14 Treating to Goal: Diabetes and Hypertension
Neil F. Gordon, MD, PhD, MPH
CONTENTS
Diabetes Mellitus 157
Hypertension 162
Summary 166
References 166
Diabetes is one of the most common chronic diseases in the United States and one of the major public health issues facing the world in the twenty-first century. The human toll of diabetes can be gauged not only by medical statistics, which show it to be the leading cause of end-stage renal disease and new cases of visual loss in persons under the age of 65 years and a major cause of macrovascular disease, but also by the quantity of health care resources consumed. Moreover, whereas the prevalence of type 1 diabetes is increasing slowly, the prevalence of type 2 diabetes is increasing explosively (1).
According to the most recent NHANES survey (1999–2000), 31% of adult Americans have prehypertension [i.e., systolic blood pressure (BP) of 120–139 mmHg and/or diastolic BP of 80–89 mmHg] and another 27% have hypertension (i.e., systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg and/or use of antihypertensive medication) (2). Recent data further indicate that the prevalence of hypertension is increasing and that control rates among those with hypertension remain low (3,4).
In this chapter, the classification, diagnosis, complications, and, especially, medical management of diabetes and hypertension are briefly reviewed.
DIABETES MELLITUS
Diabetes Classification and Diagnosis
In 1997, the American Diabetes Association (ADA) revised their classification and diagnostic criteria (5). The revised classification includes four major clinical classes of diabetes, namely:
• Type 1 diabetes (results from beta-cell destruction, usually leading to absolute insulin deficiency).
From: Contemporary Cardiology: Cardiac Rehabilitation
Edited by: W. E. Kraus and S. J. Keteyian © Humana Press Inc., Totowa, NJ 157
• Type 2 diabetes (results from a progressive insulin secretory defect on the background of insulin resistance).
• Other specific types of diabetes mellitus due to other causes, e.g., genetic defects in beta-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 acquired immunodeficiency syndrome or after organ transplantation).
• Gestational diabetes mellitus (diagnosed during pregnancy).
For the clinician and patient, it is less important to label the particular type of diabetes than it is to understand the pathogenesis of the hyperglycemia and to manage it effectively (5).
The vast majority of cases of diabetes fall into two broad etiopathogenetic categories, namely, type 1 diabetes and type 2 diabetes. Generally, people with type 1 diabetes present with acute symptoms of diabetes and marked hyperglycemia. Type 2 diabetes (90–95% of individuals with diabetes) is far more prevalent than type 1 diabetes (5–10%
of individuals with diabetes) but frequently goes undiagnosed for many years because the hyperglycemia develops gradually and, at earlier stages, is often not severe enough for the patient to notice any of the classic symptoms of diabetes. Unfortunately, this relatively symptom-free undiagnosed period of diabetes is not benign – approximately 20% of newly diagnosed patients with type 2 diabetes already have evidence of chronic complications (1).
Criteria for the diagnosis of diabetes in nonpregnant adults are shown in Table 1.
Hyperglycemia not sufficient to meet the diagnostic criteria for diabetes is categorized as impaired fasting glucose (fasting plasma glucose= 100 to 125 mg/dl) or impaired glucose tolerance (2-h plasma glucose= 140–199 mg/dl), and both of these conditions have been officially termed “prediabetes” (5,6).
Complications of Diabetes
Acute, potentially life-threatening consequences of untreated or poorly managed diabetes are hyperglycemia with ketoacidosis or nonketotic hyperosmolar syndrome.
Ketoacidosis seldom occurs spontaneously in persons with type 2 diabetes; when
Table 1
Criteria for the Diagnosis of Diabetes Mellitus
1. Symptoms of diabetes plus casual plasma glucose concentration ≥ 200 mg/dl. Casual is defined as any time of day without regard to time since last meal. The classic symptoms of diabetes include polyuria, polydipsia, and unexplained weight loss.
Or
2. Fasting plasma glucose≥ 126 mg/dl. Fasting is defined as no caloric intake for at least 8 h.
Or
3. Two-hour postload plasma glucose≥ 200 mg/dl during an oral glucose tolerance test. The test should be performed as described by the World Health Organization, using a glucose load containing the equivalent of 75-g anhydrous glucose dissolved in water.
In the absence of unequivocal hyperglycemia, these criteria should be confirmed by repeat testing on a different day. The third measure (oral glucose tolerance test) is not recommended for routine clinical use (5).
seen, it usually arises in association with the stress of another illness such as acute infection. Hypoglycemia is most likely to occur in patients with diabetes who receive treatment with insulin and, to a lesser degree, insulin secretagogues (i.e., sulfonylureas or meglitinides).
Some of the major long-term complications of diabetes include retinopathy with potential loss of vision; nephropathy leading to renal failure; peripheral neuropathy with risk of foot ulcers, amputation, and Charcot joints; and autonomic neuropathy causing gastrointestinal, genitourinary, and cardiovascular symptoms and sexual dysfunction.
Most importantly, a large body of epidemiological and pathological data document that both type 1 and type 2 diabetes are independent risk factors for atherosclerotic cardiovascular disease in both men and women (7).
Medical Management of Diabetes
A cardinal feature in preventing the complications of diabetes is early diagnosis and management. People with diabetes should receive medical care from a physician- coordinated team including (but not limited to) physicians, nurses, dietitians, exercise physiologists, and mental health professionals with expertise and special interest in diabetes. The treatment plan should recognize diabetes self-management education as an integral component of care. Although glycemic control is fundamental to the management of diabetes, it must be emphasized that diabetes care is complex and requires that many issues (beyond glycemic control) be addressed. In this respect, a large body of evidence exists, which supports a range of interventions to improve diabetes outcomes. The standards of medical care for patients with diabetes, as recom- mended by the ADA (6), can be summarized as follows (Table 2).
Recommended glycemic goals for nonpregnant individuals are summarized in Table 2. Hemoglobin A1c (A1C) testing should be performed at least two times a year in patients who are meeting treatment goals (and who have stable glycemic control) and quarterly in patients whose therapy has changed or who are not meeting glycemic goals. The management plan (i.e., lifestyle intervention and insulin therapy/oral antidi- abetic medications) should be developed or adjusted to achieve normal or near-normal glycemia with an A1C test goal of < 7% for patients in general and as close to normal
< 6% as possible without significant hypoglycemia for the individual patient. The patient should be instructed in self-monitoring of blood glucose, and the patient’s technique and ability to use data to adjust therapy should be routinely evaluated.
People with diabetes should receive individualized medical nutrition therapy (MNT) as needed to achieve treatment goals, preferably provided by a registered dietitian familiar with the components of MNT (8). A program of regular physical activity, adapted to the presence of complications, is recommended for all patients with diabetes who are capable of participating (6,9) – see chap. 19 for exercise-specific guidelines.
In addition to MNT and regular physical activity, cigarette smokers should receive smoking cessation counseling and other forms of treatment as a routine component of diabetes care.
A target BP goal of < 130/80 mmHg is recommended. BP should be measured at every routine diabetes visit. Patients with a systolic BP of 130–139 mmHg or a diastolic BP of 80–89 mmHg should be given lifestyle/behavioral therapy alone for a maximum of 3 months and then, if targets are not achieved, in addition, be treated
Table 2
Summary of Recommendations for Adults with Diabetes Glycemic control
A1C < 70%∗
Preprandial capillary plasma glucose 90–130 mg/dl Peak postprandial capillary plasma glucose† < 180 mg/dl
Blood pressure < 130/80 mmHg
Lipids‡
LDL < 100 mg/dl
Triglycerides < 150 mg/dl
HDL > 40 mg/dl§
Key concepts in setting glycemic goals
• A1C is the primary target for glycemic control
• Goals should be individualized
• Certain populations (children, pregnant women, and elderly) require special considerations
• More stringent glycemic goals (i.e., a normal A1C, < 6%) may further reduce complications at the cost of increased risk of hypoglycemia
• Less intensive glycemic goals may be indicated in patients with severe or frequent hypoglycemia
• Postprandial glucose may be targeted if A1C goals are not met despite reaching preprandial glucose goals
A1C, hemoglobin A1c; HDL, high-density lipoprotein; LDL, low-density lipoprotein.
∗Referenced to a nondiabetic range of 4.0–6.0% using a Diabetes Control and Compli- cations Trial (DCCT)-based assay.
†Postprandial glucose measurements should be made 1–2 h after the beginning of the meal, generally peak levels in patients with diabetes.
‡Current guidelines suggest that in patients with triglycerides≥ 200 mg/dl, the “non-HDL cholesterol” (total cholesterol minus HDL) be utilized. The goal is < 130 mg/dl.
§For women, it has been suggested that the HDL goal be increased by 10 mg/dl (8).
pharmacologically. Patients with hypertension (systolic BP≥ 140 mmHg or diastolic BP≥ 90 mmHg) should receive drug therapy in addition to lifestyle/behavioral therapy.
In hypertensive patients with microalbuminuria or clinical albuminuria/nephropathy, an angiotensin-converting enzyme (ACE) inhibitor or angiotensin-receptor blocker (ARB) should be used. Initial drug therapy for hypertensive patients should be with a drug class demonstrated to reduce cardiovascular events in patients with diabetes (i.e., ACE inhibitors, ARBs, beta-blockers, diuretics, and calcium channel blockers).
Low-density lipoprotein (LDL) cholesterol should be lowered to < 100 mg/dl as the primary goal of therapy for adults; an LDL goal of < 70 mg/dl is a therapeutic option for patients with diabetes with cardiovascular disease. Triglycerides should be lowered to < 150 mg/dl and high-density lipoprotein (HDL) cholesterol raised to > 40 mg/dl in men and > 50 mg/dl in women. Lifestyle modification focusing on the reduction of saturated fat and cholesterol intake, weight loss (if indicated), and increased physical activity has been shown to improve the lipid profile in patients with diabetes and is recommended for all patients. For those diabetic patients with cardiovascular disease or over the age of 40 years, statin therapy to achieve an LDL cholesterol reduction
of 30–40% regardless of baseline LDL cholesterol levels is recommended. For those diabetic patients under the age of 40 years without cardiovascular disease but at increased risk due to other cardiovascular risk factors who do not achieve lipid goals with lifestyle modification alone, the addition of statin therapy is also appropriate.
Lowering triglycerides and/or increasing HDL cholesterol with a fibrate or niacin should be considered in diabetic patients with elevated triglycerides and/or low HDL cholesterol.
Aspirin therapy (75–162 mg/day) is recommended as a secondary prevention strategy in those with diabetes and a history of cardiovascular disease. Aspirin therapy (75–162 mg/day) is recommended as a primary prevention strategy in those with type 1 or type 2 diabetes at increased cardiovascular risk (including those who are > 40 years of age). Aspirin therapy should also be considered for primary prevention in patients between the age of 30 and 40 years with diabetes, particularly in the presence of other cardiovascular risk factors. Combination therapy using other antiplatelet agents such as clopidogrel in addition to aspirin should be considered in certain specific subsets of patients with diabetes with cardiovascular disease.
In asymptomatic patients without documented cardiovascular disease, a risk factor evaluation should be considered to stratify patients by 10-year risk, and risk factors should be treated accordingly. The screening of asymptomatic patients with cardiac stress testing remains controversial. Candidates for a screening exercise stress test include those with a history of peripheral or carotid occlusive disease and those with a sedentary lifestyle who are > 35 years of age and plan to begin a vigorous exercise program. Candidates for a diagnostic exercise test include those with typical or atypical cardiac symptoms and those with an abnormal resting electrocardiogram.
Patients with an abnormal exercise test and patients unable to perform an exercise test require additional or alternative testing. Stress nuclear perfusion imaging and stress echocardiography are considered to be valuable next-level diagnostic procedures.
In patients > 55 years of age, with or without hypertension but with cardiovascular disease or another cardiovascular risk factor (e.g., dyslipidemia, microalbuminuria, or smoking), an ACE inhibitor (if not contraindicated) should be considered to reduce the risk of cardiovascular events. In patients with a prior myocardial infarction or in patients undergoing major surgery, beta-blockers should be considered to reduce mortality. In patients with treated heart failure, metformin use is contraindicated. The thiazolidinediones are associated with fluid retention, and their use can be complicated by the development of heart failure. Caution in prescribing thiazolidinediones in the setting of known heart failure or other heart diseases, as well as in patients with pre-existing edema or concurrent insulin therapy, is required.
An annual test for the presence of microalbuminuria should be performed in type 1 diabetic patients who have had diabetes ≥ 5 years and all type 2 diabetic patients starting at diagnosis. Serum creatinine should be measured at least annually for the estimation of glomerular filtration rate in all adults with diabetes regardless of the degree of urine albumin excretion. The serum creatinine alone should not be used as a measure of kidney function but instead used to estimate glomerular filtration rate and stage the level of chronic kidney disease. To reduce the risk and/or slow the progression of nephropathy, we should optimize both glucose and BP control. In the treatment of microalbuminuria/macroalbuminuria/nephropathy, either ACE inhibitors or ARBs
should be used (except during pregnancy). With the onset of overt nephropathy, dietary protein intake should be restricted to≤ 08 g/kg body weight/day (approximately 10%
of daily calories); further restriction may be useful in selected patients.
A comprehensive foot examination should be performed annually on patients with diabetes to identify risk factors predictive of ulcers and amputations. Patients’ feet should be visually inspected at each routine visit. All patients, especially those with risk factors or prior lower-extremity complications, should be educated about the risk and prevention of foot problems and self-care behavior reinforced. A multidisciplinary approach is recommended for persons with foot ulcers and high-risk feet, especially those with a history of prior ulcer or amputation. Patients with significant claudication or a positive ankle–brachial index should be referred for further vascular assessment and exercise training, medications, and surgical options considered.
Patients with type 1 diabetes should have an initial dilated and comprehensive eye examination by an ophthalmologist or optometrist within 3–5 years after the onset of diabetes. Patients with type 2 diabetes should have an initial dilated and comprehensive eye examination by an ophthalmologist or optometrist shortly after the diagnosis of diabetes. Subsequent examinations for type 1 and type 2 diabetic patients should be repeated annually. Patients with any level of macular edema, severe nonproliferative diabetic retinopathy, or any proliferative diabetic retinopathy should be promptly referred to an ophthalmologist who is knowledgeable and experienced in the management and treatment of diabetic retinopathy. Laser therapy can reduce the risk of vision loss in patients with high-risk characteristics.
All patients should be screened for distal symmetric polyneuropathy at diagnosis and at least annually thereafter, using simple clinical tests. Once the diagnosis of distal symmetric polyneuropathy is established, special foot care is appropriate for insensate feet to decrease the risk of amputation. Screening for autonomic neuropathy should be instituted at diagnosis of type 2 diabetes and 5 years after the diagnosis of type 1 diabetes. A wide variety of medications may be considered for the relief of specific symptoms related to neuropathy (including tricyclic drugs, anticonvulsants, and duloxitene for the management of neuropathic pain; metoclopramide for gastroparesis;
and various medications for bladder and erectile dysfunction).
An influenza vaccine should be provided annually to all adult diabetic patients.
In addition, adults with diabetes should receive at least one lifetime pneumococcal vaccine. A one-time revaccination is recommended for individuals > 64 years of age previously immunized when they were < 65 years of age if the vaccine was administered > 5 years ago.
HYPERTENSION
Hypertension Classification and Diagnosis
An accurate BP reading is the most important part of the classification and diagnosis of hypertension. Table 3 provides The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) classification of BP for adults aged 18 years or older (10). The JNC 7 classification is based on the mean of two or more properly measured seated BP readings on each of two or more office visits.
Table 3
Classification and Management of Blood Pressure for Adults∗ Initial drug therapy
BP
classification
SBP
mmHg∗ DPB mmHg∗
Lifestyle modifi- cation
Without compelling indication
With compelling indications†
Normal < 120 And < 80 Encourage
Prehypertension 120–139 Or 80–89 Yes No antihypertensive drug indicated.
Drug(s) for compelling indications.‡ Stage 1
hypertension
140–159 Or 90–99 Yes Antihypertensive drug(s) indicated.
Drug(s) for compelling indications.‡ Other antihyper- tensive drugs, as needed.
Stage 2 hypertension
≥ 160 Or≥ 100 Yes Antihypertensive drug(s) indicated.
Two-drug combination for most.†
DBP, diastolic blood pressure; SBP, systolic blood pressure.
∗Treatment determined by highest BP category.
†Initial combined therapy should be used cautiously in those at risk for orthostatic hypotension.
‡Compelling indications include heart failure, postmyocardial infarction, high coronary artery disease risk, diabetes, chronic kidney disease, and recurrent stroke prevention. Treat patients with chronic kidney disease or diabetes to BP goal of < 130/80 mmHg (10).
In addition to BP determination, evaluation of patients with hypertension has three primary objectives, namely, to assess lifestyle and identify other cardiovascular risk factors or concomitant disorders that may impact prognosis and help guide therapy, to reveal identifiable causes of hypertension, and to assess the presence or absence of cardiovascular disease and target organ damage. The medical history, physical examination, routine laboratory tests, and other diagnostic procedures are needed to obtain the required information (10).
In more than 95% of cases, the etiology of hypertension is unknown, and it is called primary, essential, or idiopathic hypertension. Secondary hypertension is hyper- tension with a known cause. Identifiable causes of hypertension include sleep apnea, drug-induced or drug-related causes, chronic kidney disease, primary aldosteronism, renovascular disease, chronic steroid therapy and Cushing syndrome, pheochromo- cytoma, coarctation of the aorta, and thyroid or parathyroid disease (10).
Complications of Hypertension
Chronic hypertension produces target organ damage to the heart, brain, kidneys, peripheral vasculature, and eyes. Fortunately, the major clinical trials of
antihypertensive therapy have demonstrated multiple benefits, including a 35–40%
reduction in the incidence of stroke, 20–25% reduction in myocardial infarction, and more than 50% reduction in heart failure (11).
The relationship between BP and risk for cardiovascular events is continuous, consistent, and independent of other cardiovascular risk factors. For individuals 40–70 years of age, each increment of 20 mmHg in systolic BP or 10 mmHg in diastolic BP doubles the risk of cardiovascular disease across the entire BP range from 115/75 to 185/115 mmHg. Although both systolic and diastolic BP are important, in persons older than 50 years, systolic BP is a much more important cardiovascular disease risk factor than diastolic BP (10).
Medical Management of Hypertension
The goals of antihypertensive therapy are to control BP and to reduce cardiovascular and renal morbidity and mortality by the least intrusive means possible. This may be achieved through lifestyle modification alone or in combination with pharmacologic treatment (Table 3). Individuals with a systolic BP of 120–139 mmHg and/or a diastolic BP of 80–89 mmHg should be considered as “prehypertensive” and also require lifestyle intervention.
The BP goal is < 130/80 mmHg in patients with hypertension with diabetes or chronic kidney disease and < 140/90 mmHg in other patients with hypertension.
Because most patients with hypertension, especially those older than 50 years, will reach the diastolic BP goal once systolic BP is at the goal level, JNC 7 recommends that the primary focus be on achieving the systolic BP goal. Fig. 1 depicts the algorithm recommended by JNC 7 for the treatment of hypertension. Therapeutic lifestyle changes and pharmacologic interventions advocated by JNC 7 and the American Heart Associ- ation can be briefly summarized as follows (10,12).
Lifestyle Modifications
Regular aerobic physical activity, such as brisk walking, should be performed for at least 30 min/day on most days of the week – see chap. 16 for exercise-specific guidelines. Overweight or obese persons should receive guidance on weight loss, with the goal ideally being to attain a body mass index < 25 kg/m2; for nonoverweight persons, a desirable body mass index of 185–249 kg/m2 should be maintained. Salt intake should be lowered as much as possible, ideally to approximately 65 mmol/day (corresponding to 1.5 g/day of sodium or 3.8 g/day of salt).
With the assistance of a dietician (if feasible), a diet rich in fruits and vegetables (8–10 servings/day), rich in low-fat dairy products (2–3 servings/day), and reduced in saturated fat and cholesterol should be recommended. Potassium intake should be increased to 120 mmol/day (4.7 g/day), which is also the level provided in Dietary Approaches to Stop Hypertension (DASH)-type diets. For those who drink alcohol, consumption should be limited to no more than 2 drinks/day in most men and 1 drink/day in women and lighter-weight persons. For overall cardiovascular risk reduction, cigarette smokers should quit smoking.
Not at Goal Blood Pressure (<140/90 mmHg) (<130/80 mmHg for patients with diabetes or chronic kidney disease)
Lifestyle modifications
Without compelling indications With compelling
indications*
Stage 1 Hypertension (SBP 140-159 or DBP 90-
99mmHg) Thiazide-type diuretics for most. May consider other antihypertensive drugs, alone or in combination.
Stage 2 Hypertension (SBP 160 or DBP ≥ 100
mmHg) Two-drug combination for most
Drug(s) for the compelling indication
Other antihypertensive drugs as needed
Initial drug choices
Not at BP goal
Optimize dosages or add additional drugs until goal blood pressure is achieved.
Consider consultation with hypertension specialist.
DBP, diastolic blood pressure; SBP, systolic blood pressure.
*Compelling indications include heart failure, postmyocardial infarction, high coronary heart disease risk, diabetes, chronic kidney disease, and recurrent stroke prevention. Treat patients with chronic kidney disease or diabetes to a goal of <130/80 mmHg(10) .
≥
Fig. 1.Algorithm for treatment of hypertension.
Pharmacologic Treatment
Most patients with hypertension who require drug therapy in addition to lifestyle modification will require two or more antihypertensive medications to achieve goal BP. If BP is > 20/10 mmHg above the goal, consideration should be given to initi- ating antihypertensive therapy with two agents, one of which should usually be a thiazide-type diuretic. Thiazide-type diuretics should be used in drug treatment for most patients with uncomplicated hypertension, either alone or combined with drugs from other classes. Certain high-risk conditions are compelling indications for the initial use of other antihypertensive drug classes. Compelling indications include heart failure (diuretics, beta-blockers, ACE inhibitors/ARBs, and aldosterone antag- onists), postmyocardial infarction (beta-blockers, ACE inhibitors/ARBs, and aldos- terone antagonists), patients at high risk for coronary artery disease (diuretics, beta- blockers, ACE inhibitors/ARBs, and calcium channel blockers), diabetes (diuretics, beta-blockers, ACE inhibitors/ARBs, and calcium channel blockers), chronic kidney disease (ACE inhibitors/ARBs), and recurrent stroke prevention (diuretics and ACE inhibitors/ARBs).
After initiation of drug therapy, most patients should return for follow-up and adjustment of medications at approximately monthly intervals until the BP goal is reached. More frequent follow-up may be needed for patients with stage 2 hypertension or with complicating comorbid conditions. Serum potassium and creatinine should be
monitored at least 1–2 times per year. Follow-up visits can usually be at 3–6-month intervals once BP is at goal and stable.
Other cardiovascular risk factors (such as serum lipids and lipoproteins and diabetes) should be treated to their respective goals. Other evidence-based cardio- protective drugs should be initiated, if clinically indicated. Low-dose aspirin therapy for cardiovascular risk reduction should only be considered when BP is controlled, because the risk of hemorrhagic stroke is increased in patients with uncontrolled hypertension.
SUMMARY
Current evidence provides a strong rationale for the long-term aggressive control of multiple cardiovascular disease risk factors as an essential strategy to normalize endothelial function; halt or reverse the progression of atherosclerosis; prevent the instability, rupture, and thrombosis of atherosclerotic plaques; and reduce mortality, recurrent hospitalization, and the ongoing cost of medical care. In this chapter, the classification, diagnosis, complications, and, especially, medical management of two of the major cardiovascular disease risk factors, namely, diabetes and hypertension, are briefly reviewed.
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