Requirements for antihypertensive therapy in diabetic patients: metabolic aspects.

AIM OF ANTIHYPERTENSIVE TREATMENT IN DIABETICS: Prevention or treatment of hypertensive in diabetic patients reduces the incidence and progression of diabetic complications of retinopathy and nephropathy, cerebro- and cardio-vascular disease, and widespread macroangiopathy. Therefore, in patients with diabetes and hypertension beside good glucose control, the basic and probably major intervention steps is to normalize blood pressure. Antihypertensive treatment usually means life-long use of antihypertensive drugs. METABOLIC EFFECTS OF DIFFERENT DRUG CLASSES: Given the known diabetogenic properties of several antihypertensive drugs and their high rate of use, in probably a substantial proportion of patients with diabetes or prone to develop diabetes, treating arterial hypertension with conventional diuretics and/or beta-blockers might, in the long term, offset the beneficial effects of lowering blood pressure. Furthermore, there are conflicting reports of increased mortality in patients treated with diuretics, beta-blockers or calcium antagonists. Consequently, metabolic aspects and side effects of antihypertensive drugs are key elements in determining the preference for a specific antihypertensive regimen. Although the impact of hyperinsulinemia/insulin resistance on morbidity and mortality is an open question, it is preferable that antihypertensive treatment does not increase insulin resistance and/or hyperinsulinemia. Chronic beta-blocker treatment can be accompanied by an increase in insulin resistance. Calcium antagonists and angiotensin converting enzyme (ACE) inhibitors and alpha(1)-blockers are neutral or might even improve insulin resistance and lipid profile. Thiazides impair glucose tolerance, increase low-density lipoprotein cholesterol and decrease potassium, although these side effects are dose-dependent. Unless diuretics are needed for reasons other than hypertension, treatment of diabetics with thiazides should be avoided until the influence of these agents on prognosis is clarified. If the addition of a diuretic is needed, the metabolically neutral indapamide would seem a reasonable choice. PREFERRED FIRST-LINE TREATMENT: On the basis of favorable pharmacological profiles, ACE inhibitors and certain calcium antagonists have emerged as the preferred first-line drugs in the treatment of the hypertensive diabetic patient. In diabetics with nephropathy, therapy is usually initiated with an ACE inhibitor. Moreover, the combination of an ACE inhibitor and a calcium antagonist that lowers the heart rate (such as verapamil) might offer even greater advantages than either class of drug alone, since they combine metabolic neutrality with added antihypertensive and renal protective efficacy.