3 5 Hypertension and Diabetes Mellitus: An Update James R. Sowers, Darren M. Allcock, and Adam T. Whaley-Connell
HYPERTENSION IN PATIENTS WITH TYPE 1 DIABETES MELLITUS, 313
PATHOPHYSIOLOGY OF HYPERTENSION IN DIABETES MELLITUS, 314
Additional Considerations in Treating Hypertension in Diabetes Mellitus, 318
HYPERTENSION IN THE CARDIOMETABOLIC SYNDROME, 313
NEPHROPATHY IN PATIENTS WITH HYPERTENSION AND DIABETES, 315
HYPERTENSION AND CARDIOVASCULAR DISEASE IN TYPE 2 DIABETES MELLITUS, 313
HYPERTENSION TREATMENT STRATEGIES IN PATIENTS WITH DIABETES, 316 Nonpharmacologic Treatment, 316 Pharmacologic Treatment, 316
STROKE IN PATIENTS WITH DIABETES AND HYPERTENSION, 314
Diabetes mellitus (DM) is the sixth leading cause of death in adults in the United States. This debilitating chronic disease affects 8.3% of the population, or approximately 25.8 million individuals.1 Among adults over 65 years of age, 10.9 million are affected, representing 26.9% of this age group (Fig. 35-1). The prevalence of DM is highest in persons above 65 years of age; however, younger individuals (under 45 years) have experienced the greatest increase in the last decade.2 Although the United States has the leading proportion of afflicted individuals, the rapid rise in the prevalence of DM is occurring globally, and soon over 300 million persons worldwide will be affected. In the United States, DM is now the leading cause of end-stage renal disease (ESRD) and nontraumatic amputations. Cardiovascular disease (CVD), however, is the major cause of premature mortality in patients with type 2 DM. Coexistent hypertension (HTN) is a major contributor to the development of CVD and renal disease in patients with diabetes.3 Hypertension is more common in persons with type 2 DM than in the general population, and individuals with HTN are 2.5 times more likely to develop DM than those who have a normal blood pressure (BP).4 HTN affects approximately 70 million individuals in the United States and is the primary diagnosis in about 35 million office visits annually.
Hypertension in Patients with Type 1 Diabetes Mellitus Patients with type 1 DM currently make up about 6% to 8% of the total DM population in the United States.5 In contrast to patients with type 2 DM, those with type 1 DM typically develop renal disease before developing HTN.3,6 However, the development of HTN accelerates the course of microvascular and macrovascular disease in these patients, which should prompt early and aggressive treatment with an angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB).3 Furthermore, β-blockers should not be used as first-line antihypertensive therapy in patients with type 1 DM because of their propensity to reduce the patient’s ability to appropriately perceive and manifest hypoglycemic symptoms, as well as their ability to respond physiologically to hypoglycemia.7 Other aspects of antihypertensive therapy are similar to those for patients with type 2 DM (see later).
Hypertension in the Cardiometabolic Syndrome The National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) defined the cardiometabolic syndrome
(CMS) as presence of any three or more of the following: BP ≥130/85 mm Hg, waist circumference >40 inches in men or >35 inches in women, triglycerides ≥150 mg/dL, HDL <40 mg/dL in men or <50 mg/dL in women, and fasting glucose ≥110 mg/dL.8 The American Diabetes Association (ADA) has lowered the impaired fasting glucose (IFG) threshold from 100 to 110 mg/dL. This syndrome represents a clustering of maladaptive characteristics that confers an increased risk of CVD. These factors are summarized in Box 35-1. In the National Health and Nutrition Examination Survey (NHANES 1999-2000), the overall prevalence of the CMS was 26.7%, which increased from the NHANES III (1988-1994) survey measurement of 23.1%. Further, an age-dependent increase in prevalence of this syndrome is apparent in both men (10.7%, 33.0%, and 39.7%) and women (18.0%, 30.6%, and 46.1%) for ages 20 to 39, 40 to 59, and >60 years, respectively.9 The Framingham Heart Study demonstrated the synergistic action of these cardiovascular (CV) risk factors in mediating CV events. Indeed, the coexistence of HTN, the CMS, and/or DM markedly increases the risk of developing macrovascular disease that includes CVD, CV, and peripheral vascular disease (PVD).3 Even mild hyperglycemia (i.e., IFG), when associated with modest HTN (systolic BP [SBP] 140-149 mm Hg), significantly increases CVD mortality. Another key risk factor is obesity, specifically central or visceral obesity, which is associated with insulin resistance and premature CVD. An increase in body mass index (BMI) is independently associated with a linear increase in SBP, diastolic BP (DBP), and pulse pressure. Insulin resistance is likely a primary contributor to the pathophysiology of the CMS. Patients with hypertension have a high prevalence of insulin resistance and a substantially higher risk of developing type 2 DM.4 Insulin resistance is characterized by impaired ability of insulin to stimulate glucose uptake in insulin sensitive tissues, particularly skeletal muscle. Factors contributing to the development of insulin resistance in patients with HTN include altered composition of skeletal muscle, decreased blood flow, delivery of insulin to skeletal muscle, and postinsulin receptor abnormalities in metabolic signaling (Box 35-2).
Hypertension and Cardiovascular Disease in Type 2 Diabetes Mellitus HTN markedly increases the risk for CVD in patients with type 2 DM.3 The Multiple Risk Factor Intervention Trial (MRFIT)10 followed more than 5000 men with DM and 350,000 nondiabetic men for 12 years to evaluate the impact of various CVD risk factors. The study confirmed that HTN, elevated cholesterol levels, and cigarette smoking were independent CVD risk factors in men