National High Blood Pressure Education Program Working Group Report on HYPERTENSION IN DIABETES NATIONAL INSTITUTES OF HEALTH National Heart, Lung, and Blood Institute National High Blood Pressure Education Program Working Group Report on HYPERTENSION IN DIABETES U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service National Institutes of Health National Heart, Lung, and Blood Institute NIH Publication No. 94-3530 April 1994 NATIONAL HIGH BLOOD PRESSURE EDUCATION PROGRAM WORKING GROUP ON HYPERTENSION IN DIABETES MEMBERS Chair: James R. Sowers, M.D. Professor of Medicine and Physiology Director Division of Endocrinology, Metabolism and Hypertension Wayne State University Detroit, Michigan Jeffrey A. Cutler, M.D., M.P.H. Acting Associate Director Clinical Applications and Prevention Programs Division of Epidemiology and Clinical Applications National Heart, Lung, and Blood Institute National Institutes of Health Bethesda, Maryland Karen Donato, M.S., R.D. Coordinator NHLBI Obesity Education Initiative Office of Prevention, Education, and Control National Heart, Lung, and Blood Institute National Institutes of Health Bethesda, Maryland Richard C. Eastman, M.D. Director Division of Diabetes, Endocrinology, and Metabolic Diseases National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health Bethesda, Maryland Bonita Falkner, M.D. Professor of Pediatrics and Medicine Medical College of Pennsylvania Philadelphia, Pennsylvania Michael J. Horan, M.D., Sc.M. Director for Cardiology Division of Heart and Vascular Diseases National Heart, Lung, and Blood Institute National Institutes of Health Bethesda, Maryland Willa A. Hsueh, M.D. Professor of Medicine Chief Division of Diabetes, Hypertension, and Nutrition Los Angeles County/University of Southern California Medical Center Los Angeles, California Barry Hyman, M.D., F.A.C.P. Clinical Associate Professor Department of Medicine and Ophthalmology Baylor College of Medicine Houston, Texas James W. Reed, M.D., F.A.C.P. Professor and Director Internal Medicine Residency Program Morehouse School of Medicine Atlanta, Georgia Edward J. Roccella, Ph.D., M.P.H. Coordinator National High Blood Pressure Education Program National Heart, Lung, and Blood Institute National Institutes of Health Bethesda, Maryland Peter J. Savage, M.D. Chief Clinical and Genetic Epidemiology Branch Division of Epidemiology and Clinical Applications National Heart, Lung, and Blood Institute National Institutes of Health Bethesda, Maryland Jay Siwek, M.D. Editor American Family Physician Chief Division of Family Medicine Department of Community and Family Medicine Georgetown University School of Medicine Washington, D.C. Michael L. Tuck, M.D. Professor of Medicine School of Medicine University of California Los Angeles Chief of Endocrinology Veterans Administration Medical Center Sepulveda, California Myron H. Weinberger, M.D. Professor of Medicine Indiana University School of Medicine Director Hypertension Research Center Indianapolis, Indiana Gordon Williams, M.D. Chief Endocrine Hypertension Division Brigham and Women's Hospital Professor of Medicine Harvard Medical School Boston, Massachusetts CONSULTANT Eva Obarzanek, Ph.D., R.D. Nutritionist Division of Epidemiology and Clinical Applications National Heart, Lung, and Blood Institute National Institutes of Health Bethesda, Maryland STAFF Margaret V. Ames, Ph.D. Program Manager National High Blood Pressure Education Program R.O.W. Sciences, Inc. Rockville, Maryland Darrell E. Anderson, M.S. Program Specialist National High Blood Pressure Education Program R.O.W. Sciences, Inc. Rockville, Maryland Gail T. Brito, R.N. University Research Corporation Bethesda, Maryland Table of Contents Page Introduction 1 Definitions and Diagnostic Criteria 2 Diabetes Mellitus 2 Diagnosis of Hypertension 2 Epidemiology 3 Epidemiology of Associations Among Diabetes, Hypertension, and Cardiovascular Disease 3 Pathogenesis Factors--Type I and Type II 3 Clinical Trials 4 Guide to Clinical Evaluation 5 Physical Examination 5 Laboratory Tests 6 Special Considerations in Diabetic Patients With Hypertension 7 Kidney Disease 7 Secondary Forms of Hypertension 7 Cardiovascular Disease 7 Cerebrovascular Disease 7 Diabetic Retinopathy 8 Hypertension With Orthostatic Hypotension 9 Autonomic Neuropathy in Diabetic Patients 9 Sexual Dysfunction 9 Lipid Disorders 10 Other Metabolic Concerns 10 Obesity 10 Pregnancy 10 Children: Type I 11 Treatment 12 Lifestyle Modifications 12 Pharmacologic Treatment of Hypertension 14 Drugs for Managing Hypertensive Emergencies in Diabetic Patients 18 Considerations in Education, Control, and Maintenance 19 References 21 INTRODUCTION Hypertension and diabetes mellitus are interrelated diseases, which, if untreated, strongly predispose to atherosclerotic cardiovascular disease. Lifestyle and genetic factors are important in the genesis of both conditions. An estimated 3 million Americans have both diabetes and hypertension.1 Hypertension is approximately twice as common in persons with diabetes as in those without.2 The prevalence of hypertension and type II diabetes, or non-insulin-dependent diabetes mellitus (NIDDM), increases with age. Hypertension occurs more frequently in persons with type I diabetes, or insulin-dependent diabetes mellitus (IDDM), than in those with type II diabetes after adjustment for age.3 The prevalence of coexistent hypertension and diabetes is almost twice as great among African Americans as among whites and is three times greater among Mexican Americans than among non-Hispanic whites.4,5 Both conditions, independently and concomitantly, are more common among the socioeconomically disadvantaged. Essential hypertension accounts for the majority of hypertension in persons with diabetes, particularly in those with type II diabetes, who constitute more than 90 percent of those with a dual diagnosis of diabetes and hypertension. Diabetic nephropathy, which occurs after 15 years of diabetes in one of three persons with type I diabetes and one of five persons with type II diabetes, appears to be an important cause of hypertension.2 Data obtained from death certificates shows that hypertensive disease has been implicated in 4.4 percent of deaths coded to diabetes, and diabetes was involved in 10 percent of deaths coded to hypertensive disease.6 Indeed, an estimated 35 to 75 percent of diabetic complications can be attributed to hypertension.7 Hypertension can exhibit several kinds of pathophysiology in patients with diabetes. Hypertension associated with diabetic nephropathy is a form of renal hypertension with sodium and fluid retention, increased peripheral vascular resistance, and increased cardiac output, especially if anemia is present. Isolated systolic hypertension can occur at any age and is considerably more common in persons with diabetes than in those without diabetes. Supine hypertension with orthostatic hypotension sometimes occurs in patients with autonomic neuropathy and is difficult to treat in persons with diabetes. In most individuals with diabetes, hypertension is characterized by increased peripheral vascular resistance.2 Patients who have both diabetes and hypertension have more renal disease and atherogenic risk factors, including dyslipidemia, hyperuricemia, elevated fibrinogen, and left ventricular hypertrophy.8,9 Hypertension contributes to the leading causes of morbidity and mortality in persons with diabetes, including coronary heart disease, stroke, peripheral vascular disease, lower extremity amputations, and end-stage renal disease.9 Hypertension also contributes to diabetic retinopathy, which is the leading cause of newly diagnosed blindness in the United States.10,11 For all these reasons, hypertension and diabetes should be recognized and treated early and aggressively. Furthermore, because considerable important information has been published since the last consensus report,4 this current consensus report and other recent consensus reports serve as an update on this important topic.12,13,14 This report serves the following purposes:  to increase awareness of the importance and implications of the problem of hypertension in persons with diabetes in community control programs; and  to guide clinicians in their care of persons with the concomitant problems of hypertension and diabetes. DEFINITIONS AND DIAGNOSTIC CRITERIA Diabetes Mellitus Diabetes mellitus comprises a genetically and clinically heterogeneous group of chronic metabolic disorders are characterized by glucose intolerance. Type I diabetes (absolutely insulin dependent) accounts for 5 to 10 percent of diagnosed cases; type II (usually with insulin resistance) comprises 90 to 95 percent of cases in the United States.3 Diagnosis of diabetes in nonpregnant adults should be restricted to those who have one of the following criteria:15  random plasma glucose level of 11 mmol/L (200 mg/dL) or greater plus classic signs and symptoms of diabetes (e.g., polydipsia, polyuria, weight loss);  fasting plasma glucose level of 7.8 mmol/L (140 mg/dL) or greater on at least two occasions; or  fasting plasma glucose level below 7.8 mmol/L (140 mg/dL) plus sustained elevated plasma glucose levels during at least two oral glucose tolerance tests. The 2-hour sample and at least one other sample between 0 and 2 hours after 75-gram glucose load should be 200 mg/dL or greater. Oral glucose tolerance testing is not necessary if patients have fasting plasma glucose level of 7.8 mmol/L (140 mg/dL) or greater. Diagnosis Of Hypertension Hypertension should not be diagnosed on the basis of a single measurement. Initial elevated readings should be confirmed on at least two subsequent visits over 1 week or more with average diastolic blood pressure of 90ÊmmHg or greater or systolic blood pressure of 140 mmHg or greater required for diagnosis of hypertension.16 Special care is warranted in diagnosing hypertension in persons with diabetes because of greater variability of blood pressure and a much greater likelihood of isolated systolic hypertension.3 Because of greater variability of blood pressures, more blood pressure measurements may be particularly useful in many of these patients. EPIDEMIOLOGY Epidemiology Of Associations Among Diabetes, Hypertension, And Cardiovascular Disease An association between overt diabetes mellitus and cardiovascular disease (CVD) has been observed in multiple studies conducted in a number of ethnic and racial groups. This excess of CVD in persons with diabetes includes increases in both incidence and case fatality rates from acute myocardial infarction, in mortality in the months following discharge after an acute myocardial infarction, in unexplained chronic congestive heart failure, in cerebrovascular disease, in peripheral vascular disease, and in renal disease. Among persons with type II diabetes in the United States, approximately 60 percent of death certificates mentioned ischemic heart disease and 20 percent mentioned other heart and vascular diseases as a contributing cause of death.17,18 The presence of diabetes may increase the risk of CVD more in women than in men.19 Obesity is a risk factor for the development of type II diabetes as well as hypertension. In addition, obesity (abdominal obesity) is associated with adverse changes in other cardiovascular risk factors. Recent studies have suggested that hyperglycemia may be part of a syndrome involving abnormalities in blood pressure and lipid levels linked to central distribution of body fat and elevations of insulin or insulin resistance.20,21 It has been suggested that the increased risk of CVD associated with diabetes may develop in the prediabetic period when glucose levels are normal or minimally elevated. Impaired glucose tolerance (IGT) is associated with a normal fasting blood glucose but an elevated postprandial blood sugar between 7.8 and 11 mmol/L (140 and 199 mg/dL). Some patients with IGT are hyperinsulinimic, and 30 percent progress to NIDDM. These observations suggest that elevations in insulin or insulin resistance may contribute to an increased risk of CVD in the general normoglycemic population.22 This syndrome may affect a substantially greater proportion of the U.S. population than the estimated 22 to 30 million with detectable abnormalities in glucose tolerance. (For more information on obesity, see section on Special Considerations in Diabetic Patients With Hypertension.) The majority of macrovascular complications of diabetes occur in persons with concomitant hypertension.2 Compared to persons with normal glucose tolerance, blood pressure is increased in both those with impaired glucose tolerance and those with diabetes. Pathogenesis Factors--Type I And Type II There are substantial differences in the etiology of hypertension in type I and type II diabetes mellitus. Diabetic nephropathy appears to be the most common cause of hypertension in those with type I diabetes. A strong family history of essential hypertension and diabetes mellitus appears to identify those persons with type I diabetes who are most likely to develop renal disease and hypertension.23 Probably an equal number of persons with type II diabetes mellitus develop renal disease, but hypertension often occurs with normal renal function associated with obesity or older age. An increased total body sodium and enhanced vascular reactivity are found in both type I and type II diabetes. These abnormalities are found in persons with diabetes, both with and without hypertension or microvascular disease, suggesting that factors secondary to diabetes can lead to hypertension. Insulin levels are high in many patients with type II diabetes and can be high during treatment of either type I or type II diabetes. Hyperinsulinemia and insulin resistance may contribute to hypertension in diabetes mellitus through effects on sodium retention or direct effects on blood vessels.22,24 CLINICAL TRIALS In the treatment of patients with both diabetes mellitus and hypertension, clinical trials relating different treatment strategies and regimens to at least the following four outcome measures are of interest: glycemic control, blood pressure control, microvascular disease (nephropathy, neuropathy, and retinopathy), and macrovascular disease. In type II diabetes, macrovascular disease is undoubtedly the most significant chronic complication from both clinical and public health perspectives. Only a few large-scale clinical trials enrolled persons with diabetes in appreciable numbers, and many details on the experience of these subjects have not been reported. Ten percent of the participants in the Hypertension Detection and Follow-up Program (HDFP) had a fasting blood glucose of 7.8 mmol/L (140 mg/dL) or greater at baseline or reported taking medication for diabetes.25 The effect of diuretic-based stepped care (SC) on total mortality in this subset did not differ significantly from the benefit in the overall cohort. For the subgroup of persons with diabetes, compared to the group receiving referred care (RC), the trends were favorable for the SC group, both overall (adjusted 5-year mortality rates of 10.9 and 12.0 per 100 for SC and RC, respectively) and especially in the group with mild hypertension (9.2 per 100 for SC and 11.0 per 100 for RC). However, these differences were not statistically significant. Results for cardiovascular end points have not been reported separately for persons with diabetes. In the Systolic Hypertension in the Elderly Program (SHEP), 10 percent of participants had diabetes.26 This trial used chlorthalidone as the primary first-step drug; however, the doses employed were lower than in HDFP. Relative risk reductions in the subgroup with diabetes for all major endpoints fatal or nonfatal stroke, CHD death or nonfatal myocardial infarction, all major cardiovascular events, and total mortality were very similar to results for the total cohort. As in HDFP, the effect of treatment on the primary end point (which was fatal and nonfatal stroke in SHEP) was not statistically different in the subgroup with diabetes, neither trial having been designed specifically to test the questions in this subgroup. However, in SHEP, there was a significant benefit for CHD in persons with diabetes when the most inclusive definition of this endpoint was employed.26 This beneficial effect occurred despite a rise of 0.3 mmol/L (5.6 mg/dl) in fasting plasma glucose with active treatment compared with placebo.27 Diuretics and beta-blockers are the only classes of drugs that have been studied and found to be effective in reducing cardiovascular morbidity and mortality in persons with hypertension. The results of planned and ongoing trials are needed to compare different classes of antihypertensive drugs for effects on cardiovascular and renal endpoints in persons both with and without diabetes. GUIDE TO CLINICAL EVALUATION Evaluation of patients with both hypertension and diabetes mellitus should take into consideration the following questions:  Is the patient taking any drug known to alter blood pressure or blood glucose?  Does the patient have a surgically curable form of hypertension?  Are target organs involved (e.g., heart, kidney, brain, eyes)?  Are cardiovascular risk factors other than hypertension and diabetes present (e.g., dyslipidemia, family history, smoking)?  Are the diabetes and hypertension well controlled? A careful history of all prescribed and over-the-counter medications should be obtained from all patients. Several medications may raise blood pressure and thus interfere with the effectiveness of antihypertensive drugs. These include oral contraceptives, steroidal compounds, nonsteroidal anti- inflammatory agents, nasal decongestants, appetite suppressants, and tricyclic antidepressants.16 Although relatively rare, coarctation of the aorta, primary hyperaldosteronism, Cushing's syndrome, and pheochromocytoma also should be considered in patients with both diabetes and hypertension, as in essential hypertension. A medical history should include (1) family history of hypertension, diabetes, renal disease and CVD; (2) patient history of CVD, cerebrovascular disease, renal disease, and retinopathy; (3) known duration and levels of elevated blood pressure and blood glucose; (4) results and side effects of previous antihypertensive and hypoglycemic therapy; (5) use of drugs that may influence blood pressure or diabetes; (6) history of weight gain or loss, proteinuria, sodium intake, other dietary factors, exercise habits, and alcohol use; (7) symptoms suggesting secondary hypertension; (8) psychosocial and environmental factors (e.g., emotional stress, cultural food practices, economic status) that may influence blood pressure or blood glucose control; (9) other cardiovascular risk factors including obesity, smoking, and hyperlipidemia; and (10) date of last eye examination. With regard to diabetes, information should be sought about the history of polyuria, polydipsia, polyphagia, fatigue, blurred vision, hypoglycemic reactions, sexual dysfunction, paresthesia or other signs of peripheral neuropathy in the extremities, and leg and foot ulcers. Physical Examination Because blood pressure may rise in response to physical exertion or emotional stress and because some patients with diabetes have blood pressures that fall when they are in the standing position, it is recommended that blood pressure be measured in the supine, seated, and standing positions after patients have had time to relax (see section on "Definitions and Diagnostic Criteria" above). Physical examination should include (1) two or more blood pressure determinations in all three positions (a wide cuff should be used to measure the pressure of patients with obese arms); (2)Êmeasurement of height and weight; (3) funduscopic examination for signs of hypertensive and diabetic retinopathy; (4) examination of the neck for carotid bruits, distended veins, and enlarged thyroid; (5) careful examination of the heart for a sustained point of maximal impulse (evidence of left ventricular hypertrophy), precordial heave, murmurs, arrhythmias, and S3 and S4 heart sounds; (6) examination of the abdomen for bruits and bladder enlargement; (7) examination of the extremities for diminished or absent peripheral arterial pulsations and edema; and (8) neurological assessment, especially sensory and vibratory. A periodic eye examination by an ophthalmologist is recommended, even in asymptomatic patients to enable recognition of treatable retinal disease.28 Physical findings that suggest secondary hypertension include abdominal or flank masses (polycystic kidneys); abdominal bruits, particularly those that lateralize or have a diastolic component (renovascular disease); delayed or absent femoral arterial pulses (aortic coarctation); truncal obesity with pigmented (purple) striae (Cushing's syndrome); and tachycardia, paroxysmal headache, sweating, and pallor (pheochromocytoma). Laboratory Tests A few simple laboratory tests should be performed before initiating therapy:  hemoglobin or hematocrit measurement; complete urinalysis;  serum potassium, serum creatinine, and serum magnesium measurement;  fasting blood glucose test;  glycosylated hemoglobin (hemoglobin A1c [HbA1c]) measurement;  fasting lipoprotein profile (LDL cholesterol, triglycerides, and HDL cholesterol); and  microalbumin excretion rate if urine dipstick protein is negative or quantitative urine protein measurement if dipstick protein is positive. A fasting lipid profile, fasting blood glucose, HbA1c, electrolytes, and creatinine should be obtained before initiating antihypertensive therapy and approximately 6 to 12 weeks after treatment has begun to assess the need for treatment of abnormal lipids and the impact of antihypertensives on circulating lipids. These laboratory tests should be repeated at least once a year. An elevated microalbumin excretion rate (greater than 200 g/L) indicates the presence of renal disease in diabetes and is a predictor of cardiovascular mortality in type II diabetes. Type and frequency of repeated laboratory tests should be based on the severity of target-organ damage and the effects of the selected treatment regimen. SPECIAL CONSIDERATIONS IN DIABETIC PATIENTS WITH HYPERTENSION Kidney Disease Diabetes mellitus is now the leading cause of end-stage renal disease in the United States. The risk of diabetic renal disease increases with age and duration of diabetes and is more prevalent in African Americans.2 The development of nephropathy after 15 years of diabetes has been observed in more than 30 percent of persons with type I diabetes and in more than 20 percent of those with type II diabetes.2 In the former, microalbuminuria, mesangial cell hypertrophy, and blood pressure are correlated and herald the development of diabetic nephropathy.29 An exaggerated blood pressure response to exercise may unmask incipient nephropathy in persons with diabetes.30 Hypertension accelerates the rate of progression of diabetic renal disease, and control of blood pressure as well as glucose may retard this progression rate.2 Secondary Forms Of Hypertension Both hypertension and diabetes mellitus are commonly found in patients with Cushing's syndrome, pheochromocytoma, and primary aldosteronism. Persons with diabetes develop more atherosclerosis and do so at an earlier age than do those without diabetes. Atherosclerotic plaques can cause narrowing of one or both renal arteries, resulting in renovascular hypertension. A recent autopsy study found that 73 percent of patients with renal artery stenosis were hypertensive and 53 percent were diabetic.31 Cardiovascular Disease Diabetes mellitus is an independent risk factor for CHD, and the risk is doubled when hypertension is present.2 Recent awareness of a link between diabetes, hypertension, dyslipidemia, and coagulation abnormalities, all of which are risk factors for CVD, has added another dimension to our understanding. Among persons with diabetes, hypertension appears to be the major risk factor for CHD, in addition to its contribution to left ventricular hypertrophy and congestive heart failure, both of which are increased with diabetes. A variety of factors may contribute to the interactions between these disorders in persons with diabetes. The risk of peripheral vascular disease in individuals with diabetes is increased by the presence of hypertension as well as dyslipidemia and hypercoagulation. Cerebrovascular Disease Both men and women with diabetes mellitus have a 2.5- to 3.5- fold increase in atherothrombotic brain infarction (ABI).32 The Framingham Heart Study showed at the 30-year followup of men and women age 35 to 64 that women with diabetes had 3.6 times the incidence of ABI as did women without diabetes and that men with diabetes had 2.5 times the incidence of ABI as did men without diabetes.33 The Honolulu Heart Program reported at 12-year followup that the incidence of thromboembolic stroke was two times higher in men with diabetes than in men without diabetes.34 In an epidemiologic study of subjects age 50 to 79, multivariate analysis with adjustment for other risk factors demonstrated that the relative risk for stroke mortality and morbidity associated with diabetes was 1.8 in men and 2.2 in women.35 The relative importance of various risk factors has been estimated in a number of ways. The National Stroke Association36 has published a list of potentially modifiable risk factors for stroke. Hypertension increases the risk of stroke by six times the average risk and has a prevalence of 35 percent. Diabetes increases the risk of stroke by two to four times, with a prevalence of 4 to 6 percent. Addition of hypertension to diabetes substantially increases the risk and prevalence of stroke in persons with diabetes. Diabetic Retinopathy Diabetic retinopathy is a highly specific vascular complication of both type I and type II diabetes mellitus. It is also the most frequent cause of new cases of blindness among American adults age 20 to 74. The prevalence of retinopathy is strongly related to the duration of diabetes. Recently, the American College of Physicians, the American Diabetes Association, and the American Academy of Ophthalmology37 have published screening guidelines for diabetic retinopathy. Among persons with diabetes who are not treated with insulin, the 6-year incidence of retinal exudates was found to be more than doubled in patients with a mean systolic blood pressure (SBP) of 145 mm Hg as compared with those whose SBP was less than 125 mmHg.11 The Wisconsin Epidemiologic Study of Diabetic Retinopathy demonstrated that SBP was a predictor of the incidence of retinopathy. Diastolic blood pressure (DBP) was found to be a significant predictor of progression of retinopathy in younger-onset persons with diabetes (almost always type I). In older individuals with diabetes, neither SBP nor DBP was found to be associated with incidence, progression, or progression to proliferative retinopathy.10 In a followup study of a large group of patients with long- duration, type I diabetes, Janka and colleagues38 identified some of the risk factors responsible for the development of severe forms of diabetic retinopathy. One definite finding was that the risk of retinopathy increased dramatically with an increase of DBP greater than 70ÊmmHg. Controlling blood pressure reduces the progression of diabetic retinopathy.39 In addition, persons with diabetes suffer a greater incidence of chronic open angle glaucoma than do persons without diabetes.40 A possible explanation may be that diabetes- induced microangiopathy renders the optic nerve head more vulnerable to an elevation of the intraocular pressure that can produce optic nerve cupping, atrophy, and visual field defects, thereby increasing the risk of developing blindness. Hypertension is a known risk factor for ischemic optic neuropathy. Thus, persons with both diabetes and hypertension are at higher risk for developing both glaucoma and ischemic optic neuropathy than are persons with diabetes who do not have hypertension.41 Hypertension With Orthostatic Hypotension Normal circulatory adjustment to upright posture includes activation of sympathetic reflexes that originate from cardiopulmonary and arterial baroreceptors. The reflex increase of vascular resistance and heart rate offsets gravitational pooling of blood in the lower part of the body and results in unchanged mean arterial pressure. A significant fall in standing blood pressure (i.e., DBP drop of 10ÊmmHg or greater) is observed in approximately 12 percent of patients with diabetes mellitus and is more frequent in the elderly and in those with long-standing and more severe forms of diabetes. Also, it may occur when individuals change from a supine to seated position and can be quite disabling. Orthostatic hypotension in persons with both diabetes and autonomic dysfunction frequently is associated with supine hypertension. Autonomic Neuropathy In Diabetic Patients It is customary to classify patients with diabetes mellitus and orthostatic hypotension as those showing signs of neuropathy and blunted sympathetic responses and those who have exaggerated sympathetic function in the upright posture. Diabetic autonomic neuropathy typically is characterized by abnormal valsalva and isometric handgrip responses, blunting of respiratory arrhythmia, and inability to increase heart rate in the upright posture.42 The less frequent hyperadrenergic type of neuropathy is characterized by excessive tachycardia and an excessive response of plasma norepinephrine to upright posture. A decreased blood volume and possibly decreased vascular responsiveness to reflexogenic elevations in norepinephrine are thought to be of pathophysiologic importance in these patients. Postural hypotension may be present even in the absence of clinical peripheral neuropathy.43 Sexual Dysfunction Both diabetes mellitus and hypertension are independently associated with an increased prevalence of sexual dysfunction in both men and women.44-52 Frequency of sexual dysfunction in men with diabetes ranges from 27.5 to 75 percent in various studies.44-47,50 Several investigations47-52 have reported an estimated 40 to 80 percent of adult men with both diabetes and hypertension to have sexual dysfunction. In addition, an increasing proportion of patients with diabetes and hypertension are elderly, and aging itself appears to have a negative impact on sexual function in both men and women.53,49 Hypertension, neuropathy, vascular insufficiency, and psychological problems all have been implicated in impotence, impaired ejaculation, and decreased libido in men and in decreased vaginal lubrication, orgasmic dysfunction, and decreased libido in women.51,52 (See figure 1.) The absence of standards for evaluation of sexual dysfunction in women has led to underreporting and inadequate comprehension of the extent of this problem in women with diabetes and hypertension. Any antihypertensive medication can contribute to sexual dysfunction, perhaps some more than others, and this should be a consideration in evaluating persons with both hypertension and diabetes who have this problem.52 Thus, patients with both diabetes and hypertension should be evaluated for sexual dysfunction; appropriate therapy, including changes in medication or referral for sex counseling, should become routine in their clinical care. Lipid Disorders Alterations in circulating lipids are different in type I versus type II diabetes mellitus. Hypertriglyceridemia occurs in type I diabetes because of a lack of insulin; in general, this can be corrected with proper insulin administration.54 Persons with type II diabetes and impaired glucose tolerance experience twice the incidence of hypertriglyceridemia and low high density lipoprotein (HDL) cholesterol of persons who do not have diabetes.55 These changes are thought to be related to insulin resistance and hyperinsulinemia.9,56 Elevated cholesterol is not more common in persons with diabetes; compared to nondiabetics; however, low density lipoprotein (LDL) cholesterol in diabetes is more prone to glycation and oxidation. These biochemical changes increase the atherogenicity and decrease the metabolism of LDL cholesterol.57 Other Metabolic Concerns The insulin resistance that leads to type II diabetes mellitus and impaired glucose tolerance is due to a defect in insulin-mediated glucose uptake by skeletal muscle.58,59,60 This is associated with hyperinsulinemia, which also characterizes impaired glucose tolerance and early type II diabetes.58,59 Insulin resistance and hyperinsulinemia have been linked epidemiologically to hypertension, dyslipidemia (which includes increased circulating triglycerides and low HDL cholesterol), and elevated uric acid.56 These associations are more common among whites and possibly African Americans, compared to American Indians and Mexican Americans61,62; whether these associations are linked pathophysiologically is currently under intense investigation. Insulin resistance and hyperinsulinemia affect the mechanisms that (1) regulate blood pressure including sodium handling, sympathetic nervous system, and vascular remodeling63 and (2) regulate liver triglyceride production and HDL cholesterol metabolism.56 Obesity Approximately 34 million adults in the United States are obese.64 The health risks of obesity rise with its severity. Obesity is associated with an increased risk for hypertension, diabetes, hypertriglyceridemia, and low HDL cholesterol as well as increased levels of total cholesterol, LDL cholesterol, and very-low density lipoprotein cholesterol.65-67 The deposition of excess fat in the upper body (abdominal obesity), with an increased waist-to-hip ratio above 0.85 in women and 0.95 in men, also has been correlated with hypertension, diabetes, dyslipidemia, and increased mortality from CHD.8 Insulin resistance has been proposed as a common link among these risk factors.68 An excess of calories, a high-fat diet that promotes positive energy balance, and a sedentary lifestyle all contribute to overweight and obesity as well as to type II diabetes.69 Pregnancy Diabetes mellitus occurs in 2 to 5 percent of pregnant women and is more common in obese women, women of certain minority populations, and older women.70-72 Of these, only 10 percent will have been known to have had diabetes prior to pregnancy. Thus, most patients with diabetes during pregnancy, or gestational diabetes, are diagnosed while pregnant. Pregnant women should be screened for gestational diabetes at 24 to 28 weeks of gestation using a 50-gram glucose challenge; a positive test occurs when the glucose level exceeds 150 mg/dL 1 hour after an oral load.73,74 It is currently unclear whether patients with gestational diabetes have a significantly increased prevalence of hypertension. Treatment of hypertension associated with gestational diabetes, in addition to dietary factors directed at the diabetic state, should include drug therapy when blood pressure is greater than 140/90 mmHg. In patients with diabetes before pregnancy and coexisting hypertension, blood pressure should be maintained at less than 140/90 mmHg.72,75 In those patients with proteinuria at the onset or the development of significant proteinuria during the first 2 trimesters of pregnancy, a more aggressive therapeutic approach is in order--maintaining DBP at 80 to 90 mmHg to prevent further renal glomerular damage.72,75 Agents used in treatment of hypertension in pregnancy include methyldopa, hydralazine, and calcium antagonists.72,75 Angiotensin-converting enzyme (ACE) inhibitors are contraindicated. There is substantial evidence that pregnant women with both diabetes and hypertension are more likely to develop superimposed preeclampsia; thus, these patients should be watched carefully for worsening hypertension and proteinuria as they approach term. Patients who have hypertension and diabetes during pregnancy are at very high risk and require special monitoring care or consultation from a perinatal specialist.71 Children: Type I Diabetes mellitus of childhood onset is usually type I, and hypertension occurs with greater frequency in such children.76 Hypertension in children or adolescents with type I diabetes often reflects incipient nephropathy but may represent essential hypertension as well. Patients, including children and adolescents, with type I diabetes who exhibit albuminuria frequently have a positive family history of hypertension.77 The Task Force on Blood Pressure Control in Children78 has established blood pressure criteria to define hypertension in children and adolescents. Children and adolescents with blood pressure levels repeatedly above the 95th percentile for age and sex meet the criteria for the diagnosis of hypertension, and these values also apply to children with diabetes. Figure 2 provides the blood pressure values for the 50th, 95th, and 99th percentiles in the childhood blood pressure distribution. Frequent measurement of blood pressure should be a routine part of the clinical management of children with diabetes. For children and adolescents with type I diabetes, lifestyle modification is beneficial for blood pressure as well as metabolic control. These lifestyle parameters include physical exercise, appropriate diet, and avoidance of tobacco. Although optimal growth is an important clinical goal for children with diabetes, obesity should be avoided.15 The development of proteinuria in children with diabetes should be considered evidence of nephropathy. With signs of nephropathy, dietary protein intake should be reduced to less than 15 percent of the total caloric intake to conserve renal function.79 When children or adolescents with diabetes are discovered to have hypertension, it is likely that the hypertension is related to the diabetes. However, if the hypertension is severe, the possibility of other underlying causes should be considered. Severe hypertension (e.g., DBP 10ÊmmHg above the 95th percentile) in children with diabetes should be evaluated carefully in consultation with a specialist. Pharmacologic therapy is appropriate for children and adolescents with diabetes when DBP is fixed at or above the 95th percentile. When pharmacologic therapy is used to lower blood pressure in children with both diabetes and hypertension, a reasonable goal is to lower the blood pressure to the 90th percentile or less. Drug regimens that are recommended for adults with both diabetes and hypertension are effective and may be used in children and adolescents. There are some special considerations in determining antihypertensive drugs for children. In general, beta-blockers are avoided because these agents may mask hypoglycemia. Centrally acting drugs, such as methyldopa, clonidine, and centrally acting beta-blockers, should be used with caution because the central action may cause excessive drowsiness or depression and may interfere with school performance. Despite the concern about long-term use of antihypertensive drugs in children, control of high blood pressure in children with diabetes is especially important because of the high risk for diabetic nephropathy. TREATMENT The goal of treating hypertension in patients with diabetes mellitus is to prevent associated morbidity and mortality.80 Clinicians must consider the severity of the levels of blood pressure and blood glucose as well as the presence of other complications or additional risk factors. The least intrusive means to managing the concomitant diseases should be sought. Lifestyle modifications--including weight management, diet (i.e., salt reduction), moderation of alcohol intake, increased physical activity, and smoking cessation--are the cornerstones of therapy. Patients must be counseled about guidelines for safe exercise, including monitoring blood glucose and taking appropriate action, altering food or insulin if needed, carrying identification (e.g., medical bracelet or tag) and easily absorbed carbohydrates (e.g., candy), and monitoring exercise intensity to avoid risk of metabolic complications.28 Figure 3 summarizes the treatment algorithm for patients with diabetes. Lifestyle Modifications Lifestyle modifications have particular relevance for all patients with hypertension and diabetes. Lifestyle modifications can enable those individuals who are on drug therapy to reduce the number and dosage of medications needed to manage their hypertension and diabetes.81,82 Weight Management Weight loss in overweight individuals can improve control of both hypertension and diabetes mellitus. Studies have shown that even modest reductions in body weight can improve blood pressure and glycemic control.83 Reductions in weight may be associated with blood pressure reductions because of reductions in insulin levels, sympathetic nervous system activity, correction of cellular cation metabolism, and vascular resistance.84,85 Even small amounts of weight loss in overweight individuals can help to reduce LDL cholesterol levels and triglycerides as well as help to raise HDL cholesterol levels.86 Weight reduction in obese individuals also diminishes the insulin response to a glucose load, probably by enhancing tissue sensitivity.87 In fact, many patients normalize blood glucose and insulin levels simply by losing weight. Reducing caloric intake by 500 calories per day or expending this amount can lead to 1 pound of weight loss per week. The recommended diet for the treatment and management of type II diabetes provides less than 30 percent of calories from fat, approximately 15 percent of calories from protein, and 55 to 60 percent of calories from carbohydrates. The assistance of a registered dietitian in devising meal plans is strongly advised. Exercise also is recommended not only for weight control but also for other beneficial effects in the management of type II diabetes and hypertension.88,89 Nutritional Considerations For patients receiving exogenous insulin, caloric intake and insulin administration should be adjusted temporally so that adequate calories are consumed to cover periods of peak insulin action. Within this framework, however, flexibility should be allowed so that patients are not locked into fixed times at which meals and snacks must be consumed on a daily basis. Thus, with proper education, patients can learn to adjust the time of insulin administration to coincide with the time of day a meal is desired.90 Recent evidence from the Diabetes Control and Complications Trial (DCCT) suggests that selected nutrition interventions healthy food choices, exchange systems, carbohydrate counting, and total available glucose (TAG), e.g., glucose available as simple sugars can be coupled with intensive insulin therapy to obtain normoglycemia.91 Carbohydrates. Approximately 50 to 60 percent of total daily calories should be derived from carbohydrates, preferably complex carbohydrates.28 Complex carbohydrates from different vegetables, fruits, and whole grains are good sources of vitamins and fiber. A diet rich in soluble fibers including oat bran, legumes, barley, and most fruits and vegetables may be effective in reducing elevated plasma glucose and cholesterol. A high-fiber diet also may aid in weight management by promoting satiety at lower levels of calorie and fat intake. For optimal blood glucose control, up to 5 percent of total carbohydrates may be derived from simple carbohydrates in the form of sucrose.28 Simple carbohydrates generally should not be consumed alone, but rather in concert with a mixed meal to slow their absorption rates.28 As with total calories, carbohydrates should be distributed evenly throughout the day. Fat, Saturated Fat, and Cholesterol. Because dyslipidemia often coexists in persons with hypertension and diabetes, the fat content of the diet should be reduced to less than 30 percent of total calories, with less than 10 percent coming from saturated fat. Cholesterol intake should be less than 300 mg per day.90 Protein. The recommendations for protein for patients with both diabetes and hypertension do not differ from the recommendations for the general population. Approximately 10 to 15 percent of total calories (15 to 20 percent in children) should be derived from plant sources of protein and lean sources of animal protein. Reduction of protein intake appears to delay the progress of diabetic nephropathy.92 Cations (electrolytes). A diet moderately restricting sodium chloride to a level of less than 100 mmol per day (approximately 2.3 grams of sodium or approximately 6 grams of sodium chloride) may reduce elevated blood pressure.16,93 Adequate dietary intake of potassium and magnesium may be particularly important in patients with diabetes. Hypomagnesemia may play a role in increasing carbohydrate intolerance, platelet aggregability, vascular resistance, and lipid abnormalities.94,95 These minerals should be consumed at the U.S. Recommended Daily Allowances. It is premature to suggest supplementation of these minerals beyond the recommended levels. Alcohol Heavy alcohol consumption may raise blood pressure and cause resistance to antihypertensive therapy.96 In addition, alcohol provides unneeded calories, displaces more nutritious foods, and may interfere with the regular routine of diabetes self-management. Therefore, alcohol should be consumed in moderation in patients with diabetes and hypertension.16 Individuals should account for additional calories from alcohol in the meal plan by reducing the fat intake allowance. Persons with hypertriglyceridemia may need to refrain totally from drinking alcohol so that their serum triglyceride levels are not exacerbated.97 Physical Activity Regular physical activity has many potential benefits for patients with diabetes and hypertension. In addition to improving insulin sensitivity and glucose tolerance in diabetes, it may help to lower blood pressure and reduce the need for as well as the dosage of, insulin or oral hypoglycemic drugs. Health professionals generally should advise patients with hypertension and diabetes who have been sedentary and are initiating an exercise program to do so gradually and after appropriate medical evaluation.98 Smoking Cigarette smoking is a major risk factor for CHD and peripheral vascular disease and is the largest preventable cause of death and disease.99 For these reasons, persons with diabetes and hypertension who smoke should be apprised of the risks associated with smoking and strongly advised to quit. For more information on smoking cessation programs, contact the National Heart, Lung, and Blood Institute (NHLBI) Information Center, P.O.ÊBox 30105, Bethesda, MD 20824-0105. Pharmacologic Treatment Of Hypertension The Joint National Committee16 recently conducted an extensive review of therapeutic approaches to treating patients with hypertension. Five classes of antihypertensive agents are generally available. However, the concomitant presence of diabetes mellitus in patients with hypertension carries a greater risk because of the independent effects of these two diseases on several common target organs (e.g., heart, kidney, vascular system, eyes). Although the general approach to using pharmacologic agents in patients with diabetes and hypertension is similar to that used with only hypertension, there are several qualifications.  Although the goal blood pressure is similar in patients with diabetes and those without diabetes, it is more important for physicians to work closely with patients with diabetes to achieve this goal. Therefore, patients with diabetes who have blood pressures at 140/90ÊmmHg or greater, specifically, remain candidates for further therapeutic intervention, and a goal blood pressure of less than 130/85 mmHg is recommended for these patients.  Diabetic renal disease is an important complication that must be taken into consideration. Thus, therapeutic decisions need to consider effects of specific antihypertensive therapy on renal function and the progression of diabetic nephropathy.  Therapeutic modalities can have adverse effects on glucose and lipid metabolism.  Autonomic dysfunction, which can result in postural hypotension, is common in diabetes and must be considered in therapeutic decisions. For those with stage 1 hypertension, a 3-month period of lifestyle modifications is indicated. If lifestyle modification does not lower the blood pressure to the goal level (130/85 mmHg), then drugs should be added. In patients with diabetes who have blood pressures greater than 140/90 mmHg, pharmacologic intervention generally is indicated. Of special concern is the proper determination of blood pressure to assess therapeutic response. A seated blood pressure is the most desirable because of its practicality and its ability to integrate both the beneficial and negative (hypotension) effects. In addition, it is highly desirable that postural blood pressure responses be assessed (i.e., supine to standing, seated to standing). Home blood pressure monitoring should be performed in conjunction with home blood glucose monitoring because good blood pressure control is critically important and blood pressure is more likely to fluctuate over a 24-hour period in individuals with diabetes and hypertension.2 Renal disease contributes to hypertension in patients with diabetes through several pathogenic mechanisms: sodium and water retention (extracellular fluid volume expansion) and increased vascular resistance. Renal disease in patients with diabetes and hypertension may be associated with mesangial cell hypertrophy, increased glomerular capillary resistance, glomerular basement membrane thickening, and renal vascular disease. Microalbuminuria indicates the presence of diabetic nephropathy, and the progression of diabetic nephropathy appears to be correlated with a rise in blood pressure. Compounding these renal abnormalities is the contribution of hyperglycemia per se to the volume expansion and consequent hypertension. Thus, therapeutic approaches should include normalization of blood glucose in addition to the use of agents that will reduce both intravascular volume and intrarenal pressure. Antihypertensive Drugs ACE inhibitors are useful in patients with diabetes mellitus because they do not adversely affect the patient's metabolic state and may reduce proteinuria associated with diabetic nephropathy.100 ACE inhibitors may be especially desirable in those patients who have evidence of renal parenchymal disease (i.e., proteinuria, microalbuminuria) because of their beneficial effects in reducing proteinuria in experimental studies and clinical studies.100,101,102,103,104 In a recently reported randomized multicenter clinical trial, during a median followup of 3 years, treatment with an ACE inhibitor significantly decreased the rate of increase in creatinine and the rate of decline of creatinine clearance. The combined end point of mortality, dialysis, and transplantation was reduced by 50 percent with ACE inhibitor therapy. These benefits appeared to occur independently of effects on blood pressure, suggesting that ACE inhibitors may have special salutary effects in persons with type I diabetes and renal disease. It has not been determined if similar beneficial effects have been observed in a similar study protocol with other antihypertensive drugs. It also has not been determined whether the results of Lewis and colleagues100 pertain to persons with type II diabetes and renal disease. A major risk of ACE inhibitors is an acceleration of renal insufficiency, particularly in those with bilateral renal artery stenosis a more common occurrence in the persons with diabetes. Close monitoring of renal function and serum potassium should be performed in the first few weeks after initiation of therapy if bilateral renal artery disease is suspected. ACE inhibitors may cause hyperkalemia particularly in those individuals with renal failure or hyporeninemic hypoaldosteronism (type IV renal tubular acidosis). Care must be exercised in initiating ACE inhibitor therapy in patients receiving diuretics because there may be a profound drop in blood pressure and a decline in renal function. Alpha-receptor blocking agents, particularly those that have 24-hour duration of action, are effective antihypertensive agents in patients with hypertension and diabetes. These agents may have beneficial lipid metabolism effects.105 However, they do need to be used with some caution as they may induce orthostatic hypotension. Calcium antagonists also may be useful in treating hypertension in patients with diabetes. Calcium antagonists do not appear to have an adverse impact on glucose, lipid metabolism, or renal function. Caution does need to be exercised because of the potential of some calcium antagonists to induce orthostatic hypotension, which may be accentuated in patients with diabetes. Thiazide diuretics are used frequently and successfully to treat hypertension in individuals with diabetes. If the dose is low (i.e., 25 mg or less hydrochlorothiazide), adverse effects on carbohydrate metabolism, hypokalemia, and hypomagnesemia are uncommon. Furthermore, this class of agents is generally as effective as ACE inhibitors in lowering blood pressure in patients with diabetes.106 Indeed, long-term data (4 years) indicate that diuretics have the same effect as ACE inhibitors on reducing the progression of renal disease in patients with type II diabetes.106 It is likely that volume expansion contributes to the elevated arterial pressure in these individuals. On the other hand, as the dose of the diuretic increases, the diuretic-induced side effects are increased in patients with diabetes (i.e., alterations in glucose and lipid metabolism, adverse effect on renal hemodynamics). The use of thiazide diuretics does not appear to increase the incidence of clinical diabetes to a greater extent than other antihypertensive drugs,107 nor do they adversely alter the beneficial mortality outcome in patients treated for diabetes and hypertension.104 Thus, thiazide diuretics are effective antihypertensive agents in these patients but should be used in low doses. Several concerns limit the usefulness of beta-blockers in treating persons with diabetes: (1) these agents have adverse effects on glucose and lipid metabolism16; (2) they can reduce awareness of hypoglycemia in patients with diabetes and prolong recovery from hypoglycemia; and (3) they can reduce peripheral blood flow in patients who already have a compromised peripheral vascular system. Thus, except under special circumstances (e.g., in the presence of angina pectoris and postmyocardial infarction), beta-blockers should be used with caution in patients with diabetes and hypertension. Potassium-sparing agents also should be used with caution in persons with diabetes because of their increased susceptibility to developing hyperkalemia. ACE inhibitors may cause hyperkalemia in patients with renal impairment. Patients with diabetes and isolated systolic hypertension, hypertensive crisis, or supine hypertension with orthostatic hypotension can be treated by algorithms similar to those used in persons without diabetes. For the rest, beginning with an ACE inhibitor, a calcium antagonist, a peripheral alpha adrenergic blocker, or a small dose of a thiazide diuretic is appropriate initial therapy. Much of the information concerning the potential benefit or risk of various therapeutic modalities in patients with diabetes and hypertension is based on limited results from clinical trials and experimental animal data. Thus, physicians still must rely heavily on clinical judgment in developing an effective treatment program for these patients. Furthermore, continued emphasis on lifestyle modification (e.g., weight reduction, aerobic exercise) remains very important even though patients require pharmacologic treatment as well. Diabetes With Renal (Parenchymal) Hypertension A persistent increase in albumin excretion rates on at least three occasions and/or a progressive decline in renal function suggests a diagnosis of renal (parenchymal) disease. Hypertension in patients with diabetic nephropathy is manifested by sodium and water retention (extracellular fluid volume expansion), increased cardiac output, and increased peripheral vascular resistance. Although these mechanisms do not differ from those usually encountered in patients with hypertension who do not have diabetes, special consideration must be given in choosing antihypertensive agents for patients with diabetes and renal disease.104 Several studies have been conducted or are in progress to determine the relative efficacy of differing antihypertensive agents on blood pressure and renal function in persons with diabetes.100,104 The results of these studies are not yet sufficient to make definite recommendations. Some of the studies have been conducted in type I diabetics, representing 5 to 10 percent of Americans with diabetes. Others have included persons with diabetes who do not have hypertension and have used microalbuminuria as a surrogate for alterations in renal function.108 Some, but not all, studies with calcium antagonists have suggested a reduction in albumin excretion, and at least one study has suggested an additive benefit when an ACE inhibitor and a calcium antagonist are combined.109 However, the longest accumulation of data is from studies from Denmark, which indicate that lowering blood pressure (i.e., with diuretics and beta-blockers) reduces the rate of progression of diabetic renal disease.110 When significant diabetic renal disease is present, the use of loop diuretics may be necessary for appropriate volume reduction.2 Diabetes With Isolated Systolic Hypertension Several recent studies demonstrate that reducing an isolated elevation of systolic pressure (SBP greater than 160 mmHg and DBP below 90 mmHg) can reduce cardiovascular morbidity and mortality from stroke.27 Thiazide diuretics can be used in small doses as initial drug therapy. Initially, patients, especially older patients, should be seen frequently (at 2- to 4-week intervals) and observed for orthostatic hypotension associated with volume depletion. If a second drug is necessary, ACE inhibitors and calcium antagonists are generally efficacious and well tolerated. ACE inhibitors also provide additional therapeutic benefits in elderly patients with congestive heart failure. If SBP fails to respond to initial and second-choice drug therapy, hydralazine can be added as a third drug. Minoxidil also may be used in resistant cases if a vasodilator has not been used as a second-choice drug. Supine Hypertension With Orthostatic Hypotension Supine hypertension with orthostatic hypotension in patients with diabetes is associated with autonomic neuropathy and is the most difficult to treat. Occasionally, the upright blood pressure falls to such an extent that patients are unable to assume the upright posture, which may be aggravated by many antihypertensive medications that cause orthostatic hypotension. To reduce symptoms, the goal of therapy is to increase the upright pressure and to lower the supine pressure. To increase the upright pressure, 9-alpha- fluorohydrocortisone, which produces sodium retention and can increase volume, is prescribed in small doses of 0.05 to 0.20 mg daily. Elevation of supine blood pressure and precipitation of heart failure are potential complications of this mineralocorticoid agent. Good elastic hose personally fitted to cover the legs and thighs and perhaps to waist level (such as Jobst stockings) are sometimes beneficial. Both drugs and mechanical maneuvers can help in lowering supine pressure. Short-acting vasodilators (i.e., ACE inhibitors, calcium antagonists, hydralazine) can be taken shortly before bedtime to reduce nocturnal supine blood pressures. Initial doses should be small and slowly titrated upward to prevent orthostatic hypotension in the morning hours. Mechanically elevating the head of the bed 10 inches will allow gravity to decrease the supine blood pressure.111 Drugs For Managing Hypertensive Emergencies In Diabetic Patients The pharmacologic treatment of hypertensive emergencies in patients with diabetes is not different from that for persons who do not have diabetes. Treatment usually is administered with parenteral agents including sodium nitroprusside, and various adrenergic blocking agents.16 However, the potential detrimental effects of several agents in producing uncontrolled profound drops in blood pressure or increased cardiac output should be considered carefully in patients with diabetes who may have concomitant CVD and cerebrovascular disease. Diazoxide may exacerbate hyperglycemia and therefore is contraindicated. CONSIDERATIONS IN EDUCATION, CONTROL, AND MAINTENANCE Long-term maintenance of an effective treatment regimen requires continuing commitment by patients and health care providers. Physicians assume primary responsibility for establishing therapy and for assisting patients in adhering to the regimen. Nurses, pharmacists, podiatrists, optometrists, registered dietitians, and other health professionals play an important role in the care, education, and support of patients.16,112 Patients should be urged to assume primary responsibility for mastering the self-care knowledge and skills necessary for following the treatment plan. Adherence to long-term antihypertensive therapy is improved when the regimens are simplified, clarified, reinforced, and coordinated with diabetes-related tasks.16,113 Patients benefit from specific and understandable written instructions regarding diet and exercise plans, medication, and common side effects. Poor adherence to therapy, both lifestyle modifications and pharmacologic therapy, has been identified as major reason for inadequate control of high blood pressure and blood glucose levels.4 Some of the common causes for the lack of poor adherence include: Cost of medication; Unclear instructions and/or instructions that are not given to the patient in writing; Inadequate or no patient education; Lack of involvement of the patient in the treatment plan; and Side effects of medication. Patient education programs should be tailored for the individual and should use culturally sensitive communication strategies. Health professionals need to be knowledgeable about ethnic, regional, and religious issues.90 The learning styles of adults tend to be more self-directed than those of children, who are more dependent on the educator for direction. However, active learning experiences have proved successful in all age groups.114 Involving spouses and other family members in the educational process provides support in the learning experience.115 Home-monitoring (with family assistance) of blood glucose or blood pressure may be used to assist patients in attaining desired levels of blood glucose and blood pressure. They also provide an objective means of evaluating the effectiveness of interventions. Home-monitoring is a potentially powerful tool for increasing patients' understanding of the therapeutic regimen and encouraging their active participation in achieving the desired health outcomes. Adherence to home-monitoring is improved by the availability of handy and easy-to-use materials for recording results, regular clinician feedback about the record of results, and patient awareness that the measurement procedure and results will be evaluated periodically for accuracy.113 Physicians may find it helpful to coordinate their resources with health education programs operated in communities, worksites, and hospitals. Such programs can help emphasize the importance of long-term control and can help in long-term monitoring. Patient awareness of blood pressure or blood glucose levels also can be increased, thus reinforcing patients' agreements with their providers on goal level. The economic burden of chronic disease can be substantial. In many settings, hypertension and diabetes mellitus represent the most commonly encountered combination of diseases. Long-term adherence to a carefully prescribed and maintained therapeutic program oriented toward ambulatory care and self-care and the judicious use of home care can prevent the need for more expensive inpatient hospital services.116 Physicians and other health care professionals need to be aware of the economic issues in providing optimal long-term cost-effective care.16 REFERENCES 1. American Diabetes Association. Diabetes 1993 Vital Statistics. American Diabetes Association. 1993. 2. Epstein M, Sowers JR. Diabetes mellitus and hypertension. Hypertension. 1992;19:403-418. 3. National Diabetes Data Group. Summary. In: Harris MI, Hamman RF, eds. Diabetes in America. NIH Publication 85- 1468. Washington, DC: US Dept of Health and Human Services; 1985:11-16. 4. Working Group on Hypertension in Diabetes National High Blood Pressure Education Program. Statement on hypertension in diabetes mellitus: final report. Arch Intern Med. 1987;147:830-842. 5. Haffner SM, Mitchell BD, Pugh JA, Stern MP, Kozlowski MK, Hazuda HP, Patterson JK, Klein R. Proteinuria in Mexican Americans and non-Hispanic whites with NIDDM. Diabetes Care. 1989;12:530-536. 6. Horan M. Diabetes in hypertension. In: Harris MI, Hamman RF, eds. Diabetes in America. NIH Publication 85-1468. Washington, DC: US Dept of Health and Human Services, 1985:17-18. Diabetes data compiled 1984. 7. Bild D, Teutsch SM. The control of hypertension in persons with diabetes: a public health approach. Public Health Rep. 1987;102:522-529. 8. DesprŽs J-P, Moorjani S, Lupien PJ, Tremblay A, Nadeau A, Bouchard C. Regional distribution of body fat, plasma lipoproteins, and cardiovascular disease. Arteriosclerosis. 1990;10:497-511. 9. Flack JM, Sowers JR. Epidemiologic and clinical aspects of insulin resistance and hyperinsulinemia. Am J Med. 1991;91(suppl 1A):11S-21S. 10. Klein R, Klein BEK, Moss SE, Davis MD, DeMets DL. Is blood pressure a predictor of the incidence or progression of diabetic retinopathy? Arch Intern Med. 1989;149:2427-2432. 11. Knowler WC, Bennett PH, Ballintine EJ. Increased incidence of retinopathy in diabetics with elevated blood pressure: a six-year follow-up study in Pima Indians. N Engl J Med. 1980;302:645-650. 12. American Diabetes Association. Consensus statement on the treatment of hypertension in diabetes. Diabetes Care. 1993;16:1394-1400. 13. Dawson KG, McKenzie JK, Ross SA, Chiasson J-L, Hamet P. Report of the Canadian Hypertension Consensus Conference, 5: hypertension and diabetes. Can Med Assoc J. 1993;149:821-826. 14. National High Blood Pressure Education Program Working Group. Working group report on hypertension and chronic renal failure. Arch Intern Med. 1991;151:1280-1287. 15. American Diabetes Association. Physician's Guide to Insulin-Dependent (Type I) Diabetes: Diagnosis and Treatment. Alexandria, Va: American Diabetes Association, Inc.; 1988. 16. Joint National Committee. The fifth report of the Joint National Committee on detection, evaluation, and treatment of high blood pressure. Arch Intern Med. 1993;153:154-183. 17. Barrett-Conner E, Orchard T. Diabetes and heart disease. In: Harris MI, Hamman RF, eds. Diabetes in America. NIH Publication 85-1468. Washington, DC: US Dept of Health and Human Services; 1985: Ch XVI, 1-41. 18. Harris MI, Entmacher PS. Mortality from diabetes. In: Harris MI, Hamman RF, eds. Diabetes in America. NIH Publication 85-1468. Washington, DC: US Dept of Health and Human Services; 1985: Ch XXIX, pp 1-48. 19. Barrett-Conner E, Wingard DL. Sex differential in ischemic heart disease mortality in diabetics: a prospective population-based study. Am J Epidemiol. 1983;118:489-496. 20. Modan M, Halkin H, Almog S, Lusky A, Eshkol A, Shefi M, Shitrit A, Fuchs Z. Hyperinsulinemia: a link between hypertension, obesity and glucose intolerance. J Clin Invest. 1985;75:809-817. 21. Reaven GM. Banting lecture 1988: role of insulin resistance in human disease. Diabetes. 1988;37:1595- 1607. 22. Sowers JR, Standley PR, Ram JL, Jacober S, Simpson L, Rose K. Hyperinsulinemia, insulin resistance, and hyperglycemia: contributing factors in the pathogenesis of hypertension and artherosclerosis. Am J Hypertens. 1993;6:260S-270S. 23. Viverti GC, Keen H, Wiseman MJ. Raised arterial pressure in parents of proteinuric insulin-dependent diabetics. Br Med J. 1987;295:575-577. 24. Pool PE. The case for metabolic hypertension: Is it time to restructure the hypertension paradigm? In: Progress in Cardiovascular Diseases. Philadelphia, Penn: W.B. Saunders Co.; 1993:1-38. 25. Hypertension Detection and Follow-up Program Cooperative Group. Five-year findings of the Hypertension Detection and Follow-up Program, 1: reduction in mortality of persons with high blood pressure, including mild hypertension. JAMA. 1979;242:2562-2571. 26. Systolic Hypertension in the Elderly Program Cooperative Research Group. Low dose diuretic-based antihypertensive treatment reduces risk in elderly diabetics with isolated systolic hypertension. Circulation. 1993;88:386. Abstract. 27. SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension: final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA. 1991;265:3255-3264. 28. American Diabetes Association. Physician's Guide to Non- Insulin Dependent (Type II) Diabetes: Diagnosis and Treatment. 2nd ed. Alexandria, Va: American Diabetes Association, Inc.; 1988. 29. Chavers BM, Bilous RW, Ellis EN, Steffes MW, Mauer SM. Glomerular lesions and urinary albumin excretion in type I diabetes without overt proteinuria. N Engl J Med. 1989;320:966-970. 30. Christensen CK. Abnormal albuminuria and blood pressure rise in incipient diabetic nephropathy induced by exercise. Kidney Int. 1984;25:819-823. 31. Sawicki PT, Kaiser S, Heinemann L, Franzel H, Berger M. Prevalence of renal artery stenosis in diabetes mellitus: an autopsy study. J Intern Med. 1991;229:489- 492. 32. Dyken ML, Wolf PA, Barnett HJM, Bergan JJ, Hass WK, Kannel WB, Kuller L, Kurtzke JF, Sundt TM. Risk factors in stroke: a statement for physicians by the Subcommittee on Risk Factors and Stroke of the Stroke Council. Stroke. 1984;15:1105-1111. 33. Wolf RN, Kannel WB. Reduction of stroke through risk factor modification. Semin Neurol. 1986;6:243-253. 34. Abbott RD, Donahue RP, MacMahon SW, Reed DM, Yano K. Diabetes and the risk of stroke. Honolulu Heart Program. JAMA. 1987;257:949-952. 35. Barrett-Conner E, Khaw KT. Diabetes mellitus: an independent risk factor for stroke? Am J Epidemiol. 1988;128:116-123. 36. National Stroke Association. Stroke prevention: the importance of risk factors. Stroke: Clin Updates. 1991;1:17-20. 37. American College of Physicians, American Diabetes Association, American Academy of Ophthalmology. Screening guidelines for diabetic retinopathy. Ann Intern Med. 1992;116:683-685. 38. Janka HU, Warram JH, Rand LI, Krolewski AS. Risk factors for progression of background retinopathy in long- standing IDDM. Diabetes. 1989;38:460-464. 39. Tuescher A, Schnell H, Wilson PWF. Incidence of diabetic retinopathy and relationship to baseline plasma glucose and blood pressure. Diabetes Care. 1988;11:246-251. 40. American Academy of Ophthalmology. Basic and Clinical Science Course 1991-1992. Section 10. Glaucoma, Lens and Anterior Segment Trauma. San Francisco, Calif: American Academy of Ophthalmology; 1991:60. 41. Repka MX, Savino PJ, Schatz NJ, Sergott RC. Clinical practice and long-term implications of anterior ischemic optic neuropathy. Am J Ophthalmol. 1983;96:478-483. 42. Onrot J, Goldberg MR, Hollister AS, Biaggioni I, Robertson RM, Robertson D. Management of chronic orthostatic hypotension. Am J Med. 1986;80:454-464. 43. Eckberg DL, Harkins SW, Fritsch JM, Musgrave GE, Gardner DF. Baroreflex control of plasma norepinephrine and heart period in healthy subjects and diabetic patients. J Clin Invest. 1986;78:366-374. 44. McCulloch DK, Campbell IW, Wu FC, Prescott RJ, Clarke BF. The prevalence of diabetic impotence. Diabetologia. 1980;18:279-283. 45. Jensen SB. Diabetic sexual dysfunction: A comparative study of 160 insulin treated diabetic men and women and an age-matched control group. Arch Sex Behav. 1981;10:493-504. 46. Fairburn OG, McCulloch DK, Wu FC. The effects of diabetes on male sexual function. Clin Endocrinol Metab. 1982;11:749-767. 47. Lipson LG. Treatment of hypertension in diabetic men: problems with sexual dysfunction. Am J Cardiol. 1984;53:46A-50A. 48. Leedom L, Feldman M, Procci W, Zeidler A. Symptoms of sexual dysfunction and depression in diabetic women. J Diabet Complications. 1991;5:38-41. 49. Labby DH. Aging's effects on sexual function: expected changes and treatable dysfunction. Postgrad Med. 1985;78:32-43. 50. House WC, Pendleton L. Sexual dysfunction in diabetes: a survey of physician's responses to patients' problems. Postgrad Med. 1986;79:227-235. 51. Hsueh WA. Sexual dysfunction with aging and systemic hypertension. Am J Cardiol. 1988;61:18H-23H. 52. Sowers JR, Zemel M. Clinical implications of hypertension in the diabetic patient. Am J Hypertens. 1990;3:415-424. 53. Leiblum S, Bachman G, Kenman E, Colburn D, Swartzman L. Vaginal atrophy in post-menopausual women: the importance of sexual activity and hormones. JAMA. 1983;249:2195-2198. 54. Bunzell JD, Chait A. Lipoprotein pathophysiology and treatment. In: Rifkin H, Porte D, eds. Diabetes Mellitus Theory and Practice. New York, NY: Elsevier; 1990:756- 767. 55. Garg A, Grundy SM. Management of dyslipidemia in NIDDM. Diabetes Care. 1990;13:153-169. 56. Zavaroni I, Bonaro E, Pagliara M, Dall'Aglio E, Luchetti L, Buonanno G, Bonati PA, Bergonzani M, Gnudi L, Passeri M, Reaven G. Risk factors for coronary artery disease in healthy persons with hyperinsulinemia and normal glucose tolerance. N Engl J Med. 1989;320:702-706. 57. Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL. Beyond cholesterol: modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med. 1989;320:915-924. 58. Kolterman IG, Insel J, Saekow M, Olefsky JM. Mechanisms of insulin resistance in human obesity. J Clin Invest. 1980;65:1272-1284. 59. Hollenbeck CB, Chen Y-DI, Reaven GM. A comparison of the relative effects of obesity and insulin-dependent diabetes mellitus on in vivo insulin stimulated glucose utilization. Diabetes. 1984;33:622-626. 60. Kida Y, Esposito-Del Puente A, Bogardus C, Mott DM. Insulin resistance is associated with reduced fasting and insulin-stimulated glycogen synthase phosphatase activity in human skeletal muscle. J Clin Invest. 1990;85:476-481. 61. Saad MF, Lilioja S, Nyomba BL, Castillo C, Ferraro R, De Gregorio M, Ravussin E, Knowler WC, Bennett PH, Howard BV, Bogardus C. Racial differences in the relation between blood pressure and insulin resistance. N Engl J Med. 1991;324:733-739. 62. Haffner SM, Fong D, Hazuda HP, Pugh JA, Patterson JK. Hyperinsulinemia, upper body adiposity, and cardiovascular risk factors in non-diabetics. Metabolism. 1988;37:338-345. 63. Hsueh WA. Insulin resistance and essential hypertension. In: Fine L, Andreucci VE, eds. Yearbook of Nephrology. New York, NY: Springer-Verlag; 1992:117-138. 64. Najjar MF, Roland M. Anthropometric Reference Data and Prevalence of Overweight, United States, 1976-80. Vital and Health Statistics, Series 11, No. 203. Washington, DC: US Dept of Health and Human Services; 1987:1-73. 65. Pi-Sunyer FX. Health implications of obesity. Am J Clin Nutr. 1991;53 (supplÊ6):1595S-1603S. 66. Wolf RN, Grundy SM. Influence of weight reduction on plasma lipoproteins in obese patients. Arteriosclerosis. 1983;3:160-169. 67. Denke MA, Sempos CT, Grundy SM. Excess body weight. an underrecognized contributor to high blood cholesterol levels in white American men. Arch Intern Med. 1993;153:1093-1103. 68. Barnard RJ, Ugianskis EJ, Martin DA, Inkeles SB. Role of diet and exercise in the management of hyperinsulinemia and associated atherosclerotic risk factors. Am J Cardiol. 1992;69:440-444. 69. Marshall S, Garvey WT, Traxinger RR. New insights into the metabolic regulation of insulin action and insulin resistance: Role of glucose and amino acids. FASEB J. 1991;5:3031-3036. 70. National Institute of Child Health and Human Development. Understanding Gestational Diabetes. NIH Publication 93-2788. Washington, DC: NICHHD; 1993. 71. National High Blood Pressure Education Program Working Group. Working group report on high blood pressure in pregnancy. Am J Obstet Gynecol. 1990;163:1689-1712. 72. Barron WM. Hypertension. In: Barron WM, Lindheimer MD, eds. Medical Disorders in Pregnancy. Chicago, Ill: Mosby-Year Book; 1991:1-42. 73. Nelson RL. Diabetes and pregnancy: control can make a difference. Mayo Clin Proc. 1986;61:825-829. 74. Freinkel N, Dooley SL, Metzger BE. Care of the pregnant woman with insulin-dependent diabetes mellitus. N Engl J Med. 1985;313:96-101. 75. Lowe SA, Rubin PC. The pharmacological management of hypertension in pregnancy. J Hypertens. 1992;10:201-207. 76. Cruickshanks KJ, Orchard TJ, Becker DJ. The cardiovascular risk profile of adolescents with insulin- dependent diabetes mellitus. Diabetes Care. 1985;8:118- 124. 77. Krolewski AS, Canessa M, Warram JH, Laffel LMB, Christlieb AR, Knowler WC, Rand LI. Predisposition to hypertension and susceptibility to renal disease in insulin-dependent diabetes mellitus. N Engl J Med. 1988;318:140-145. 78. Task Force on Blood Pressure Control in Children. Report of the Second Task Force on Blood Pressure Control in Children 1987. Pediatrics. 1987;79:1-25. 79. Christensen CK, Mogensen CE. The course of incipient diabetic neuropathy: studies on albumin excretion and blood pressure. Diabetic Med. 1985;2:97-102. 80. Moser M, Ross H. The treatment of hypertension in diabetic patients. Diabetes Care. 1993;16:542-547. 81. Little P, Girling G, Hasler A, Trafford A. A controlled trial of a low sodium, low fat, high fibre diet in treated hypertensive patients: effect on antihypertensive drug requirement in clinical practice. J Hum Hypertens. 1991;5:175-181. 82. Runyan JW. Diabetes, hypertension and other associated diseases. Prim Care. 1988;15:251-276. 83. National High Blood Pressure Education Program Working Group. Working group report on primary prevention of hypertension. Arch Intern Med. 1993;153:186-208. 84. Jacobs DB, Sowers JR, Hmeidan A, Niyogi T, Simpson L, Standley PR. Effects of weight reduction on cellular cation metabolism and vascular resistance. Hypertension. 1993;21:308-314. 85. Tuck ML, Sowers JR, Dornfeld L, Kledzik G, Maxwell M. The effect of weight reduction on blood pressure, plasma renin activity, and plasma aldosterone levels in obese patients. N Engl J Med. 1981;304:903-933. 86. Adult Treatment Panel II. Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). JAMA. 1993;269:3015-3023. 87. Olefsky J, Reaven GM, Farquhar JW. Effects of weight reduction on obesity: studies of lipid and carbohydrate metabolism in normal and hyperlipoproteinemic subjects. J Clin Invest. 1974:53:64-76. 88. King AC, Tribble DL. The role of exercise in weight regulation in nonathletes. Sports Med. 1991;11:331-349. 89. Paffenbarger RS Jr, Wing AL, Hyde RT, Jung DL. Physical activity and incidence of hypertension in college alumni. Am J Epidemiol. 1983;117:245-257. 90. Lyon RB, Vinci DM. Nutrition management of insulin- dependent diabetes mellitus in adults: review of the Diabetes Care and Education dietetic practice group. J Am Diet Assoc. 1993;93:309-314, 317. 91. The DCCT Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329:977-986. 92. Levine SE, D'Elia JA, Bistrain B, Smith-Ossman S, Gleason R, Mitch WE, Miller D. Protein-restricted diets in diabetic neuropathy. Nephron. 1989;52:55-61. 93. Dodson PM, Beevers M, Hallworth R, Webberley MJ, Fletcher RF, Taylor KG. Sodium restriction and blood pressure in hypertensive type II diabetics: randomised blind controlled and crossover studies of moderate sodium restriction and sodium supplementation. Br Med J. 1989;298:227-230. 94. Resnick LM. Hypertension and abnormal glucose homeostasis. Possible role of divalent ion metabolism. Am J Med. 1989;87:17S-22S. 95. Nadler J, Malayan S, Luong H, Shaw S, Natarajan R, Ruda R. Evidence that intracellular free magnesium deficiency plays a role in increased platelet reactivity in type II diabetes mellitus. Diabetes Care. 1992;15:835-841. 96. World Hypertension League. Alcohol and hypertension implications for management: a consensus statement by the World Hypertension League. J Hum Hypertens. 1991;5:1854-1856. 97. Connell JE, Thomas-Dobersen D. Nutritional management of children and adolescents with insulin-dependent diabetes mellitus: a review of the Diabetes Care and Education dietetic practice group. J Am Diet Assoc. 1991;91:1556- 1564. 98. Goldberg AP. Aerobic and resistive exercise modify risk factors for coronary heart disease. Med Sci Sports Exerc. 1989;21:669-674. 99. Surgeon General. Report on Nutrition and Health. Washington, DC: US Dept of Health and Human Services, Public Health Service; 1988. 100. Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin converting enzyme inhibition in diabetic nephropathy. N Engl J Med. 1993;323:1456-1462. 101. Marre M, Chatellier G, LeBlanc H, Guyene TT, Menard J, Passa P. Prevention of diabetic nephropathy with enalapril in normotensive diabetics with microalbuminuria. Br Med J. 1988;297:1092-1095. 102. Parving HH, Hommel E, Nielsen MD, Giese J. Effect of captopril on blood pressure and kidney function in normotensive, insulin-dependent diabetics with nephropathy. Br Med J. 1989;299:533-536. 103. Bain R, Rohde R, Hunsicker LG, McGill J, Kobrin S, Lewis EJ. A controlled clinical trial of angiotensin- converting enzyme inhibition in type I diabetic nephropathy: study design and patient characteristics. The Collaborative Study Group. J Am Soc Nephrol. 1992;3(suppl 4):S97-S103. 104. Kasiske BL, Kalil RSN, Ma JZ, Liao M, Keane WF. Effect of antihypertensive therapy on the kidney in patients with diabetes: a meta-regression analysis. Ann Intern Med. 1993;118:129-138. 105. Neaton JD, Grimm RH, Prineas RJ, Stamler J, Grandits GA, Elmer PJ, Cutler JA, Flack JM, Schoenberger JA, McDonald R, Lewis CE, Liebson PR, for the Treatment of Mild Hypertension Study Research Group. Treatment of mild hypertension study: final results. JAMA. 1993;270:713- 724. 106. Walker WG, Hermann JA, Anderson JE. Randomized doubly blinded trial of enalapril (E) vs hydrochlorothiazide (H) on glomular filtration rate (GFR) in diabetic nephropathy: early vs late results. Hypertension. 1993;22:410. Abstract. 107. Gurwitz JH, Bohn RL, Glynn RJ, Monane M, Mogun H, Avorn J. Antihypertensive drug therapy and the initiation of treatment for diabetes mellitus. Ann Intern Med. 1992;118:273-278. 108. Ravid M, Savin H, Jutrin I, Bental T, Katz B, Lishner M. Long-term stabilizing effect of angiotensin-converting enzyme inhibition on plasma creatinine and on proteinuria in normotensive type II diabetic patients. Ann Intern Med. 1993;118:577-581. 109. Bakris GL, Barnhill BW, Sadler R. Treatment of arterial hypertension in diabetic humans: importance of therapeutic selection. Kidney Int. 1992;41:912-919. 110. Parving HH, Andersen AR, Smidt UM, Svendsen PA. Early aggressive antihypertensive treatment reduces rate of decline in kidney function in diabetic nephropathy. Lancet. 1983;1:1176-1179. 111. National High Blood Pressure Education Program Joint National Committee. The 1984 report of the Joint National Committee on detection, evaluation, and treatment of high blood pressure. Arch Intern Med. 1984;144:1045-1057. 112. Levine DM. The physician's role in health-promotion and disease prevention. Bull N Y Acad Med. 1987;63:950-956. 113. Working Group on Health Education and High Blood Pressure Control. Improving Adherence Among Hypertensive Patients. NN 250. Washington, DC: US Dept of Health and Human Services; 1987. 114. Greene DS, Beaudin BP, Bryan JM. Addressing attitudes during diabetes education: suggestions from adult education. Diabetes Educator. 1991;17:470-473. 115. Istre SM. The art and science of successful teaching. Diabetes Educator. 1989;15:67-75. 116. Runyan JW. The Memphis Chronic Disease Program: comparisons in outcome and the nurses' extended role. JAMA. 1975;231:254-257.