I n t r o d u c t i o n

Diabetes and Hypertension: A Comprehensive

Report on Management and the Prevention of
Cardiovascular and Renal Complications
Yehuda Handelsman, MD

e are witnessing a global epidemic of diabetes. A recent report in 2011 by the Centers
for Disease Control and Prevention (CDC) estimates the number of people with diabetes in the
United States at 26 million, which is 11.3% of
adults older than 20 years.1 Seven million of
those are not aware that they have diabetes.
More alarming is the number of people with prediabetes, which is estimated at 79 million, corresponding to more than a third of adults older
than 20. According to the CDC, prediabetes
raises the risk of type 2 diabetes, heart disease,
and stroke.1 In 2008, the CDC estimated the
number of persons with diabetes to be 23.6 million and those with prediabetes to be 57 million.
This increase in such a short time underscores the
urgently progressive rate of the epidemic. In fact,
nearly 50% of adults older than 20 have some
form of dysglycemia, which increases their risk
for complications, including microvascular and
macrovascular disease (in particular kidney disease), retinopathy, blindness, amputation, and
cardiovascular disease (CVD).1,2 Half of all
Americans 65 years and older have prediabetes,
and nearly 27% have diabetes.1 Diabetes is the
seventh leading cause of death in the United
States and costs $174 billion annually.1

From the Metabolic Institute of America, Tarzana, CA

Address for correspondence:
Yehuda Handelsman, MD, Metabolic Institute of
America, 18372 Clark Street #212, Tarzana, CA
91356
E-mail: [email protected]

doi: 10.1111/j.1751-7176.2011.00453.x

VOL. 13 NO. 4 APRIL 2011

The majority of persons with diabetes and the

metabolic syndrome have hypertension that is associated with obesity, insulin resistance (IR), and dyslipidemia.3 Approximately 75% to 76% of people
with diabetes, prediabetes, and the metabolic syndrome have hypertension.46 Patients with diabetes
are 2 to 4 times more likely to develop CVD compared with patients without diabetes.7 However,
patients with diabetes and hypertension have a further increased risk of developing macrovascular
and microvascular disease and kidney disease,
including end-stage kidney disease.2,6,8 Hypertension often precedes type 2 diabetes; alternatively,
diabetes may precede hypertension.2,6 The etiologic factors linking diabetes and hypertension are
not fully clear. Genetic factors, IR, inflammation,
the renin-angiotensin-aldosterone system (RAAS),
sodium retention, and hyperglycemia are implicated.912 The activation of the RAAS system and
IR may trigger production of reactive oxygen species and increased oxidative stress, which may lead
to endothelial dysfunction and atherogenesis.911
Intensive treatment of hypertension as part of the
management of diabetes will result in reduced risk
of microvascular and macrovascular diseases such
as myocardial infarction, congestive heart failure,
blindness, and chronic kidney disease.2,13
The goal recommended by the American
Diabetes Association (ADA) and the American
Association of Clinical Endocrinologists (AACE)
for treating hypertension in diabetes is a blood pressure (BP) goal of <130 80 mm Hg.14,15 This goal
has been under attack recently based on recent published results from studies such as the Action to Control Cardiovascular Risk in Diabetes (ACCORD)

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hypertension trial and the Investigational Vertebroplasty Efficacy and Safety Trial (INVEST).16,17
Results from the Veterans Affairs Diabetes Trial
(VADT) point out increased rates of CVD when systolic BP is >140 mm Hg and diastolic BP is <70
mm Hg, perhaps underscoring the importance of
pulse pressure, although this study also emphasizes
the need for prompt treatment.18
The mainstay of treating hypertension and diabetes is lifestyle modification and, in particular,
implementation of the Dietary Approaches to Stop
Hypertension (DASH) diet.1,19 The comprehensive
approach to managing diabetes and preventing
complication is one that addresses all risk factors.
A good example of this was performed in the Multifactorial Intervention and CVD Events in Type 2
Diabetes (Steno-2) trial. This investigation reported that during 7.8 years, there was a significant
(P=.007) reduction of 53% in the composite end
point of nonfatal myocardial infarction, cardiovascular death, coronary artery bypass graft surgery,
percutaneous transluminal coronary angioplasty,
nonfatal stroke, cardiovascular death, amputation,
peripheral vascular surgery, and a 13-year reduction in mortality comparing intense (50%) vs conventional (30%) care (P=.02).20,21
The recommended initial treatment of hypertension in diabetes is an angiotensin-converting
enzyme (ACE) inhibitor or angiotensin receptor
blocker (ARB),14,15 but what should be the second
and third drug has become controversial, particularly as drugs such as amlodipine are challenging
the traditional thiazides. An interesting result from
the ACCORD trial was that treating hypertension
in diabetes was beneficial in reducing kidney disease but not retinopathy,16 and in persons with prediabetes, the ARB valsartan reduced development
of new-onset diabetes but had no effect on reducing
microvascular or macrovascular disease.22
Understanding the need to address hypertension
management in diabetes and recognizing its important role in morbidity and mortality, I am appreciative of the invitation I received from The Journal of
Clinical Hypertension and its Editor in Chief, Dr
Michael Weber, to serve as the guest editor of this
focus issue of the Journal. We decided to add
key issues in the clinical management of hypertension in diabetes, prediabetes, dyslipidemia, and
its comorbidities. Knowing that there are areas of
uncertainty, conflicting data, and controversies, we
invited globally recognized and established leaders
in their respective fields of diabetes. We asked them
to write expert review articles, commentaries, and
even to join in debate, thus allowing them to

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complement the available information with their

own opinions and scientific expertise.
The issue starts with pathophysiology. Drs
Willa A. Hsueh and Kathleen Wyne examine the
role of the RAAS system in the development of
both hypertension and diabetes and its potential
effect on CVD. Dr Gerald Reaven, one of the first
scientists to recognize the background of what
came to be known as the metabolic syndrome,
examines the relationships among IR, diabetes,
hypertension, and CVD, providing critically
needed background to this complex clinical constellation. Drs Samuel Dagogo-Jack and Amanda
Long discuss the comorbidities of hypertension
and diabetes and propose how understanding their
mechanisms helps provide an approach to target
organ protection.
One of the direct complications of diabetes
aggravated by hypertension is chronic kidney disease. Drs Ele Ferrannini and Anna Solini discuss
the pathophysiology, diagnosis, and management
of this critical condition that accounts for the
majority of patients who require hemodialysis in
this country. The recommended BP goal in treating
hypertension of 130 80 mm Hg in patients with
diabetes proposed by the major societies (ADA,
AACE, National Kidney Foundation) has been
questioned lately. Drs David Kendall (pro) and
George Bakris (con) are debating the appropriate
goal. This is a difficult area and these experts
provide valuable insights in setting appropriate
targets.
A most important populationprobably the
largestis comprised of people with prediabetes,
often with other features of the (cardio)metabolic
syndrome. This population does not have established management guidelines, although there have
been statements by the AACE. Dr Alan Garber
addresses this condition and its complications, providing guidance on its diagnosis and management
designed to slow the development of diabetes and
CVD. Another group of patients with special issues
are women with diabetes and hypertension in pregnancy. Drs Shanon Sullivan, Jason Umans, and
Robert Ratner evaluate the consequence of these
two conditions on the mother and the fetus during
pregnancy, discussing management to prevent
complications. In recent years, we are also paying
attention to the pharmaceutical management of
hypertension in diabetes. Where do drugs such as
ACE inhibitors, ARBs, and diuretics fit in? Are
b-blockers contraindicated? Or is the only priority
BP control and which drug should be used is a less
important question? Dr Eberhard Ritz takes the

VOL. 13 NO. 4 APRIL 2011

side of ACE inhibitors, Drs Joseph Izzo and

Adrienne Zion highlight the value of ARBs, and
Drs Gary Sander and Thomas Giles address the
pros and cons of diuretics and b-blockers, recognizing that not all b-blockers or diuretics are the same.
Dr Domenic Sica evaluates the importance of BP
control as compared with the pleitropic effects of
specific drugs.
Drs RA Ajjan and Peter Grant discuss the role
of antiplatelet therapy in the prevention of CVD in
patients with hypertension and diabetes, highlighting safety issues and addressing specific drug effects
in management and prevention. We complete this
focus issue of the journal with a comprehensive
clinical approach to the treatment of hypertension
in diabetes by Drs Mariela Glandt and Zachary
Bloomgarden.
I hope that you will find this issue of the journal
to be informative, scientifically stimulating, and
most importantly, clinically relevant to the care we
provide to our high-risk patients with diabetes,
hypertension, dyslipidemias, and CVD.
Acknowledgments: I am indebted to our highly distinguished
faculty for their gracious and enthusiastic response to our
invitation and the exceptional level of expertise, knowledge,
and direction they provide. A special thanks is due to
Dr Michael Weber for his wisdom and guidance. I would also
like to acknowledge Liz Ferretti, managing editor of the
Journal, for her many critical contributions to the production
of this focus issue on patients with diabetes.

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