Antihypertensive Therapy and the Risk of New-Onset Diabetes

Abstract

Numerous studies have consistently demonstrated that certain classes of antihypertensive medications have differential effects on carbohydrate and lipid metabolism in humans. In general, higher doses of thiazide diuretics (i.e., ≥25 mg/day hydrochlorothiazide) and β-blockers, at any antihypertensive dose, worsen glycemic control, with β-blockers worsening insulin sensitivity (1). Conversely, ACE inhibitors, angiotensin II receptor blockers, and calcium channel blockers (CCBs) have neutral or beneficial effects on these variables (2,3). It is noteworthy, however, that not all drugs within the same class have similar effects on insulin sensitivity. This is exemplified by the effects of vasodilating β-blockers failing to worsen insulin resistance and consequently having neutral effects on glycemic control (4,5). These aforementioned observations are evident in 11 randomized clinical outcome trials where development of new-onset diabetes was evaluated as a secondary end point (Table 1) (6–11). In contrast to this general trend, the STOP-2 (Swedish Trial in Old Patients with Hypertension 2) reported no difference in diabetes incidence between conventional treatment (β-blockers or diuretics) and either ACE inhibitor–or CCB-based treatment (12). Moreover, in addition to prospective randomized trials, some long-term epidemiological studies, such as the ARIC (Atherosclerosis Research in Communities) study, have linked different classes of antihypertensive agents with development of new-onset diabetes (13). All of these studies, however, have limitations to their conclusions. First, all had cardiovascular outcomes rather than incidence of new-onset diabetes as a primary end point. Second, it is difficult to assess the effects of a single class of agents since many studies …