potential decreased insulin
requirement with avoidance of DKA; this is most safely and easily accomplished
with an IV insulin infusion.
• For patients with type 2 diabetes that were not on insulin prior to pregnancy, it may be acceptable to hold insulin during labor and delivery, and
follow the glucoses postpartum to determine whether a subcutaneous regimen is
needed.
• For patients on insulin prior to the pregnancy, resume prepregnancy doses
immediately postpartum. Monitoring glucose frequently (7–8 times daily) is
critically important during this period of glucose management and insulin
adjustment.
• Breastfeeding can lower a patient’s insulin requirement, and should prompt close
glucose monitoring.
What if My Patient Has an Insulin Allergy?
Often the insulin “allergy” is a skin reaction to insulin that is injected incorrectly.
Ask the staff nurse to review insulin injection with the patient. If this is not the
case, and the patient truly appears to be allergic to insulin, you must consult
endocrinology for assistance.
136
M.E. Cox and M.J. Crowley
Questions from Outpatients
Diabetes-related phone calls from outpatients occur frequently. The following are
situations that should be dealt with immediately:
What Should I Do When My Hyperglycemic Patient Has Positive
Urine Ketones?
Many patients with type 1 or ketosis-prone type 2 diabetes have urine ketone test
strips at home, and know to test their urine for ketones when hyperglycemic. If a
hyperglycemic patient has ketonuria, this generally warrants a trip to the emergency
room. Selected patients can be managed from home if they are able to eat and drink,
but this should be done under the supervision of an endocrinologist. Patients without access to ketone strips who are experiencing persistent nausea, vomiting, and
abdominal pain in the setting of hyperglycemia should proceed to the emergency
room.
What Should I Do if My Patient Calls with Hypoglycemia?
If at any time a patient exhibits neuroglycopenic symptoms such as altered mental
status, coma, or seizure, immediately call 911. If the hypoglycemic outpatient is
unable to take anything by mouth, a family member should use a glucagon emergency injection kit if available. Otherwise, recommend immediate treatment with
15 g carbohydrates (see “Hypoglycemia” section). After treatment, repeat the glucose measurement in 15–20 min. If the patient remains hypoglycemic, re-treat,
recheck, and repeat until the blood glucose is above 70. If the glucose remains below
70 after three treatments, consider calling 911, especially if the patient’s mental status worsens at any time. If the patient is able to safely resolve mild hypoglycemia at
home, recommend a small snack with mixed carbohydrate, fat, and protein content,
such as cheese with crackers, to maintain normoglycemia. Discuss the medication
regimen with the patient or a family member in order to ascertain the cause for the
hypoglycemic episode, and determine whether insulin or other medications need
to be changed or discontinued. If a cause for the hypoglycemia cannot be determined or if it recurs, the patient must be evaluated immediately (see Chapter 10:
Hypoglycemia).
What Should I Do if My Patient’s Insulin Pump Malfunctions
at Home?
Ideally, patients on CSII should have a supply of backup subcutaneous insulin,
with needles, syringes, and a plan for use in the event of equipment failure. If not,
make immediate pharmacy arrangements for insulin and supplies, and work with
the patient to compose a temporary subcutaneous insulin plan (see “What if my
14
Frequently Asked Questions
137
patient’s insulin pump malfunctions in the hospital?” section above and Chapter 8).
If the patient is hyperglycemic, recommend that he or she check for urine ketones
as above and refer to the emergency room if indicated. The patient also should
call the pump manufacturer (the phone number is on the back of the pump) and
request a replacement immediately. Manufacturers often will send replacements by
overnight mail.
Bibliography
Bode BW, Braithwaite SS, Steed RD, Davidson PC. Intravenous insulin infusion therapy: indications, methods, and transition to subcutaneous insulin therapy. Endocr Pract. 2004;10(suppl 2):
71–80.
Braithwaite S, Buie M, Thompson C, et al. Hospital hypoglycemia: not only treatment but also
prevention. Endocr Pract. 2004;10(suppl 2):89–99.
Clement S, Braithwaite SS, Magee MF, et al. American Diabetes Association Diabetes in Hospitals
Writing Committee. Management of diabetes and hyperglycemia in hospitals. Diabetes Care.
2004;27(2):553–591.
Cochran E, Musso E, Gorden P. The use of U-500 in patients with extreme insulin resistance.
Diabetes Care. 2005;28(5):1240–1244.
Cryer P, Axelrod L, Grossman A, et al. Evaluation and management of adult hypoglycemic disorders: an endocrine society practice guideline. J Clin Endocrinol Metab. 2009;94(3):709–728.
Davidson P, Hebblewhite H, Steed R, Bode B. Analysis of guidelines for basal-bolus insulin
dosing: basal insulin, correction factor, and carbohydrate-to-insulin ratio. Endocr Pract.
2008;14(9):1095–1101.
Fischer KF, Lees JA, Newman JH. Hypoglycemia in hospitalized patients: causes and outcomes. N
Engl J Med. 1986;315(20):1245–1250.
Hirsch I, Braithwaite S, Verderese C. Practical Management of Inpatient Hyperglycemia. Lakeville,
CT: Hilliard Publishing; 2005.
Lien LF, Bethel MA, Feinglos MN. In-hospital management of type 2 diabetes mellitus. Med Clin
N Am. 2004;88(4):1085–1105.
Lien LF, Lane JD. Chapter 29: Pharmacologic factors affecting glycemic control. In: Feinglos
MN, Bethel MA, eds. Contemporary endocrinology: type 2 diabetes mellitus: an evidence-based
approach to practical management. Totowa, NJ: Humana Press; 2008.
Moghissi E, Korytkowski M, DiNardo M, et al. American Association of Clinical Endocrinologists
and American Diabetes Association consensus statement on inpatient glycemic control. Endocr
Pract. 2009;15(4):353–369.
Umpierrez GE, Palacio A, Smiley D. Sliding scale insulin use: myth or insanity? Am J Med.
2007;120(7):563–567.
Subject Index
Note: The letters ‘t’ and ‘f’ followed by the locators represents ‘tables’ and ‘figures’ respectively.
A
AADE7TM self-care behaviors
being active, 44
glucose monitoring, 45
healthy coping, 45
healthy eating, 44
medications, 45
problem solving, 45
reducing risks, 45
Abnormal glucose measurements, 122–129
Acidosis, 22, 51–52, 54–55, 57, 60,
78t, 81t, 82
Active insulin time, 68
ADA, see American Diabetes Association
(ADA)
Adult Treatment Panel (ATP), 37, 83–84
AG, see Anion gap (AG)
All or none approach, 106
α (alpha)-glucosidase inhibitor
R
)
acarbose (precose
inpatient considerations, 85
mechanism and efficacy, 85
safety, 85
American Diabetes Association (ADA), 1–2,
31, 33, 37t, 44, 47, 56, 63, 111, 126
Amylin analog
R
)
pramlintide (symlin
inpatient considerations, 88
mechanism and efficacy, 87
safety, 87–88
Analog insulins, 4, 130
See also Insulin, types, rapid-acting insulin
Anion gap (AG), 22, 36, 54–56, 59–60, 126
Antibiotic therapy, 71
R
), 4t–5t, 13, 22–23, 67, 96,
Aspart (Novolog
104t, 105, 108, 122, 129t, 130
ATP, see Adult Treatment Panel (ATP)
Autoantibody
categories of, 35
markers, 30t, 35
zinc transporter antibody ZnT8, 35
B
Basal-bolus insulin
correctional insulin scale, 8
for patients with type 1/type 2 diabetes, 7
Basal-bolus insulin regimen, 8, 12–13,
105, 110
Basal dose calculation, 14, 24–25, 73
Basal insulin, 6–8, 13–14, 19, 23–25, 67, 95,
118, 122, 127, 131–134
Basal rate, 67, 69, 71, 73
Bedside glucose monitoring, 18
Biguanides
R
/glucophage
metformin (glucophage
R
XR )
inpatient considerations, 82
mechanism and efficacy, 81
safety, 82
Blood glucose monitoring, 20, 46, 48, 69, 94,
115t–116t, 118
Blood Glucose Test, 47, 107f
BMI, see Body mass index (BMI)
Body mass index (BMI), 10
Bolus calculator, 68
Bolus feeding, 115t, 117
Bolus wizard, 69
R
),
Bromocriptine mesylate (Cycloset
80t–81t, 88
C
Calorie counting, 64
Carbohydrate counting, 63–66
Carbohydrate serving, 64
Cardiovascular risk assessment
high-sensitivity C-reactive protein (hsCRP)
increase in total CRP, 38
L.F. Lien et al. (eds.), Glycemic Control in the Hospitalized Patient,
C Springer Science+Business Media, LLC 2011
DOI 10.1007/978-1-60761-006-9,
139
140
Cardiovascular risk assessment (cont.)
traditional assays, 38
lipid profile, 37
CDE, see Certified Diabetes Educators (CDE)
Celiac disease, 65
Centers for Disease Control and Prevention
(CDC), 1
Certified Diabetes Educators (CDE), 47, 102
CGM, see Continuous glucose monitoring
(CGM)
Continuous feeding, 115t
Continuous glucose monitoring (CGM), 73–74
Continuous subcutaneous insulin infusion
(CSII), 64, 67–69, 72–73, 96t, 104t,
106, 119, 122, 130, 134, 136
Correctional insulin scale, 8, 12, 14–15, 73,
105, 107, 135
Correction dose insulin, 122, 126–127
Counterregulatory hormones, 52, 58, 91, 94–95
C-peptide, 2t, 30t, 34–35
CSII, see Continuous subcutaneous insulin
infusion (CSII)
CSII continuation, eligible criterias, 68
Cystic fibrosis, 3, 65, 120
D
Dawn phenomenon, 9, 14
DCCT, see Diabetes Control and Complication
Trial (DCCT)
Dental disease, 65
Detemir insulin, 6
R
Detemir (Levemir
), 4t, 6, 13, 23, 56, 73, 96t,
104t, 105, 108, 122, 129t
10% dextrose (D10), 93t, 97f, 117–118, 124,
131, 134
50% dextrose (D50), 93, 93t, 94f, 98,
121–122, 123f
Diabetes
education, 41–48, 111
in labor, 135
medication, 46, 110, 125–126, 129,
131–132
self-care, 42, 67, 111
Diabetes Control and Complication Trial
(DCCT), 43
Diabetes mellitus, physiology of
exogenous insulin, types
intermediate-acting insulin, 5
long-acting (basal) insulin, 6
rapid-acting insulin, 4
regular and NPH insulin, mixture
of, 5
short-acting insulin, 5
Subject Index
pathophysiology
characteristics, 2t
MODY, 3–4
type 1 diabetes, 3
type 2 diabetes, 3
prevalence
Diabetes Prevention Program (DPP), 43, 87
Diabetic ketoacidosis (DKA), 2t, 3, 7, 14, 17,
18t, 30t, 36, 46, 51–62, 72, 78t– 80t,
126, 132, 135
Dipeptidyl peptidase-4 inhibitors
R
)/saxagliptin
sitagliptin (januvia
R
(onglyza
)
inpatient considerations, 87
mechanism and efficacy, 87
safety, 87
Discharge planning, 45–46, 65
Discharge regimens, 44, 102, 103t–104t
DKA, see Diabetic ketoacidosis
(DKA)
DKA resolution, 56
Dopamine agonist
R
)
bromocriptine mesylate (cycloset
inpatient considerations, 88
mechanism and efficacy, 88
safety, 88
DPP, see Diabetes Prevention Program
(DPP)
E
Education constructs, 44
Electrolytes
bicarbonate, 57–58
phosphate, 58
potassium, 57
sodium, 57
Empathetic listening, 43
Endocrinology consultation
retrospective study, 119
situations considered, 119–120
Enteral nutrition, 8, 113, 117–118,
122, 134
Euglycemic DKA, 55
R
), 79t, 81t, 86, 132
Exenatide (Byetta
F
Fasting plasma glucose (FPG), 2t, 31
FDA, see Food and Drug Administration
(FDA)
Food and Drug Administration (FDA), 32,
88, 128
FPG, see Fasting plasma glucose (FPG)
Fructosamine, 30t, 33–34
Subject Index
G
Gastroparesis, 65, 80t, 86
GDH-PQQ, see Glucose dehydrogenase
pyrroloquinoline quinone
(GDH-PQQ)
GFR, see Glomerular filtration rate (GFR)
Glargine insulin, 6
R
Glargine (Lantus
), 4t, 6, 13, 23, 56, 73, 96t,
104t, 105, 108, 122, 129t, 134
R
Glimeperide (Amaryl
), 78t
R
Glipizide (Glucotrol
), 78t, 81t, 83
Glomerular filtration rate (GFR), 10, 12t
Glucagon, 52, 86–87, 91, 93, 98, 108, 122, 136
Glucagon-like peptide-1 analogs
R
exenatide (byetta
), liraglutide
R
(victoz α )
inpatient considerations, 86
mechanism and efficacy, 86
safety, 86
Glucometer, 109, 121
Gluconeogenesis, 82, 91
Glucose
homeostasis, 1, 3, 35
meters, 29, 32–33, 74, 109–110, 121
monitoring, 9, 11, 18–20, 45–48, 58, 69,
73–74, 93t, 94, 96, 98, 105–106,
115t–116t, 118, 121–122, 124, 135
plasma, 29–30
POCT, 32
sensor, 67–74, 130
testing device, 109
urinary, 32–33
Glucose-based tests
diabetes screening and diagnosis
plasma glucose-based tests, categories
of, 31
plasma glucose
uses of, 29
POCT glucose, 32
urinary glucose, 32–33
Glucose dehydrogenase pyrroloquinoline
quinone (GDH-PQQ), 32, 128
R
Glulisine (Apidra
), 4t, 13, 22–23, 67, 96t,
104t, 105, 108, 122, 129t
R
R
Glyburide (Diaâeta
, Micronase
), 78t,
81t, 83
Glycated proteins
conditions causing inaccurate A1C
readings
anemia, 33–34
pregnancy, 34
recent blood transfusion, 33
splenectomy, 34
141
fructosamine, 34
hemoglobin A1C
A1C value and average glucose,
relationship, 33
insulin, pro-insulin, and C-peptide
final phase of production, 35
markers of, 35
measurement, 35
point-of-care A1C
use in office-based setting, 34
H
Hardware malfunction, 133
Heart Protection Study (HPS), 37–38
Hematocrit level, 32, 128
Hemoglobin A1C , 10, 33–34, 45–46, 55, 125
High-Sensitivity C-Reactive Protein (hsCRP),
30t, 38
HOMA, see Homeostatic model
assessment (HOMA)
Homeostatic model assessment (HOMA), 35
Hospitalized patients with diabetes mellitus
autoantibody markers, 35
cardiovascular risk assessment
high-sensitivity C-Reactive Protein
(hsCRP), 38
lipid profile, 37–38
glucose-based tests
diabetes screening and diagnosis, 31
plasma glucose, 29–30
POCT glucose, 32
urinary glucose, 32–33
glycated proteins
conditions causing inaccurate A1C
readings, 33–34
fructosamine, 34
hemoglobin A1C , 33
point-of-care A1C, 34
insulin, pro-insulin, and C-peptide, 34–35
ketones
serum, 36
urine, 36
urine microalbumin, 36–37
HPS, see Heart Protection Study (HPS)
HsCRP, see High-Sensitivity C-Reactive
Protein (hsCRP)
R
,5
Humulin
Hyperglycemia, 125–126
Hyperglycemia with enteral and parenteral
nutrition/management
description, 113–114
enteral feeding formulas, 114t
in enteral feeding, 117–118
142
Hyperglycemia with enteral (cont.)
insulin regimens for enteral feeding,
115t–116t
total parenteral nutrition, 118
Hyperglycemic emergencies
diabetic ketoacidosis
case presentation, 51
clinical presentation and manifestations,
52–53
evaluation, 54–55
laboratory findings, 55
management, 57–58
pathogenesis, 52
precipitants, 53–54
simplified pathophysiology, 53f
DKA, 58
HHS, 62
hyperosmolar hyperglycemic state
clinical presentation and
manifestations, 59
differential diagnosis, 54
evaluation, 59–60
laboratory findings, 60
management, 60
Hyperosmolar hyperglycemic state (HHS)
clinical presentation and manifestations, 59
differential diagnosis, 59
evaluation, 59–60
HHS/DKA, differentiation, 58
laboratory findings, 60
management
electrolytes, 61–62
insulin, 61
IV fluids, 61
vigilance, 62
precipitants, 59
Hyperosmolar nonketotic hyperglycemia
(HONK/HNKH), 58
See also Hyperosmolar hyperglycemic
state (HHS)
Hypoglycemia, 121–124, 136
prevention of
appropriate glucose monitoring
frequency, 96–98
appropriate glucose targets, 95–96
appropriate insulin/medication
dosages, 95
D10 algorithm, 97f
Periprocedural insulin management, 96t
recognition of
diagnosis, 92
hypoglycemia unawareness, causes, 92t
mechanisms, 91–92
Subject Index
neurogenic/autonomic symptoms, 92
neuroglycopenic symptoms, 92
Whipple’s triad components, 92
risk factors, 98
treatment of
algorithm, 94f
rule of 15s, 92
steps to confirm and treat, 93t
Hypoglycemia unawareness, 9, 11t, 15t, 74,
80t, 92t, 96, 98, 110, 120
Hyponatremia, 55, 57, 60
I
Ineffective insulin infusion, 133–134
Inpatient diabetes education, 41–48
content
AADE7TM self-care behaviors, 44–45
published recommendations, synthesis
of, 45–46
educators
CDE, nurse, and dietician, 47–48
physician and other providers, 47
staff nurse, 47
self-care education
factors interfering, 42–44
need in hospital, 42
strategies, 44
training and support for healthcare
providers, 48
Inpatient diabetes self-management, 91
Insulin
allergy, 135
to carbohydrate ratio, 68–69, 73, 134
drip, 17–26
pump, 67–74, 104t, 106, 130, 134, 136–137
malfunctions, 134–137
See also Insulin pumps and glucose
sensors
reactions, 92
resistance, 1–3, 10, 35, 81–83, 98, 125, 134
teaching, 102
types
intermediate-acting insulin, 5
long-acting (basal) insulin, 6
mixture of regular and nph insulin, 5
rapid-acting insulin, 4, 4t
short-acting insulin, 4t, 5
See also IV insulin infusions
Insulin/non-insulin antidiabetic medication,
77–89, 102, 103t, 122, 125, 129,
132–133
Insulin pumps and glucose sensors
appropriate documentation of settings,
69–70
Subject Index
continuous glucose monitoring, 73–74
CSII continuation, 68
pump site reactions
allergic reactions, 72
site infection, 71–72
transition to subcutaneous insulin,
72–73
removal procedures, 68–69
troubleshooting
hyperglycemia, 70
hypoglycemia, 70–71
Insulin sensitivity factor (ISF), 68–69, 73, 135
ISF, see Insulin sensitivity factor (ISF)
IV insulin infusions
adjusting the rates
implementation of nomogram, 19
multiplication factor, 19
titrated dose according to institution’s
protocol, 20f–21f
indications, 18t
scenarios for use, 17
special scenario, 19–22
starting
bedside glucose monitoring, 18
initial rate calculations, 18t
transitioning to subcutaneous insulin
in NPO patient, 22–26
overlap and subcutaneous insulin
initiation, 26
K
Ketones
serum
measurement of, 36
production of, 36
treatment, 36
urine
measurement, 36
primary advantage of, 36
Ketosis, 54, 136
L
LADA, see Latent autoimmune diabetes of the
adult (LADA)
R
Lantus
, 4t, 6, 13, 23, 56, 73, 96t, 104t, 105,
108, 122, 129t
Latent autoimmune diabetes of the adult
(LADA), 3
LDL, see Low-density lipoprotein (LDL)
R
Levemir
, 4t, 6, 13, 23, 56, 73, 96t, 104t, 105,
108, 122, 129t, 134
Lien-Spratt IV insulin nomogram, 19, 21f
Lipid panel, 30t, 38
Liquid diet, 64
143
R
), 78t, 81t, 86
Liraglutide (Victoza
R
Lispro (Humalog
), 4t, 13, 22–23, 67, 96t,
104t, 105, 108, 122, 129t, 130
Long-acting insulin, 5, 13–14, 23–24, 56, 73,
96t, 104t, 105, 107–108, 115t–116t,
118, 122, 134
Low-density lipoprotein (LDL), 37–38
M
Maturity onset diabetes of the young (MODY),
3–4, 120
Mealtime dose calculation, 73
Medical nutrition therapy (MNT), 63–66, 110
carbohydrate serving, 64
goals, 63
hospital care
discharge planning, 65
nutrition consult, 64
related comorbidities, assessment,
64–65
supervised calorie counting, 64
Medication timing and administration,
129–133
Meglitinides
R
repaglinide (prandin
)/nateglinide
R
(starlix
)
inpatient considerations, 85
mechanism and efficacy, 84
safety, 84–85
R
Metformin (Glucophage
), 78t, 81t
MNT, see Medical nutrition therapy (MNT)
MODY, see Maturity onset diabetes of the
young (MODY)
Multidisciplinary teamwork, 46
N
R
Nateglinide (Starlix
), 79t, 81t, 84, 132
Neutral protamine hagedorn (NPH), 4t, 5,
13–14, 25–26, 96, 103t–104t, 105,
110, 115t, 122, 129t, 130
Nocturnal feeding, 115t–116t, 117, 131
Non-insulin antidiabetic medications in
inpatient setting
α (alpha)-glucosidase inhibitor
R
acarbose (precose
), 85
amylin analog
R
pramlintide (symlin
), 87–88
biguanides
R
metformin (glucophage
/glucophage
R
XR
), 81–82
and cardiovascular health, 88–89
dipeptidyl peptidase-4 inhibitors
R
sitagliptin (januvia
)/saxagliptin
R
(onglyza
), 87
144
Non-insulin antidiabetic medications (cont.)
dopamine agonist
R
bromocriptine mesylate (cycloset
),
88
glucagon-like peptide-1 analogs
R
exenatide (byetta
), liraglutide
R
(victozα ), 86
meglitinides
R
repaglinide (prandin
)/nateglinide
R
(starlix
), 84–85
sulfonylureas
R
glipizide (glucotrol
)/glimepiride
R
(amaryl )/glyburide
R
(diaßeta
/glynase prestabs
R
R
/micronase
), 83–84
thiazolidinediones
R
pioglitazone (actos
)/rosiglitazone
R
(avandia
), 82–83
and toxicities, 81t
R
Novolin
, 4t–5t, 12–13, 20, 23, 96t, 103, 122,
129t
NPH, see Neutral protamine hagedorn (NPH)
NPH insulin, 5, 13–14, 25–26, 96t, 103t, 105,
115t, 129
Nutrition counseling, 44, 64–65
O
Off-pump plan, 69, 73
OGTT, see Oral glucose tolerance test (OGTT)
Oral glucose tolerance test (OGTT), 2t, 31–32
P
Patient-centered approaches, 43
R
Pioglitazone (Actos
), 78t, 82–83
Plasma glucose, 2t, 29–32, 54–55, 59, 68, 77,
84, 86, 93, 121–122, 126–128, 135
Plasma glucose-based tests, categories of
fasting plasma glucose (FPG), 31
oral glucose tolerance test (OGTT), 31–32
random plasma glucose (RPG), 31
Plate method, 65
POCT, see Point-of-care glucose test (POCT)
POCT and plasma glucose readings, 127–129
Point-of-care glucose test (POCT), 29, 32, 96,
121–122, 124–128, 130
Positive urine ketones, 136
R
Pramlintide (Symlin
), 80t–81t, 87–88
Prandial insulin, 5, 7, 12, 23–25, 88, 95,
121–122, 122, 124, 131–132, 134
Prediabetes and diabetes, ADA diagnostic
criteria, 2t
Premixed insulin regimen, 102
Pro-insulin, 30t, 34–35
Pseudohyponatremia, 60
Subject Index
Pump(s)
self-management orders, 69–70
site reactions, 71–73
therapy, 71
R
Random plasma glucose (RPG), 2t, 31
Rapid-acting insulin, 4–5, 13–14, 20, 22–24,
56, 67, 73, 96t, 102t, 104t, 105–106,
108, 115t, 122, 127, 130, 133
See also Insulin
Regular insulin, 5, 13–14, 18, 20, 25–26,
56, 58, 73, 96t, 103t–104t, 105,
115t–116t, 117–118, 122, 133–134
R
Repaglinide (Prandin
), 79t, 81t, 84–85, 132
R
), 79t, 81t
Rosiglitazone (Avandia
RPG, see Random plasma glucose (RPG)
Rule of 15s, 92, 98, 123
Rule of thumb, discharge planning, 65
S
R
), 80t, 81t, 87
Saxagliptin (Onglyza
Self-care education
factors interfering
patient misconceptions, 42
provider misconceptions, 42
specific tactics, 42–43
Severe hyperglycemia, 18t, 35, 37, 58, 60,
126–127, 131
R
), 80t, 81t, 87
Sitagliptin (Januvia
Sliding scale, 8, 43, 105, 126
Somogyi effect, 9
Split-mix insulin regimen, 13, 105
Subcutaneous insulin
basal-bolus insulin
special care situations, 8
blood glucose targets, 9
choosing an insulin regimen
correctional insulin scale, 14–15
intermediate- and short-acting insulin,
13–14
long- and rapid-acting insulin, 13
for patients taking glucocorticoids, 12
for patients with renal impairment, 12
renal impairment modified, 12t
scenarios and examples, 10–12
situations modified for insulin dose, 11t
total daily dose, distribution, 12–13
total daily insulin dose, calculation, 10
glucose monitoring
frequency, 9
outpatient to inpatient care, transition, 8
Sulfonylureas
Subject Index
R
glipizide (glucotrol
)/glimepiride
R
(amaryl
)/glyburide
R
R
(diaßeta
/glynase prestabs
/
R
micronase
)
inpatient considerations, 84
mechanism and efficacy, 83
safety, 84
Supervised calorie counting, 64
T
Target blood glucose range, 67, 106
Teachable moment, 45, 47
Thiazolidinediones
R
pioglitazone (actos
)/rosiglitazone
R
(avandia )
hypoglycemia, risk factors, 84t
inpatient considerations, 83
mechanism and efficacy, 82–83
safety, 83
Total daily dose of insulin, 11t, 114
Total Parenteral Nutrition (TPN), 7–8, 13, 72,
116t, 118, 122
Total plasma osmolality, 55
TPN, see Total parenteral nutrition (TPN)
Transitioning to outpatient care
behavior recommendations, 110
checklist for discharge, 102f
choice of discharge regimen, 102–105
basal-bolus insulin regimen, 105
premixed insulin regimen, 102
split-mix insulin regimen, 105
follow-up appointments, 110–111
145
glucose monitoring post-discharge and
reporting results, 105–106
hypo- and hyperglycemia, 106
sample discharge instructions, 107f
insulin teaching, 102
medication regimen, 101–102
prescriptions, 106–110
sample prescriptions, 109f
recording and reporting, 106
sample discharge instructions, 111
target glucose ranges, 106
Troubleshooting, 70–71
Tube feeding, 97, 113, 115t, 133–134
Type 1 diabetes, 2t, 3, 7–8, 10–11, 14, 19, 30t,
35, 46, 51, 65, 67, 78t–80t, 87, 91,
103t, 110, 117, 119, 125, 131, 135
Type 2 diabetes, 2t, 3, 7, 10–11, 31–32, 35,
37–38, 58, 67, 77, 80t, 88, 103t,
117, 125, 135–136
U
U-500 insulin, 133
Urine microalbumin, 30, 36–37, 45
other possible causes, 37
identification, 37
W
Water deficit, 56
Whipple’s triad components, 92, 98
Z
Zinc transporter antibody ZnT8, 35