ADA 2014 - Standards of Medical Care in Diabetes

S14 Diabetes Care Volume 37, Supplement 1, January 2014
Standards of Medical Care in American Diabetes Association
Diabetesd2014
Diabetes mellitus is a complex, chronic illness requiring continuous medical care
with multifactorial risk reduction strategies beyond glycemic control. Ongoing
patient self-management education and support are critical to preventing acute
complications and reducing the risk of long-term complications. Significant
evidence exists that supports a range of interventions to improve diabetes
outcomes.
The American Diabetes Association’s (ADA’s) Standards of Care are intended to
provide clinicians, patients, researchers, payers, and other interested
individuals with the components of diabetes care, general treatment goals,
and tools to evaluate the quality of care. The Standards of Care
POSITION STATEMENT
recommendations are not intended to preclude clinical judgment and must be

applied in the context of excellent clinical care and with adjustments for
individual preferences, comorbidities, and other patient factors. For
more detailed information about management of diabetes, refer to
references 1,2.
The recommendations include screening, diagnostic, and therapeutic actions that
are known or believed to favorably affect health outcomes of patients with
diabetes. Many of these interventions have also been shown to be cost-effective
(3). A grading system (Table 1) developed by ADA and modeled after existing
methods was used to clarify and codify the evidence that forms the basis for the
recommendations. The letters A, B, C, or E show the evidence level that supports
each recommendation. The Standards of Care conclude with evidence and
recommendations for strategies to improve the process of diabetes care. It must
be emphasized that clinical evidence and expert recommendations alone cannot
improve patients’ lives, but must be effectively translated into clinical
management.
I. CLASSIFICATION AND DIAGNOSIS

A. Classification
Diabetes can be classified into four clinical categories:
c Type 1 diabetes (due to b-cell destruction, usually leading to absolute insulin

deficiency)
c Type 2 diabetes (due to a progressive insulin secretory defect on the background
of insulin resistance)
c Other specific types of diabetes due to other causes, e.g., genetic defects in b-cell
function, genetic defects in insulin action, diseases of the exocrine pancreas (such
as cystic fibrosis), and drug- or chemical-induced (such as in the treatment of HIV/
AIDS or after organ transplantation)
c Gestational diabetes mellitus (GDM) (diabetes diagnosed during pregnancy that
is not clearly overt diabetes)
Some patients cannot be clearly classified as type 1 or type 2 diabetic.

Clinical presentation and disease progression vary considerably in both types of
diabetes. Occasionally, patients diagnosed with type 2 diabetes may present
Originally approved 1988. Most recent review/
with ketoacidosis. Children with type 1 diabetes typically present with the
revision October 2013.
hallmark symptoms of polyuria/polydipsia and occasionally with diabetic DOI: 10.2337/dc14-S014
ketoacidosis (DKA). However, difficulties in diagnosis may occur in children, © 2014 by the American Diabetes Association.
adolescents, and adults, with the true diagnosis becoming more obvious See http://creativecommons.org/licenses/by-
over time. nc-nd/3.0/ for details.
care.diabetesjournals.org Position Statement S15
Table 1—ADA evidence grading system for Clinical Practice Recommendations abnormal hemoglobins should be used.
Level of
An updated list is available at www.ngsp.
evidence Description org/interf.asp. In situations of abnormal
red cell turnover, such as pregnancy,
A Clear evidence from well-conducted, generalizable RCTs that are adequately
powered, including:
recent blood loss or transfusion, or some
c Evidence from a well-conducted multicenter trial anemias, only blood glucose criteria
c Evidence from a meta-analysis that incorporated quality ratings in the analysis should be used to diagnose diabetes.
Compelling nonexperimental evidence, i.e., “all or none” rule developed
by the Center for Evidence-Based Medicine at the University of Oxford Fasting and Two-Hour Plasma
Supportive evidence from well-conducted RCTs that are adequately powered, Glucose
including: In addition to the A1C test, the FPG and
c Evidence from a well-conducted trial at one or more institutions
2-h PG may also be used to diagnose
c Evidence from a meta-analysis that incorporated quality ratings in the analysis
diabetes. The current diagnostic criteria
B Supportive evidence from well-conducted cohort studies
c Evidence from a well-conducted prospective cohort study or registry
for diabetes are summarized in Table 2.
c Evidence from a well-conducted meta-analysis of cohort studies The concordance between the FPG and
Supportive evidence from a well-conducted case-control study 2-h PG tests is ,100%. The concordance
C Supportive evidence from poorly controlled or uncontrolled studies between A1C and either glucose-based
c Evidence from randomized clinical trials with one or more major or three test is also imperfect. National Health
or more minor methodological flaws that could invalidate the results and Nutrition Examination Survey
c Evidence from observational studies with high potential for bias (such as case (NHANES) data indicate that the A1C cut
series with comparison with historical controls)
point of $6.5% identifies one-third
c Evidence from case series or case reports
Conflicting evidence with the weight of evidence supporting the recommendation
fewer cases of undiagnosed diabetes
E Expert consensus or clinical experience
than a fasting glucose cut point of
$126 mg/dL (7.0 mmol/L) (11).
Numerous studies have confirmed that,
B. Diagnosis of Diabetes cost, the limited availability of A1C at these cut points, the 2-h OGTT value
Diabetes is usually diagnosed based on testing in certain regions of the diagnoses more screened people with
plasma glucose criteria, either the developing world, and the incomplete diabetes (12). In reality, a large portion
fasting plasma glucose (FPG) or the 2-h correlation between A1C and average of the diabetic population remains
plasma glucose (2-h PG) value after a glucose in certain individuals. undiagnosed. Of note, the lower
75-g oral glucose tolerance test (OGTT) sensitivity of A1C at the designated cut
Race/Ethnicity point may be offset by the test’s ability
(4). Recently, an International Expert
A1C levels may vary with patients’ race/ to facilitate the diagnosis.
Committee added the A1C (threshold
ethnicity (6,7). Glycation rates may differ
$6.5%) as a third option to diagnose
by race. For example, African Americans
diabetes (5) (Table 2).
may have higher rates of glycation, but this
Table 2—Criteria for the diagnosis of
A1C is controversial. A recent epidemiological
diabetes
The A1C test should be performed study found that, when matched for FPG, A1C $6.5%. The test should be performed
using a method that is certified by the African Americans (with and without in a laboratory using a method that is
National Glycohemoglobin diabetes) had higher A1C than non- NGSP certified and standardized to the
Standardization Program (NGSP) and Hispanic whites, but also had higher levels DCCT assay.*
standardized or traceable to the of fructosamine and glycated albumin and OR
Diabetes Control and Complications lower levels of 1,5 anhydroglucitol, FPG $126 mg/dL (7.0 mmol/L). Fasting
Trial (DCCT) reference assay. Although suggesting that their glycemic burden is defined as no caloric intake for at
point-of-care (POC) A1C assays may be (particularly postprandially) may be least 8 h.*
NGSP-certified, proficiency testing is not higher (8). Epidemiological studies OR
mandated for performing the test, so forming the framework for Two-hour PG $200 mg/dL (11.1 mmol/L)
use of these assays for diagnostic recommending A1C to diagnose diabetes during an OGTT. The test should be
performed as described by the WHO,
purposes may be problematic. have all been in adult populations. It is
using a glucose load containing the
Epidemiological data show a similar unclear if the same A1C cut point should equivalent of 75 g anhydrous glucose
relationship of A1C with the risk of be used to diagnose children or dissolved in water.*
retinopathy as seen with FPG and 2-h adolescents with diabetes (9,10). OR
PG. The A1C has several advantages to Anemias/Hemoglobinopathies In a patient with classic symptoms of
the FPG and OGTT, including greater Interpreting A1C levels in the presence of hyperglycemia or hyperglycemic crisis,
convenience (fasting not required), certain anemias and hemoglobinopathies a random plasma glucose $200 mg/dL
(11.1 mmol/L).
possibly greater preanalytical stability, is particularly problematic. For patients
and less day-to-day perturbations with an abnormal hemoglobin but normal *In the absence of unequivocal
during stress and illness. These red cell turnover, such as sickle cell trait, hyperglycemia, result should be confirmed
by repeat testing.
advantages must be balanced by greater an A1C assay without interference from
S16 Position Statement Diabetes Care Volume 37, Supplement 1, January 2014
As with most diagnostic tests, a test It should be noted that the World Health follow-up should be pursued for those
result should be repeated when feasible Organization (WHO) and a number of considered at very high risk (e.g., those
to rule out laboratory error (e.g., an other diabetes organizations define the with A1Cs .6.0%). Table 3 summarizes
elevated A1C should be repeated when cutoff for IFG at 110 mg/dL (6.1 mmol/L). the categories of prediabetes.
feasible, and not necessarily in 3 months). “Prediabetes” is the term used for
Unless there is a clear clinical diagnosis individuals with IFG and/or IGT, II. TESTING FOR DIABETES IN
(e.g., a patient in a hyperglycemic crisis or indicating the relatively high risk for the ASYMPTOMATIC PATIENTS
classic symptoms of hyperglycemia and a
future development of diabetes. IFG and Recommendations
random plasma glucose $200 mg/dL), it
IGT should not be viewed as clinical c Testing to detect type 2 diabetes and
is preferable that the same test be
entities in their own right but rather risk prediabetes in asymptomatic people
repeated for confirmation, since there
factors for diabetes and cardiovascular should be considered in adults of any
will be a greater likelihood of
disease (CVD). IFG and IGT are age who are overweight or obese
concurrence. For example, if the A1C is
7.0% and a repeat result is 6.8%, the
associated with obesity (especially (BMI $25 kg/m2) and who have one
abdominal or visceral obesity), or more additional risk factors for
diagnosis of diabetes is confirmed. If two
dyslipidemia with high triglycerides diabetes (Table 4). In those without
different tests (such as A1C and FPG) are
and/or low HDL cholesterol, and these risk factors, testing should
both above the diagnostic threshold, this
also confirms the diagnosis. hypertension. begin at age 45 years. B
c If tests are normal, repeat testing
On the other hand, if a patient has As with the glucose measures, several
prospective studies that used A1C to at least at 3-year intervals is
discordant results on two different reasonable. E
tests, then the test result that is above predict the progression to diabetes
c To test for diabetes or prediabetes,
the diagnostic cut point should be demonstrated a strong, continuous
association between A1C and the A1C, FPG, or 2-h 75-g OGTT are
repeated. The diagnosis is made on the appropriate. B
basis of the confirmed test. For subsequent diabetes. In a systematic
c In those identified with prediabetes,
example, if a patient meets the review of 44,203 individuals from 16
identify and, if appropriate, treat
diabetes criterion of the A1C (two cohort studies with a follow-up interval
other CVD risk factors. B
results $6.5%) but not the FPG averaging 5.6 years (range 2.8–12
(,126 mg/dL or 7.0 mmol/L), or vice years), those with an A1C between 5.5
and 6.0% had a substantially increased The same tests are used for both
versa, that person should be
risk of diabetes (5-year incidences from screening and diagnosing diabetes.
considered to have diabetes.
9 to 25%). An A1C range of 6.0–6.5% Diabetes may be identified anywhere
Since there is preanalytic and analytic along the spectrum of clinical scenarios:
had a 5-year risk of developing diabetes
variability of all the tests, it is possible from a seemingly low-risk individual
between 25–50%, and a relative risk
that an abnormal result (i.e., above the who happens to have glucose testing,
(RR) 20 times higher compared with an
diagnostic threshold), when repeated, to a higher-risk individual whom the
A1C of 5.0% (15). In a community-based
will produce a value below the provider tests because of high suspicion
study of African American and non-
diagnostic cut point. This is least likely
Hispanic white adults without diabetes, of diabetes, and finally, to the
for A1C, somewhat more likely for FPG, symptomatic patient. The discussion
and most likely for the 2-h PG. Barring a baseline A1C was a stronger predictor of
herein is primarily framed as testing for
laboratory error, such patients will likely subsequent diabetes and
diabetes in asymptomatic individuals.
have test results near the margins of the cardiovascular events than fasting
The same assays used for testing will
diagnostic threshold. The health care glucose (16). Other analyses suggest
also detect individuals with
professional might opt to follow the that an A1C of 5.7% is associated with
prediabetes.
patient closely and repeat the test in similar diabetes risk to the high-risk
3–6 months. participants in the Diabetes Prevention
Program (DPP) (17).
C. Categories of Increased Risk for Table 3—Categories of increased risk
Diabetes (Prediabetes) Hence, it is reasonable to consider an
for diabetes (prediabetes)*
In 1997 and 2003, the Expert Committee A1C range of 5.7–6.4% as identifying FPG 100 mg/dL (5.6 mmol/L) to 125 mg/dL
on Diagnosis and Classification of individuals with prediabetes. As with (6.9 mmol/L) (IFG)
Diabetes Mellitus (13,14) recognized a those with IFG and IGT, individuals with OR
group of individuals whose glucose an A1C of 5.7–6.4% should be informed 2-h PG in the 75-g OGTT 140 mg/dL
levels did not meet the criteria for of their increased risk for diabetes and (7.8 mmol/L) to 199 mg/dL
diabetes, but were too high to be CVD and counseled about effective (11.0 mmol/L) (IGT)
considered normal. These persons were strategies to lower their risks (see OR
defined as having impaired fasting Section IV). Similar to glucose A1C 5.7–6.4%
glucose (IFG) (FPG levels 100–125 mg/dL measurements, the continuum of risk is *For all three tests, risk is continuous,
[5.6–6.9 mmol/L]), or impaired glucose curvilinear, so as A1C rises, the diabetes extending below the lower limit of the range
tolerance (IGT) (2-h PG OGTT values of risk rises disproportionately (15). and becoming disproportionately greater at
higher ends of the range.
140–199 mg/dL [7.8–11.0 mmol/L]). Aggressive interventions and vigilant
Table 4—Criteria for testing for diabetes in asymptomatic adult individuals in Chinese, and 26 kg/m2 in African
1. Testing should be considered in all adults who are overweight (BMI $25 kg/m2*) and have Americans (21). Disparities in screening
additional risk factors: rates, not explainable by insurance
c physical inactivity status, are highlighted by evidence that
c first-degree relative with diabetes despite much higher prevalence of type 2
c high-risk race/ethnicity (e.g., African American, Latino, Native American, Asian
diabetes, ethnic minorities in an insured
American, Pacific Islander)
c women who delivered a baby weighing .9 lb or were diagnosed with GDM
population are no more likely than non-
c hypertension ($140/90 mmHg or on therapy for hypertension) Hispanic whites to be screened for
c HDL cholesterol level ,35 mg/dL (0.90 mmol/L) and/or a triglyceride level diabetes (22). Because age is a major risk
.250 mg/dL (2.82 mmol/L) factor for diabetes, in those without these
c women with polycystic ovarian syndrome risk factors, testing should begin at age
c A1C $5.7%, IGT, or IFG on previous testing 45 years.
c other clinical conditions associated with insulin resistance (e.g., severe obesity,
acanthosis nigricans) The A1C, FPG, or the 2-h OGTT are
c history of CVD appropriate for testing. It should be
2. In the absence of the above criteria, testing for diabetes should begin at age 45 years. noted that the tests do not necessarily
3. If results are normal, testing should be repeated at least at 3-year intervals, with detect diabetes in the same individuals.
consideration of more frequent testing depending on initial results (e.g., those with The efficacy of interventions for primary
prediabetes should be tested yearly) and risk status. prevention of type 2 diabetes (23–29)
*At-risk BMI may be lower in some ethnic groups. has primarily been demonstrated
among individuals with IGT, not for
individuals with isolated IFG or for
A. Testing for Type 2 Diabetes and with intensive treatment. Incidence of individuals with specific A1C levels.
Risk of Future Diabetes in Adults first CVD event and mortality rates were
Testing Interval
Prediabetes and diabetes meet not significantly different between
The appropriate interval between tests
established criteria for conditions in groups (18). This study would seem to
is not known (30). The rationale for the
which early detection is appropriate. add support for early treatment of
3-year interval is that false negatives will
Both conditions are common, are screen-detected diabetes, as risk factor
be repeated before substantial time
increasing in prevalence, and impose control was excellent even in the
elapses. It is also unlikely that an
significant public health burdens. There routine treatment arm and both groups
individual will develop significant
is often a long presymptomatic phase had lower event rates than predicted.
complications of diabetes within 3 years
before the diagnosis of type 2 diabetes The absence of a control unscreened
of a negative test result. In the modeling
is made. Simple tests to detect arm limits the ability to definitely prove
study, repeat screening every 3 or 5 years
preclinical disease are readily available. that screening impacts outcomes.
was cost-effective (19).
The duration of glycemic burden is a Mathematical modeling studies
strong predictor of adverse outcomes, suggest that screening, independent of Community Screening
and effective interventions exist to risk factors, beginning at age 30 or Testing should be carried out within the
prevent progression of prediabetes to 45 years is highly cost-effective health care setting because of the need
diabetes (see Section IV) and to reduce (,$11,000 per quality-adjusted life- for follow-up and discussion of
risk of complications of diabetes (see year gained) (19). abnormal results. Community screening
Section VI). outside a health care setting is not
BMI Cut Points recommended because people with
Type 2 diabetes is frequently not Testing recommendations for diabetes positive tests may not seek, or have
diagnosed until complications appear. in asymptomatic, undiagnosed adults access to, appropriate follow-up testing
Approximately one-fourth of the U.S. are listed in Table 4. Testing should be and care. Conversely, there may be
population may have undiagnosed considered in adults of any age with BMI failure to ensure appropriate repeat
diabetes. Mass screening of $25 kg/m2 and one or more of the testing for individuals who test
asymptomatic individuals has not known risk factors for diabetes. In negative. Community screening may
effectively identified those with addition to the listed risk factors, certain also be poorly targeted; i.e., it may fail to
prediabetes or diabetes, and rigorous medications, such as glucocorticoids reach the groups most at risk and
clinical trials to provide such proof are and antipsychotics (20), are known to inappropriately test those at low risk or
unlikely to occur. In a large randomized increase the risk of type 2 diabetes. even those already diagnosed.
controlled trial (RCT) in Europe, general There is compelling evidence that lower
practice patients between the ages of BMI cut points suggest diabetes risk in B. Screening for Type 2 Diabetes in
40–69 years were screened for diabetes, some racial and ethnic groups. In a large Children
then randomized by practice to routine multiethnic cohort study, for an Recommendation
diabetes care or intensive treatment of equivalent incidence rate of diabetes c Testing to detect type 2 diabetes and
multiple risk factors. After 5.3 years of conferred by a BMI of 30 kg/m2 in non- prediabetes should be considered in
follow-up, CVD risk factors were Hispanic whites, the BMI cutoff value children and adolescents who are
modestly but significantly improved was 24 kg/m2 in South Asians, 25 kg/m2 overweight and who have two or
more additional risk factors for C. Screening for Type 1 Diabetes Individuals who screen positive will be
diabetes (Table 5). E Recommendation counseled about the risk of
c Inform type 1 diabetic patients of the developing diabetes, diabetes
In the last decade, the incidence of type 2 opportunity to have their relatives symptoms, and the prevention of DKA.
diabetes in adolescents has increased screened for type 1 diabetes risk in the Numerous clinical studies are being
dramatically, especially in minority setting of a clinical research study. E conducted to test various methods of
populations (31). As with adult preventing type 1 diabetes in those
recommendations, children and youth at with evidence of autoimmunity (www
increased risk for the presence or the Type 1 diabetic patients often present
.clinicaltrials.gov).
development of type 2 diabetes should be with acute symptoms of diabetes and
tested within the health care setting (32). markedly elevated blood glucose levels, III. DETECTION AND DIAGNOSIS OF
and some cases are diagnosed with life- GESTATIONAL DIABETES MELLITUS
A1C in Pediatrics threatening ketoacidosis. The incidence Recommendations
Recent studies question the validity of and prevalence of type 1 diabetes is
c Screen for undiagnosed type 2
A1C in the pediatric population, increasing (31,37,38). Several studies
diabetes at the first prenatal visit in
especially in ethnic minorities, and suggest that measuring islet
those with risk factors, using standard
suggest OGTT or FPG as more suitable autoantibodies in relatives of those with
diagnostic criteria. B
diagnostic tests (33). However, many of type 1 diabetes may identify individuals
c Screen for GDM at 24–28 weeks of
these studies do not recognize that who are at risk for developing type 1
gestation in pregnant women not
diabetes diagnostic criteria are based diabetes. Such testing, coupled with
previously known to have diabetes. A
upon long-term health outcomes, and education about diabetes symptoms
c Screen women with GDM for
validations are not currently available in and close follow-up in an observational
persistent diabetes at 6–12 weeks
the pediatric population (34). ADA clinical study, may enable earlier
postpartum, using the OGTT and
acknowledges the limited data identification of type 1 diabetes onset.
nonpregnancy diagnostic criteria. E
supporting A1C for diagnosing diabetes A recent study reported the risk of
c Women with a history of GDM should
in children and adolescents. However, progression to type 1 diabetes from the
have lifelong screening for the
aside from rare instances, such as cystic time of seroconversion to autoantibody
development of diabetes or
fibrosis and hemoglobinopathies, positivity in three pediatric cohorts from
prediabetes at least every 3 years. B
ADA continues to recommend A1C in Finland, Germany, and the U.S. Of the
c Women with a history of GDM found
this cohort (35,36). The modified 585 children who developed more than
to have prediabetes should receive
recommendations of the ADA two autoantibodies, nearly 70%
lifestyle interventions or metformin
consensus statement “Type 2 Diabetes developed type 1 diabetes within 10
to prevent diabetes. A
in Children and Adolescents” are years and 84% within 15 years (39,40).
c Further research is needed to
summarized in Table 5. These findings are highly significant
establish a uniform approach to
because, while the German group was
diagnosing GDM. E
Table 5—Testing for type 2 diabetes recruited from offspring of parents with
in asymptomatic children* type 1 diabetes, the Finnish and For many years, GDM was defined as
Criteria Colorado groups were recruited from any degree of glucose intolerance with
c Overweight (BMI .85th percentile for the general population. Remarkably, the
age and sex, weight for height .85th onset or first recognition during
findings in all three groups were the pregnancy (13), whether or not the
percentile, or weight .120% of ideal
same, suggesting that the same condition persisted after pregnancy,
for height)
sequence of events led to clinical and not excluding the possibility that
Plus any two of the following risk factors:
c Family history of type 2 diabetes in
disease in both “sporadic” and genetic unrecognized glucose intolerance may
first- or second-degree relative cases of type 1 diabetes. There is have antedated or begun concomitantly
c Race/ethnicity (Native American, evidence to suggest that early diagnosis with the pregnancy. This definition
African American, Latino, Asian may limit acute complications (39) and facilitated a uniform strategy for
American, Pacific Islander) extend long-term endogenous insulin
c Signs of insulin resistance or
detection and classification of GDM, but
production (41). While there is its limitations were recognized for many
conditions associated with insulin
resistance (acanthosis nigricans,
currently a lack of accepted screening years. As the ongoing epidemic of
hypertension, dyslipidemia, programs, one should consider referring obesity and diabetes has led to more
polycystic ovarian syndrome, or relatives of those with type 1 diabetes type 2 diabetes in women of
small-for-gestational-age birth weight) for antibody testing for risk assessment childbearing age, the number of
c Maternal history of diabetes or GDM in the setting of a clinical research study
during the child’s gestation
pregnant women with undiagnosed
(http://www2.diabetestrialnet.org). type 2 diabetes has increased (42).
Age of initiation: age 10 years or at onset
of puberty, if puberty occurs at Widespread clinical testing of Because of this, it is reasonable to
a younger age asymptomatic low-risk individuals is not screen women with risk factors for type
Frequency: every 3 years currently recommended. Higher-risk 2 diabetes (Table 4) at their initial
individuals may be screened, but only in prenatal visit, using standard diagnostic
*Persons aged 18 years and younger.
the context of a clinical research setting. criteria (Table 2). Women with diabetes
in the first trimester should receive a Table 6—Screening for and diagnosis hyperglycemia impacts prognosis of
diagnosis of overt, not gestational, of GDM future diabetes for the mother and
diabetes. “One-step” (IADPSG consensus) future obesity, diabetes risk, or other
GDM carries risks for the mother and
Perform a 75-g OGTT, with plasma glucose metabolic consequences for the
measurement fasting and at 1 and 2 h, offspring. The frequency of follow-up
neonate. Not all adverse outcomes are at 24–28 weeks of gestation in women
of equal clinical importance. The and blood glucose monitoring for these
not previously diagnosed with overt
Hyperglycemia and Adverse Pregnancy diabetes.
women has also not yet been
Outcome (HAPO) study (43), a large- The OGTT should be performed in the standardized, but is likely to be less
scale (;25,000 pregnant women) morning after an overnight fast of at intensive than for women diagnosed by
least 8 h. the older criteria.
multinational epidemiological study,
The diagnosis of GDM is made when any of
demonstrated that risk of adverse the following plasma glucose values are National Institutes of Health
maternal, fetal, and neonatal exceeded: Consensus Report
outcomes continuously increased as a c Fasting: $92 mg/dL (5.1 mmol/L) Since this initial IADPSG
function of maternal glycemia at 24–28 c 1 h: $180 mg/dL (10.0 mmol/L)
recommendation, the National
weeks, even within ranges previously c 2 h: $153 mg/dL (8.5 mmol/L)
Institutes of Health (NIH) completed a
considered normal for pregnancy. For “Two-step” (NIH consensus)
consensus development conference
Perform a 50-g GLT (nonfasting), with
most complications, there was no involving a 15-member panel with
plasma glucose measurement at 1 h
threshold for risk. These results have (Step 1), at 24–28 weeks of gestation in representatives from obstetrics/
led to careful reconsideration of the women not previously diagnosed with gynecology, maternal-fetal medicine,
diagnostic criteria for GDM. GDM overt diabetes. pediatrics, diabetes research,
screening can be accomplished with If the plasma glucose level measured 1 h biostatistics, and other related fields
either of two strategies: after the load is $140 mg/dL* (10.0 (48). Reviewing the same available data,
mmol/L), proceed to 100-g OGTT (Step 2).
the NIH consensus panel recommended
The 100-g OGTT should be performed
1. “One-step” 2-h 75-g OGTT or continuation of the “two-step”
when the patient is fasting.
2. “Two-step” approach with a 1-h The diagnosis of GDM is made when the approach of screening with a 1-h 50-g
50-g (nonfasting) screen followed plasma glucose level measured 3 h after glucose load test (GLT) followed by a 3-h
by a 3-h 100-g OGTT for those who the test is $140 mg/dL (7.8 mmol/L). 100-g OGTT for those who screen
screen positive (Table 6) *The American College of Obstetricians and positive, a strategy commonly used in
Gynecologists (ACOG) recommends a lower the U.S. Key factors reported in the NIH
Different diagnostic criteria will identify threshold of 135 mg/dL in high-risk ethnic panel’s decision-making process were
different magnitudes of maternal minorities with higher prevalence of GDM.
the lack of clinical trial interventions
hyperglycemia and maternal/fetal risk. demonstrating the benefits of the “one-
In the 2011 Standards of Care (44), ADA step” strategy and the potential
for the first time recommended that all recommended these diagnostic criteria negative consequences of identifying a
pregnant women not known to have changes in the context of worrisome large new group of women with GDM.
prior diabetes undergo a 75-g OGTT at worldwide increases in obesity and Moreover, screening with a 50-g GLT
24–28 weeks of gestation based on an diabetes rates with the intent of does not require fasting and is
International Association of Diabetes optimizing gestational outcomes for therefore easier to accomplish for
and Pregnancy Study Groups (IADPSG) women and their babies. It is important many women. Treatment of higher
consensus meeting (45). Diagnostic cut to note that 80–90% of women in both threshold maternal hyperglycemia, as
points for the fasting, 1-h, and 2-h PG of the mild GDM studies (whose glucose identified by the two-step approach,
measurements were defined that values overlapped with the thresholds reduces rates of neonatal macrosomia,
conveyed an odds ratio for adverse recommended herein) could be LGA, and shoulder dystocia, without
outcomes of at least 1.75 compared managed with lifestyle therapy alone. increasing small-for-gestational-age
with women with the mean glucose The expected benefits to these births (49).
levels in the HAPO study, a strategy pregnancies and offspring are inferred How do two different groups of experts
anticipated to significantly increase the from intervention trials that focused on arrive at different GDM screening and
prevalence of GDM (from 5–6% to women with lower levels of diagnosis recommendations? Because
;15–20%), primarily because only one hyperglycemia than identified using glycemic dysregulation exists on a
abnormal value, not two, is sufficient to older GDM diagnostic criteria and that continuum, the decision to pick a single
make the diagnosis. ADA recognized found modest benefits including binary threshold for diagnosis requires
that the anticipated increase in the reduced rates of large-for-gestational- balancing the harms and benefits
incidence of GDM diagnosed by these age (LGA) births (46,47). However, while associated with greater versus lesser
criteria would have significant impact on treatment of lower threshold sensitivity. While data from the HAPO
the costs, medical infrastructure hyperglycemia can reduce LGA, it has study demonstrated a correlation
capacity, and potential for increased not been shown to reduce primary between increased fasting glucose
“medicalization” of pregnancies cesarean delivery rates. Data are lacking levels identified through the “one-step”
previously categorized as normal, but on how treatment of lower threshold strategy with increased odds for adverse
pregnancy outcomes, this large patterns. Adjusting for BMI moderately, in the DPP are cost-effective (56), and
observational study was not designed but not completely, attenuated this actual cost data from the DPP and
to determine the benefit of association (52). DPPOS confirm that lifestyle
intervention. Moreover, there are no interventions are highly cost-effective
IV. PREVENTION/DELAY OF TYPE 2
available cost-effective analyses to (57). Group delivery of the DPP
DIABETES
examine the balance of achieved intervention in community settings has
benefits versus the increased costs Recommendations the potential to be significantly less
generated by this strategy. c Patients with IGT A, IFG E, or an A1C expensive while still achieving similar
The conflicting recommendations from 5.7–6.4% E should be referred to an weight loss (58). The Centers for Disease
these two consensus panels underscore effective ongoing support program Control and Prevention (CDC) helps
several key points: targeting weight loss of 7% of body coordinate the National Diabetes
weight and increasing physical Prevention Program, a resource designed
1. There are insufficient data to activity to at least 150 min/week of to bring evidence-based lifestyle change
strongly demonstrate the superiority moderate activity such as walking. programs for preventing type 2 diabetes
c Follow-up counseling appears to be to communities (http://www.cdc.gov/
of one strategy over the other.
2. The decision of which strategy to important for success. B diabetes/prevention/index.htm).
c Based on the cost-effectiveness of
implement must therefore be made Given the clinical trial results and the
based on the relative values placed diabetes prevention, such programs
known risks of progression of
on currently unmeasured factors should be covered by third-party
prediabetes to diabetes, persons with
(e.g., cost-benefit estimation, payers. B
an A1C of 5.7–6.4%, IGT, or IFG should
c Metformin therapy for prevention of
willingness to change practice based be counseled on lifestyle changes with
on correlation studies rather than type 2 diabetes may be considered
goals similar to those of the DPP (7%
clinical intervention trial results, in those with IGT A, IFG E, or an
weight loss and moderate physical
relative role of cost considerations, A1C 5.7–6.4% E, especially for those
activity of at least 150 min/week).
and available infrastructure). with BMI .35 kg/m2, aged
Metformin has a strong evidence base
3. Further research is needed to resolve ,60 years, and women with prior
GDM. A and demonstrated long-term safety as
these uncertainties. pharmacological therapy for diabetes
c At least annual monitoring for the
development of diabetes in those prevention (59). For other drugs, cost,
There remains strong consensus that side effects, and lack of a persistent
establishing a uniform approach to with prediabetes is suggested. E
c Screening for and treatment of effect require consideration (60).
diagnosing GDM will have extensive
benefits for patients, caregivers, and modifiable risk factors for CVD is
Metformin
policymakers. Longer-term outcome suggested. B
Metformin was less effective than
studies are currently underway. lifestyle modification in the DPP and
RCTs have shown that individuals at high
Because some cases of GDM may DPPOS, but may be cost-saving over a
risk for developing type 2 diabetes (IFG,
represent preexisting undiagnosed type 10-year period (57). It was as effective as
IGT, or both) can significantly decrease
2 diabetes, women with a history of lifestyle modification in participants
the rate of diabetes onset with
GDM should be screened for diabetes with a BMI $35 kg/m2, but not
particular interventions (23–29). These
6–12 weeks postpartum, using significantly better than placebo in
include intensive lifestyle modification
nonpregnant OGTT criteria. Because of those over age 60 years (23). In the DPP,
programs that have been shown to be
their antepartum treatment for for women with a history of GDM,
very effective (;58% reduction after
hyperglycemia, A1C for diagnosis of metformin and intensive lifestyle
3 years) and pharmacological agents
modification led to an equivalent 50%
persistent diabetes at the postpartum metformin, a-glucosidase inhibitors,
visit is not recommended (50). Women reduction in diabetes risk (61).
orlistat, and thiazolidinediones, each of
with a history of GDM have a greatly Metformin therefore might reasonably
which has been shown to decrease
increased subsequent diabetes risk (51) be recommended for very-high-risk
incident diabetes to various degrees.
and should be followed up with individuals (e.g., history of GDM, very
Follow-up of all three large studies of
subsequent screening for the obese, and/or those with more severe
lifestyle intervention has shown
development of diabetes or or progressive hyperglycemia).
sustained reduction in the rate of
prediabetes, as outlined in Section II. conversion to type 2 diabetes, with 43% People with prediabetes often have
Lifestyle interventions or metformin reduction at 20 years in the Da Qing other cardiovascular risk factors, such as
should be offered to women with a study (53), 43% reduction at 7 years in obesity, hypertension, and
history of GDM who develop the Finnish Diabetes Prevention Study dyslipidemia, and are at increased risk
prediabetes, as discussed in Section IV. (DPS) (54), and 34% reduction at 10 for CVD events. While treatment goals
In the prospective Nurses’ Health Study years in the U.S. Diabetes Prevention are the same as for other patients
II, subsequent diabetes risk after a Program Outcomes Study (DPPOS) (55). without diabetes, increased vigilance is
history of GDM was significantly lower A cost-effectiveness model suggested warranted to identify and treat these
in women who followed healthy eating that lifestyle interventions as delivered and other risk factors (e.g., smoking).
V. DIABETES CARE enable the health care team to The management plan should be
A. Initial Evaluation optimally manage the patient with formulated as a collaborative
A complete medical evaluation should diabetes. therapeutic alliance among the patient
be performed to classify the diabetes, and family, the physician, and other
detect the presence of diabetes B. Management members of the health care team. A
complications, review previous People with diabetes should receive variety of strategies and techniques
treatment and risk factor control in medical care from a team that may should be used to provide adequate
patients with established diabetes, include physicians, nurse practitioners, education and development of
assist in formulating a management physician’s assistants, nurses, dietitians, problem-solving skills in the numerous
plan, and provide a basis for continuing pharmacists, and mental health aspects of diabetes management.
care. Laboratory tests appropriate to professionals with expertise in diabetes. Treatment goals and plans should be
the evaluation of each patient’s In this collaborative and integrated individualized and take patient
medical condition should be team approach, the individuals with preferences into account. The
completed. A focus on the components diabetes must also assume an active management plan should recognize
of comprehensive care (Table 7) will role in their care. diabetes self-management education
(DSME) and ongoing diabetes support as
integral components of care. In
developing the plan, consideration
Table 7—Components of the comprehensive diabetes evaluation
Medical history should be given to the patient’s age,
c Age and characteristics of onset of diabetes (e.g., DKA, asymptomatic laboratory finding) school or work schedule and conditions,
c Eating patterns, physical activity habits, nutritional status, and weight history; growth and physical activity, eating patterns, social
development in children and adolescents situation and cultural factors, presence
c Diabetes education history of diabetes complications, health
c Review of previous treatment regimens and response to therapy (A1C records)
priorities, and other medical conditions.
c Current treatment of diabetes, including medications, medication adherence and barriers
thereto, meal plan, physical activity patterns, and readiness for behavior change C. Glycemic Control
c Results of glucose monitoring and patient’s use of data
1. Assessment of Glycemic Control
c DKA frequency, severity, and cause
Two primary techniques are available
c Hypoglycemic episodes
c Hypoglycemia awareness
for health providers and patients to
c Any severe hypoglycemia: frequency and cause assess the effectiveness of the
c History of diabetes-related complications management plan on glycemic control:
c Microvascular: retinopathy, nephropathy, neuropathy (sensory, including history of patient self-monitoring of blood glucose
foot lesions; autonomic, including sexual dysfunction and gastroparesis) (SMBG) or interstitial glucose, and A1C.
c Macrovascular: CHD, cerebrovascular disease, and PAD
c Other: psychosocial problems,* dental disease* a. Glucose Monitoring
Physical examination Recommendations
c Height, weight, BMI c Patients on multiple-dose insulin
c Blood pressure determination, including orthostatic measurements when indicated (MDI) or insulin pump therapy should
c Fundoscopic examination* do SMBG prior to meals and snacks,
c Thyroid palpation
occasionally postprandially, at
c Skin examination (for acanthosis nigricans and insulin injection sites)
c Comprehensive foot examination
bedtime, prior to exercise, when they
c Inspection suspect low blood glucose, after
c Palpation of dorsalis pedis and posterior tibial pulses treating low blood glucose until they
c Presence/absence of patellar and Achilles reflexes are normoglycemic, and prior to
c Determination of proprioception, vibration, and monofilament sensation critical tasks such as driving. B
Laboratory evaluation c When prescribed as part of a broader
c A1C, if results not available within past 2–3 months educational context, SMBG results
c If not performed/available within past year
may be helpful to guide treatment
c Fasting lipid profile, including total, LDL, and HDL cholesterol and triglycerides
c Liver function tests
decisions and/or patient self-
c Test for urine albumin excretion with spot urine albumin-to-creatinine ratio management for patients using less
c Serum creatinine and calculated GFR frequent insulin injections or
c TSH in type 1 diabetes, dyslipidemia, or women over age 50 years noninsulin therapies. E
Referrals c When prescribing SMBG, ensure that
c Eye care professional for annual dilated eye exam patients receive ongoing instruction
c Family planning for women of reproductive age and regular evaluation of SMBG
c Registered dietitian for MNT
technique and SMBG results, as well
c DSME
c Dentist for comprehensive periodontal examination
as their ability to use SMBG data to
c Mental health professional, if needed adjust therapy. E
c When used properly, continuous
*See appropriate referrals for these categories.
glucose monitoring (CGM) in
conjunction with intensive insulin complications (63). For patients on of 322 type 1 diabetic patients showed
regimens is a useful tool to lower A1C nonintensive insulin regimens, such as that adults aged $25 years using
in selected adults (aged $25 years) those with type 2 diabetes on basal intensive insulin therapy and CGM
with type 1 diabetes. A insulin, when to prescribe SMBG and the experienced a 0.5% reduction in A1C
c Although the evidence for A1C testing frequency are unclear because (from ;7.6 to 7.1%) compared with usual
lowering is less strong in children, there is insufficient evidence for testing intensive insulin therapy with SMBG (72).
teens, and younger adults, CGM may in this cohort. Sensor use in those ,25 years of age
be helpful in these groups. Success Several randomized trials have called (children, teens, and adults) did not result
correlates with adherence to ongoing into question the clinical utility and cost- in significant A1C lowering, and there was
use of the device. C effectiveness of routine SMBG in no significant difference in hypoglycemia
c CGM may be a supplemental tool to in any group. The greatest predictor of
noninsulin-treated patients (64–66).
SMBG in those with hypoglycemia A1C lowering for all age-groups was
A recent meta-analysis suggested that
unawareness and/or frequent frequency of sensor use, which was lower
SMBG reduced A1C by 0.25% at
hypoglycemic episodes. E in younger age-groups. In a smaller RCT of
6 months (67), but a Cochrane review
129 adults and children with baseline A1C
Major clinical trials of insulin-treated concluded that the overall effect of
,7.0%, outcomes combining A1C and
patients that demonstrated the benefits SMBG in such patients is minimal up to
hypoglycemia favored the group using
of intensive glycemic control on 6 months after initiation and subsides
CGM, suggesting that CGM is also
diabetes complications have included after 12 months (68). A key
beneficial for individuals with type 1
SMBG as part of multifactorial consideration is that SMBG alone does
diabetes who have already achieved
interventions, suggesting that SMBG is a not lower blood glucose level; to be
excellent control (72).
component of effective therapy. SMBG useful, the information must be
allows patients to evaluate their integrated into clinical and self- Overall, meta-analyses suggest that
individual response to therapy and management plans. compared with SMBG, CGM use is
assess whether glycemic targets are associated with A1C lowering by
SMBG accuracy is instrument and user
being achieved. Results of SMBG can be ;0.26% (73). The technology may be
dependent (69), so it is important to
useful in preventing hypoglycemia and particularly useful in those with
evaluate each patient’s monitoring
adjusting medications (particularly hypoglycemia unawareness and/or
technique, both initially and at regular
prandial insulin doses), medical frequent hypoglycemic episodes,
intervals thereafter. Optimal use of
nutrition therapy (MNT), and physical although studies have not shown
SMBG requires proper review and
activity. Evidence also supports a significant reductions in severe
interpretation of the data, both by the
correlation between SMBG frequency hypoglycemia (73). A CGM device
patient and provider. Among patients
and lower A1C (62). equipped with an automatic low glucose
who checked their blood glucose at least
suspend feature was recently approved
SMBG frequency and timing should be once daily, many reported taking no by the U.S. Food and Drug
dictated by the patient’s specific needs action when results were high or low Administration (FDA). The ASPIRE trial
and goals. SMBG is especially important (70). In one study of insulin-naı̈ve of 247 patients showed that sensor-
for patients treated with insulin to patients with suboptimal initial glycemic augmented insulin pump therapy with a
monitor for and prevent asymptomatic control, use of structured SMBG (a low glucose suspend significantly
hypoglycemia and hyperglycemia. Most paper tool to collect and interpret reduced nocturnal hypoglycemia,
patients with type 1 diabetes or on 7-point SMBG profiles over 3 days at without increasing A1C levels for those
intensive insulin regimens (MDI or least quarterly) reduced A1C by 0.3% over 16 years of age (74). These devices
insulin pump therapy) should consider more than an active control group (71). may offer the opportunity to reduce
SMBG prior to meals and snacks, Patients should be taught how to use severe hypoglycemia for those with a
occasionally postprandially, at bedtime, SMBG data to adjust food intake, history of nocturnal hypoglycemia. CGM
prior to exercise, when they suspect low exercise, or pharmacological therapy to forms the underpinning for the “artificial
blood glucose, after treating low blood achieve specific goals. The ongoing need pancreas” or the closed-loop system.
glucose until they are normoglycemic, for and frequency of SMBG should be However, before CGM is widely adopted,
and prior to critical tasks such as driving. reevaluated at each routine visit. data must be reported and analyzed
For many patients, this will require using a standard universal template that
testing 6–8 times daily, although Continuous Glucose Monitoring is predictable and intuitive (75).
individual needs may vary. A database Real-time CGM through the
study of almost 27,000 children and measurement of interstitial glucose b. A1C
adolescents with type 1 diabetes (which correlates well with plasma Recommendations
showed that, after adjustment for glucose) is available. These sensors c Perform the A1C test at least two
multiple confounders, increased daily require calibration with SMBG, and the times a year in patients who are
frequency of SMBG was significantly latter are still required for making acute meeting treatment goals (and who
associated with lower A1C (20.2% per treatment decisions. CGM devices have have stable glycemic control). E
additional test per day, leveling off at alarms for hypo- and hyperglycemic c Perform the A1C test quarterly in
five tests per day) and with fewer acute excursions. A 26-week randomized trial patients whose therapy has changed
or who are not meeting glycemic Table 8—Correlation of A1C with to different interpretations of the clinical
goals. E average glucose meaning of given levels of A1C in those
c Use of POC testing for A1C provides Mean plasma glucose populations.
the opportunity for more timely For patients in whom A1C/eAG and
A1C (%) mg/dL mmol/L
treatment changes. E measured blood glucose appear
6 126 7.0
discrepant, clinicians should consider the
A1C reflects average glycemia over 7 154 8.6
possibilities of hemoglobinopathy or
several months (69) and has strong 8 183 10.2
altered red cell turnover, and the options of
predictive value for diabetes 9 212 11.8
more frequent and/or different timing
complications (76,77). Thus, A1C testing 10 240 13.4
of SMBG or use of CGM. Other measures
should be performed routinely in all 11 269 14.9
of chronic glycemia such as fructosamine
patients with diabetes: at initial 12 298 16.5
are available, but their linkage to
assessment and as part of continuing These estimates are based on ADAG data of average glucose and their prognostic
care. Measurement approximately ;2,700 glucose measurements over 3 significance are not as clear as for A1C.
every 3 months determines whether a months per A1C measurement in 507 adults
with type 1, type 2, and no diabetes. The 2. Glycemic Goals in Adults
patient’s glycemic targets have been
correlation between A1C and average Recommendations
reached and maintained. The frequency glucose was 0.92 (ref. 78). A calculator for
of A1C testing should be dependent on converting A1C results into eAG, in either c Lowering A1C to below or around 7%
the clinical situation, the treatment mg/dL or mmol/L, is available at http:// has been shown to reduce
professional.diabetes.org/eAG. microvascular complications of
regimen used, and the clinician’s
judgment. Some patients with stable diabetes and, if implemented soon
glycemia well within target may do well after the diagnosis of diabetes, is
with testing only twice per year. Chemistry have determined that the associated with long-term reduction
Unstable or highly intensively managed correlation (r 5 0.92) is strong enough to in macrovascular disease.
patients (e.g., pregnant type 1 diabetic justify reporting both the A1C result and Therefore, a reasonable A1C goal for
women) may require testing more an estimated average glucose (eAG) many nonpregnant adults is ,7%. B
frequently than every 3 months. result when a clinician orders the A1C c Providers might reasonably suggest
test. The table in pre-2009 versions of the more stringent A1C goals (such as
A1C Limitations Standards of Medical Care in Diabetes ,6.5%) for selected individual
As mentioned above, the A1C test is describing the correlation between A1C patients, if this can be achieved
subject to certain limitations. and mean glucose was derived from without significant hypoglycemia or
Conditions that affect erythrocyte relatively sparse data (one 7-point profile other adverse effects of treatment.
turnover (hemolysis, blood loss) and over 1 day per A1C reading) in the Appropriate patients might include
hemoglobin variants must be primarily non-Hispanic white type 1 those with short duration of diabetes,
considered, particularly when the A1C diabetic participants in the DCCT (79). long life expectancy, and no
result does not correlate with the Clinicians should note that the numbers significant CVD. C
patient’s clinical situation (69). A1C also in the table are now different because c Less stringent A1C goals (such as ,8%)
does not provide a measure of glycemic they are based on ;2,800 readings per may be appropriate for patients with a
variability or hypoglycemia. For patients A1C in the ADAG trial. history of severe hypoglycemia, limited
prone to glycemic variability, especially life expectancy, advanced
In the ADAG study, there were no
type 1 diabetic patients or type 2 microvascular or macrovascular
significant differences among racial and
diabetic patients with severe insulin complications, and extensive comorbid
ethnic groups in the regression lines
deficiency, glycemic control is best conditions and in those with long-
between A1C and mean glucose,
evaluated by the combination of results standing diabetes in whom the general
although there was a trend toward a
from self-monitoring and the A1C. The goal is difficult to attain despite DSME,
difference between the African/African
A1C may also confirm the accuracy of appropriate glucose monitoring, and
American and non-Hispanic white
the patient’s meter (or the patient’s effective doses of multiple glucose-
cohorts. A small study comparing A1C to
reported SMBG results) and the lowering agents including insulin. B
CGM data in type 1 diabetic children
adequacy of the SMBG testing schedule.
found a highly statistically significant Diabetes Control and Complications
A1C and Plasma Glucose correlation between A1C and mean blood Trial/Epidemiology of Diabetes
Table 8 contains the correlation glucose, although the correlation (r 5 Interventions and Complications
between A1C levels and mean plasma 0.7) was significantly lower than in the Hyperglycemia defines diabetes, and
glucose levels based on data from the ADAG trial (80). Whether there are glycemic control is fundamental to
international A1C-Derived Average significant differences in how A1C relates diabetes management. The DCCT study
Glucose (ADAG) trial using frequent to average glucose in children or in (76), a prospective RCT of intensive
SMBG and CGM in 507 adults (83% non- African American patients is an area for versus standard glycemic control in
Hispanic whites) with type 1, type 2, further study (33,81). For the time being, patients with relatively recently
and no diabetes (78). The ADA and the the question has not led to different diagnosed type 1 diabetes showed
American Association for Clinical recommendations about testing A1C or definitively that improved glycemic
control is associated with significantly when setting glycemic targets. either known CVD or multiple
decreased rates of microvascular However, based on physician judgment cardiovascular risk factors. Details of
(retinopathy and nephropathy) and and patient preferences, select patients, these studies are reviewed extensively in
neuropathic complications. Follow-up especially those with little comorbidity an ADA position statement (94).
of the DCCT cohorts in the Epidemiology and long life expectancy, may benefit
ACCORD
of Diabetes Interventions and from adopting more intensive glycemic
The ACCORD study participants had
Complications (EDIC) study (82,83) targets (e.g., A1C target ,6.5%) as long
either known CVD or two or more major
demonstrated persistence of these as significant hypoglycemia does not
cardiovascular risk factors and were
microvascular benefits in previously become a barrier.
randomized to intensive glycemic
intensively treated subjects, even Cardiovascular Disease Outcomes control (goal A1C ,6%) or standard
though their glycemic control CVD is a more common cause of death glycemic control (goal A1C 7–8%). The
approximated that of previous standard than microvascular complications in glycemic control comparison was halted
arm subjects during follow-up. populations with diabetes. However, it early due to an increased mortality rate
Kumamoto and UK Prospective
is less clearly impacted by hyperglycemia in the intensive compared with the
Diabetes Study
levels or intensity of glycemic control. In standard arm (1.41 vs. 1.14%/year;
The Kumamoto (84) and UK Prospective the DCCT, there was a trend toward lower hazard ratio [HR] 1.22 [95% CI 1.01–
Diabetes Study (UKPDS) (85,86) risk of CVD events with intensive control. 1.46]); with a similar increase in
confirmed that intensive glycemic In the 9-year post-DCCT follow-up of the cardiovascular deaths. Initial analysis of
control was associated with significantly EDIC cohort, participants previously the ACCORD data (evaluating variables
decreased rates of microvascular and randomized to the intensive arm had a including weight gain, use of any specific
neuropathic complications in type 2 significant 57% reduction in the risk of drug or drug combination, and
diabetic patients. Long-term follow-up nonfatal myocardial infarction (MI), hypoglycemia) did not identify a clear
of the UKPDS cohorts showed enduring stroke, or CVD death compared with those explanation for the excess mortality in
effects of early glycemic control on most previously in the standard arm (92). The the intensive arm (91). A subsequent
microvascular complications (87). Three benefit of intensive glycemic control in this analysis showed no increase in mortality
landmark trials (ACCORD, ADVANCE, type 1 diabetic cohort has recently been in the intensive arm participants who
and VADT, described in further detail shown to persist for several decades (93). achieved A1C levels below 7%, nor in
below) were designed to examine the In type 2 diabetes, there is evidence that those who lowered their A1C quickly
impact of intensive A1C control on CVD more intensive treatment of glycemia in after trial enrollment. There was no A1C
outcomes and showed that lower A1C newly diagnosed patients may reduce long- level at which intensive versus standard
levels were associated with reduced term CVD rates. During the UKPDS trial, arm participants had significantly
onset or progression of microvascular there was a 16% reduction in CVD events lower mortality. The highest risk for
complications (88–90). (combined fatal or nonfatal MI and sudden mortality was observed in intensive arm
death) in the intensive glycemic control participants with the highest A1C levels
Epidemiological analyses of the DCCT
arm that did not reach statistical (95). Severe hypoglycemia was
and UKPDS (76,77) demonstrate a
curvilinear relationship between significance (P 5 0.052), and there was no significantly more likely in participants
suggestion of benefit on other CVD randomized to the intensive glycemic
A1C and microvascular complications.
outcomes (e.g., stroke). However, after control arm. Unlike the DCCT, where
Such analyses suggest that, on a
10 years of follow-up, those originally lower achieved A1C levels were related
population level, the greatest number of
randomized to intensive glycemic control to significantly increased rates of severe
complications will be averted by taking
had significant long-term reductions in MI hypoglycemia, in ACCORD every 1%
patients from very poor control to fair/
(15% with sulfonylurea or insulin as initial decline in A1C from baseline to 4
good control. These analyses also
pharmacotherapy, 33% with metformin as months into the trial was associated
suggest that further lowering of A1C
initial pharmacotherapy) and in all-cause with a significant decrease in the rate of
from 7 to 6% is associated with further
mortality (13% and 27%, respectively) (87). severe hypoglycemia in both arms (95).
reduction in the risk of microvascular
complications, though the absolute risk The Action to Control Cardiovascular Risk ADVANCE
reductions become much smaller. Given in Diabetes (ACCORD), Action in Diabetes The primary outcome of ADVANCE was a
the substantially increased risk of and Vascular Disease: Preterax and combination of microvascular events
hypoglycemia in type 1 diabetes trials, Diamicron Modified Release Controlled (nephropathy and retinopathy) and
and now seen in recent type 2 diabetes Evaluation (ADVANCE), and the Veterans major adverse cardiovascular events
trials, the risks of lower glycemic targets Affairs Diabetes Trial (VADT) studies (MI, stroke, and cardiovascular death).
may outweigh the potential benefits on suggested no significant reduction in CVD Intensive glycemic control (A1C ,6.5%,
microvascular complications on a outcomes with intensive glycemic control vs. treatment to local standards)
population level. The concerning in participants who had more advanced significantly reduced the primary end
mortality findings in the ACCORD trial type 2 diabetes than UKPDS participants. point, primarily due to a significant
(91) and the relatively much greater All three trials were conducted in reduction in the microvascular
effort required to achieve near- participants with more long-standing outcome, specifically development of
euglycemia should also be considered diabetes (mean duration 8–11 years) and albuminuria (.300 mg/24 h), with
no significant reduction in the advanced atherosclerosis, and advanced associated with increased cardiovascular
macrovascular outcome. There was no age/frailty may benefit from less risk independent of FPG in some
difference in overall or cardiovascular aggressive targets. Providers should be epidemiological studies. In diabetic
mortality between the two arms (89). vigilant in preventing severe subjects, surrogate measures of vascular
hypoglycemia in patients with advanced pathology, such as endothelial
VADT dysfunction, are negatively affected by
disease and should not aggressively
The primary outcome of the VADT was a postprandial hyperglycemia (101). It is
attempt to achieve near-normal A1C
composite of CVD events. The trial clear that postprandial hyperglycemia,
levels in patients in whom such targets
randomized type 2 diabetic participants like preprandial hyperglycemia,
cannot be safely and reasonably
who were uncontrolled on insulin or on
achieved. Severe or frequent contributes to elevated A1C levels, with
maximal dose oral agents (median entry
hypoglycemia is an absolute indication its relative contribution being greater at
A1C 9.4%) to a strategy of intensive
for the modification of treatment A1C levels that are closer to 7%. However,
glycemic control (goal A1C ,6.0%) or
regimens, including setting higher outcome studies have clearly shown
standard glycemic control, with a
glycemic goals. Many factors, including A1C to be the primary predictor of
planned A1C separation of at least 1.5%.
patient preferences, should be taken into complications, and landmark glycemic
The cumulative primary outcome was
account when developing a patient’s control trials such as the DCCT and UKPDS
nonsignificantly lower in the intensive
individualized goals (99) (Fig. 1). relied overwhelmingly on preprandial
arm (88). An ancillary study of the VADT
SMBG. Additionally, an RCT in patients
demonstrated that intensive glycemic
Glycemic Goals with known CVD found no CVD benefit of
control significantly reduced the
Recommended glycemic goals for many insulin regimens targeting postprandial
primary CVD outcome in individuals
nonpregnant adults are shown in glucose compared with those targeting
with less atherosclerosis at baseline but
Table 9. The recommendations are preprandial glucose (102). A reasonable
not in persons with more extensive
based on those for A1C values, with recommendation for postprandial testing
baseline atherosclerosis (96). A post hoc
blood glucose levels that appear to and targets is that for individuals who
analysis showed that mortality in the
correlate with achievement of an A1C of have premeal glucose values within
intensive versus standard glycemic
,7%. The issue of pre- versus target but have A1C values above
control arm was related to duration of
postprandial SMBG targets is complex target, monitoring postprandial plasma
diabetes at study enrollment. Those
(100). Elevated postchallenge (2-h glucose (PPG) 1–2 h after the start of the
with diabetes duration less than 15
OGTT) glucose values have been meal and treatment aimed at reducing
years had a mortality benefit in the
intensive arm, while those with duration
of 20 years or more had higher mortality
in the intensive arm (97).
The evidence for a cardiovascular
benefit of intensive glycemic control
primarily rests on long-term follow-up
of study cohorts treated early in the
course of type 1 and type 2 diabetes,
and a subset analyses of ACCORD,
ADVANCE, and VADT. A group-level
meta-analysis of the latter three trials
suggests that glucose lowering has a
modest (9%) but statistically significant
reduction in major CVD outcomes,
primarily nonfatal MI, with no
significant effect on mortality. However,
heterogeneity of the mortality effects
across studies was noted. A prespecified
subgroup analysis suggested that major
CVD outcome reduction occurred in
patients without known CVD at baseline
(HR 0.84 [95% CI 0.74–0.94]) (98).
Conversely, the mortality findings in
ACCORD and subgroup analyses of the Figure 1—Approach to management of hyperglycemia. Depiction of the elements of decision
VADT suggest that the potential risks of making used to determine appropriate efforts to achieve glycemic targets. Characteristics/
intensive glycemic control may predicaments toward the left justify more stringent efforts to lower A1C, whereas those toward
the right are compatible with less stringent efforts. Where possible, such decisions should be
outweigh its benefits in some patients. made in conjunction with the patient, reflecting his or her preferences, needs, and values. This
Those with long duration of diabetes, “scale” is not designed to be applied rigidly but to be used as a broad construct to help guide
known history of severe hypoglycemia, clinical decisions. Adapted with permission from Ismail-Beigi et al. (99).
Table 9—Summary of glycemic recommendations for many nonpregnant 1. Use MDI injections (3–4 injections
adults with diabetes per day of basal and prandial insulin)
A1C ,7.0%* or CSII therapy.
Preprandial capillary plasma glucose 70–130 mg/dL* (3.9–7.2 mmol/L) 2. Match prandial insulin to
Peak postprandial capillary plasma glucose† ,180 mg/dL* (,10.0 mmol/L) carbohydrate intake, premeal
c *Goals should be individualized based on: blood glucose, and anticipated
c duration of diabetes activity.
c age/life expectancy 3. For most patients (especially
c comorbid conditions
with hypoglycemia), use insulin
c known CVD or advanced microvascular
complications
analogs.
c hypoglycemia unawareness 4. For patients with frequent
c individual patient considerations nocturnal hypoglycemia and/or
c More or less stringent glycemic goals hypoglycemia unawareness, use of
may be appropriate for individual patients sensor-augmented low glucose
c Postprandial glucose may be targeted if A1C
suspend threshold pump may be
goals are not met despite reaching
considered.
preprandial glucose goals
†Postprandial glucose measurements should be made 1–2 h after the beginning of the meal,
generally peak levels in patients with diabetes. There are excellent reviews to guide
the initiation and management of
insulin therapy to achieve desired
PPG values to ,180 mg/dL may help (three to four injections per day of basal glycemic goals (105,107,108). Although
lower A1C. and prandial insulin) or continuous most studies of MDI versus pump
subcutaneous insulin infusion (CSII). A therapy have been small and of short
Glycemic goals for children are provided
c Most people with type 1 diabetes duration, a systematic review and
in Section VIII.A.1.a.
should be educated in how to match meta-analysis concluded that there
Glycemic Goals in Pregnant Women prandial insulin dose to carbohydrate were no systematic differences in A1C
The goals for glycemic control for intake, premeal blood glucose, and or severe hypoglycemia rates in
women with GDM are based on anticipated activity. E children and adults between the two
recommendations from the Fifth c Most people with type 1 diabetes forms of intensive insulin therapy (73).
International Workshop-Conference on should use insulin analogs to reduce Recently, a large randomized trial in
Gestational Diabetes Mellitus (103) and hypoglycemia risk. A type 1 diabetic patients with nocturnal
have the following targets for maternal hypoglycemia reported that sensor-
capillary glucose concentrations: Screening
augmented insulin pump therapy with
c Consider screening those with type 1
the threshold-suspend feature reduced
c Preprandial: #95 mg/dL (5.3 diabetes for other autoimmune
nocturnal hypoglycemia, without
mmol/L), and either: diseases (thyroid, vitamin B12
increasing glycated hemoglobin values
c 1-h postmeal: #140 mg/dL deficiency, celiac) as appropriate. B
(74). Overall, intensive management
(7.8 mmol/L) or The DCCT clearly showed that intensive through pump therapy/CGM and active
c 2-h postmeal: #120 mg/dL insulin therapy (three or more injections patient/family participation should be
(6.7 mmol/L) per day of insulin, or CSII (or insulin strongly encouraged (109–111). For
pump therapy) was a key part of selected individuals who have
For women with preexisting type 1 or
improved glycemia and better mastered carbohydrate counting,
type 2 diabetes who become pregnant,
outcomes (76,92). The study was carried education on the impact of protein and
the following are recommended as
out with short- and intermediate-acting fat on glycemic excursions can be
optimal glycemic goals, if they can be
human insulins. Despite better incorporated into diabetes
achieved without excessive
microvascular outcomes, intensive management (112).
hypoglycemia (104):
insulin therapy was associated with a
c Premeal, bedtime, and overnight high rate of severe hypoglycemia (62
Screening
glucose 60–99 mg/dL (3.3–5.4 mmol/L) episodes per 100 patient-years of Because of the increased frequency of
c Peak postprandial glucose 100–129 therapy). Since the DCCT, a number of other autoimmune diseases in type 1
mg/dL (5.4–7.1 mmol/L) rapid-acting and long-acting insulin diabetes, screening for thyroid
c A1C ,6.0% analogs have been developed. These dysfunction, vitamin B12 deficiency, and
analogs are associated with less celiac disease should be considered
D. Pharmacological and Overall hypoglycemia with equal A1C lowering based on signs and symptoms. Periodic
Approaches to Treatment in type 1 diabetes (105,106). screening in asymptomatic individuals
1. Insulin Therapy for Type 1 Diabetes Recommended therapy for type 1 has been recommended, but the
c Most people with type 1 diabetes diabetes consists of the following effectiveness and optimal frequency are
should be treated with MDI injections components: unclear.
Figure 2—Antihyperglycemic therapy in type 2 diabetes: general recommendations. DPP-4-i, DPP-4 inhibitor; Fx’s, bone fractures; GI, gastrointestinal; GLP-1-
RA, GLP-1 receptor agonist; HF, heart failure; SU, sulfonylurea; TZD, thiazolidinedione. For further details, see ref. 113. Adapted with permission.
2. Pharmacological Therapy for Considerations include efficacy, cost, on body weight, and hypoglycemia risk.
Hyperglycemia in Type 2 Diabetes potential side effects, effects on The position statement reaffirms
Recommendations weight, comorbidities, hypoglycemia metformin as the preferred initial agent,
c Metformin, if not contraindicated risk, and patient preferences. E barring contraindication or intolerance,
and if tolerated, is the preferred c Due to the progressive nature of type either in addition to lifestyle counseling
initial pharmacological agent for type 2 diabetes, insulin therapy is and support for weight loss and exercise,
2 diabetes. A eventually indicated for many or when lifestyle efforts alone have not
c In newly diagnosed type 2 diabetic patients with type 2 diabetes. B achieved or maintained glycemic goals.
patients with markedly symptomatic Metformin has a long-standing evidence
and/or elevated blood glucose levels The ADA and the European Association for base for efficacy and safety, is inexpensive,
or A1C, consider insulin therapy, with the Study of Diabetes (EASD) formed a and may reduce risk of cardiovascular
or without additional agents, from joint task force to evaluate the data and events (87). When metformin fails to
the outset. E develop recommendations for the use of achieve or maintain glycemic goals,
c If noninsulin monotherapy at antihyperglycemic agents in type 2 another agent should be added. Although
maximum tolerated dose does not diabetic patients (113). This 2012 position there are numerous trials comparing
achieve or maintain the A1C target statement is less prescriptive than prior dual therapy to metformin alone, few
over 3 months, add a second oral algorithms and discusses advantages and directly compare drugs as add-on
agent, a glucagon-like peptide 1 (GLP- disadvantages of the available medication therapy. Comparative effectiveness
1) receptor agonist, or insulin. A classes and considerations for their use. A meta-analyses (114) suggest that
c A patient-centered approach should patient-centered approach is stressed, overall, each new class of noninsulin
be used to guide choice of including patient preferences, cost and agents added to initial therapy lowers
pharmacological agents. potential side effects of each class, effects A1C around 0.9–1.1%.
Many patients with type 2 diabetes carbohydrate, protein, and fat for all c In people with type 2 diabetes, a
eventually require and benefit from people with diabetes B; therefore, Mediterranean-style, MUFA-rich
insulin therapy. The progressive nature macronutrient distribution should be eating pattern may benefit glycemic
of type 2 diabetes and its therapies based on individualized assessment control and CVD risk factors and
should be regularly and objectively of current eating patterns, can therefore be recommended as
explained to patients. Providers should preferences, and metabolic goals. E an effective alternative to a lower-
avoid using insulin as a threat or c A variety of eating patterns fat, higher-carbohydrate eating
describing it as a failure or punishment. (combinations of different foods or pattern. B
Equipping patients with an algorithm for food groups) are acceptable for the c As recommended for the general
self-titration of insulin doses based on management of diabetes. Personal public, an increase in foods
SMBG results improves glycemic control preference (e.g., tradition, culture, containing long-chain n-3 fatty acids
in type 2 diabetic patients initiating religion, health beliefs and goals, (EPA and DHA) (from fatty fish)
insulin (115). Refer to the ADA-EASD economics) and metabolic goals and n-3 linolenic acid (ALA) is
position statement for more details on should be considered when recommended for individuals with
pharmacotherapy for hyperglycemia in recommending one eating pattern diabetes because of their beneficial
type 2 diabetes (113) (Fig. 2). over another. E effects on lipoproteins, prevention of
heart disease, and associations with
Carbohydrate Amount and Quality
E. Medical Nutrition Therapy positive health outcomes in
General Recommendations c Monitoring carbohydrate intake, observational studies. B
whether by carbohydrate counting c The amount of dietary saturated fat,
c Nutrition therapy is recommended
or experience-based estimation, cholesterol, and trans fat
for all people with type 1 and type 2
remains a key strategy in achieving recommended for people with
diabetes as an effective component
of the overall treatment plan. A glycemic control. B diabetes is the same as that
c For good health, carbohydrate intake
c Individuals who have prediabetes or recommended for the general
diabetes should receive from vegetables, fruits, whole grains, population. C
individualized MNT as needed to legumes, and dairy products should
achieve treatment goals, preferably be advised over intake from other Supplements for Diabetes Management
provided by a registered dietitian carbohydrate sources, especially c There is no clear evidence of benefit
familiar with the components of those that contain added fats, sugars, from vitamin or mineral
diabetes MNT. A or sodium. B supplementation in people with
c Substituting low-glycemic load foods
c Because diabetes nutrition therapy diabetes who do not have underlying
can result in cost savings B and for higher-glycemic load foods may deficiencies. C
improved outcomes such as modestly improve glycemic control. C c Routine supplementation with
c People with diabetes should consume
reduction in A1C A, nutrition therapy antioxidants, such as vitamins E and C
should be adequately reimbursed by at least the amount of fiber and whole and carotene, is not advised because of
insurance and other payers. E grains recommended for the general lack of evidence of efficacy and concern
public. C related to long-term safety. A
Energy Balance, Overweight, and Obesity c While substituting sucrose- c Evidence does not support
c For overweight or obese adults with containing foods for isocaloric recommending n-3 (EPA and DHA)
type 2 diabetes or at risk for diabetes, amounts of other carbohydrates may supplements for people with
reducing energy intake while have similar blood glucose effects, diabetes for the prevention or
maintaining a healthful eating consumption should be minimized to treatment of cardiovascular
pattern is recommended to promote avoid displacing nutrient-dense food events. A
weight loss. A choices. A c There is insufficient evidence to
c Modest weight loss may provide c People with diabetes and those at risk support the routine use of
clinical benefits (improved glycemia, for diabetes should limit or avoid micronutrients such as chromium,
blood pressure, and/or lipids) in some intake of sugar-sweetened beverages magnesium, and vitamin D to
individuals with diabetes, especially (from any caloric sweetener including improve glycemic control in people
those early in the disease process. To high-fructose corn syrup and sucrose)
with diabetes. C
achieve modest weight loss, to reduce risk for weight gain and c There is insufficient evidence to
intensive lifestyle interventions worsening of cardiometabolic risk support the use of cinnamon or other
(counseling about nutrition therapy, profile. B
herbs/supplements for the treatment
physical activity, and behavior Dietary Fat Quantity and Quality of diabetes. C
change) with ongoing support are c It is reasonable for individualized
c Evidence is inconclusive for an ideal
recommended. A meal planning to include optimization
amount of total fat intake for people
Eating Patterns and Macronutrient with diabetes; therefore, goals should of food choices to meet
Distribution be individualized. C Fat quality recommended daily allowance/
c Evidence suggests that there is not an appears to be far more important dietary reference intake for all
ideal percentage of calories from than quantity. B micronutrients. E
Alcohol therapy or individualized education protein (158–160). A variety of eating

c If adults with diabetes choose to sessions have reported A1C decreases patterns have been shown to be
drink alcohol, they should be advised of 0.3–1% for type 1 diabetes (117–120) effective in managing diabetes,
to do so in moderation (one drink and 0.5–2% for type 2 diabetes including Mediterranean-style
per day or less for adult women and (85,121–137). (144,146,169), Dietary Approaches to
two drinks per day or less for adult Individuals with type 1 diabetes should Stop Hypertension (DASH)-style (161),
men). E be offered intensive insulin therapy plant-based (vegan or vegetarian) (129),
c Alcohol consumption may place lower-fat (145), and
education using the carbohydrate-
people with diabetes at increased risk counting meal planning approach lower-carbohydrate patterns
for delayed hypoglycemia, especially (117,119,120,124,138–140); this (144,163).
if taking insulin or insulin
approach has been shown to improve Studies examining the ideal amount of
secretagogues. Education and
glycemic control (139,141). Consistent carbohydrate intake for people with
awareness regarding the recognition
carbohydrate intake with respect to diabetes are inconclusive, although
and management of delayed
time and amount can result in improved monitoring carbohydrate intake and
hypoglycemia is warranted. C
glycemic control for individuals using considering the available insulin are key
Sodium fixed daily insulin doses (142,143). A strategies for improving postprandial
c The recommendation for the general simple diabetes meal planning approach glucose control (117,142,143,158). The
population to reduce sodium to such as portion control or healthful food literature concerning glycemic index
,2,300 mg/day is also appropriate choices may be better suited for and glycemic load in individuals with
for people with diabetes. B individuals with health literacy and diabetes is complex, although
c For individuals with both diabetes numeracy concerns (125–127). reductions in A1C of 20.2% to 20.5%
and hypertension, further reduction have been demonstrated in some
Weight loss of 2–8 kg may provide
in sodium intake should be studies. In many studies, it is often
clinical benefits in those with type 2
individualized. B difficult to discern the independent
diabetes, especially early in the disease
Primary Prevention of Type 2 Diabetes process (144–146). Weight loss studies effect of fiber compared with that of
c Among individuals at high risk for have used a variety of energy-restricted glycemic index on glycemic control and
developing type 2 diabetes, eating patterns, with no clear evidence other outcomes. Improvements in CVD
structured programs that emphasize that one eating pattern or optimal risk measures are mixed (164). Recent
lifestyle changes that include macronutrient distribution was ideal. studies have shown modest effect of
moderate weight loss (7% of body Although several studies resulted in fiber on lowering preprandial glucose
weight) and regular physical activity improvements in A1C at 1 year and mixed results on improving CVD risk
(150 min/week), with dietary (144,145,147–149), not all weight loss factors. A systematic review (157) found
strategies including reduced calories interventions led to 1-year A1C consumption of whole grains was not
and reduced intake of dietary fat, can improvements (128,150–154). The most associated with improvements in glycemic
reduce the risk for developing consistently identified changes in control in people with type 2 diabetes,
diabetes and are therefore cardiovascular risk factors were an although it may reduce systemic
recommended. A increase in HDL cholesterol (144,145, inflammation. One study did find a
c Individuals at high risk for type 2 potential benefit of whole grain intake in
147,149,153,155), decrease in
diabetes should be encouraged to triglycerides (144,145,149,155,156) reducing mortality and CVD (165).
achieve the U.S. Department of and decrease in blood pressure Limited research exists concerning the
Agriculture (USDA) recommendation (144,145,147,151,153,155). ideal amount of fat for individuals with
for dietary fiber (14 g fiber/1,000 kcal) diabetes. The Institute of Medicine has
and foods containing whole grains Intensive lifestyle programs with
frequent follow-up are required to defined an acceptable macronutrient
(one-half of grain intake). B
achieve significant reductions in excess distribution range (AMDR) for all adults
body weight and improve clinical for total fat of 20–35% of energy with no
The ADA recently released an updated
indicators (145,146). Several studies tolerable upper intake level defined.
position statement on nutrition therapy
have attempted to identify the optimal This AMDR was based on evidence for
for adults living with diabetes (116).
mix of macronutrients for meal plans of CHD risk with a low intake of fat and high
Nutrition therapy is an integral
people with diabetes. However, a recent intake of carbohydrate, and evidence
component of diabetes prevention,
systematic review (157) found that for increased obesity and CHD with high
management, and self-management
education. All individuals with diabetes there was no ideal macronutrient intake of fat (166). The type of fatty
should receive individualized MNT distribution and that macronutrient acids consumed is more important than
preferably provided by a registered proportions should be individualized. total amount of fat when looking at
dietitian who is knowledgeable and Studies show that people with diabetes metabolic goals and risk of CVD
skilled in providing diabetes MNT. on average eat about 45% of their (146,167,168).
Comprehensive group diabetes calories from carbohydrate, ;36–40% Multiple RCTs including patients with
education programs including nutrition of calories from fat, and ;16–18% from type 2 diabetes have reported improved
glycemic control and/or blood lipids 2 diabetes (204) have warranted caution team to improve clinical outcomes,
when a Mediterranean-style, MUFA- for universal sodium restriction to 1,500 health status, and quality of life in a
rich eating pattern was consumed mg in this population. For individuals cost-effective manner (206).
(144,146,151,169–171). Some of these with diabetes and hypertension, setting a DSME and DSMS are essential elements
studies also included caloric restriction, sodium intake goal of ,2,300 mg/day of diabetes care (207–209), and the current
which may have contributed to should be considered only on an National Standards for Diabetes Self-
improvements in glycemic control or individual basis. Goal sodium intake Management Education and Support (206)
blood lipids (169,170). The ideal ratio of recommendations should take into are based on evidence for their benefits.
n-6 to n-3 fatty acids has not been account palatability, availability, additional Education helps people with diabetes
determined; however, PUFA and MUFA cost of specialty low sodium products, and initiate effective self-management and
are recommended substitutes for the difficulty of achieving both low sodium cope with diabetes when they are first
saturated or trans fat (167,172). recommendations and a nutritionally diagnosed. Ongoing DSME and DSMS also
adequate diet (205). For complete
A recent systematic review (157) help people with diabetes maintain
discussion and references of all
concluded that supplementation with effective self-management throughout a
recommendations, see “Nutrition Therapy
n-3 fatty acids did not improve lifetime of diabetes as they face new
Recommendations for the Management
glycemic control but that higher dose challenges and treatment advances
of Adults With Diabetes” (116).
supplementation decreased become available. DSME enables patients
triglycerides in individuals with type 2 F. Diabetes Self-Management (including youth) to optimize metabolic
diabetes. Six short-duration RCTs Education and Support control, prevent and manage
comparing n-3 supplements to placebo Recommendations
complications, and maximize quality of life,
published since the systematic review in a cost-effective manner (208,210).
c People with diabetes should receive
reported minimal or no beneficial Current best practice of DSME is a skills-
DSME and diabetes self-management
effects (173,174) or mixed/ based approach that focuses on helping
support (DSMS) according to National
inconsistent beneficial effects those with diabetes make informed self-
Standards for Diabetes Self-
(175–177) on CVD risk factors and management choices (206,208). DSME
Management Education and Support
other health issues. Three longer- has changed from a didactic approach
when their diabetes is diagnosed and
duration studies also reported mixed as needed thereafter. B focusing on providing information
outcomes (178–180). Thus, RCTs do c Effective self-management and to more theoretically based
not support recommending n-3 quality of life are the key outcomes of empowerment models that focus on
supplements for primary or secondary DSME and DSMS and should be helping those with diabetes make
prevention of CVD. Little evidence has measured and monitored as part of informed self-management decisions
been published about the relationship care. C (208). Diabetes care has shifted to an
between dietary intake of saturated c DSME and DSMS should address approach that is more patient centered
fatty acids and dietary cholesterol and psychosocial issues, since emotional and places the person with diabetes and
glycemic control and CVD risk in people well-being is associated with positive his or her family at the center of the care
with diabetes. Therefore, people with diabetes outcomes. C model working in collaboration with
diabetes should follow the guidelines c DSME and DSMS programs are health care professionals. Patient-
for the general population for the appropriate venues for people with centered care is respectful of and
recommended intakes of saturated fat, prediabetes to receive education and responsive to individual patient
dietary cholesterol, and trans fat (167). support to develop and maintain preferences, needs, and values and
Published data on the effects of plant behaviors that can prevent or delay ensures that patient values guide all
stanols and sterols on CVD risk in the onset of diabetes. C decision making (211).
individuals with diabetes include four c Because DSME and DSMS can result
RCTs that reported beneficial effects for in cost-savings and improved Evidence for the Benefits of Diabetes
total, LDL, and non-HDL cholesterol outcomes B, DSME and DSMS should Self-Management Education and
(181–184). be adequately reimbursed by third- Support
party payers. E Multiple studies have found that DSME
There is limited evidence that the use of is associated with improved diabetes
vitamin, mineral, or herbal supplements knowledge and improved self-care
DSME and DSMS are the ongoing
is necessary in the management of behavior (206,207), improved clinical
processes of facilitating the knowledge,
diabetes (185–201). skill, and ability necessary for diabetes outcomes such as lower A1C (209,212–
Limited studies have been published on self-care. This process incorporates the 216), lower self-reported weight (207),
sodium reduction in people with needs, goals, and life experiences of the improved quality of life (213,216,217),
diabetes. A recent Cochrane review person with diabetes. The overall healthy coping (218,219), and lower
found that decreasing sodium intake objectives of DSME and DSMS are to costs (220,221). Better outcomes were
reduces blood pressure in those with support informed decision making, self- reported for DSME interventions that
diabetes (202). However, two other care behaviors, problem solving, and were longer and included follow-up
studies in type 1 diabetes (203) and type active collaboration with the health care support (DSMS) (207,222–224), that
were culturally (225,226) and age Reimbursement for Diabetes Self- improvements in A1C and in fitness
appropriate (227,228) and were tailored Management Education and Support (248). Other benefits include slowing
to individual needs and preferences, DSME, when provided by a program that the decline in mobility among
and that addressed psychosocial issues meets national standards for DSME and overweight patients with diabetes
and incorporated behavioral strategies is recognized by ADA or other approval (249). A joint position statement of ADA
(207,208,218,219,229–231). Both bodies, is reimbursed as part of the and the American College of Sports
individual and group approaches have Medicare program as overseen by the Medicine summarizes the evidence for
been found effective (232,233). There is Centers for Medicare and Medicaid the benefits of exercise in people with
growing evidence for the role of a Services (CMS). DSME is also covered type 2 diabetes (250).
community health workers (234) and by most health insurance plans.
peer (235–239) and lay leaders (240) in Although DSMS has been shown to be Frequency and Type of Exercise
delivering DSME and DSMS as part of instrumental for improving outcomes, The U.S. Department of Health and
the DSME/S team (241). as described in “Evidence for the Human Services’ Physical Activity
Benefits of Diabetes Self-Management Guidelines for Americans (251) suggest
Diabetes education is associated with
Education and Support,” and can be that adults over age 18 years do 150
increased use of primary and preventive
provided in formats such as phone calls min/week of moderate-intensity, or 75
services (220,242,243) and lower use of
and via telehealth, it currently has min/week of vigorous aerobic physical
acute, inpatient hospital services (220).
limited reimbursement as face-to-face activity, or an equivalent combination of
Patients who participate in diabetes
visits included as follow-up to DSME. the two. In addition, the guidelines
education are more likely to follow best
practice treatment recommendations, suggest that adults also do muscle-
G. Physical Activity strengthening activities that involve all
particularly among the Medicare
Recommendations
population, and have lower Medicare and major muscle groups 2 or more days/
c As is the case for all children, children week. The guidelines suggest that adults
commercial claim costs (221,242).
with diabetes or prediabetes should over age 65 years, or those with
The National Standards for Diabetes be encouraged to engage in at least disabilities, follow the adult guidelines if
Self-Management Education and 60 min of physical activity each day. B possible or (if this is not possible) be as
Support c Adults with diabetes should be advised physically active as they are able.
The National Standards for Diabetes to perform at least 150 min/week of Studies included in the meta-analysis of
Self-Management Education and Support moderate-intensity aerobic physical effects of exercise interventions on
are designed to define quality DSME and activity (50–70% of maximum heart glycemic control (246) had a mean of 3.4
DSMS and to assist diabetes educators rate), spread over at least 3 days/week sessions/week, with a mean of 49 min/
in a variety of settings to provide with no more than 2 consecutive days session. The DPP lifestyle intervention,
evidence-based education and self- without exercise. A which included 150 min/week of
management support (206). The c In the absence of contraindications, moderate-intensity exercise, had a
standards are reviewed and updated adults with type 2 diabetes should be beneficial effect on glycemia in those
every 5 years by a task force representing encouraged to perform resistance with prediabetes. Therefore, it seems
key organizations involved in the field of training at least twice per week. A reasonable to recommend that people
diabetes education and care. with diabetes follow the physical
Exercise is an important part of the
activity guidelines for the general
Diabetes Self-Management Education diabetes management plan. Regular
population.
and Support Providers and People exercise has been shown to improve
With Prediabetes blood glucose control, reduce Progressive resistance exercise
The standards for DSME and DSMS also cardiovascular risk factors, contribute to improves insulin sensitivity in older men
apply to the education and support of weight loss, and improve well-being. with type 2 diabetes to the same or
people with prediabetes. Currently, there Furthermore, regular exercise may even a greater extent as aerobic
are significant barriers to the provision of prevent type 2 diabetes in high-risk exercise (252). Clinical trials have
education and support to those with individuals (23–25). Structured exercise provided strong evidence for the A1C
prediabetes. However, the strategies for interventions of at least 8 weeks’ lowering value of resistance training in
supporting successful behavior change duration have been shown to lower A1C older adults with type 2 diabetes
and the healthy behaviors recommended by an average of 0.66% in people with (253,254), and for an additive benefit of
for people with prediabetes are largely type 2 diabetes, even with no significant combined aerobic and resistance
identical to those for people with diabetes. change in BMI (246). There are exercise in adults with type 2 diabetes
As barriers to care are overcome, considerable data for the health (255,256). In the absence of
providers of DSME and DSMS, given their benefits (e.g., increased cardiovascular contraindications, patients with type 2
training and experience, are particularly fitness, muscle strength, improved diabetes should be encouraged to do at
well equipped to assist people with insulin sensitivity, etc.) of regular least two weekly sessions of resistance
prediabetes in developing and maintaining physical activity for those with type 1 exercise (exercise with free weights or
behaviors that can prevent or delay the diabetes (247). Higher levels of exercise weight machines), with each session
onset of diabetes (206,244,245). intensity are associated with greater consisting of at least one set of five or
more different resistance exercises Exercise in the Presence of Specific H. Psychosocial Assessment and Care
involving the large muscle groups (250). Long-Term Complications of Diabetes Recommendations
Pre-exercise Evaluation of the Retinopathy. In the presence of c It is reasonable to include assessment

Diabetic Patient proliferative diabetic retinopathy of the patient’s psychological and social
As discussed more fully in Section VI.A.5, (PDR) or severe non-PDR (NPDR), situation as an ongoing part of the
the area of screening asymptomatic vigorous aerobic or resistance medical management of diabetes. B
diabetic patients for coronary artery exercise may be contraindicated c Psychosocial screening and follow-up
disease (CAD) remains unclear. An ADA because of the risk of triggering may include, but are not limited to,
consensus statement on this issue vitreous hemorrhage or retinal attitudes about the illness,
concluded that routine screening is not detachment (259). expectations for medical
recommended (257). Providers should Peripheral Neuropathy. Decreased pain management and outcomes, affect/
use clinical judgment in this area. sensation and a higher pain threshold in mood, general and diabetes-related
Certainly, high-risk patients should be the extremities result in increased risk of quality of life, resources (financial,
encouraged to start with short periods skin breakdown and infection and of social, and emotional), and
of low-intensity exercise and increase Charcot joint destruction with some psychiatric history. E
the intensity and duration slowly. c Routinely screen for psychosocial
forms of exercise. However, studies
Providers should assess patients for have shown that moderate-intensity problems such as depression and
conditions that might contraindicate walking may not lead to increased risk of diabetes-related distress, anxiety,
certain types of exercise or predispose foot ulcers or reulceration in those with eating disorders, and cognitive
to injury, such as uncontrolled peripheral neuropathy (260). In impairment. B
hypertension, severe autonomic addition, 150 min/week of moderate Emotional well-being is an important part
neuropathy, severe peripheral exercise was reported to improve of diabetes care and self-management.
neuropathy or history of foot lesions, outcomes in patients with milder forms Psychological and social problems can
and unstable proliferative retinopathy. of neuropathy (260a). All individuals impair the individual’s (263–265) or
The patient’s age and previous physical with peripheral neuropathy should wear family’s ability (266) to carry out diabetes
activity level should be considered. For proper footwear and examine their feet care tasks and therefore compromise
type 1 diabetic patients, the provider daily to detect lesions early. Anyone health status. There are opportunities for
should customize the exercise regimen with a foot injury or open sore should be the clinician to routinely assess
to the individual’s needs. Those with restricted to non–weight-bearing psychosocial status in a timely and
complications may require a more activities. efficient manner so that referral for
thorough evaluation (247). appropriate services can be
Autonomic Neuropathy. Autonomic
Exercise in the Presence of neuropathy can increase the risk of accomplished. A systematic review and
Nonoptimal Glycemic Control exercise-induced injury or adverse meta-analysis showed that psychosocial
Hyperglycemia. When people with type 1 event through decreased cardiac interventions modestly but significantly
diabetes are deprived of insulin for responsiveness to exercise, postural improved A1C (standardized mean
12–48 h and are ketotic, exercise can hypotension, impaired thermoregulation, difference 20.29%) and mental health
worsen hyperglycemia and ketosis impaired night vision due to impaired outcomes. However, there was a limited
(258); therefore, vigorous activity papillary reaction, and higher association between the effects on A1C
should be avoided in the presence of susceptibility to hypoglycemia (454). and mental health, and no intervention
ketosis. However, it is not necessary to Cardiovascular autonomic neuropathy characteristics predicted benefit on both
postpone exercise based simply on (CAN) is also an independent risk outcomes (267).
hyperglycemia, provided the patient factor for cardiovascular death and Screening
feels well and urine and/or blood silent myocardial ischemia (261). Key opportunities for routine screening of
ketones are negative. Therefore, individuals with diabetic psychosocial status occur at diagnosis,
Hypoglycemia. In individuals taking autonomic neuropathy should during regularly scheduled management
insulin and/or insulin secretagogues, undergo cardiac investigation before visits, during hospitalizations, with the
physical activity can cause hypoglycemia beginning physical activity more discovery of complications, or when
if medication dose or carbohydrate intense than that to which they are problems with glucose control, quality of
consumption is not altered. For accustomed. life, or self-management are identified.
individuals on these therapies, added Albuminuria and Nephropathy. Physical Patients are likely to exhibit psychological
carbohydrate should be ingested if pre- activity can acutely increase urinary vulnerability at diagnosis and when their
exercise glucose levels are ,100 mg/dL protein excretion. However, there is no medical status changes, e.g., end of the
(5.6 mmol/L). Hypoglycemia is less evidence that vigorous exercise honeymoon period, when the need for
common in diabetic individuals who are increases the rate of progression of intensified treatment is evident, and
not treated with insulin or insulin diabetic kidney disease and likely no when complications are discovered.
secretagogues, and no preventive need for any specific exercise Depression affects about 20–25% of
measures for hypoglycemia are usually restrictions for people with diabetic people with diabetes (268) and increases
advised in these cases. kidney disease (262). the risk for MI and post-MI (269) and
all-cause mortality (270). There appears interventions to enhance self- with hyperglycemia in the hospital, see
to be a bidirectional relationship with management and address severe Section IX.A. For further information on
both diabetes (271) and metabolic distress have demonstrated efficacy in management of DKA or hyperglycemic
syndrome (272) and depression. diabetes-related distress (219). nonketotic hyperosmolar state, refer to
Diabetes-related distress is distinct from the ADA statement on hyperglycemic
I. When Treatment Goals Are Not Met crises (288).
clinical depression and is very common
Some people with diabetes and their
(273–276) among people with diabetes
health care providers may not achieve K. Hypoglycemia
and their family members (266).
the desired treatment goals (Table 9). Recommendations
Prevalence is reported as 18–45%, with
Rethinking the treatment regimen may c Individuals at risk for hypoglycemia
an incidence of 38–48% over 18 months.
require assessment of barriers including should be asked about symptomatic
High levels of distress are significantly
income, health literacy, diabetes- and asymptomatic hypoglycemia at
linked to A1C, self-efficacy, dietary and
related distress, depression, and each encounter. C
exercise behaviors (219,274), and
competing demands, including those c Glucose (15–20 g) is the preferred
medication taking (277). Other issues
related to family responsibilities and treatment for the conscious
known to impact self-management and
dynamics. Other strategies may include individual with hypoglycemia,
health outcomes include but are not
culturally appropriate and enhanced although any form of carbohydrate
limited to attitudes about the illness,
DSME and DSMS, comanagement with a that contains glucose may be used.
expectations for medical management
diabetes team, referral to a medical After 15 min of treatment, if SMBG
and outcomes, anxiety, general and
social worker for assistance with shows continued hypoglycemia, the
diabetes-related quality of life, resources
insurance coverage, assessing treatment should be repeated. Once
(financial, social, and emotional) (278)
medication-taking behaviors, or change SMBG returns to normal, the
and psychiatric history (279,280).
in pharmacological therapy. Initiation of individual should consume a meal or
Screening tools are available for a number
or increase in SMBG, use of CGM, snack to prevent recurrence of
of these areas (229,281,282).
frequent contact with the patient, or hypoglycemia. E
referral to a mental health professional c Glucagon should be prescribed for
Referral to Mental Health Specialist or physician with special expertise in all individuals at significant risk of
Indications for referral to a mental diabetes may be useful. severe hypoglycemia, and caregivers
health specialist familiar with diabetes or family members of these
management may include gross J. Intercurrent Illness individuals should be instructed on
disregard for the medical regimen (by The stress of illness, trauma, and/or its administration. Glucagon
self or others) (283), depression, surgery frequently aggravates glycemic administration is not limited to
possibility of self-harm, debilitating control and may precipitate DKA or health care professionals. E
anxiety (alone or with depression), nonketotic hyperosmolar state, life- c Hypoglycemia unawareness or one or
indications of an eating disorder (284), threatening conditions that require more episodes of severe hypoglycemia
or cognitive functioning that immediate medical care to prevent should trigger re-evaluation of the
significantly impairs judgment. It is complications and death. Any condition treatment regimen. E
preferable to incorporate leading to deterioration in glycemic c Insulin-treated patients with
psychological assessment and control necessitates more frequent hypoglycemia unawareness or an
treatment into routine care rather than monitoring of blood glucose and (in episode of severe hypoglycemia
waiting for a specific problem or ketosis-prone patients) urine or blood should be advised to raise their
deterioration in metabolic or ketones. If accompanied by ketosis, glycemic targets to strictly avoid
psychological status (229,273). In the vomiting, or alteration in level of further hypoglycemia for at least
recent DAWN2 study, significant consciousness, marked hyperglycemia several weeks, to partially reverse
diabetes-related distress was reported requires temporary adjustment of the hypoglycemia unawareness and
by 44.6% of the participants, but only treatment regimen and immediate reduce risk of future episodes. A
23.7% reported that their health care interaction with the diabetes care team. c Ongoing assessment of cognitive
team asked them how diabetes The patient treated with noninsulin function is suggested with increased
impacted their life (273). therapies or MNT alone may vigilance for hypoglycemia by the
Although the clinician may not feel temporarily require insulin. Adequate clinician, patient, and caregivers if
qualified to treat psychological fluid and caloric intake must be assured. low cognition and/or declining
problems (285), using the patient- Infection or dehydration is more likely cognition is found. B
provider relationship as a foundation to necessitate hospitalization of the
can increase the likelihood that the person with diabetes than the person Hypoglycemia is the leading limiting
patient will accept referral for other without diabetes. factor in the glycemic management of
services. Collaborative care The hospitalized patient should be type 1 and insulin-treated type 2
interventions and use of a team treated by a physician with expertise in diabetes (289). Mild hypoglycemia may
approach have demonstrated efficacy in diabetes management. For further be inconvenient or frightening to
diabetes and depression (286,287), and information on management of patients patients with diabetes. Severe
hypoglycemia can cause acute harm to Hypoglycemia treatment requires patients (296). Hence, patients with one
the person with diabetes or others, ingestion of glucose- or carbohydrate- or more episodes of severe hypoglycemia
especially if it causes falls, motor vehicle containing foods. The acute glycemic may benefit from at least short-term
accidents, or other injury. A large cohort response correlates better with the relaxation of glycemic targets.
study suggested that among older glucose content than with the L. Bariatric Surgery
adults with type 2 diabetes, a history of carbohydrate content of the food. Pure
Recommendations
severe hypoglycemia was associated glucose is the preferred treatment, but
c Bariatric surgery may be considered
with greater risk of dementia (290). any form of carbohydrate that contains
glucose will raise blood glucose. Added for adults with BMI .35 kg/m2 and
Conversely, in a substudy of the
fat may retard and then prolong the acute type 2 diabetes, especially if diabetes
ACCORD trial, cognitive impairment at
glycemic response. Ongoing insulin or associated comorbidities are
baseline or decline in cognitive function
activity or insulin secretagogues may lead difficult to control with lifestyle and
during the trial was significantly
to recurrent hypoglycemia unless further pharmacological therapy. B
associated with subsequent episodes of
c Patients with type 2 diabetes who
severe hypoglycemia (291). Evidence food is ingested after recovery.
have undergone bariatric surgery
from the DCCT/EDIC trial, which
Glucagon need lifelong lifestyle support and
involved younger adults and
Those in close contact with, or having medical monitoring. B
adolescents with type 1 diabetes,
custodial care of, people with c Although small trials have shown
suggested no association of frequency
hypoglycemia-prone diabetes (family glycemic benefit of bariatric surgery
of severe hypoglycemia with cognitive
members, roommates, school in patients with type 2 diabetes and
decline (292), as discussed in Section
personnel, child care providers, BMI 30–35 kg/m2, there is currently
VIII.A.1.a.
correctional institution staff, or insufficient evidence to generally
As described in Section V.b.2, severe coworkers) should be instructed on use recommend surgery in patients with
hypoglycemia was associated with of glucagon kits. An individual does not BMI ,35 kg/m2 outside of a research
mortality in participants in both the need to be a health care professional to protocol. E
standard and intensive glycemia arms safely administer glucagon. A glucagon c The long-term benefits, cost-
of the ACCORD trial, but the kit requires a prescription. Care should effectiveness, and risks of bariatric
relationships with achieved A1C and be taken to ensure that glucagon kits are surgery in individuals with type 2
treatment intensity were not not expired. diabetes should be studied in well-
straightforward. An association of designed controlled trials with
Hypoglycemia Prevention
severe hypoglycemia with mortality optimal medical and lifestyle therapy
Hypoglycemia prevention is a critical
was also found in the ADVANCE trial as the comparator. E
component of diabetes management.
(293). An association of self-reported
SMBG and, for some patients, CGM are
severe hypoglycemia with 5-year Bariatric and metabolic surgeries, either
key tools to assess therapy and detect
mortality has also been reported in gastric banding or procedures that involve
incipient hypoglycemia. Patients should
clinical practice (294). bypassing, transposing, or resecting
understand situations that increase their
In 2013, ADA and The Endocrine Society sections of the small intestine, when part
risk of hypoglycemia, such as when
published a consensus report on the of a comprehensive team approach, can
fasting for tests or procedures, during or
impact and treatment of hypoglycemia be an effective weight loss treatment for
after intense exercise, and during sleep,
on diabetic patients. Severe severe obesity, and national guidelines
and that hypoglycemia may increase the
hypoglycemia was defined as an event support its consideration for people with
risk of harm to self or others, such as with
requiring assistance of another person. type 2 diabetes who have BMI exceeding
driving. Teaching people with diabetes to
Young children with type 1 diabetes and 35 kg/m2.
balance insulin use, carbohydrate intake,
the elderly were noted as particularly and exercise is a necessary but not Advantages
vulnerable due to their limited ability to always sufficient strategy for prevention. Bariatric surgery has been shown to lead
recognize hypoglycemic symptoms and In type 1 diabetes and severely insulin- to near- or complete normalization of
effectively communicate their needs. deficient type 2 diabetes, hypoglycemia glycemia in ;40–95% of patients with
The report recommended that short- unawareness, or hypoglycemia- type 2 diabetes, depending on the study
acting insulin sliding scales, often used in associated autonomic failure, can and the surgical procedure (297–300).
long-term care facilities, should be severely compromise stringent diabetes A meta-analysis of bariatric surgery
avoided and complex regimens control and quality of life. The deficient studies involving 3,188 patients with
simplified. Individualized patient counter-regulatory hormone release and diabetes reported that 78% had
education, dietary intervention (e.g., autonomic responses in this syndrome remission of diabetes (normalization of
bedtime snack to prevent overnight are both risk factors for, and caused by, blood glucose levels in the absence of
hypoglycemia), exercise management, hypoglycemia. A corollary to this “vicious medications) and that the remission
medication adjustment, glucose cycle” is that several weeks of avoidance rates were sustained in studies that had
monitoring, and routine clinical of hypoglycemia has been demonstrated follow-up exceeding 2 years (301).
surveillance may improve patient to improve counter-regulation and Remission rates tend to be lower with
outcomes (295). awareness to some extent in many procedures that only constrict the
stomach and higher with those that decreased mortality compared with hospitalizations for influenza and its
bypass portions of the small intestine. usual care (mean follow-up 6.7 years) complications. People with diabetes
Additionally, intestinal bypass procedures (309). A study that followed patients may be at increased risk of the
may have glycemic effects that are who had undergone laparoscopic bacteremic form of pneumococcal
independent of their effects on weight, adjustable gastric banding (LAGB) for infection and have been reported to
perhaps involving the incretin axis. 12 years found that 60% were satisfied have a high risk of nosocomial
There is also evidence for diabetes with the procedure. Nearly one out of bacteremia, which has a mortality rate
remission following bariatric surgery in three patients experienced band erosion, as high as 50% (311).
persons with type 2 diabetes who are and almost half had required removal of Safe and effective vaccines that greatly
less severely obese. One randomized their bands. The authors’ conclusion was reduce the risk of serious complications
trial compared adjustable gastric that “LAGB appears to result in relatively from these diseases are available
banding to “best available” medical and poor long-term outcomes” (310). (312,313). In a case-control series,
lifestyle therapy in subjects with type 2 Understanding the mechanisms of influenza vaccine was shown to reduce
diabetes and BMI 30–40 kg/m2 (302). glycemic improvement, long-term diabetes-related hospital admission by
Overall, 73% of surgically treated benefits, and risks of bariatric surgery in as much as 79% during flu epidemics
patients achieved “remission” of their individuals with type 2 diabetes, (312). There is sufficient evidence to
diabetes, compared with 13% of those especially those who are not severely support that people with diabetes
treated medically. The latter group lost obese, will require well designed clinical have appropriate serologic and clinical
only 1.7% of body weight, suggesting trials, with optimal medical and lifestyle responses to these vaccinations.
that their therapy was not optimal. therapy, and cardiovascular risk factors as The CDC Advisory Committee on
Overall the trial had 60 subjects, and the comparator. Immunization Practices recommends
only 13 had a BMI under 35 kg/m2, influenza and pneumococcal vaccines for
M. Immunization
making it difficult to generalize these all individuals with diabetes (http://
Recommendations
results widely to diabetic patients who www.cdc.gov/vaccines/recs/).
c Annually provide an influenza vaccine
are less severely obese or with longer Hepatitis B Vaccine
duration of diabetes. In a recent to all diabetic patients $6 months of
age. C Late in 2012, the Advisory Committee
nonrandomized study of 66 people with on Immunization Practices of the CDC
c Administer pneumococcal
BMI 30–35 kg/m2, 88% of participants recommended that all previously
had remission of their type 2 diabetes polysaccharide vaccine to all diabetic
patients $2 years of age. A one-time unvaccinated adults with diabetes aged
up to 6 years after surgery (303). 19–59 years be vaccinated against
revaccination is recommended for
Disadvantages individuals .65 years of age who hepatitis B virus (HBV) as soon as
Bariatric surgery is costly in the short have been immunized .5 years ago. possible after a diagnosis of diabetes is
term and has associated risks. Morbidity Other indications for repeat made. Additionally, after assessing risk
and mortality rates directly related to the vaccination include nephrotic and likelihood of an adequate immune
surgery have been reduced considerably syndrome, chronic renal disease, and response, vaccinations for those aged
in recent years, with 30-day mortality other immunocompromised states, 60 years and over should also be
rates now 0.28%, similar to those of such as after transplantation. C considered (314). At least 29 outbreaks
laparoscopic cholecystectomy (304). c Administer hepatitis B vaccination to of HBV in long-term care facilities and
Longer-term concerns include vitamin unvaccinated adults with diabetes who hospitals have been reported to the
and mineral deficiencies, osteoporosis, are aged 19–59 years. C CDC, with the majority involving adults
and rare but often severe hypoglycemia c Consider administering hepatitis B with diabetes receiving “assisted blood
from insulin hypersecretion. Cohort vaccination to unvaccinated adults glucose monitoring,” in which such
studies attempting to match subjects with diabetes who are aged $60 monitoring is done by a health care
suggest that the procedure may reduce years. C professional with responsibility for
longer-term mortality rates (305). more than one patient. HBV is highly
Retrospective analyses and modeling Influenza and pneumonia are common, transmissible and stable for long
studies suggest that these procedures preventable infectious diseases periods of time on surfaces such as
may be cost-effective for patients with associated with high mortality and lancing devices and blood glucose
type 2 diabetes, when one considers morbidity in the elderly and in people meters, even when no blood is visible.
reduction in subsequent health care costs with chronic diseases. Though there are Blood sufficient to transmit the virus
(297,306–308). limited studies reporting the morbidity has also been found in the reservoirs of
Caution about the benefits of bariatric and mortality of influenza and insulin pens, resulting in warnings
surgery is warranted. A propensity pneumococcal pneumonia specifically in against sharing such devices between
score-adjusted analyses of older people with diabetes, observational patients.
severely obese patients with high studies of patients with a variety of CDC analyses suggest that, excluding
baseline mortality in Veterans Affairs chronic illnesses, including diabetes, persons with HBV-related risk
Medical Centers found that bariatric show that these conditions are behaviors, acute HBV infection is about
surgery was not associated with associated with an increase in twice as high among adults with
diabetes aged 23 years and over 1. Hypertension/Blood Pressure Control c In pregnant patients with diabetes
compared with adults without diabetes. Recommendations and chronic hypertension, blood
Seroprevalence of antibody to HBV core Screening and Diagnosis pressure target goals of 110–129/
antigen, suggesting past or current c Blood pressure should be measured 65–79 mmHg are suggested in the
infection, is 60% higher among adults at every routine visit. Patients found interest of long-term maternal health
with diabetes than those without, and to have elevated blood pressure and minimizing impaired fetal
there is some evidence that diabetes should have blood pressure growth. ACE inhibitors and ARBs are
imparts a higher HBV case fatality rate. confirmed on a separate day. B contraindicated during pregnancy. E
The age differentiation in the Goals
recommendations stems from CDC Hypertension is a common comorbidity
c People with diabetes and
economic models suggesting that of diabetes, affecting the majority of
hypertension should be treated to a patients, with prevalence depending on
vaccination of adults with diabetes
systolic blood pressure (SBP) goal of type of diabetes, age, obesity, and
who were aged 20–59 years would cost
,140 mmHg. B ethnicity. Hypertension is a major risk
an estimated $75,000 per quality-
c Lower systolic targets, such as ,130 factor for both CVD and microvascular
adjusted life-year saved, while cost per
mmHg, may be appropriate for complications. In type 1 diabetes,
quality-adjusted life-year saved
certain individuals, such as younger hypertension is often the result of
increased significantly at higher ages.
patients, if it can be achieved without underlying nephropathy, while in type 2
In addition to competing causes of
undue treatment burden. C diabetes it usually coexists with other
mortality in older adults, the immune
c Patients with diabetes should be
response to the vaccine declines with cardiometabolic risk factors.
treated to a diastolic blood pressure
age (314).
(DBP) ,80 mmHg. B Screening and Diagnosis
These new recommendations regarding Blood pressure measurement should be
Treatment
HBV vaccinations serve as a reminder to done by a trained individual and follow
clinicians that children and adults with c Patients with blood pressure .120/80 the guidelines established for
diabetes need a number of vaccinations, mmHg should be advised on lifestyle nondiabetic individuals: measurement
both those specifically indicated changes to reduce blood pressure. B in the seated position, with feet on the
c Patients with confirmed blood floor and arm supported at heart level,
because of diabetes as well as those
recommended for the general pressure higher than 140/80 mmHg after 5 min of rest. Cuff size should be
population (http://www.cdc.gov/ should, in addition to lifestyle appropriate for the upper arm
vaccines/recs/). therapy, have prompt initiation and circumference. Elevated values should
timely subsequent titration of be confirmed on a separate day.
VI. PREVENTION AND pharmacological therapy to achieve
blood pressure goals. B Home blood pressure self-monitoring and
MANAGEMENT OF DIABETES 24-h ambulatory blood pressure
c Lifestyle therapy for elevated blood
COMPLICATIONS monitoring may provide additional
pressure consists of weight loss, if
For prevention and management of
overweight; DASH-style dietary evidence of “white coat” and masked
diabetes complications in children and hypertension and other discrepancies
pattern including reducing sodium
adolescents, please refer to Section VIII.
and increasing potassium intake; between office and “true” blood pressure.
Diabetes Care in Specific Populations. Studies in nondiabetic populations found
moderation of alcohol intake; and
increased physical activity. B that home measurements may better
A. Cardiovascular Disease
CVD is the major cause of morbidity and c Pharmacological therapy for patients correlate with CVD risk than office
mortality for individuals with diabetes, with diabetes and hypertension measurements (318,319). However, most
and the largest contributor to the direct should comprise a regimen that of the evidence of benefits of
and indirect costs of diabetes. The includes either an ACE inhibitor or an hypertension treatment in people with
common conditions coexisting with type angiotensin receptor blocker (ARB). If diabetes is based on office measurements.
2 diabetes (e.g., hypertension and one class is not tolerated, the other Treatment Goals
dyslipidemia) are clear risk factors for should be substituted. C Epidemiological analyses show that
CVD, and diabetes itself confers c Multiple-drug therapy (two or more blood pressures .115/75 mmHg are
independent risk. Numerous studies agents at maximal doses) is generally associated with increased
have shown the efficacy of controlling required to achieve blood pressure cardiovascular event rates and mortality
individual cardiovascular risk factors in targets. B in individuals with diabetes (320–322)
preventing or slowing CVD in people c Administer one or more and that SBP .120 mmHg predict long-
with diabetes. Large benefits are seen antihypertensive medications at term end-stage renal disease (ESRD).
when multiple risk factors are addressed bedtime. A Randomized clinical trials have
globally (315,316). There is evidence c If ACE inhibitors, ARBs, or diuretics demonstrated the benefit (reduction of
that measures of 10-year CHD risk are used, serum creatinine/estimated CHD events, stroke, and nephropathy)
among U.S. adults with diabetes have glomerular filtration rate (eGFR) and of lowering blood pressure to ,140
improved significantly over the past serum potassium levels should be mmHg systolic and ,80 mmHg
decade (317). monitored. E diastolic in individuals with diabetes
(320,323–325). There is limited evidence inappropriate for defining blood of reducing sodium intake (,1,500 mg/
for the benefits of lower SBP targets. pressure targets, since sicker patients day) and excess body weight; increasing
The ACCORD trial examined whether a may have low blood pressures or, consumption of fruits, vegetables (8–10
lower SBP of ,120 mmHg provides conversely, healthier or more adherent servings per day), and low-fat dairy
greater cardiovascular protection patients may achieve goals more products (2–3 servings per day);
than an SBP level of 130–140 mmHg in readily. A recent meta-analysis of avoiding excessive alcohol consumption
randomized trials of adults with type 2 (no more than 2 servings per day in men
patients with type 2 diabetes at high risk
diabetes comparing prespecified blood and no more than 1 serving per day in
for CVD (326). The HR for the primary
pressure targets found no significant women) (332); and increasing activity
end point (nonfatal MI, nonfatal stroke,
reduction in mortality or nonfatal MI. levels (320). These nonpharmacological
and CVD death) in the intensive (blood
There was a statistically significant 35% strategies may also positively affect
pressure 11/64 on 3.4 medications)
relative reduction in stroke, but the glycemia and lipid control and as a result
versus standard group (blood pressure
absolute risk reduction was only 1% should be encouraged in those with
143/70 on 2.1 medications) was 0.88
(330). Microvascular complications even mildly elevated blood pressure.
(95% CI 0.73–1.06; P 5 0.20). Of the
were not examined. Another meta- Their effects on cardiovascular events
prespecified secondary end points, only
analysis that included both trials have not been established.
stroke and nonfatal stroke were comparing blood pressure goals and Nonpharmacological therapy is
statistically significantly reduced by trials comparing treatment strategies reasonable in diabetic individuals with
intensive blood pressure treatment. concluded that a systolic treatment goal mildly elevated blood pressure (SBP
The number needed to treat to prevent of 130–135 mmHg was acceptable. With .120 mmHg or DBP .80 mmHg). If the
one stroke over the course of 5 years goals ,130 mmHg, there were greater blood pressure is confirmed to be $140
with intensive blood pressure reductions in stroke, a 10% reduction in mmHg systolic and/or $80 mmHg
management was 89. Serious adverse mortality, but no reduction of other diastolic, pharmacological therapy
event rates (including syncope and CVD events and increased rates of should be initiated along with
hyperkalemia) were higher with serious adverse events. SBP ,130 nonpharmacological therapy (320).
intensive targets (3.3% vs. 1.3%; P 5 mmHg was associated with reduced Lowering of blood pressure with
0.001). Albuminuria rates were reduced onset and progression of albuminuria. regimens based on a variety of
with more intensive blood pressure However, there was heterogeneity in antihypertensive drugs, including ACE
goals, but there were no differences in the measure, rates of more advanced inhibitors, ARBs, b-blockers, diuretics,
renal function nor in other renal disease outcomes were not and calcium channel blockers, has been
microvascular complications. affected, and there were no significant shown to be effective in reducing
The ADVANCE trial (treatment with an changes in retinopathy or neuropathy cardiovascular events. Several studies
ACE inhibitor and a thiazide-type diuretic) (331). suggested that ACE inhibitors may be
showed a reduced death rate but not in The clear body of evidence that SBP superior to dihydropyridine calcium
the composite macrovascular outcome. .140 mmHg is harmful suggests that channel blockers in reducing
However, the ADVANCE trial had no clinicians should promptly initiate and cardiovascular events (333–335).
specified targets for the randomized titrate therapy in an ongoing fashion to However, several studies have shown
comparison and the mean SBP in the achieve and maintain SBP ,140 mmHg no specific advantage to ACE inhibitors
intensive group (135 mmHg) was not as in virtually all patients. Additionally, as initial treatment of hypertension in
low as the mean SBP even in the ACCORD patients with long life expectancy (in the general hypertensive population,
standard-therapy group (327). Post hoc whom there may be renal benefits from but rather an advantage on
analysis of achieved blood pressure in long-term stricter blood pressure cardiovascular outcomes of initial
several hypertension treatment trials control) or those in whom stroke risk is a therapy with low-dose thiazide
have suggested no benefit of lower concern might, as part of shared diuretics (320,336,337).
achieved SBP. As an example, among decision making, appropriately have
In people with diabetes, inhibitors of the
6,400 patients with diabetes and CAD lower systolic targets such as ,130
renin-angiotensin system (RAS) may
enrolled in one trial, “tight control” mmHg. This is especially true if it can be
have unique advantages for initial or
(achieved SBP ,130 mmHg) was not achieved with few drugs and without
early therapy of hypertension. In a
associated with improved cardiovascular side effects of therapy.
nonhypertension trial of high-risk
outcomes compared with “usual care” individuals, including a large subset with
Treatment Strategies
(achieved SBP 130–140 mmHg) (328). diabetes, an ACE inhibitor reduced CVD
Although there are no well-controlled
Similar findings emerged from an analysis outcomes (338). In patients with
studies of diet and exercise in the
of another trial. Those with SBP (,115 treatment of elevated blood pressure or congestive heart failure (CHF), including
mmHg) had increased rates of CVD hypertension in individuals with diabetic subgroups, ARBs have been
events, although they had lower rates of diabetes, the DASH study in nondiabetic shown to reduce major CVD outcomes
stroke (329). individuals has shown antihypertensive (339–342), and in type 2 diabetic
Observational data, including that effects similar to pharmacological patients with significant nephropathy,
derived from clinical trials, may be monotherapy. Lifestyle therapy consists ARBs were superior to calcium channel
blockers for reducing heart failure (343). confirmed adherence to optimal doses c Statin therapy should be added to
Though evidence for distinct of at least three antihypertensive agents lifestyle therapy, regardless of baseline
advantages of RAS inhibitors on CVD of different classifications, one of which lipid levels, for diabetic patients:
outcomes in diabetes remains should be a diuretic, clinicians should c with overt CVD A
conflicting (323,337), the high CVD consider an evaluation for secondary c without CVD who are over the age of 40
risks associated with diabetes, and the forms of hypertension. Growing years and have one or more other CVD
high prevalence of undiagnosed CVD, evidence suggests that there is an risk factors (family history of CVD,
may still favor recommendations for association between increase in sleep- hypertension, smoking, dyslipidemia,
their use as first-line hypertension time blood pressure and incidence of or albuminuria). A
therapy in people with diabetes (320). CVD events. A recent RCT of 448
c For lower-risk patients than the above
participants with type 2 diabetes and
The blood pressure arm of the ADVANCE (e.g., without overt CVD and under the
hypertension demonstrated reduced
trial demonstrated that routine age of 40 years), statin therapy should
cardiovascular events and mortality
administration of a fixed combination of be considered in addition to lifestyle
with median follow-up of 5.4 years if at
the ACE inhibitor perindopril and the therapy if LDL cholesterol remains
least one antihypertensive medication
diuretic indapamide significantly was given at bedtime (345). above 100 mg/dL or in those with
reduced combined microvascular and multiple CVD risk factors. C
macrovascular outcomes, as well as CVD Pregnancy and Antihypertensives c In individuals without overt CVD,
and total mortality. The improved In a pregnancy complicated by diabetes the goal is LDL cholesterol ,100
outcomes could also have been due to and chronic hypertension, target blood mg/dL (2.6 mmol/L). B
lower achieved blood pressure in the pressure goals of SBP 110–129 mmHg c In individuals with overt CVD, a lower
perindopril-indapamide arm (327). and DBP 65–79 mmHg are reasonable, LDL cholesterol goal of ,70 mg/dL
Another trial showed a decrease in as they contribute to improved long- (1.8 mmol/L), with a high dose of a
morbidity and mortality in those receiving term maternal health. Lower blood statin, is an option. B
benazepril and amlodipine versus pressure levels may be associated with c If drug-treated patients do not reach the
benazepril and hydrochlorothiazide impaired fetal growth. During above targets on maximum tolerated
(HCTZ). The compelling benefits of RAS pregnancy, treatment with ACE statin therapy, a reduction in LDL
inhibitors in diabetic patients with inhibitors and ARBs is contraindicated, cholesterol of ;30–40% from baseline
albuminuria or renal insufficiency since they may cause fetal damage. is an alternative therapeutic goal. B
provide additional rationale for these Antihypertensive drugs known to be c Triglyceride levels ,150 mg/dL (1.7
agents (see Section VI.B). If needed to effective and safe in pregnancy include mmol/L) and HDL cholesterol .40
achieve blood pressure targets, methyldopa, labetalol, diltiazem, mg/dL (1.0 mmol/L) in men and .50
amlodipine, HCTZ, or chlorthalidone can clonidine, and prazosin. Chronic diuretic mg/dL (1.3 mmol/L) in women are
be added. If eGFR is ,30 mL/min/m2, use during pregnancy has been desirable. C However, LDL
a loop diuretic, rather than HCTZ or associated with restricted maternal cholesterol–targeted statin therapy
chlorthalidone should be prescribed. plasma volume, which may reduce remains the preferred strategy. A
uteroplacental perfusion (346). c Combination therapy has been shown
Titration of and/or addition of further
blood pressure medications should be not to provide additional
2. Dyslipidemia/Lipid Management
made in timely fashion to overcome cardiovascular benefit above statin
Recommendations
clinical inertia in achieving blood therapy alone and is not generally
Screening
recommended. A
pressure targets. c In most adult patients with diabetes, c Statin therapy is contraindicated in
Health information technology measure fasting lipid profile at least pregnancy. B
potentially can be used as a safe and annually. B
c In adults with low-risk lipid values Evidence for Benefits of Lipid-
effective tool to enable attainment of
(LDL cholesterol ,100 mg/dL, HDL Lowering Therapy
blood pressure goals. Using a
cholesterol .50 mg/dL, and Patients with type 2 diabetes have an
telemonitoring intervention to direct
triglycerides ,150 mg/dL), lipid increased prevalence of lipid
titrations of antihypertensive
assessments may be repeated every 2 abnormalities, contributing to their high
medications between medical office
years. E risk of CVD. Multiple clinical trials have
visits has been demonstrated to have a
demonstrated significant effects of
profound impact on SBP control (344). Treatment Recommendations and Goals pharmacological (primarily statin)
An important caveat is that most c Lifestyle modification focusing on the therapy on CVD outcomes in subjects
patients with hypertension require reduction of saturated fat, trans fat, and with CHD and for primary CVD
multiple-drug therapy to reach cholesterol intake; increase of n-3 fatty prevention (347,348). Subanalyses of
treatment goals (320). Identifying and acids, viscous fiber and plant stanols/ diabetic subgroups of larger trials
addressing barriers to medication sterols; weight loss (if indicated); and (349–353) and trials specifically in
adherence (such as cost and side increased physical activity should be subjects with diabetes (354,355) showed
effects) should routinely be done. If recommended to improve the lipid significant primary and secondary
blood pressure is refractory despite profile in patients with diabetes. A prevention of CVD events 1/2 CHD
deaths in diabetic patients. Meta- levels, are the most prevalent pattern of Hence, combination lipid-lowering
analyses including data from over dyslipidemia in persons with type 2 therapy cannot be broadly
18,000 patients with diabetes from diabetes. However, the evidence base recommended.
14 randomized trials of statin therapy for drugs that target these lipid fractions Dyslipidemia Treatment and Target
(mean follow-up 4.3 years), is significantly less robust than that for Lipid Levels
demonstrate a 9% proportional statin therapy (363). Nicotinic acid has Unless they have severe
reduction in all-cause mortality, and been shown to reduce CVD outcomes hypertriglyceridemia at risk for
13% reduction in vascular mortality, (364), although the study was done in a pancreatitis, for most diabetic patients
for each mmol/L reduction in LDL nondiabetic cohort. Gemfibrozil has the first priority of dyslipidemia therapy
cholesterol (356). As in those without been shown to decrease rates of CVD is to lower LDL cholesterol to ,100
diabetes, absolute reductions in “hard” events in subjects without diabetes mg/dL (2.60 mmol/L) (371). Lifestyle
CVD outcomes (CHD death and (365,366) and in a subgroup with diabetes intervention, including MNT, increased
nonfatal MI) are greatest in people in one of the larger trials (365). However, physical activity, weight loss, and
with high baseline CVD risk (known in a large trial specific to diabetic patients, smoking cessation, may allow some
CVD and/or very high LDL cholesterol fenofibrate failed to reduce overall patients to reach lipid goals. Nutrition
levels), but the overall benefits of cardiovascular outcomes (367). intervention should be tailored
statin therapy in people with diabetes according to each patient’s age,
at moderate or high risk for CVD are Combination Therapy diabetes type, pharmacological
convincing (357,358). Combination therapy, with a statin treatment, lipid levels, and other
and a fibrate or statin and niacin, may be medical conditions. Recommendations
Diabetes With Statin Use efficacious for treatment for all three
There is an increased risk of incident should focus on the reduction of
lipid fractions, but this combination is saturated fat, cholesterol, and trans
diabetes with statin use (359,360), associated with an increased risk for
which may be limited to those with unsaturated fat intake and increases in
abnormal transaminase levels, myositis, n-3 fatty acids, viscous fiber (such as in
diabetes risk factors. These patients or rhabdomyolysis. The risk of
may benefit additionally from diabetes oats, legumes, and citrus), and plant
rhabdomyolysis is higher with higher stanols/sterols. Glycemic control can also
screening when on statin therapy. In an doses of statins and with renal
analysis of one of the initial studies beneficially modify plasma lipid levels,
insufficiency and seems to be lower when particularly in patients with very high
suggesting that statins are linked to risk statins are combined with fenofibrate
of diabetes, the cardiovascular event triglycerides and poor glycemic control.
than gemfibrozil (368). In the ACCORD
rate reduction with statins outweighed study, the combination of fenofibrate and In those with clinical CVD or over age
the risk of incident diabetes even for simvastatin did not reduce the rate of fatal 40 years with other CVD risk factors,
patients at highest risk for diabetes cardiovascular events, nonfatal MI, or pharmacological treatment should be
(361). The absolute risk increase was nonfatal stroke, as compared with added to lifestyle therapy regardless of
small (over 5 years of follow-up, 1.2% of simvastatin alone, in patients with type 2 baseline lipid levels. Statins are the
participants on placebo developed diabetes who were at high risk for CVD. drugs of choice for LDL cholesterol
diabetes and 1.5% on rosuvastatin) Prespecified subgroup analyses suggested lowering and cardioprotection. In
(362). A meta-analysis of 13 randomized heterogeneity in treatment effects patients other than those described
statin trials with 91,140 participants according to sex, with a benefit of above, statin treatment should be
showed an odds ratio of 1.09 for a new combination therapy for men and possible considered if there is an inadequate LDL
diagnosis of diabetes, so that (on average) harm for women, and a possible benefit cholesterol response to lifestyle
treatment of 255 patients with statins for for patients with both triglyceride level modifications and improved glucose
4 years resulted in one additional case $204 mg/dL and HDL cholesterol level control or if the patient has increased
of diabetes, while simultaneously #34 mg/dL (369). The AIM-HIGH trial cardiovascular risk (e.g., multiple
preventing 5.4 vascular events among randomized over 3,000 patients (about cardiovascular risk factors or long
those 255 patients (360). The relative risk- one-third with diabetes) with established diabetes duration).
benefit ratio favoring statins is further CVD, low levels of HDL cholesterol, and Very little clinical trial evidence exists
supported by meta-analysis of individual triglyceride levels of 150–400 mg/dL to for type 2 diabetic patients under the
data of over 170,000 persons from 27 statin therapy plus extended release age of 40 years or for type 1 diabetic
randomized trials. This demonstrated niacin or matching placebo. The trial was patients of any age. In the Heart
that individuals at low risk of vascular halted early due to lack of efficacy on the Protection Study (lower age limit 40
disease, including those undergoing primary CVD outcome (first event of the years), the subgroup of ;600 patients
primary prevention, received benefits composite of death from coronary heart with type 1 diabetes had a
from statins that included reductions in disease (CHD), nonfatal MI, ischemic proportionately similar reduction in risk
major vascular events and vascular death stroke, hospitalization for an acute to patients with type 2 diabetes,
without increase in incidence of cancer or coronary syndrome, or symptom-driven although not statistically significant
deaths from other causes (348). coronary or cerebral revascularization) (350). Although the data are not
Low levels of HDL cholesterol, often and a possible increase in ischemic stroke definitive, similar lipid-lowering goals
associated with elevated triglyceride in those on combination therapy (370). for both type 1 and type 2 diabetic
patients should be considered, doses of statins fail to significantly lower Table 10 summarizes common
particularly if they have other LDL cholesterol (,30% reduction from treatment goals for A1C, blood
cardiovascular risk factors. the patient’s baseline), there is no pressure, and LDL cholesterol.
Alternative Lipoprotein Goals strong evidence that combination
therapy should be used to achieve 3. Antiplatelet Agents
Most trials of statins and CVD outcome
additional LDL cholesterol lowering. Recommendations
tested specific doses of statins against
Niacin, fenofibrate, ezetimibe, and bile c Consider aspirin therapy (75–162 mg/
placebo or other statins, rather than
aiming for specific LDL cholesterol goals acid sequestrants all offer additional LDL day) as a primary prevention strategy in
(372). Placebo-controlled trials generally cholesterol lowering to statins alone. those with type 1 or type 2 diabetes at
achieved LDL cholesterol reductions of However, there is insufficient evidence increased cardiovascular risk (10-year
30–40% from baseline. Hence, LDL that such combination therapy for LDL risk .10%). This includes most men
cholesterol lowering of this magnitude is cholesterol lowering provides a aged .50 years or women aged .60
an acceptable outcome for patients who significant increment in CVD risk years who have at least one additional
cannot reach LDL cholesterol goals due to reduction over statin therapy alone. major risk factor (family history of CVD,
severe baseline elevations in LDL hypertension, smoking, dyslipidemia, or
cholesterol and/or intolerance of Treatment of Other Lipoprotein albuminuria). C
maximal, or any, statin doses. Fractions or Targets c Aspirin should not be recommended
Additionally for those with baseline LDL Hypertriglyceridemia should be for CVD prevention for adults with
cholesterol minimally above 100 mg/dL, addressed with dietary and lifestyle diabetes at low CVD risk (10-year CVD
prescribing statin therapy to lower LDL changes. Severe hypertriglyceridemia risk ,5%, such as in men aged ,50
cholesterol about 30–40% from baseline (.1,000 mg/dL) may warrant years and women aged ,60 years
is probably more effective than immediate pharmacological therapy with no major additional CVD risk
prescribing just enough to get LDL (fibric acid derivative, niacin, or fish oil) factors), since the potential adverse
cholesterol slightly below 100 mg/dL. to reduce the risk of acute pancreatitis. effects from bleeding likely offset the
If severe hypertriglyceridemia is absent, potential benefits. C
Clinical trials in high-risk patients, such
then therapy targeting HDL cholesterol c In patients in these age-groups
as those with acute coronary syndromes
or triglycerides lacks the strong with multiple other risk factors (e.g.,
or previous cardiovascular events (373–
evidence base of statin therapy. If the 10-year risk 5–10%), clinical judgment
375), have demonstrated that more
HDL cholesterol is ,40 mg/dL and the is required. E
aggressive therapy with high doses of
LDL cholesterol between 100 and 129 c Use aspirin therapy (75–162 mg/day)
statins to achieve an LDL cholesterol of
mg/dL, a fibrate or niacin might be used, as a secondary prevention strategy in
,70 mg/dL led to a significant reduction
especially if a patient is intolerant to those with diabetes with a history of
in further events. A reduction in LDL
statins. Niacin is the most effective drug CVD. A
cholesterol to ,70 mg/dL is an option in
for raising HDL cholesterol. It can c For patients with CVD and documented
very-high-risk diabetic patients with
significantly increase blood glucose at aspirin allergy, clopidogrel (75 mg/day)
overt CVD (371). Some experts
high doses, but at modest doses should be used. B
recommend a greater focus on non-HDL
(750–2,000 mg/day), significant c Dual antiplatelet therapy is
cholesterol, apolipoprotein B (apoB), or
improvements in LDL cholesterol, HDL reasonable for up to a year after an
lipoprotein particle measurements to
cholesterol, and triglyceride levels are acute coronary syndrome. B
assess residual CVD risk in statin-treated
accompanied by only modest changes in
patients who are likely to have small LDL
glucose that are generally amenable to Aspirin has been shown to be effective
particles, such as people with diabetes
adjustment of diabetes therapy in reducing cardiovascular morbidity
(376), but it is unclear whether clinical
(370,379,380). and mortality in high-risk patients with
management would change with these
measurements.
In individual patients, the high variable
response seen with LDL cholesterol Table 10—Summary of recommendations for glycemic, blood pressure, and lipid
lowering with statins is poorly control for most adults with diabetes
A1C ,7.0%*
understood (377). Reduction of CVD
Blood pressure ,140/80 mmHg**
events with statins correlates very
closely with LDL cholesterol lowering Lipids
LDL cholesterol ,100 mg/dL (,2.6 mmol/L)†
(347). If initial attempts to prescribe a
Statin therapy for those with history of MI or age over 40
statin leads to side effects, clinicians plus other risk factors
should attempt to find a dose or
*More or less stringent glycemic goals may be appropriate for individual patients. Goals should
alternative statin that is tolerable. be individualized based on duration of diabetes, age/life expectancy, comorbid conditions,
There is evidence for significant LDL known CVD or advanced microvascular complications, hypoglycemia unawareness, and
cholesterol lowering from even individual patient considerations. **Based on patient characteristics and response to therapy,
extremely low, less than daily, statin lower SBP targets may be appropriate. †In individuals with overt CVD, a lower LDL cholesterol
goal of ,70 mg/dL (1.8 mmol/L), using a high dose of a statin, is an option.
doses (378). When maximally tolerated
previous MI or stroke (secondary do not have equal effects on long-term variety of ex vivo and in vitro methods
prevention). Its net benefit in primary health (384). (platelet aggrenometry, measurement
prevention among patients with no In 2010, a position statement of the of thromboxane B2), these observations
previous cardiovascular events is more ADA, the American Heart Association alone are insufficient to empirically
controversial, both for patients with and (AHA), and the American College of recommend higher doses of aspirin be
without a history of diabetes (381,382). Cardiology Foundation (ACCF) used in the diabetic patient at this time.
Two RCTs of aspirin specifically in recommends that low-dose (75–162 A P2Y12 receptor antagonist in
patients with diabetes failed to show a mg/day) aspirin for primary prevention combination with aspirin should be used
significant reduction in CVD end points, is reasonable for adults with diabetes for at least 1 year in patients following
raising further questions about the and no previous history of vascular an acute coronary syndrome. Evidence
efficacy of aspirin for primary supports use of either ticagrelor or
disease who are at increased CVD risk
prevention in people with diabetes clopidogrel if no percutaneous coronary
(10-year risk of CVD events over 10%) and
(190,383). intervention (PCI) was performed, and
who are not at increased risk for bleeding.
The Antithrombotic Trialists’ (ATT) This generally includes most men over the use of clopidogrel, ticagrelor, or
collaborators published an individual age 50 years and women over age 60 prasugrel if PCI was performed (388).
patient-level meta-analysis of the six years who also have one or more of the
large trials of aspirin for primary following major risk factors: 1) smoking, 4. Smoking Cessation
prevention in the general population. 2) hypertension, 3) dyslipidemia, 4) family Recommendations
These trials collectively enrolled over history of premature CVD, and 5) c Advise all patients not to smoke or
95,000 participants, including almost albuminuria (385). use tobacco products. A
4,000 with diabetes. Overall, they found c Include smoking cessation
However, aspirin is no longer
that aspirin reduced the risk of vascular counseling and other forms of
recommended for those at low CVD risk
events by 12% (RR 0.88 [95% CI 0.82– treatment as a routine component of
(women under age 60 years and men
0.94]). The largest reduction was for diabetes care. B
under age 50 years with no major CVD
nonfatal MI with little effect on CHD
risk factors; 10-year CVD risk under 5%)
death (RR 0.95 [95% CI 0.78–1.15]) or Results from epidemiological, case-
as the low benefit is likely to be
total stroke. There was some evidence control, and cohort studies provide
outweighed by the risks of significant
of a difference in aspirin effect by sex: convincing evidence to support the
aspirin significantly reduced CVD events bleeding. Clinical judgment should be
causal link between cigarette smoking
in men, but not in women. Conversely, used for those at intermediate risk
and health risks. Much of the work
aspirin had no effect on stroke in men but (younger patients with one or more risk
documenting the effect of smoking on
significantly reduced stroke in women. factors or older patients with no risk
health did not separately discuss results
Notably, sex differences in aspirin’s factors; those with 10-year CVD risk of on subsets of individuals with diabetes,
effects have not been observed in studies 5–10%) until further research is available. but suggests that the identified risks are
of secondary prevention (381). In the six Aspirin use in patients under the age of at least equivalent to those found in the
trials examined by the ATT collaborators, 21 years is contraindicated due to the general population. Other studies of
the effects of aspirin on major vascular associated risk of Reye syndrome. individuals with diabetes consistently
events were similar for patients with or Average daily dosages used in most demonstrate that smokers (and persons
without diabetes: RR 0.88 (95% CI 0.67– clinical trials involving patients with exposed to second-hand smoke) have a
1.15) and 0.87 (0.79–0.96), respectively. diabetes ranged from 50 to 650 mg but heightened risk of CVD, premature
The confidence interval was wider for were mostly in the range of 100 to 325 death, and increased rate of
those with diabetes because of their mg/day. There is little evidence to microvascular complications of
smaller number. support any specific dose, but using the diabetes. Smoking may have a role in the
Based on the currently available lowest possible dosage may help reduce development of type 2 diabetes. One
evidence, aspirin appears to have a side effects (386). In the U.S., the most study in smokers with newly diagnosed
modest effect on ischemic vascular common low dose tablet is 81 mg. type 2 diabetes found that smoking
events with the absolute decrease in Although platelets from patients with cessation was associated with
events depending on the underlying diabetes have altered function, it is amelioration of metabolic parameters
CVD risk. The main adverse effects unclear what, if any, impact that finding and reduced blood pressure and
appear to be an increased risk of has on the required dose of aspirin for albuminuria at 1 year (389).
gastrointestinal bleeding. The excess cardioprotective effects in the patient The routine and thorough assessment
risk may be as high as 1–5 per 1,000 per with diabetes. Many alternate pathways of tobacco use is key to prevent smoking
year in real-world settings. In adults for platelet activation exist that are or encourage cessation. Numerous
with CVD risk greater than 1% per year, independent of thromboxane A2 and large randomized clinical trials
the number of CVD events prevented thus not sensitive to the effects of have demonstrated the efficacy and
will be similar to or greater than the aspirin (387). Therefore, while “aspirin cost-effectiveness of brief counseling
number of episodes of bleeding resistance” appears higher in the in smoking cessation, including the use
induced, although these complications diabetic patients when measured by a of quitlines, in reducing tobacco use.
For the patient motivated to quit, the recommended to reduce CVD events in burden have more future cardiac events
addition of pharmacological therapy to overweight or obese adults with type 2 (400–402), the role of these tests
counseling is more effective than either diabetes (155). Patients at increased beyond risk stratification is not clear.
treatment alone. Special considerations CVD risk should receive aspirin and a Their routine use leads to radiation
should include assessment of level statin, and ACE inhibitor or ARB exposure and may result in unnecessary
of nicotine dependence, which is therapy if hypertensive, unless there invasive testing such as coronary
associated with difficulty in quitting and are contraindications to a particular angiography and revascularization
relapse (390). Although some patients drug class. While clear benefit exists procedures. The ultimate balance of
may gain weight in the period shortly for ACE inhibitor and ARB therapy in benefit, cost, and risks of such an
after smoking cessation, recent research patients with nephropathy or approach in asymptomatic patients
has demonstrated that this weight gain hypertension, the benefits in patients remains controversial, particularly in
does not diminish the substantial CVD with CVD in the absence of these the modern setting of aggressive CVD
risk benefit realized from smoking conditions are less clear, especially risk factor control.
cessation (391). when LDL cholesterol is concomitantly A systematic review of 34,000 patients
controlled (392,393). showed that metformin is as safe as
5. Cardiovascular Disease Candidates for advanced or invasive other glucose-lowering treatments in
Recommendations cardiac testing include those with patients with diabetes and CHF, even in
Screening 1) typical or atypical cardiac symptoms those with reduced left ventricular
c In asymptomatic patients, routine and 2) an abnormal resting ECG. The ejection fraction or concomitant chronic
screening for CAD is not screening of asymptomatic patients kidney disease (CKD); however,
recommended because it does not with high CVD risk is not recommended metformin should be avoided in
improve outcomes as long as CVD risk (257), in part because these high-risk hospitalized patients (403).
factors are treated. A patients should already be receiving
Treatment
intensive medical therapy, an approach B. Nephropathy
that provides similar benefit as invasive General Recommendations
c In patients with known CVD, consider
revascularization (394,395). There is c Optimize glucose control to reduce
ACE inhibitor therapy C and use
also some evidence that silent MI may the risk or slow the progression of
aspirin and statin therapy A (if not
reverse over time, adding to the nephropathy. A
contraindicated) to reduce the risk of
controversy concerning aggressive c Optimize blood pressure control to
cardiovascular events.
screening strategies (396). Finally, a reduce the risk or slow the
c In patients with a prior MI, b-blockers
recent randomized observational trial progression of nephropathy. A
should be continued for at least 2
demonstrated no clinical benefit to
years after the event. B Screening
routine screening of asymptomatic
c In patients with symptomatic heart
patients with type 2 diabetes and c Perform an annual test to quantitate
failure, avoid thiazolidinedione urine albumin excretion in type 1
normal ECGs (397). Despite abnormal
treatment. C diabetic patients with diabetes
myocardial perfusion imaging in more
c In patients with stable CHF,
than one in five patients, cardiac duration of $5 years and in all type 2
metformin may be used if renal diabetic patients starting at
outcomes were essentially equal (and
function is normal but should be diagnosis. B
very low) in screened versus unscreened
avoided in unstable or hospitalized
patients. Accordingly, the overall Treatment
patients with CHF. B
effectiveness, especially the cost- c An ACE inhibitor or ARB for the
In all patients with diabetes, effectiveness, of such an indiscriminate primary prevention of diabetic kidney
cardiovascular risk factors should be screening strategy is now questioned. disease is not recommended in
assessed at least annually. These risk Despite the intuitive appeal, recent diabetic patients with normal blood
factors include dyslipidemia, studies have found that a risk factor– pressure and albumin excretion ,30
hypertension, smoking, a positive family based approach to the initial diagnostic mg/24 h. B
history of premature coronary disease, evaluation and subsequent follow-up c Either ACE inhibitors or ARBs (but not
and the presence of albuminuria. for CAD fails to identify which patients both in combination) are
Abnormal risk factors should be treated with type 2 diabetes will have silent recommended for the treatment of
as described elsewhere in these ischemia on screening tests (398,399). the nonpregnant patient with
guidelines. Intensive lifestyle The effectiveness of newer noninvasive modestly elevated (30–299 mg/24 h)
intervention focusing on weight loss CAD screening methods, such as C or higher levels (.300 mg/24 h) of
through decreased caloric intake and computed tomography (CT) and CT urinary albumin excretion. A
increased physical activity as performed angiography, to identify patient c For people with diabetes and diabetic
in the Look AHEAD trial may be subgroups for different treatment kidney disease (albuminuria .30 mg/
considered for improving glucose strategies remains unproven. Although 24 h), reducing the amount of dietary
control, fitness, and some CVD risk asymptomatic diabetic patients found protein below usual intake is not
factors. However, it is not to have a higher coronary disease recommended because it does not
alter glycemic measures, A number of interventions have been renin-angiotensin-aldosterone system

cardiovascular risk measures, or the demonstrated to reduce the risk and (e.g., an ACE inhibitor plus an ARB, a
course of GFR decline. A slow the progression of renal disease. mineralocorticoid antagonist, or a direct
c When ACE inhibitors, ARBs, or Intensive diabetes management renin inhibitor) provide additional
diuretics are used, monitor serum with the goal of achieving near- lowering of albuminuria (424–427).
creatinine and potassium levels for normoglycemia has been shown in large However, such combinations have been
the development of increased prospective randomized studies to found to provide no additional
creatinine or changes in potassium. E delay the onset and progression of cardiovascular benefit and have higher
c Continued monitoring of urine increased urinary albumin excretion in adverse event rates (428). At least one
albumin excretion to assess both patients with type 1 (413) and type 2 randomized clinical trial has shown an
response to therapy and (85,86,89,90) diabetes. The UKPDS increase in adverse events, particularly
progression of disease is provided strong evidence that blood impaired kidney function and
reasonable. E pressure control can reduce the hyperkalemia, compared with either
c When eGFR is ,60 mL/min/1.73 m2, development of nephropathy (323). In agent alone, despite a reduction in
evaluate and manage potential addition, large prospective randomized albuminuria using combination therapy
complications of CKD. E studies in patients with type 1 diabetes (410).
c Consider referral to a physician have demonstrated that achievement Diuretics, calcium channel blockers, and
experienced in the care of kidney of lower levels of SBP (,140 mmHg) b-blockers should be used as additional
disease for uncertainty about the resulting from treatment using ACE therapy to further lower blood pressure
etiology of kidney disease, difficult inhibitors provides a selective benefit in patients already treated with ACE
management issues, or advanced over other antihypertensive drug inhibitors or ARBs (343) or as alternate
kidney disease. B classes in delaying the progression of therapy in the rare individual unable to
increased urinary albumin excretion tolerate ACE inhibitors or ARBs.
To be consistent with newer and can slow the decline in GFR in
patients with higher levels of Studies in patients with varying stages of
nomenclature intended to emphasize nephropathy have shown that protein
the continuous nature of albuminuria albuminuria (414,415). In type 2
diabetes with hypertension and restriction of dietary protein helps slow
as a risk factor, the terms the progression of albuminuria, GFR
“microalbuminuria” (30–299 mg/24 h) normoalbuminuria, RAS inhibition has
been demonstrated to delay onset of decline, and occurrence of ESRD (429–
and “macroalbuminuria” (.300 432), although more recent studies have
elevated albuminuria (416,417). In the
mg/24 h) will no longer be used, but provided conflicting results (157).
latter study, there was an unexpected
rather referred to as persistent Dietary protein restriction might be
higher rate of fatal cardiovascular
albuminuria at levels 30–299 mg/24 h considered particularly in patients
events with olmesartan among patients
and levels $300 mg/24 h. Normal whose nephropathy seems to be
with preexisting CHD.
albumin excretion is currently defined progressing despite optimal glucose and
as ,30 mg/24 h. ACE inhibitors have been shown to blood pressure control and use of ACE
reduce major CVD outcomes (i.e., MI, inhibitor and/or ARBs (432).
Diabetic nephropathy occurs in 20–40% stroke, death) in patients with diabetes
of patients with diabetes and is the (338), thus further supporting the use of Assessment of Albuminuria Status and
single leading cause of ESRD. Persistent these agents in patients with elevated Renal Function
albuminuria in the range of 30–299 mg/ albuminuria, a CVD risk factor. ARBs do Screening for increased urinary albumin
24 h has been shown to be an early stage not prevent onset of elevated excretion can be performed by
of diabetic nephropathy in type 1 albuminuria in normotensive patients measurement of the albumin-to-
diabetes and a marker for development with type 1 or type 2 diabetes (418,419); creatinine ratio in a random spot
of nephropathy in type 2 diabetes. It is a however, ARBs have been shown to collection; 24-h or timed collections are
well-established marker of increased reduce the progression rate of albumin more burdensome and add little to
CVD risk (404–406). However, there is levels from 30 to 299 mg/24 h to levels prediction or accuracy (433,434).
increasing evidence of spontaneous $300 mg/24 h as well as ESRD in Measurement of a spot urine for
remission of albumin levels 30–299 mg/ patients with type 2 diabetes (420–422). albumin alone (whether by
24 h in up to 40% of patients with type 1 Some evidence suggests that ARBs have a immunoassay or by using a dipstick test
diabetes. About 30–40% remain with smaller magnitude of rise in potassium specific for albuminuria) without
30–299 mg/24 h and do not progress to compared with ACE inhibitors in people simultaneously measuring urine
more elevated levels of albuminuria with nephropathy (423). creatinine is less expensive but
($300 mg/24 h) over 5–10 years of In the absence of side effects or adverse susceptible to false-negative and
follow-up (407–410). Patients with events (e.g., hyperkalemia or acute -positive determinations as a result of
persistent albuminuria (30–299 mg/24 h) kidney injury), it is suggested to titrate variation in urine concentration due to
who progress to more significant levels up to the maximum approved dose for hydration and other factors.
($300 mg/24 h are likely to progress to the treatment of hypertension. Abnormalities of albumin excretion and
ESRD (411,412). Combinations of drugs that block the the linkage between albumin-to-creatinine
ratio and 24-h albumin excretion Table 12—Stages of chronic kidney disease
are defined in Table 11. Because of GFR (mL/min/1.73 m2 body
variability in urinary albumin Stage Description surface area)
excretion, two of three specimens
1 Kidney damage* with normal or increased GFR $90
collected within a 3- to 6-month period
2 Kidney damage* with mildly decreased GFR 60–89
should be abnormal before considering a
3 Moderately decreased GFR 30–59
patient to have developed increased
4 Severely decreased GFR 15–29
urinary albumin excretion or had a
progression in albuminuria. Exercise 5 Kidney failure ,15 or dialysis
within 24 h, infection, fever, CHF, *Kidney damage defined as abnormalities on pathologic, urine, blood, or imaging tests. Adapted
marked hyperglycemia, and marked from Levey et al. (434).
hypertension may elevate urinary
albumin excretion over baseline
values. CKD-EPI equation. GFR calculators are advanced kidney disease. The threshold
available at http://www.nkdep.nih.gov. for referral may vary depending on the
Information on presence of abnormal frequency with which a provider
urine albumin excretion in addition to The role of continued annual
quantitative assessment of albumin encounters diabetic patients with
level of GFR may be used to stage CKD. significant kidney disease. Consultation
The National Kidney Foundation excretion after diagnosis of albuminuria
and institution of ACE inhibitor or ARB with a nephrologist when stage 4 CKD
classification (Table 12) is primarily develops has been found to reduce cost,
based on GFR levels and may be therapy and blood pressure control is
unclear. Continued surveillance can improve quality of care, and keep
superseded by other systems in which people off dialysis longer (438).
staging includes other variables such as assess both response to therapy and
progression of disease. Some suggest However, nonrenal specialists should
urinary albumin excretion (435). not delay educating their patients about
Studies have found decreased GFR in that reducing albuminuria to the normal
(,30 mg/g) or near-normal range may the progressive nature of diabetic
the absence of increased urine albumin kidney disease, the renal preservation
excretion in a substantial percentage improve renal and cardiovascular
prognosis, but this approach has not benefits of aggressive treatment of
of adults with diabetes (436). blood pressure, blood glucose, and
Substantial evidence shows that in been formally evaluated in prospective
trials, and more recent evidence hyperlipidemia, and the potential need
patients with type 1 diabetes and for renal transplant.
persistent albumin levels 30–299 reported spontaneous remission of
mg/24 h, screening with albumin albuminuria in up to 40% of type 1
diabetic patients. C. Retinopathy
excretion rate alone would miss .20%
General Recommendations
of progressive disease (410). Serum Conversely, patients with increasing
creatinine with estimated GFR should albumin levels, declining GFR, increasing c Optimize glycemic control to reduce
therefore be assessed at least annually blood pressure, retinopathy, the risk or slow the progression of
in all adults with diabetes, regardless macrovascular disease, elevated lipids retinopathy. A
of the degree of urine albumin and/or uric acid concentrations, or c Optimize blood pressure control to
excretion. a family history of CKD are more likely to reduce the risk or slow the
experience a progression of diabetic progression of retinopathy. A
Serum creatinine should be used to
estimate GFR and to stage the level of kidney disease (410). Screening
CKD, if present. eGFR is commonly Complications of kidney disease c Adults with type 1 diabetes should
coreported by laboratories or can be correlate with level of kidney function. have an initial dilated and
estimated using formulae such as the When the eGFR is ,60 mL/min/1.73 m2, comprehensive eye examination by
Modification of Diet in Renal Disease screening for complications of CKD is an ophthalmologist or optometrist
(MDRD) study equation (437) or the indicated (Table 13). Early vaccination within 5 years after the onset of
against HBV is indicated in patients likely diabetes. B
to progress to end-stage kidney disease. c Patients with type 2 diabetes should
Table 11—Definitions of Consider referral to a physician have an initial dilated and
abnormalities in albumin excretion experienced in the care of kidney comprehensive eye examination by
Spot collection disease when there is uncertainty about an ophthalmologist or optometrist
Category (mg/mg creatinine) the etiology of kidney disease (heavy shortly after the diagnosis of
Normal ,30 proteinuria, active urine sediment, diabetes. B
Increased urinary $30 absence of retinopathy, rapid decline in c If there is no evidence of retinopathy
albumin excretion* GFR, and resistant hypertension). Other for one or more eye exams, then
*Historically, ratios between 30 and 299 triggers for referral may include difficult exams every 2 years may be
have been called microalbuminuria and management issues (anemia, secondary considered. If diabetic retinopathy is
those 300 or greater have been called hyperparathyroidism, metabolic bone present, subsequent examinations
macroalbuminuria (or clinical albuminuria).
disease, or electrolyte disturbance) or for type 1 and type 2 diabetic patients
Table 13—Management of CKD in diabetes although tight targets (systolic ,120

GFR Recommended
mmHg) do not impart additional benefit
(442). Several case series and a
All patients Yearly measurement of creatinine, urinary albumin excretion, potassium
controlled prospective study suggest
45–60 Referral to a nephrologist if possibility for nondiabetic kidney disease exists
that pregnancy in type 1 diabetic
(duration of type 1 diabetes ,10 years, heavy proteinuria, abnormal
findings on renal ultrasound, resistant hypertension, rapid fall in GFR, or patients may aggravate retinopathy
active urinary sediment on ultrasound) (443,444). Laser photocoagulation
Consider need for dose adjustment of medications surgery can minimize this risk (444).
Monitor eGFR every 6 months
One of the main motivations for
Monitor electrolytes, bicarbonate, hemoglobin, calcium, phosphorus,
parathyroid hormone at least yearly screening for diabetic retinopathy is the
Assure vitamin D sufficiency long-established efficacy of laser
Consider bone density testing photocoagulation surgery in preventing
Referral for dietary counseling visual loss. Two large trials, the Diabetic
30–44 Monitor eGFR every 3 months Retinopathy Study (DRS) in patients
Monitor electrolytes, bicarbonate, calcium, phosphorus, parathyroid with PDR and the Early Treatment
hormone, hemoglobin, albumin, weight every 3–6 months
Diabetic Retinopathy Study (ETDRS) in
Consider need for dose adjustment of medications
patients with macular edema, provide
,30 Referral to a nephrologist
the strongest support for the
Adapted from http://www.kidney.org/professionals/KDOQI/guideline_diabetes. therapeutic benefits of
photocoagulation surgery. The DRS
(445) showed that panretinal
should be repeated annually by an loss in patients with high-risk PDR, photocoagulation surgery reduced the
ophthalmologist or optometrist. If clinically significant macular edema, risk of severe vision loss from PDR from
retinopathy is progressing or sight and in some cases severe NPDR. A 15.9% in untreated eyes to 6.4% in
threatening, then examinations will c Anti-vascular endothelial growth treated eyes, with greatest risk-benefit
be required more frequently. B factor (VEGF) therapy is indicated for ratio in those with baseline disease (disc
c High-quality fundus photographs can diabetic macular edema. A neovascularization or vitreous
detect most clinically significant c The presence of retinopathy is not a hemorrhage).
diabetic retinopathy. Interpretation contraindication to aspirin therapy
of the images should be performed for cardioprotection, as this therapy The ETDRS (446) established the benefit
by a trained eye care provider. While does not increase the risk of retinal of focal laser photocoagulation surgery
retinal photography may serve as a hemorrhage. A in eyes with macular edema, particularly
screening tool for retinopathy, it is those with clinically significant macular
not a substitute for a comprehensive Diabetic retinopathy is a highly specific edema, with reduction of doubling of
eye exam, which should be vascular complication of both type 1 and the visual angle (e.g., 20/50 to 20/100)
performed at least initially and at type 2 diabetes, with prevalence from 20% in untreated eyes to 8%
intervals thereafter as recommended strongly related to the duration of in treated eyes. The ETDRS also
by an eye care professional. E diabetes. Diabetic retinopathy is the verified the benefits of panretinal
c Women with preexisting diabetes most frequent cause of new cases of photocoagulation for high-risk PDR and
who are planning pregnancy or who blindness among adults aged 20–74 in older-onset patients with severe
have become pregnant should have a years. Glaucoma, cataracts, and other NPDR or less-than-high-risk PDR.
comprehensive eye examination disorders of the eye occur earlier and Laser photocoagulation surgery in both
and be counseled on the risk of more frequently in people with trials was beneficial in reducing the risk
development and/or progression diabetes. of further visual loss, but generally not
of diabetic retinopathy. Eye beneficial in reversing already
In addition to duration of diabetes,
examination should occur in the first diminished acuity. Recombinant
factors that increase the risk of, or are
trimester with close follow-up monoclonal neutralizing antibody to
associated with, retinopathy include
throughout pregnancy and for 1 year VEGF improves vision and reduces the
chronic hyperglycemia (439),
postpartum. B need for laser photocoagulation in
nephropathy (440), and hypertension
Treatment (441). Intensive diabetes management patients with macular edema (447).
with the goal of achieving near- Other emerging therapies for
c Promptly refer patients with any level
of macular edema, severe NPDR, or normoglycemia has been shown in large retinopathy include sustained
any PDR to an ophthalmologist who is prospective randomized studies to intravitreal delivery of fluocinolone
knowledgeable and experienced in prevent and/or delay the onset and (448) and the possibility of prevention
the management and treatment of progression of diabetic retinopathy with fenofibrate (449,450).
diabetic retinopathy. A (76,85,86,442). Lowering blood The preventive effects of therapy and
c Laser photocoagulation therapy is pressure has been shown to decrease the fact that patients with PDR or
indicated to reduce the risk of vision the progression of retinopathy (323), macular edema may be asymptomatic
provide strong support for a screening diagnosis of type 1 diabetes and at Effective symptomatic treatments are
program to detect diabetic least annually thereafter, using available for the neuropathic pain of
retinopathy. Because retinopathy is simple clinical tests. B DPN such as neuropathic pain (455)
estimated to take at least 5 years to c Electrophysiological testing or and for limited symptoms of
develop after the onset of referral to a neurologist is rarely autonomic neuropathy.
hyperglycemia, patients with type 1 needed, except in situations Diagnosis of Neuropathy
diabetes should have an initial dilated where the clinical features are Distal Symmetric Polyneuropathy. Patients
and comprehensive eye examination atypical. E with diabetes should be screened
within 5 years after the diabetes (451). c Screening for signs and symptoms of annually for DPN symptoms using
Patients with type 2 diabetes, who CAN should be instituted at diagnosis simple clinical tests. Symptoms vary
may have had years of undiagnosed of type 2 diabetes and 5 years after according to the class of sensory fibers
diabetes and who have a significant the diagnosis of type 1 diabetes. involved. The most common symptoms
risk of prevalent diabetic retinopathy Special testing is rarely needed and are induced by the involvement of small
at time of diagnosis should have an may not affect management or fibers and include pain, dysesthesias
initial dilated and comprehensive eye outcomes. E (unpleasant abnormal sensations of
examination. Examinations should be c Medications for the relief of specific burning and tingling associated with
performed by an ophthalmologist or symptoms related to painful DPN and peripheral nerve lesions), and
optometrist who is knowledgeable autonomic neuropathy are numbness. Clinical tests include
and experienced in diagnosing recommended because they may assessment of vibration threshold
diabetic retinopathy. Subsequent
reduce pain B and improve quality of using a 128-Hz tuning fork, pinprick
examinations for type 1 and type 2
life. E sensation and light touch perception
diabetic patients are generally
using a 10-g monofilament, and ankle
repeated annually. Exams every 2 years
The diabetic neuropathies are reflexes. Assessment should follow the
may be cost-effective after one or
heterogeneous with diverse clinical typical DPN pattern, starting distally
more normal eye exams, and in a
manifestations. They may be focal or (the dorsal aspect of the hallux) on both
population with well-controlled type 2
diffuse. The most prevalent sides and move proximally until
diabetes there was essentially no risk
neuropathies are chronic sensorimotor threshold is detected. Several clinical
of development of significant
DPN and autonomic neuropathy. instruments that combine more than
retinopathy with a 3-year interval
Although DPN is a diagnosis of one test have .87% sensitivity in
after a normal examination (452).
exclusion, complex investigations or detecting DPN (83,456,457).
Examinations will be required more
frequently if retinopathy is referral for neurology consultation to In patients with severe or atypical
progressing. exclude other conditions is rarely neuropathy, causes other than diabetes
needed. should always be considered, such as
Retinal photography, with remote
The early recognition and appropriate neurotoxic medications, heavy metal
reading by experts, has great potential
management of neuropathy in the poisoning, alcohol abuse, vitamin B12
in areas where qualified eye care
patient with diabetes is important for a deficiency (especially in those taking
professionals are not available. It may
number of reasons: metformin for prolonged periods) (458),
also enhance efficiency and reduce costs
renal disease, chronic inflammatory
when the expertise of ophthalmologists
1. Nondiabetic neuropathies may be demyelinating neuropathy, inherited
can be used for more complex
present in patients with diabetes and neuropathies, and vasculitis (459).
examinations and for therapy (453). In-
person exams are still necessary when may be treatable. Diabetic Autonomic Neuropathy. The
the photos are unacceptable and for 2. A number of treatment options exist symptoms and signs of autonomic
follow-up of abnormalities detected. for symptomatic diabetic dysfunction should be elicited carefully
Photos are not a substitute for a neuropathy. during the history and physical
comprehensive eye exam, which should 3. Up to 50% of DPN may be examination. Major clinical
be performed at least initially and at asymptomatic and patients are at manifestations of diabetic autonomic
intervals thereafter as recommended by risk for insensate injury to their feet. neuropathy include resting tachycardia,
an eye care professional. Results of eye 4. Autonomic neuropathy and exercise intolerance, orthostatic
examinations should be documented particularly CAN is an independent hypotension, constipation,
and transmitted to the referring health risk factor for cardiovascular gastroparesis, erectile dysfunction,
care professional. mortality (261,454). sudomotor dysfunction, impaired
neurovascular function, and,
D. Neuropathy Specific treatment for the underlying potentially, autonomic failure in
Recommendations nerve damage is currently not response to hypoglycemia.
c All patients should be screened for available, other than improved
distal symmetric polyneuropathy glycemic control, which may modestly Cardiovascular Autonomic Neuropathy.
(DPN) starting at diagnosis of type 2 slow progression in type 2 diabetes CAN is the most studied and clinically
diabetes and 5 years after the (90) but not reverse neuronal loss. important form of diabetic autonomic
neuropathy because of its association patients with type 1 diabetes for many require the use of both pharmacological
with mortality risk independent of years (461–464). While the evidence is and nonpharmacological measures
other cardiovascular risk factors not as strong for type 2 diabetes as for (e.g., avoiding medications that
(261,397). In early stages CAN may be type 1 diabetes, some studies have aggravate hypotension, using
completely asymptomatic and detected demonstrated a modest slowing of compressive garments over the legs and
by changes in heart rate variability and progression (90,465) without reversal of abdomen).
abnormal cardiovascular reflex tests neuronal loss. Several observational Gastroparesis Symptoms. Gastroparesis
(R-R response to deep breathing, studies further suggest that neuropathic symptoms may improve with dietary
standing and Valsalva maneuver). symptoms improve not only with changes and prokinetic agents such as
Advanced disease may be indicated by optimization of control but also with the erythromycin. Recently, the European
resting tachycardia (.100 bpm) and avoidance of extreme blood glucose Medicines Agency (www.ema.europa.
orthostasis (a fall in SBP .20 mmHg or fluctuations. eu/docs/en_GB/document_library/
DBP of at least 10 mmHg upon standing Distal Symmetric Polyneuropathy. DPN Press_release/2013/07/WC500146614.
without an appropriate heart rate symptoms, and especially neuropathic pdf) decided that risks of extrapyramidal
response). The standard cardiovascular pain, can be severe, have sudden onset, symptoms with metoclopramide
reflex testing, especially the deep- and are associated with lower quality of outweigh benefits. In Europe,
breathing test, is noninvasive, easy to life, limited mobility, depression, and metoclopramide use is now restricted
perform, reliable, and reproducible and social dysfunction (466). There is limited to a maximum use of 5 days and is no
has prognostic value. Although some clinical evidence regarding the most longer indicated for the long-term
societies have developed guidelines for effective treatments for individual treatment of gastroparesis. Although the
screening for CAN, the benefits of patient needs given the wide range of FDA decision is pending, it is suggested
sophisticated testing beyond risk available medications (467,468). Two that metoclopramide be reserved to only
stratification are not clear (460). drugs have been approved for relief of the most severe cases that are
Gastrointestinal Neuropathies. DPN pain in the U.S.dpregabalin and unresponsive to other therapies. Side
Gastrointestinal neuropathies (e.g., duloxetinedbut neither of these effects should be closely monitored.
esophageal enteropathy, gastroparesis, affords complete relief, even when used Erectile Dysfunction.Treatments for
constipation, diarrhea, fecal in combination. Venlafaxine, erectile dysfunction may include
incontinence) may involve any section amitriptyline, gabapentin, valproate, phosphodiesterase type 5 inhibitors,
of the gastrointestinal tract. Gastroparesis opioids (morphine sulfate, tramadol, intracorporeal or intraurethral
should be suspected in individuals with and oxycodone controlled-release) may prostaglandins, vacuum devices, or
erratic glucose control or with upper also be effective and could be penile prostheses. Interventions for
gastrointestinal symptoms without other considered for treatment of painful other manifestations of autonomic
identified cause. Evaluation of solid-phase DPN. Head-to-head treatment neuropathy are described in the ADA
gastric emptying using double-isotope comparisons and studies that include statement on neuropathy (468). As with
scintigraphy may be done if symptoms are quality-of-life outcomes are rare, so DPN treatments, these interventions do
suggestive, but test results often correlate treatment decisions must often follow a not change the underlying pathology
poorly with symptoms. Constipation is trial-and-error approach. Given the and natural history of the disease
the most common lower-gastrointestinal range of partially effective treatment process, but may have a positive impact
symptom but can alternate with episodes options, a tailored and step-wise on the quality of life of the patient.
of diarrhea. pharmacological strategy with careful
Genitourinary Tract Disturbances. attention to relative symptom
E. Foot Care
Diabetic autonomic neuropathy is also improvement, medication adherence,
Recommendations
associated with genitourinary tract and medication side effects is
c For all patients with diabetes,
disturbances. In men, diabetic recommended to achieve pain reduction
and improve quality of life (455). perform an annual comprehensive
autonomic neuropathy may cause foot examination to identify risk
erectile dysfunction and/or retrograde Autonomic Neuropathy. An intensive factors predictive of ulcers and
ejaculation. Evaluation of bladder multifactorial cardiovascular risk amputations. The foot examination
dysfunction should be performed for intervention targeting glucose, blood should include inspection,
individuals with diabetes who have pressure, lipids, smoking, and other assessment of foot pulses, and testing
recurrent urinary tract infections, lifestyle factors has been shown to reduce for loss of protective sensation (LOPS)
pyelonephritis, incontinence, or a the progression and development of CAN (10-g monofilament plus testing any
palpable bladder. among patients with type 2 diabetes one of the following: vibration using
Treatment (469). 128-Hz tuning fork, pinprick
Glycemic Control. Tight and stable Orthostatic Hypotension. Treatment of sensation, ankle reflexes, or vibration
glycemic control, implemented as early orthostatic hypotension is challenging. perception threshold). B
as possible has been shown to The therapeutic goal is to minimize c Provide general foot self-care
effectively prevent the development of postural symptoms rather than to education to all patients with
DPN and autonomic neuropathy in restore normotension. Most patients diabetes. B
c A multidisciplinary approach is examination to identify high-risk (e.g., smoking, hypertension,

recommended for individuals with conditions at least annually. Clinicians hyperlipidemia, or duration of diabetes
foot ulcers and high-risk feet, should ask about history of previous .10 years). Refer patients with
especially those with a history of prior foot ulceration or amputation, significant symptoms or a positive ABI
ulcer or amputation. B neuropathic or peripheral vascular for further vascular assessment and
c Refer patients who smoke, have LOPS symptoms, impaired vision, tobacco consider exercise, medications, and
and structural abnormalities, or have use, and foot care practices. A general surgical options (471).
history of prior lower-extremity inspection of skin integrity and
complications to foot care specialists musculoskeletal deformities should be Patient Education
for ongoing preventive care and done in a well-lit room. Vascular Patients with diabetes and high-risk foot
lifelong surveillance. C assessment would include inspection conditions should be educated
c Initial screening for peripheral and assessment of pedal pulses. regarding their risk factors and
arterial disease (PAD) should appropriate management. Patients at
The neurological exam recommended is
include a history for claudication and risk should understand the implications
designed to identify LOPS rather than
an assessment of the pedal pulses. of LOPS, the importance of foot
early neuropathy. The clinical
Consider obtaining an ankle-brachial monitoring on a daily basis, the proper
examination to identify LOPS is simple
index (ABI), as many patients with care of the foot, including nail and skin
and requires no expensive equipment.
PAD are asymptomatic. C care, and the selection of appropriate
Five simple clinical tests (use of a 10-g
c Refer patients with significant footwear. Patients with LOPS should be
monofilament, vibration testing using a
claudication or a positive ABI for educated on ways to substitute other
128-Hz tuning fork, tests of pinprick
further vascular assessment and sensory modalities (hand palpation,
sensation, ankle reflex assessment, and
consider exercise, medications, and visual inspection) for surveillance of
testing vibration perception threshold
surgical options. C early foot problems. Patients’
with a biothesiometer), each with
understanding of these issues and their
evidence from well-conducted
Amputation and foot ulceration, physical ability to conduct proper foot
prospective clinical cohort studies, are
consequences of diabetic neuropathy surveillance and care should be
considered useful in the diagnosis of
and/or PAD, are common and are major assessed. Patients with visual
LOPS in the diabetic foot. The task force
causes of morbidity and disability in difficulties, physical constraints
agreed that any of the five tests listed
people with diabetes. Loss of 10-g preventing movement, or cognitive
could be used by clinicians to identify
monofilament perception and reduced problems that impair their ability to
LOPS, although ideally two of these
vibration perception predict foot assess the condition of the foot and to
should be regularly performed during
ulcers (468). Early recognition and institute appropriate responses will
the screening examdnormally the 10-g
management of risk factors can prevent need other people, such as family
monofilament and one other test. One
or delay adverse outcomes. members, to assist in their care.
or more abnormal tests would suggest
The risk of ulcers or amputations is LOPS, while at least two normal tests Treatment
increased in people who have the (and no abnormal test) would rule out People with neuropathy or evidence of
following risk factors: LOPS. The last test listed, vibration increased plantar pressure (e.g.,
assessment using a biothesiometer or erythema, warmth, callus, or measured
c Previous amputation similar instrument, is widely used in the pressure) may be adequately managed
c Past foot ulcer history U.S.; however, identification of the with well-fitted walking shoes or athletic
c Peripheral neuropathy patient with LOPS can easily be carried shoes that cushion the feet and
c Foot deformity out without this or other expensive redistribute pressure. Callus can be
c Peripheral vascular disease equipment. debrided with a scalpel by a foot care
c Visual impairment
Screening
specialist or other health professional
c Diabetic nephropathy (especially
Initial screening for PAD should with experience and training in foot
patients on dialysis)
include a history for claudication and an care. People with bony deformities (e.g.,
c Poor glycemic control
assessment of the pedal pulses. A hammertoes, prominent metatarsal
c Cigarette smoking
diagnostic ABI should be performed in heads, bunions) may need extra-wide
In 2008, ADA published screening any patient with symptoms of PAD. Due or -deep shoes. People with extreme
recommendations (470). Clinicians are to the high estimated prevalence of PAD bony deformities (e.g., Charcot foot)
encouraged to review this report for in patients with diabetes and the fact who cannot be accommodated with
further details and practical descriptions that many patients with PAD are commercial therapeutic footwear may
of how to perform components of the asymptomatic, an ADA consensus need custom-molded shoes.
comprehensive foot examination. statement on PAD (471) suggested Most diabetic foot infections are
that a screening ABI be performed in polymicrobial, with aerobic gram-
Examination patients over 50 years of age and be positive cocci (GPC), and especially
All adults with diabetes should considered in patients under 50 years of staphylococci, the most common
undergo a comprehensive foot age who have other PAD risk factors causative organisms.
Wounds without evidence of soft tissue in men and women (478). The fracture, although fracture risk was
or bone infection do not require prevalence in general populations with higher in diabetic participants
antibiotic therapy. type 2 diabetes may be up to 23% (479) compared with participants without
Empiric antibiotic therapy can be and in obese participants enrolled in the diabetes for a given T score and age or
narrowly targeted at GPC in many Look AHEAD trial exceeded 80% (480). for a given FRAX score risk (489). It is
acutely infected patients, but those at Treatment of sleep apnea significantly appropriate to assess fracture history
risk for infection with antibiotic- improves quality of life and blood and risk factors in older patients with
resistant organisms or with chronic, pressure control. The evidence for a diabetes and recommend BMD testing if
previously treated, or severe infections treatment effect on glycemic control is appropriate for the patient’s age and
require broader spectrum regimens and mixed (481). sex. Prevention strategies are the same
should be referred to specialized care as for the general population. For type 2
Fatty Liver Disease diabetic patients with fracture risk
centers (472). Foot ulcers and wound Unexplained elevations of hepatic
care may require care by a podiatrist, factors, avoiding use of
transaminase concentrations are thiazolidinediones is warranted.
orthopedic or vascular surgeon, or significantly associated with higher BMI,
rehabilitation specialist experienced in waist circumference, triglycerides, and Cognitive Impairment
the management of individuals with fasting insulin, and with lower HDL Diabetes is associated with significantly
diabetes. Guidelines for treatment of cholesterol. In a prospective analysis, increased risk and rate of cognitive
diabetic foot ulcers have recently been diabetes was significantly associated decline and increased risk of dementia
updated (472). with incident nonalcoholic chronic liver (490,491). In a 15-year prospective
disease and with hepatocellular study of community-dwelling people
VII. ASSESSMENT OF COMMON carcinoma (482). Interventions that over the age of 60 years, the presence of
COMORBID CONDITIONS improve metabolic abnormalities in diabetes at baseline significantly
Recommendation patients with diabetes (weight loss, increased the age- and sex-adjusted
glycemic control, treatment with incidence of all-cause dementia,
c Consider assessing for and addressing
specific drugs for hyperglycemia or Alzheimer disease, and vascular
common comorbid conditions that
dyslipidemia) are also beneficial for dementia compared with rates in those
may complicate the management of
fatty liver disease (483). with normal glucose tolerance (492).
diabetes. B
In a substudy of the ACCORD study,
Cancer there were no differences in cognitive
Improved disease prevention and
Diabetes (possibly only type 2 diabetes) outcomes between intensive and
treatment efficacy means that patients
is associated with increased risk of standard glycemic control, although
with diabetes are living longer, often
cancers of the liver, pancreas, there was significantly less of a
with multiple comorbidities requiring
endometrium, colon/rectum, breast, decrement in total brain volume by MRI
complicated medical regimens (473). In
and bladder (484). The association may in participants in the intensive arm
addition to the commonly appreciated
result from shared risk factors between (493). The effects of hyperglycemia and
comorbidities of obesity, hypertension,
type 2 diabetes and cancer (obesity, age, insulin on the brain are areas of intense
and dyslipidemia, diabetes
physical inactivity) but may also be due research interest.
management is often complicated by
to hyperinsulinemia or hyperglycemia Low Testosterone in Men
concurrent conditions such as heart
(485,486). Patients with diabetes Mean levels of testosterone are lower in
failure, depression and anxiety, arthritis,
should be encouraged to undergo men with diabetes compared with age-
and other diseases or conditions at rates
recommended age- and sex-appropriate matched men without diabetes, but
higher than those of age-matched
cancer screenings and to reduce their obesity is a major confounder (494).
people without diabetes. These
modifiable cancer risk factors (obesity, Treatment in asymptomatic men is
concurrent conditions present clinical
smoking, physical inactivity). controversial. The evidence for effects
challenges related to polypharmacy,
prevalent symptoms, and complexity of Fractures
of testosterone replacement on
care (474–477). Age-matched hip fracture risk is outcomes is mixed, and recent
significantly increased in both type 1 guidelines suggest that screening and
Depression treatment of men without symptoms
(summary RR 6.3) and type 2 diabetes
As discussed in Section V.H, depression, are not recommended (495).
(summary RR 1.7) in both sexes (487).
anxiety, and other mental health
Type 1 diabetes is associated with Periodontal Disease
symptoms are highly prevalent in
osteoporosis, but in type 2 diabetes Periodontal disease is more severe, but
people with diabetes and are associated
an increased risk of hip fracture is not necessarily more prevalent, in
with worse outcomes.
seen despite higher bone mineral patients with diabetes than in those
Obstructive Sleep Apnea density (BMD) (488). In three large without (496). Current evidence
Age-adjusted rates of obstructive sleep observational studies of older adults, suggests that periodontal disease
apnea, a risk factor for CVD, are femoral neck BMD T score and the WHO adversely affects diabetes outcomes,
significantly higher (4- to 10-fold) with Fracture Risk Algorithm (FRAX) score although evidence for treatment
obesity, especially with central obesity, were associated with hip and nonspine benefits is currently lacking (477).
Hearing Impairment and family. The balance between adult lower A1C should be balanced against
Hearing impairment, both high supervision and self-care should be the risks of hypoglycemia and the
frequency and low/mid frequency, is defined at the first interaction and re- developmental burdens of intensive
more common in people with diabetes, evaluated at each clinic visit. This regimens in children and youth. Age-
perhaps due to neuropathy and/or relationship will evolve as the child specific glycemic and A1C goals are
vascular disease. In NHANES analysis, reaches physical, psychological, and presented in Table 14.
hearing impairment was about twice as emotional maturity.
great in people with diabetes compared b. Screening and Management of
a. Glycemic Control Complications
with those without, after adjusting for
Recommendation
age and other risk factors for hearing i. Nephropathy
impairment (497). c Consider age when setting glycemic
Recommendations
goals in children and adolescents with
Screening
type 1 diabetes. E
VIII. DIABETES CARE IN SPECIFIC c Annual screening for albumin levels,
POPULATIONS Current standards for diabetes with a random spot urine sample for
A. Children and Adolescents management reflect the need to lower albumin-to-creatinine ratio (ACR),
1. Type 1 Diabetes glucose as safely possible. This should should be considered for the child at
Three-quarters of all cases of type 1 be done with step-wise goals. Special the start of puberty or at age $10
diabetes are diagnosed in individuals consideration should be given to the years, whichever is earlier, once the
,18 years of age. The provider must unique risks of hypoglycemia in young youth has had diabetes for 5 years. B
consider the unique aspects of care children. For young children (,7 years Treatment
and management of children and old), glycemic goals may need to be
c Treatment with an ACE inhibitor,
adolescents with type 1 diabetes, such modified since most at that age have a
titrated to normalization of albumin
as changes in insulin sensitivity related form of “hypoglycemic unawareness,”
excretion, should be considered
to sexual maturity and physical growth, including immaturity of and a relative
when elevated ACR is subsequently
ability to provide self-care, supervision inability to recognize and respond to
confirmed on two additional
in child care and school, and unique hypoglycemic symptoms. This places
specimens from different days. This
neurological vulnerability to them at greater risk for severe
should be obtained over a 6-month
hypoglycemia and DKA. Attention to hypoglycemia. While it was previously
interval following efforts to improve
family dynamics, developmental stages, thought that young children were at risk
glycemic control and normalize blood
and physiological differences related to for cognitive impairment after episodes
pressure for age. E
sexual maturity are all essential in of severe hypoglycemia, current data
developing and implementing an have not confirmed this (295,499,500). Recent research demonstrates the
optimal diabetes regimen. Due to the Furthermore, new therapeutic importance of good glycemic and blood
paucity of clinical research in children, modalities, such as rapid and long-acting pressue control, especially as diabetes
the recommendations for children and insulin analogs, technological advances duration increases (506).
adolescents are less likely to be based (e.g., low glucose suspend), and
on clinical trial evidence. However, education may mitigate the incidence ii. Hypertension
expert opinion and a review of available of severe hypoglycemia (501). In
Recommendations
and relevant experimental data are adolescents, the DCCT demonstrated
Screening
summarized in the ADA statement on that near-normalization of blood glucose
c Blood pressure should be measured at
care of children and adolescents with levels was more difficult to achieve
type 1 diabetes (498). compared with adults. Nevertheless, the each routine visit. Children found to have
increased frequency of basal-bolus high-normal blood pressure or
The care of a child or adolescent with hypertension should have blood pressure
type 1 diabetes should be provided by a regimens and insulin pumps in youth
from infancy through adolescence has confirmed on a separate day. B
multidisciplinary team of specialists
trained in pediatric diabetes been associated with more children Treatment
management. At the very least, reaching ADA blood glucose targets c Initial treatment of high-normal
education of the child and family should (502–504) in those families in which blood pressure (SBP or DBP
be provided by health care providers both parents and the child with diabetes consistently above the 90th
trained and experienced in childhood participate jointly to perform the percentile for age, sex, and height)
diabetes and sensitive to the challenges required diabetes-related tasks. includes dietary intervention and
posed by diabetes in this age-group. It is Furthermore, studies documenting exercise, aimed at weight control
essential that DSME, MNT, and neurocognitive imaging differences of and increased physical activity, if
psychosocial support be provided at hyperglycemia in children provide appropriate. If target blood pressure
diagnosis and regularly thereafter by another compelling motivation for is not reached with 3–6 months
individuals experienced with the achieving glycemic targets (505). of lifestyle intervention,
educational, nutritional, behavioral, and In selecting glycemic goals, the long- pharmacological treatment should
emotional needs of the growing child term health benefits of achieving a be considered. E
Table 14—Plasma blood glucose and A1C goals for type 1 diabetes by age-group
Plasma blood glucose goal range
(mg/dL)
Values by age (years) Before meals Bedtime/overnight A1C Rationale
Toddlers and preschoolers (0–6) 100–180 110–200 ,8.5% c Vulnerability to hypoglycemia
c Insulin sensitivity
c Unpredictability in dietary intake and physical activity
c A lower goal (,8.0%) is reasonable if it can be achieved
without excessive hypoglycemia
School age (6–12) 90–180 100–180 ,8% c Vulnerability of hypoglycemia
c A lower goal (,7.5%) is reasonable if it can be achieved
Adolescents and young adults (13–19) 90–130 90–150 ,7.5% c A lower goal (,7.0%) is reasonable if it can be achieved
Key concepts in setting glycemic goals:
c Goals should be individualized and lower goals may be reasonable based on benefit-risk assessment.
c Blood glucose goals should be modified in children with frequent hypoglycemia or hypoglycemia unawareness.
c Postprandial blood glucose values should be measured when there is a discrepancy between preprandial blood glucose values and A1C levels and
to help assess glycemia in those on basal-bolus regimens.
c Pharmacological treatment of cardiovascular event before age 55 Children diagnosed with type 1 diabetes
hypertension (SBP or DBP years, or if family history is unknown, have a high risk of early subclinical
consistently above the 95th then consider obtaining a fasting lipid (507,508) and clinical (509) CVD.
percentile for age, sex, and height or profile in children .2 years of age soon Although intervention data are lacking,
consistently .130/80 mmHg, if 95% after the diagnosis (after glucose the AHA categorizes children with type 1
exceeds that value) should be control has been established). If family diabetes in the highest tier for
considered as soon as the diagnosis is history is not of concern, then consider cardiovascular risk and recommends
confirmed. E the first lipid screening at puberty ($10 both lifestyle and pharmacological
c ACE inhibitors should be considered years). For children diagnosed with treatment for those with elevated LDL
for the initial pharmacological diabetes at or after puberty, consider cholesterol levels (510,511). Initial
treatment of hypertension, following obtaining a fasting lipid profile soon therapy should be with a Step 2 AHA
appropriate reproductive counseling after the diagnosis (after glucose diet, which restricts saturated fat to 7%
due to its potential teratogenic control has been established). E of total calories and restricts dietary
effects. E c For both age-groups, if lipids are cholesterol to 200 mg/day. Data from
c The goal of treatment is blood abnormal, annual monitoring is randomized clinical trials in children as
pressure consistently ,130/80 or reasonable. If LDL cholesterol values young as 7 months of age indicate that
below the 90th percentile for are within the accepted risk levels this diet is safe and does not interfere
age, sex, and height, whichever is (,100 mg/dL [2.6 mmol/L]), a lipid with normal growth and development
lower. E profile repeated every 5 years is (512,513). Abnormal results from a
reasonable. E random lipid panel should be confirmed
Blood pressure measurements should with a fasting lipid panel. Evidence has
Treatment
be determined correctly, using the shown that improved glucose control
c Initial therapy may consist of correlates with a more favorable lipid
appropriate size cuff, and with the child
seated and relaxed. Hypertension optimization of glucose control and profile. However, improved glycemic
should be confirmed on at least three MNT using a Step 2 AHA diet aimed control alone will not reverse significant
separate days. Normal blood pressure at a decrease in the amount of dyslipidemia (514). Neither long-term
levels for age, sex, and height saturated fat in the diet. E safety nor cardiovascular outcome
c After the age of 10 years, the addition efficacy of statin therapy has been
and appropriate methods for
determinations are available online at of a statin in patients who, after MNT established for children. However,
www.nhlbi.nih.gov/health/prof/heart/ and lifestyle changes, have LDL studies have shown short-term safety
hbp/hbp_ped.pdf. cholesterol .160 mg/dL (4.1 mmol/L) equivalent to that seen in adults and
or LDL cholesterol .130 mg/dL (3.4 efficacy in lowering LDL cholesterol
iii. Dyslipidemia mmol/L) and one or more CVD risk levels, improving endothelial function
Recommendations factors is reasonable. E and causing regression of carotid
Screening c The goal of therapy is an LDL intimal thickening (515–517). Statins
c If there is a family history of cholesterol value ,100 mg/dL are not approved for use under the age
hypercholesterolemia or a (2.6 mmol/L). E of 10 years, and statin treatment
should generally not be used in disease in asymptomatic children with vi. Hypothyroidism
children with type 1 diabetes prior positive antibodies. E Recommendations
to this age. For postpubertal girls, c Children with biopsy-confirmed
c Consider screening children with type
issues of pregnancy prevention are celiac disease should be placed on a
1 diabetes for antithyroid peroxidase
paramount, since statins are category X gluten-free diet and have
and antithyroglobulin antibodies
in pregnancy (see Section VIII.B for consultation with a dietitian
soon after diagnosis. E
more information). experienced in managing both
c Measuring thyroid-stimulating
iv. Retinopathy diabetes and celiac disease. B
hormone (TSH) concentrations soon
Recommendations after diagnosis of type 1 diabetes,
c An initial dilated and comprehensive Celiac disease is an immune-mediated after metabolic control has been
eye examination should be disorder that occurs with increased established, is reasonable. If normal,
frequency in patients with type 1 consider rechecking every 1–2 years,
considered for the child at the start of
diabetes (1–16% of individuals especially if the patient develops
puberty or at age $10 years,
compared with 0.3–1% in the general symptoms of thyroid dysfunction,
whichever is earlier, once the youth
population) (519,520). Symptoms of thyromegaly, an abnormal growth
has had diabetes for 3–5 years. B
celiac disease include diarrhea, weight rate, or unusual glycemic variation. E
c After the initial examination, annual
routine follow-up is generally loss or poor weight gain, growth
failure, abdominal pain, chronic Autoimmune thyroid disease is the most
recommended. Less frequent
fatigue, malnutrition due to common autoimmune disorder
examinations may be acceptable on
malabsorption, and other associated with diabetes, occurring in
the advice of an eye care
gastrointestinal problems, and 17–30% of patients with type 1 diabetes
professional. E
unexplained hypoglycemia or erratic (524). About one-quarter of type 1
blood glucose concentrations. diabetic children have thyroid
Although retinopathy (like albuminuria)
autoantibodies at the time of diagnosis
most commonly occurs after the onset
Screening (525), and the presence of thyroid
of puberty and after 5–10 years of
Screening for celiac disease includes autoantibodies is predictive of thyroid
diabetes duration (518), it has been
measuring serum levels of tissue dysfunction, generally hypothyroidism
reported in prepubertal children and
transglutaminase or antiendomysial but less commonly hyperthyroidism
with diabetes duration of only 1–2 antibodies, then small-bowel biopsy in (526). Subclinical hypothyroidism may
years. Referrals should be made to eye antibody-positive children. European be associated with increased risk of
care professionals with expertise in guidelines on screening for celiac disease symptomatic hypoglycemia (527) and
diabetic retinopathy, an understanding in children (not specific to children with with reduced linear growth (528).
of retinopathy risk in the pediatric type 1 diabetes) suggested that biopsy Hyperthyroidism alters glucose
population, and experience in may not be necessary in symptomatic metabolism, potentially resulting in
counseling the pediatric patient and children with positive antibodies, as long deterioration of metabolic control.
family on the importance of early as further testing such as genetic or HLA
prevention/intervention. c. Self-Management
testing was supportive, but that
v. Celiac Disease asymptomatic at-risk children should No matter how sound the medical
have biopsies (521). One small study that regimen, it can only be as good as the
Recommendations
included children with and without type 1 ability of the family and/or individual to
c Consider screening children with type implement it. Family involvement
diabetes suggested that antibody-
1 diabetes for celiac disease by remains an important component of
positive but biopsy-negative children
measuring IgA antitissue optimal diabetes management
were similar clinically to those who were
transglutaminase or antiendomysial throughout childhood and adolescence.
biopsy-positive.
antibodies, with documentation of Health care providers who care for
normal total serum IgA levels, soon Treatment children and adolescents, therefore,
after the diagnosis of diabetes. E Biopsy-negative children had benefits must be capable of evaluating the
c Testing should be considered in from a gluten-free diet, but worsening educational, behavioral, emotional, and
children with a positive family history on a usual diet (522). This was a small psychosocial factors that impact
of celiac disease, growth failure, study, and children with type 1 diabetes implementation of a treatment plan and
failure to gain weight, weight loss, already follow a careful diet. However, it must work with the individual and
diarrhea, flatulence, abdominal pain, is difficult to advocate for not family to overcome barriers or redefine
or signs of malabsorption or in confirming the diagnosis by biopsy goals as appropriate.
children with frequent unexplained before recommending a lifelong gluten-
hypoglycemia or deterioration in free diet, especially in asymptomatic d. School and Day Care
glycemic control. E children. In symptomatic children with Since a large portion of a child’s day is
c Consider referral to a gastroenterologist type 1 diabetes and celiac disease, spent in school, close communication
for evaluation with possible endoscopy gluten-free diets reduce symptoms and with and cooperation of school or day
and biopsy for confirmation of celiac rates of hypoglycemia (523). care personnel is essential for optimal
diabetes management, safety, and specific recommendations, is found (32) provides guidance on the
maximal academic opportunities. See in the ADA position statement prevention, screening, and treatment of
the ADA position statement “Diabetes “Diabetes Care for Emerging Adults: type 2 diabetes and its comorbidities in
Care in the School and Day Care Setting” Recommendations for Transition From young people.
(529) for further discussion. Pediatric to Adult Diabetes Care 3. Monogenic Diabetes Syndromes
e. Transition From Pediatric to Adult Systems” (532). Monogenic forms of diabetes
Care The National Diabetes Education (neonatal diabetes or maturity-onset
Recommendations Program (NDEP) has materials available diabetes of the young) represent a
c As teens transition into emerging to facilitate the transition process small fraction of children with diabetes
adulthood, health care providers (http://ndep.nih.gov/transitions/), and (,5%), but readily available
and families must recognize their The Endocrine Society in collaboration commercial genetic testing now
many vulnerabilities B and with ADA and other organizations has enables a true genetic diagnosis with
prepare the developing teen, developed transition tools for clinicians increasing frequency. It is important
beginning in early to mid and youth/families (http://www.endo- to correctly diagnose one of the
adolescence and at least 1 year prior society.org/clinicalpractice/ monogenic forms of diabetes, as these
to the transition. E transition_of_care.cfm). children may be incorrectly diagnosed
c Both pediatricians and adult health 2. Type 2 Diabetes
with type 1 or type 2 diabetes, leading
care providers should assist in The CDC recently published projections to suboptimal treatment regimens and
providing support and links to for type 2 diabetes prevalence using the delays in diagnosing other family
resources for the teen and emerging SEARCH database. Assuming a 2.3% members.
adult. B annual increase, the prevalence of type The diagnosis of monogenic diabetes
2 diabetes in those under 20 years of age should be considered in children with
Care and close supervision of diabetes will quadruple in 40 years (31,38). Given the following situations:
management is increasingly shifted the current obesity epidemic,
from parents and other older adults distinguishing between type 1 and type c Diabetes diagnosed within the first six
throughout childhood and adolescence; 2 diabetes in children can be difficult. months of life.
however, the shift from pediatrics to Autoantigens and ketosis may be c Strong family history of diabetes but
adult health care providers often occurs present in a substantial number of without typical features of type 2
very abruptly as the older teen enters patients with features of type 2 diabetes diabetes (nonobese, low-risk ethnic
the next developmental stage referred (including obesity and acanthosis group).
to as emerging adulthood (530), nigricans). Such a distinction at c Mild fasting hyperglycemia (100–150
a critical period for young people who diagnosis is critical since treatment mg/dL [5.5–8.5 mmol]), especially if
have diabetes. During this period of regimens, educational approaches, young and nonobese.
major life transitions, youth begin to dietary counsel, and outcomes will c Diabetes but with negative auto-
move out of their parents’ home and differ markedly between the two antibodies without signs of obesity or
must become more fully responsible for diagnoses. insulin resistance.
their diabetes care including the many Type 2 diabetes has a significant
aspects of self-management, making A recent international consensus
incidence of comorbidities already
medical appointments, and financing present at the time of diagnosis (535). It
document discusses in further detail the
health care once they are no longer diagnosis and management of children
is recommended that blood pressure
covered under their parents health with monogenic forms of diabetes
measurement, a fasting lipid profile,
insurance (531,532). In addition to (536).
assessment for albumin excretion, and
lapses in health care, this is also a period dilated eye examination be performed
of deterioration in glycemic control, at diagnosis. Thereafter, screening B. Preconception Care
increased occurrence of acute guidelines and treatment Recommendations
complications, psycho-social- recommendations for hypertension, c A1C levels should be as close to
emotional-behavioral issues, and dyslipidemia, albumin excretion, and normal as possible (,7%) in an
emergence of chronic complications retinopathy in youth with type 2 individual patient before conception
(531–534). diabetes are similar to those for youth is attempted. B
Though scientific evidence continues to with type 1 diabetes. Additional c Starting at puberty, preconception
be limited, it is clear that early and problems that may need to be counseling should be incorporated in
ongoing attention be given to addressed include polycystic ovarian the routine diabetes clinic visit for all
comprehensive and coordinated disease and the various comorbidities women of childbearing potential. B
planning for seamless transition of all associated with pediatric obesity such as c Women with diabetes who are
youth from pediatric to adult health sleep apnea, hepatic steatosis, contemplating pregnancy should be
care (531,532). A comprehensive orthopedic complications, and evaluated and, if indicated, treated for
discussion regarding the challenges psychosocial concerns. The ADA diabetic retinopathy, nephropathy,
faced during this period, including consensus statement on this subject neuropathy, and CVD. B
c Medications used by such women participated in preconception care absolutely contraindicated during
should be evaluated prior to (range 1.0–1.7% of infants) was much pregnancy. Statins are category X
conception, since drugs commonly lower than the incidence in women who (contraindicated for use in pregnancy)
used to treat diabetes and its did not participate (range 1.4–10.9% of and should be discontinued before
complications may be infants) (104). One limitation of these conception, as should ACE inhibitors
contraindicated or not recommended studies is that participation in (539). ARBs are category C (risk cannot
in pregnancy, including statins, ACE preconception care was self-selected be ruled out) in the first trimester but
inhibitors, ARBs, and most noninsulin rather than randomized. Thus, it is category D (positive evidence of risk) in
therapies. E impossible to be certain that the lower later pregnancy and should generally be
c Since many pregnancies are malformation rates resulted fully from discontinued before pregnancy. Since
unplanned, consider the potential improved diabetes care. Nonetheless, many pregnancies are unplanned,
risks and benefits of medications that the evidence supports the concept that health care professionals caring for any
are contraindicated in pregnancy in malformations can be reduced or woman of childbearing potential should
all women of childbearing potential prevented by careful management of consider the potential risks and benefits
and counsel women using such diabetes before pregnancy (537). of medications that are contraindicated
medications accordingly. E in pregnancy. Women using
Planned pregnancies greatly facilitate
preconception diabetes care. medications such as statins or ACE
Major congenital malformations remain inhibitors need ongoing family planning
the leading cause of mortality and Unfortunately, nearly two-thirds of
pregnancies in women with diabetes are counseling. Among the oral antidiabetic
serious morbidity in infants of mothers agents, metformin and acarbose are
with type 1 and type 2 diabetes. unplanned, potentially leading to
malformations in infants of diabetic classified as category B (no evidence of
Observational studies indicate that the risk in humans) and all others as
risk of malformations increases mothers. To minimize the occurrence of
these devastating malformations, category C. Potential risks and benefits
continuously with increasing maternal of oral antidiabetic agents in the
glycemia during the first 6–8 weeks of beginning at the onset of puberty or at
diagnosis, all women with diabetes with preconception period must be carefully
gestation, as defined by first-trimester weighed, recognizing that data are
A1C concentrations. There is no childbearing potential should receive
1) education about the risk of insufficient to establish the safety of
threshold for A1C values below which these agents in pregnancy.
risk disappears entirely. However, malformations associated with
malformation rates above the 1–2% unplanned pregnancies and poor For further discussion of preconception
background rate of nondiabetic metabolic control and 2) use of effective care, see the ADA consensus statement
pregnancies appear to be limited to contraception at all times, unless the on preexisting diabetes and pregnancy
pregnancies in which first-trimester A1C patient has good metabolic control and (104) and the position statement (540).
concentrations are .1% above the is actively trying to conceive. A recent
study showed that preconception C. Older Adults
normal range for a nondiabetic
pregnant woman. counseling using simple educational Recommendations
tools enabled adolescent girls to make c Older adults who are functional,
Preconception Care well-informed decisions lasting up to 9 cognitively intact, and have
Preconception care of diabetes appears months (538). significant life expectancy should
to reduce the risk of congenital Women contemplating pregnancy need receive diabetes care with goals
malformations. Five nonrandomized to be seen frequently by a similar to those developed for
studies compared rates of major multidisciplinary team experienced in younger adults. E
malformations in infants between diabetes management both before and c Glycemic goals for some older adults
women who participated in during pregnancy. The goals of might reasonably be relaxed, using
preconception diabetes care programs preconception care are to 1) involve and individual criteria, but hyperglycemia
and women who initiated intensive empower the patient on diabetes leading to symptoms or risk of acute
diabetes management after they were management, 2) achieve the lowest A1C hyperglycemic complications should
already pregnant. The preconception test results possible without excessive be avoided in all patients. E
care programs were multidisciplinary hypoglycemia, 3) assure effective c Other cardiovascular risk factors
and designed to train patients in contraception until stable and should be treated in older adults with
diabetes self-management with diet, acceptable glycemia is achieved, and 4) consideration of the time frame of
intensified insulin therapy, and SMBG. identify, evaluate, and treat long-term benefit and the individual patient.
Goals were set to achieve normal blood diabetes complications such as Treatment of hypertension is
glucose concentrations, and .80% of retinopathy, nephropathy, neuropathy, indicated in virtually all older adults,
subjects achieved normal A1C hypertension, and CHD (104). and lipid and aspirin therapy may
concentrations before they became benefit those with life expectancy at
pregnant. In all five studies, the Drugs Contraindicated in Pregnancy least equal to the time frame of
incidence of major congenital Drugs commonly used in the diabetes primary or secondary prevention
malformations in women who treatment may be relatively or trials. E
c Screening for diabetes complications adults with diabetes is complicated by expected to live long enough to reap the
should be individualized in older their clinical and functional benefits of long-term intensive diabetes
adults, but particular attention heterogeneity. Some older individuals management, who have good cognitive
should be paid to complications developed diabetes years earlier and and functional function, and who choose
that would lead to functional may have significant complications; to do so via shared decision making may
impairment. E others who are newly diagnosed may be treated using therapeutic
have had years of undiagnosed diabetes interventions and goals similar to those
Diabetes is an important health with resultant complications or may for younger adults with diabetes. As with
condition for the aging population; at have truly recent-onset disease and few all patients, DSME and ongoing DSMS are
least 20% of patients over the age of 65 or no complications. Some older adults vital components of diabetes care for
years have diabetes, and this number with diabetes are frail and have other older adults and their caregivers.
can be expected to grow rapidly in the underlying chronic conditions, For patients with advanced diabetes
coming decades. Older individuals with substantial diabetes-related complications, life-limiting comorbid
diabetes have higher rates of premature comorbidity, or limited physical or illness, or substantial cognitive or
death, functional disability, and cognitive functioning. Other older functional impairment, it is reasonable
coexisting illnesses such as individuals with diabetes have little to set less intensive glycemic target
hypertension, CHD, and stroke than comorbidity and are active. Life goals. These patients are less likely to
those without diabetes. Older adults expectancies are highly variable for this benefit from reducing the risk of
with diabetes are also at greater risk population, but often longer than microvascular complications and more
than other older adults for several clinicians realize. Providers caring for likely to suffer serious adverse effects
common geriatric syndromes, such as older adults with diabetes must take this from hypoglycemia. However, patients
polypharmacy, depression, cognitive heterogeneity into consideration when with poorly controlled diabetes may be
impairment, urinary incontinence, setting and prioritizing treatment goals subject to acute complications of
injurious falls, and persistent pain. (Table 15). diabetes, including dehydration, poor
A consensus report on diabetes There are few long-term studies in older wound healing, and hyperglycemic
and older adults (541) influenced adults demonstrating the benefits of hyperosmolar coma. Glycemic goals at a
the following discussion and intensive glycemic, blood pressure, and minimum should avoid these
recommendations. The care of older lipid control. Patients who can be consequences.
Table 15—Framework for considering treatment goals for glycemia, blood pressure, and dyslipidemia in older adults
with diabetes
Fasting or Bedtime Blood
Patient characteristics/ Reasonable preprandial glucose pressure
health status Rationale A1C goal‡ glucose (mg/dL) (mg/dL) (mmHg) Lipids
Healthy (few coexisting Longer remaining life ,7.5% 90–130 90–150 ,140/80 Statin unless
chronic illnesses, intact expectancy contraindicated or not
cognitive and functional tolerated
status)
Complex/intermediate Intermediate remaining ,8.0% 90–150 100–180 ,140/80 Statin unless
(multiple coexisting life expectancy, high contraindicated or not
chronic illnesses* or 21 treatment burden, tolerated
instrumental ADL hypoglycemia
impairments or mild-to- vulnerability, fall risk
moderate cognitive
impairment)
Very complex/poor health Limited remaining life ,8.5%† 100–180 110–200 ,150/90 Consider likelihood of
(long-term care or end- expectancy makes benefit with statin
stage chronic illnesses** benefit uncertain (secondary prevention
or moderate-to-severe more so than primary)
cognitive impairment or
21 ADL dependencies)
This represents a consensus framework for considering treatment goals for glycemia, blood pressure, and dyslipidemia in older adults with diabetes.
The patient characteristic categories are general concepts. Not every patient will clearly fall into a particular category. Consideration of patient/
caregiver preferences is an important aspect of treatment individualization. Additionally, a patient’s health status and preferences may change over
time. ADL, activities of daily living. ‡A lower goal may be set for an individual if achievable without recurrent or severe hypoglycemia or undue
treatment burden. *Coexisting chronic illnesses are conditions serious enough to require medications or lifestyle management and may include
arthritis, cancer, CHF, depression, emphysema, falls, hypertension, incontinence, stage 3 or worse CKD, MI, and stroke. By multiple, we mean at least
three, but many patients may have five or more (132). **The presence of a single end-stage chronic illness such as stage 3-4 CHF or oxygen-
dependent lung disease, CKD requiring dialysis, or uncontrolled metastatic cancer may cause significant symptoms or impairment of functional
status and significantly reduce life expectancy. †A1C of 8.5% equates to an eAG of ;200 mg/dL. Looser glycemic targets than this may expose
patients to acute risks from glycosuria, dehydration, hyperglycemic hyperosmolar syndrome, and poor wound healing.
Although hyperglycemia control may be c Annual monitoring for complications treatment of persistent
important in older individuals with of diabetes is recommended, hyperglycemia starting at a
diabetes, greater reductions in morbidity beginning 5 years after the diagnosis threshold of no greater than 180
and mortality may result from control of of CFRD. E mg/dL (10 mmol/L). Once insulin
other cardiovascular risk factors rather than therapy is started, a glucose range
from tight glycemic control alone. There is CFRD is the most common comorbidity of 140–180 mg/dL (7.8–10 mmol/L)
strong evidence from clinical trials of the in persons with cystic fibrosis, occurring is recommended for the majority of
value of treating hypertension in the elderly in about 20% of adolescents and 40– critically ill patients. A
(542,543). There is less evidence for lipid- 50% of adults. Diabetes in this More stringent goals, such as 110–
lowering and aspirin therapy, although the population is associated with worse 140 mg/dL (6.1–7.8 mmol/L) may
benefits of these interventions for primary nutritional status, more severe be appropriate for selected
and secondary prevention are likely to inflammatory lung disease, and greater patients, as long as this can be
apply to older adults whose life mortality from respiratory failure. achieved without significant
expectancies equal or exceed the time Insulin insufficiency related to partial hypoglycemia. C
frames seen in clinical trials. fibrotic destruction of the islet mass is Critically ill patients require an
the primary defect in CFRD. Genetically intravenous insulin protocol that
Special care is required in prescribing determined function of the remaining has demonstrated efficacy and
and monitoring pharmacological b-cells and insulin resistance associated safety in achieving the desired
therapy in older adults. Costs may be a with infection and inflammation may glucose range without increasing
significant factor, especially since also play a role. Encouraging data risk for severe hypoglycemia. E
older adults tend to be on many suggest that improved screening Non–critically ill patients: There is
medications. Metformin may be (544,545) and aggressive insulin therapy no clear evidence for specific
contraindicated because of renal have narrowed the gap in mortality blood glucose goals. If treated
insufficiency or significant heart failure. between cystic fibrosis patients with with insulin, the premeal blood
Thiazolidinediones, if used at all, should and without diabetes, and have glucose targets generally ,140
be used very cautiously in those with, or eliminated the sex difference in mg/dL (7.8 mmol/L) with random
at risk for, CHF, and have also been mortality (546). Recent trials comparing blood glucose ,180 mg/dL (10.0
associated with fractures. Sulfonylureas, insulin with oral repaglinide showed no mmol/L) are reasonable,
other insulin secretagogues, and insulin significant difference between the provided these targets can be
can cause hypoglycemia. Insulin use groups. Insulin remains the most widely safely achieved. More stringent
requires that patients or caregivers have used therapy for CFRD (547). targets may be appropriate in
good visual and motor skills and
Recommendations for the clinical stable patients with previous
cognitive ability. DPP-4 inhibitors have
management of CFRD can be found in tight glycemic control. Less
few side effects, but their costs may be a
the recent ADA position statement on stringent targets may be
barrier to some older patients; the latter
this topic (548). appropriate in those with severe
is also the case for GLP-1 agonists.
comorbidities. E
Screening for diabetes complications in Scheduled subcutaneous insulin
older adults also should be IX. DIABETES CARE IN SPECIFIC
with basal, nutritional, and
SETTINGS
individualized. Particular attention correctional components is the
should be paid to complications that can A. Diabetes Care in the Hospital preferred method for achieving
develop over short periods of time and/ Recommendations and maintaining glucose control in
or that would significantly impair c Diabetes discharge planning should non–critically ill patients. C
functional status, such as visual and start at hospital admission, and clear Glucose monitoring should be
lower-extremity complications. diabetes management instructions initiated in any patient not known
should be provided at discharge. E to be diabetic who receives
D. Cystic Fibrosis–Related Diabetes c The sole use of sliding scale insulin in therapy associated with high risk
Recommendations the inpatient hospital setting is for hyperglycemia, including
c Annual screening for CFRD with OGTT discouraged. E high-dose glucocorticoid
should begin by age 10 years in all c All patients with diabetes admitted to therapy, initiation of enteral or
patients with cystic fibrosis who do not the hospital should have their parenteral nutrition, or other
have CFRD. B A1C as a screening test diabetes clearly identified in the medications such as octreotide or
for CFRD is not recommended. B medical record. E immunosuppressive medications. B
c During a period of stable health, the c All patients with diabetes should have If hyperglycemia is documented
diagnosis of CFRD can be made in an order for blood glucose monitoring, and persistent, consider treating
cystic fibrosis patients according to with results available to all members of such patients to the same glycemic
usual glucose criteria. E the health care team. E goals as in patients with known
c Patients with CFRD should be treated c Goals for blood glucose levels: diabetes. E
with insulin to attain individualized Critically ill patients: Insulin A hypoglycemia management
glycemic goals. A therapy should be initiated for protocol should be adopted and
implemented by each hospital or diabetes) to poor outcomes. Cohort ,140 mg/dL and that a highly stringent
hospital system. A plan for studies as well as a few early RCTs target of ,110 mg/dL may actually be
preventing and treating suggested that intensive treatment of dangerous.
hypoglycemia should be hyperglycemia improved hospital In a meta-analysis of 26 trials (N 5
established for each patient. outcomes (549–551). In general, these 13,567), which included the NICE-
Episodes of hypoglycemia in the studies were heterogeneous in terms of SUGAR data, the pooled RR of death
hospital should be documented in patient population, blood glucose with intensive insulin therapy was 0.93
the medical record and tracked. E targets and insulin protocols used, as compared with conventional therapy
Consider obtaining an A1C in provision of nutritional support and the (95% CI 0.83–1.04) (557). Approximately
patients with diabetes admitted to proportion of patients receiving insulin, half of these trials reported
the hospital if the result of testing which limits the ability to make hypoglycemia, with a pooled RR of
in the previous 2–3 months is not meaningful comparisons among them. intensive therapy of 6.0 (95% CI 4.5–
available. E Trials in critically ill patients have failed 8.0). The specific ICU setting influenced
Consider obtaining an A1C in to show a significant improvement in the findings, with patients in surgical
patients with risk factors for mortality with intensive glycemic ICUs appearing to benefit from intensive
undiagnosed diabetes who exhibit control (552,553) or have even shown insulin therapy (RR 0.63 [95% CI 0.44–
hyperglycemia in the hospital. E increased mortality risk (554). 0.91]), while those in other medical and
Patients with hyperglycemia in the Moreover, these recent RCTs have mixed critical care settings did not. It
hospital who do not have a prior highlighted the risk of severe was concluded that, overall, intensive
diagnosis of diabetes should have hypoglycemia resulting from such insulin therapy increased the risk of
appropriate plans for follow-up efforts (552–557). hypoglycemia but provided no overall
testing and care documented at The largest study to date, NICE- benefit on mortality in the critically ill,
discharge. E SUGAR, a multicenter, multinational although a possible mortality benefit to
RCT, compared the effect of intensive patients admitted to the surgical ICU
Hyperglycemia in the hospital can
glycemic control (target 81–108 mg/dL, was suggested.
represent previously known diabetes,
mean blood glucose attained
previously undiagnosed diabetes, or 1. Glycemic Targets in Hospitalized
115 mg/dL) to standard glycemic
hospital-related hyperglycemia (fasting Patients
control (target 144–180 mg/dL, mean
blood glucose $126 mg/dL or random
blood glucose attained 144 mg/dL) on Definition of Glucose Abnormalities in
blood glucose $200 mg/dL occurring
outcomes among 6,104 critically ill the Hospital Setting
during the hospitalization that reverts to Hyperglycemia in the hospital has been
participants, almost all of whom
normal after hospital discharge). The required mechanical ventilation (554). defined as any blood glucose .140 mg/
difficulty distinguishing between the Ninety-day mortality was significantly dL (7.8 mmol/L). Levels that are
second and third categories during the higher in the intensive versus the significantly and persistently above this
hospitalization may be overcome by conventional group in both surgical and may require treatment in hospitalized
measuring an A1C in undiagnosed medical patients, as was mortality from patients. A1C values .6.5% suggest, in
patients with hyperglycemia, as long as cardiovascular causes. Severe undiagnosed patients, that diabetes
conditions interfering with A1C utility hypoglycemia was also more common preceded hospitalization (558).
(hemolysis, blood transfusion) have not in the intensively treated group (6.8% Hypoglycemia has been defined as any
occurred. Hyperglycemia management vs. 0.5%; P , 0.001). The precise reason blood glucose ,70 mg/dL (3.9 mmol/L).
in the hospital has been considered for the increased mortality in the This is the standard definition in
secondary in importance to the tightly controlled group is unknown. outpatients and correlates with the
condition that prompted admission. The study results lie in stark contrast initial threshold for the release of
However, a body of literature now to a 2001 single-center study that counter-regulatory hormones. Severe
supports targeted glucose control in the reported a 42% relative reduction hypoglycemia in hospitalized patients
hospital setting for potential improved in intensive care unit (ICU) mortality in has been defined by many as ,40 mg/
clinical outcomes. Hyperglycemia in the critically ill surgical patients treated dL (2.2 mmol/L), although this is lower
hospital may result from stress, to a target blood glucose of 80–110 mg/dL than the ;50 mg/dL (2.8 mmol/L) level
decompensation of type 1 or type 2 or (549). Importantly, the control group in at which cognitive impairment begins in
other forms of diabetes, and/or may be NICE-SUGAR had reasonably good blood normal individuals (559). Both hyper-
iatrogenic due to withholding of glucose management, maintained at a and hypoglycemia among inpatients are
antihyperglycemic medications or mean glucose of 144 mg/dL, only associated with adverse short- and
administration of hyperglycemia- 29 mg/dL above the intensively managed long-term outcomes. Early recognition
provoking agents such as patients. This study’s findings do not and treatment of mild to moderate
glucocorticoids or vasopressors. disprove the notion that glycemic control hypoglycemia (40–69 mg/dL [2.2–3.8
There is substantial observational in the ICU is important. However, they do mmol/L]) can prevent deterioration to a
evidence linking hyperglycemia in strongly suggest that it may not be more severe episode with potential
hospitalized patients (with or without necessary to target blood glucose values adverse sequelae (560).
Critically Ill Patients comorbidities, as well as in those in feedings and with high dose
Based on the weight of the available patient-care settings where frequent glucocorticoid therapy (560).
evidence, for the majority of critically ill glucose monitoring or close nursing There are no data on the safety and
patients in the ICU setting, insulin supervision is not feasible. efficacy of oral agents and injectable
infusion should be used to control
Clinical judgment, combined with noninsulin therapies such as GLP-1
hyperglycemia, with a starting threshold
ongoing assessment of the patient’s analogs and pramlintide in the hospital.
of no higher than 180 mg/dL (10.0
clinical status, including changes in the They appear to have a limited role in
mmol/L). Once intravenous insulin is
trajectory of glucose measures, the hyperglycemia management in
started, the glucose level should be
severity of illness, nutritional status, or conjunction with acute illness.
maintained between 140 and 180 mg/dL
concomitant medications that might Continuation of these agents may be
(7.8 and 10.0 mmol/L). Greater benefit
affect glucose levels (e.g., steroids, appropriate in selected stable patients
maybe realized at the lower end of this
octreotide) must be incorporated into who are expected to consume meals at
range. Although strong evidence is
the day-to-day decisions regarding regular intervals. They may be initiated
lacking, lower glucose targets may be
insulin dosing (560). or resumed in anticipation of discharge
appropriate in selected patients. One
once the patient is clinically stable.
small study suggested that ICU patients 2. Antihyperglycemic Agents in Specific caution is required with
treated to targets of 120–140 had less Hospitalized Patients metformin, due to the possibility that a
negative nitrogen balance than those In most clinical situations in the hospital, contraindication may develop during
treated to higher targets (561). insulin therapy is the preferred method the hospitalization, such as renal
However, targets ,110 mg/dL of glycemic control (560). In the ICU, insufficiency, unstable hemodynamic
(6.1 mmol/L) are not recommended. intravenous infusion is the preferred status, or need for an imaging study that
Insulin infusion protocols with route of insulin administration. When requires a radiocontrast dye.
demonstrated safety and efficacy, the patient is transitioned off
resulting in low rates of hypoglycemia, intravenous insulin to subcutaneous 3. Preventing Hypoglycemia
are highly recommended (560). therapy, precautions should be taken to Patients with or without diabetes may
prevent hyperglycemia escape experience hypoglycemia in the hospital
Non–critically Ill Patients setting in association with altered
With no prospective RCT data to inform (564,565). Outside of critical care units,
scheduled subcutaneous insulin that nutritional state, heart failure, renal or
specific glycemic targets in non– liver disease, malignancy, infection, or
critically ill patients, recommendations delivers basal, nutritional, and
correctional (supplemental) sepsis. Additional triggering events
are based on clinical experience and leading to iatrogenic hypoglycemia
judgment (562). For the majority of components is recommended. Typical
dosing schemes are based on body include sudden reduction of
non–critically ill patients treated with corticosteroid dose, altered ability of
insulin, premeal glucose targets should weight, with some evidence that
patients with renal insufficiency should the patient to report symptoms,
generally be ,140 mg/dL (7.8 mmol/L) reduced oral intake, emesis, new NPO
with random blood glucose ,180 mg/dL be treated with lower doses (566).
status, inappropriate timing of short- or
(10.0 mmol/L), as long as these targets The sole use of sliding scale insulin is rapid-acting insulin in relation to meals,
can be safely achieved. To avoid strongly discouraged in hospitalized reduced infusion rate of intravenous
hypoglycemia, consideration should be patients. A more physiological insulin dextrose, and unexpected interruption
given to reassessing the insulin regimen regimen including basal, prandial, and of enteral feedings or parenteral
if blood glucose levels fall below correctional insulin is recommended. nutrition.
100 mg/dL (5.6 mmol/L). Modifying the The insulin regimen must also
regimen is required when blood glucose Despite the preventable nature of
incorporate prandial carbohydrate
values are ,70 mg/dL (3.9 mmol/L), many inpatient episodes of
intake (567). For type 1 diabetic
unless the event is easily explained by hypoglycemia, institutions are more
patients, dosing insulin solely based on
other factors (such as a missed meal). likely to have nursing protocols for
premeal glucose would likely deliver
There is some evidence that systematic hypoglycemia treatment than for its
suboptimal insulin doses and may
attention to hyperglycemia in the prevention. Tracking such episodes
potentially lead to DKA. It increases both
emergency room leads to better and analyzing their causes are
hypoglycemia and hyperglycemia risks
glycemic control in the hospital for important quality improvement
and has been shown in a randomized
those subsequently admitted (563). activities (295).
trial to be associated with adverse
Patients with a prior history of outcomes in general surgery patients 4. Diabetes Care Providers in the
successful tight glycemic control in the with type 2 diabetes (568). The reader is Hospital
outpatient setting who are clinically referred to publications and reviews Inpatient diabetes management may be
stable may be maintained with a glucose that describe currently available insulin effectively championed and/or provided
range below the aforementioned cut preparations and protocols and provide by primary care physicians,
points. Conversely, higher glucose guidance in use of insulin therapy in endocrinologists, intensivists, or
ranges may be acceptable in terminally specific clinical settings including hospitalists. Involvement of
ill patients or in patients with severe parenteral nutrition (569), enteral tube appropriately trained specialists or
specialty teams may reduce length of calories to meet metabolic demands, commercially available capillary blood
stay, improve glycemic control, and and create a discharge plan for follow- glucose meters introduce a correction
improve outcomes (560). Standardized up care (551,573). The ADA does not factor of ;1.12 to report a “plasma-
orders for scheduled and correction- endorse any single meal plan or adjusted” value (578).
dose insulin should be implemented, specified percentages of macronutrients, Significant discrepancies between
and sole reliance on a sliding scale and the term “ADA diet” should no capillary, venous, and arterial plasma
regimen strongly discouraged. As longer be used. Current nutrition samples have been observed in patients
hospitals move to comply with recommendations advise with low or high hemoglobin
“meaningful use” regulations for individualization based on treatment concentrations, hypoperfusion, and the
electronic health records, as mandated goals, physiological parameters, and presence of interfering substances
by the Health Information Technology medication use. Consistent particularly maltose, as contained in
Act, efforts should be made to assure carbohydrate meal plans are preferred immunoglobulins (579). Analytical
that all components of structured by many hospitals since they facilitate variability has been described with
insulin order sets are incorporated into matching the prandial insulin dose to the several meters (580). Increasingly
electronic insulin order sets (570,571). amount of carbohydrate consumed newer generation POC blood glucose
A team approach is needed to establish (574). Because of the complexity of meters correct for variation in
hospital pathways. To achieve glycemic nutrition issues in the hospital, a hematocrit and for interfering
targets associated with improved registered dietitian, knowledgeable and substances. Any glucose result that
hospital outcomes, hospitals will need skilled in MNT, should serve as an does not correlate with the patient’s
multidisciplinary support to develop inpatient team member. The dietitian is status should be confirmed through
insulin management protocols that responsible for integrating information conventional laboratory sampling of
effectively and safely enable about the patient’s clinical condition, plasma glucose. The FDA has become
achievement of glycemic targets (572). eating, and lifestyle habits and for increasingly concerned about the use of
establishing treatment goals in order to POC blood glucose meters in the
5. Self-Management in the Hospital determine a realistic plan for nutrition hospital and is presently reviewing
Diabetes self-management in the hospital therapy (116). matters related to their use.
may be appropriate for competent youth 7. Bedside Blood Glucose Monitoring
8. Discharge Planning and DSME
and adult patients who have a stable level Bedside POC blood glucose monitoring Transition from the acute care setting
of consciousness and reasonably stable is used to guide insulin dosing. In the is a high-risk time for all patients, not
daily insulin requirements, successfully patient receiving nutrition, the timing just those with diabetes or new
conduct self-management of diabetes at of glucose monitoring should match hyperglycemia. Although there is an
home, have physical skills needed to carbohydrate exposure. In the patient extensive literature concerning safe
successfully self-administer insulin and not receiving nutrition, glucose transition within and from the hospital,
perform SMBG, have adequate oral monitoring is performed every 4–6 h little of it is specific to diabetes (581).
intake, are proficient in carbohydrate (575,576). More frequent blood glucose Diabetes discharge planning is not a
counting, use multiple daily insulin testing ranging from every 30 min to separate entity, but is an important part
injections or insulin pump therapy, and every 2 h is required for patients on of an overall discharge plan. As such,
understand sick-day management. The intravenous insulin infusions. discharge planning begins at
patient and physician, in consultation
Safety standards should be established admission to the hospital and is
with nursing staff, must agree that
for blood glucose monitoring updated as projected patient needs
patient self-management is appropriate
prohibiting sharing of finger-stick change.
while hospitalized.
lancing devices, lancets, needles, and Inpatients may be discharged to varied
Patients who use CSII pump therapy in meters to reduce the risk of settings, including home (with or without
the outpatient setting can be candidates transmission of blood-borne diseases. visiting nurse services), assisted living,
for diabetes self-management in the Shared lancing devices carry essentially rehabilitation, or skilled nursing facilities.
hospital, provided that they have the the same risk as sharing syringes and The latter two sites are generally staffed
mental and physical capacity to do so needles (577). by health professionals, so diabetes
(560). A hospital policy and procedures
Accuracy of blood glucose discharge planning will be limited to
delineating inpatient guidelines for CSII
measurements using POC meters has communication of medication and diet
therapy are advisable, and availability
limitations that must be considered. orders. For the patient who is discharged
of hospital personnel with expertise in
Although the FDA allows a 1/2 20% to assisted living or to home, the optimal
CSII therapy is essential. It is important
error for blood glucose meters, program will need to consider the type
that nursing personnel document basal
questions about the appropriateness of and severity of diabetes, the effects of the
rates and bolus doses taken on a daily
these criteria have been raised (388). patient’s illness on blood glucose levels,
basis.
Glucose measures differ significantly and the capacities and desires of the
6. MNT in the Hospital between plasma and whole blood, terms patient. Smooth transition to outpatient
The goals of MNT are to optimize that are often used interchangeably and care should be ensured. The Agency for
glycemic control, provide adequate can lead to misinterpretation. Most Healthcare Research and Quality
recommends that, at a minimum, DSME should start upon admission or as plan for determining the cause of
discharge plans include the following: soon as feasible, especially in those new hyperglycemia, related complications
to insulin therapy or in whom the and comorbidities, and recommended
c Medication reconciliation: the diabetes regimen has been substantially treatments can assist outpatient
patient’s medications must be cross- altered during the hospitalization. providers as they assume ongoing
checked to ensure that no chronic care.
It is recommended that the following
medications were stopped and to
areas of knowledge be reviewed and B. Diabetes and Employment
ensure the safety of new
addressed prior to hospital discharge: Any person with diabetes, whether
prescriptions.
c Prescriptions for new or changed insulin treated or noninsulin treated,
c Identification of the health care
medication should be filled and should be eligible for any employment
provider who will provide diabetes for which he or she is otherwise
reviewed with the patient and care after discharge
family at or before discharge qualified. Employment decisions should
c Level of understanding related to the
c Structured discharge never be based on generalizations or
diagnosis of diabetes, SMBG, and stereotypes regarding the effects of
communication: Information on explanation of home blood glucose goals
medication changes, pending tests diabetes. When questions arise about
c Definition, recognition, treatment,
and studies, and follow-up needs the medical fitness of a person with
and prevention of hyperglycemia and diabetes for a particular job, a health
must be accurately and promptly hypoglycemia
communicated to outpatient care professional with expertise in
c Information on consistent eating
physicians. treating diabetes should perform an
patterns individualized assessment. See the ADA
c Discharge summaries should be
c When and how to take blood
transmitted to the primary physician position statement on diabetes and
glucose–lowering medications employment (583).
as soon as possible after discharge. including insulin administration (if
c Appointment keeping behavior is
going home on insulin) C. Diabetes and Driving
enhanced when the inpatient team c Sick-day management A large percentage of people with
schedules outpatient medical c Proper use and disposal of needles diabetes in the U.S. and elsewhere
follow-up prior to discharge. Ideally and syringes seek a license to drive, either for
the inpatient care providers or case
personal or employment purposes.
managers/discharge planners will It is important that patients be provided There has been considerable debate
schedule follow-up visit(s) with with appropriate durable medical whether, and the extent to which,
the appropriate professionals, equipment, medication, supplies and diabetes may be a relevant factor in
including primary care provider, prescriptions at the time of discharge in determining the driver ability and
endocrinologist, and diabetes order to avoid a potentially dangerous eligibility for a license.
educator (582). hiatus in care. These supplies/
People with diabetes are subject to a
prescriptions should include the
Teaching diabetes self-management to great variety of licensing requirements
following:
patients in hospitals is a challenging applied by both state and federal
task. Patients are ill, under increased c Insulin (vials or pens) if needed jurisdictions, which may lead to loss of
stress related to their hospitalization c Syringes or pen needles (if needed) employment or significant restrictions
and diagnosis, and in an environment c Oral medications (if needed) on a person’s license. Presence of a
not conducive to learning. Ideally, c Blood glucose meter and strips medical condition that can lead to
people with diabetes should be taught c Lancets and lancing device significantly impaired consciousness or
at a time and place conducive to c Urine ketone strips (type 1) cognition may lead to drivers being
learning: as an outpatient in a c Glucagon emergency kit (insulin evaluated for fitness to drive. For
recognized program of diabetes treated) diabetes, this typically arises when
education. For the hospitalized patient, c Medical alert application/charm the person has had a hypoglycemic
diabetes “survival skills” education is episode behind the wheel, even if
generally a feasible approach to provide More expanded diabetes education can this did not lead to a motor vehicle
sufficient information and training to be arranged in the community. An accident.
enable safe care at home. Patients outpatient follow-up visit with the Epidemiological and simulator data
hospitalized because of a crisis related primary care provider, endocrinologist, suggest that people with insulin-treated
to diabetes management or poor care at or diabetes educator within 1 month of diabetes have a small increase in risk of
home require education to prevent discharge is advised for all patients motor vehicle accidents, primarily due
subsequent episodes of hospitalization. having hyperglycemia in the hospital. to hypoglycemia and decreased
Assessing the need for a home health Clear communication with outpatient awareness of hypoglycemia. This
referral or referral to an outpatient providers either directly or via hospital increase (RR 1.12–1.19) is much smaller
diabetes education program should be discharge summaries facilitates safe than the risks associated with teenage
part of discharge planning for all transitions to outpatient care. Providing male drivers (RR 42), driving at night
patients. information regarding the cause or the (RR 142), driving on rural roads
compared with urban roads (RR 9.2), individual patient preferences, with chronic disease: 1) delivery system
and obstructive sleep apnea (RR 2.4), all prognoses, and comorbidities. B design (moving from a reactive to a
of which are accepted for unrestricted c A patient-centered communication proactive care delivery system where
licensure. style should be used that planned visits are coordinated through a
The ADA position statement on diabetes incorporates patient preferences, team-based approach, 2) self-
and driving (584) recommends against assesses literacy and numeracy, management support, 3) decision
blanket restrictions based on the and addresses cultural barriers to support (basing care on evidence-
diagnosis of diabetes and urges care. B based, effective care guidelines),
individual assessment by a health care 4) clinical information systems (using
professional knowledgeable in diabetes There has been steady improvement in registries that can provide patient-
if restrictions on licensure are being the proportion of diabetic patients specific and population-based support
considered. Patients should be achieving recommended levels of A1C, to the care team), 5) community
evaluated for decreased awareness of blood pressure, and LDL cholesterol in resources and policies (identifying or
hypoglycemia, hypoglycemia episodes the last 10 years, both in primary care developing resources to support
while driving, or severe hypoglycemia. settings and in endocrinology practices. healthy lifestyles), and 6) health
Patients with retinopathy or peripheral Mean A1C nationally has declined from systems (to create a quality-oriented
neuropathy require assessment to 7.82% in 1999–2000 to 7.18% in 2004 culture). Redefinition of the roles of the
determine if those complications based on NHANES data (586). This has clinic staff and promoting self-
interfere with operation of a motor been accompanied by improvements in management on the part of the patient
vehicle. Health care professionals lipids and blood pressure control and led are fundamental to the successful
should be cognizant of the potential risk to substantial reductions in end-stage implementation of the CCM (591).
of driving with diabetes and counsel microvascular complications in those Collaborative, multidisciplinary teams
their patients about detecting and with diabetes. Nevertheless, between are best suited to provide such care for
avoiding hypoglycemia while driving. 33.4 to 48.7% of patients with diabetes people with chronic conditions such as
still do not meet targets for glycemic, diabetes and to facilitate patients’
D. Diabetes Management in blood pressure, and cholesterol control, performance of appropriate self-
Correctional Institutions and only 14.3% meet targets for the management (222,224,287,592).
People with diabetes in correctional combination of all three measures and NDEP maintains an online resource
facilities should receive care that meets nonsmoking status (317). Evidence also (www.betterdiabetescare.nih.gov) to
national standards. Because it is suggests that progress in risk factor help health care professionals design
estimated that nearly 80,000 inmates control (particularly tobacco use) may and implement more effective health
have diabetes, correctional institutions be slowing (317,587). Certain patient care delivery systems for those with
should have written policies and groups, such as patients with complex diabetes. Three specific objectives, with
procedures for the management of comorbidities, financial or other social references to literature that outlines
diabetes and for training of medical and hardships, and/or limited English practical strategies to achieve each, are
correctional staff in diabetes care proficiency, may present particular outlined below.
practices. See the ADA position challenges to goal-based care (588,589).
statement on diabetes management in Persistent variation in quality of Objective 1: Optimize Provider and
correctional institutions (585) for diabetes care across providers and Team Behavior
further discussion. across practice settings even after The care team should prioritize timely
and appropriate intensification of
adjusting for patient factors indicates
lifestyle and/or pharmaceutical
X. STRATEGIES FOR IMPROVING that there remains potential for
therapy of patients who have not
DIABETES CARE substantial further improvements in
achieved beneficial levels of blood
Recommendations
diabetes care.
pressure, lipid, or glucose control (593).
c Care should be aligned with While numerous interventions to Strategies such as explicit goal setting
components of the Chronic Care improve adherence to the with patients (594); identifying and
Model (CCM) to ensure productive recommended standards have been addressing language, numeracy, or
interactions between a prepared implemented, a major barrier to optimal cultural barriers to care (595–598);
proactive practice team and an care is a delivery system that too often is integrating evidence-based guidelines
informed activated patient. A fragmented, lacks clinical information and clinical information tools into the
c When feasible, care systems should capabilities, often duplicates services, process of care (599–601); and
support team-based care, community and is poorly designed for the incorporating care management teams
involvement, patient registries, and coordinated delivery of chronic care. including nurses, pharmacists, and
embedded decision support tools to The CCM has been shown to be an other providers (602–604) have each
meet patient needs. B effective framework for improving the been shown to optimize provider and
c Treatment decisions should be timely quality of diabetes care (590). The CCM team behavior and thereby catalyze
and based on evidence-based includes six core elements for the reduction in A1C, blood pressure, and
guidelines that are tailored to provision of optimal care of patients LDL cholesterol.
Objective 2: Support Patient Behavior incentives to improve diabetes population in 1988–2006. Diabetes Care
Change care (620). 2010;33:562–568
Successful diabetes care requires a 12. Picón MJ, Murri M, Mu~noz A, Fernández-
It is clear that optimal diabetes Garcı́a JC, Gomez-Huelgas R, Tinahones FJ.
systematic approach to supporting
management requires an organized, Hemoglobin A1c versus oral glucose
patients’ behavior change efforts,
systematic approach and involvement tolerance test in postpartum diabetes
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ADA 2014 - Standards of Medical Care in Diabetes

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S14 Diabetes Care Volume 37, Supplement 1, January 2014

Standards of Medical Care in American Diabetes Association

recommendations are not intended to preclude clinical judgment and must be

I. CLASSIFICATION AND DIAGNOSIS

c Type 1 diabetes (due to b-cell destruction, usually leading to absolute insulin

Some patients cannot be clearly classiﬁed as type 1 or type 2 diabetic.

Alcohol therapy or individualized education protein (158–160). A variety of eating

Pre-exercise Evaluation of the Retinopathy. In the presence of c It is reasonable to include assessment

alter glycemic measures, A number of interventions have been renin-angiotensin-aldosterone system

Table 13—Management of CKD in diabetes although tight targets (systolic ,120

c A multidisciplinary approach is examination to identify high-risk (e.g., smoking, hypertension,

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