Antihypertensive agents, insulin sensitivity, and new-onset diabetes

Abstract

The effects of the antihypertensive drugs on carbohydrate metabolism and the development of diabetes have been a major research field for more than two decades. Many clinical studies have investigated the effects of the antihypertensive classes on insulin sensitivity and glycemic control, whereas several observational studies and large outcome trials have examined associations of antihypertensive agents with diabetes incidence. In general, thiazide diuretics and conventional beta blockers decrease insulin sensitivity and increase new-onset diabetes, whereas angiotensin-converting enzyme inhibitors, calcium channel blockers, and angiotensin II receptor blockers have neutral or beneficial effects on these parameters. However, several issues in this field, such as the specific properties of newer agents and the relationship of adverse metabolic outcomes and cardiovascular risk, remain to be fully elucidated. This article presents and evaluates the current knowledge in this important area.

Impact of Chronic Kidney Disease and Diabetes Mellitus on Choice of Renin Angiotensin System-Inhibitors in Patients with Hypertension and Heart Failure

“…For more than two decades one of the most active area of research topics in the field of hypertension therapeutics was the possible effects of major antihypertensive drug classes on carbohydrate metabolism and the development of new-onset DM [ 14 ]. In this regard, numerous clinical studies have investigated the impact of antihypertensive agents on insulin sensitivity (IS) and glycemic control, whereas large outcome trials have explored the potential association between antihypertensive agents and incident DM.…”

“…In this regard, numerous clinical studies have investigated the impact of antihypertensive agents on insulin sensitivity (IS) and glycemic control, whereas large outcome trials have explored the potential association between antihypertensive agents and incident DM. Another important issue is the possible harmful impact of antihypertensive therapyrelated new-onset DM on cardiovascular outcomes [ 14 ]; thus, presence of DM should be taken into consideration in the choice of the appropriate BP-lowering therapy in patients with hypertension and HF.…”

Lipid Effects of Antihypertensive Medications

“…RAAS blockers have beneficial effects on lipids and are thought to be protective or at least neutral for development of insulin resistance [13,52]. In a meta-analysis of 474 trials, ACE inhibitors decreased total cholesterol levels in patients with diabetes (but not LDL) and also decreased triglyceride levels, especially in patients with high baseline triglycerides [9].…”

Mechanistic Insights into Diuretic-Induced Insulin Resistance

“…5 Any medication that worsens insulin sensitivity, ie, thiazide diuretics or most ␤-blockers will hasten the development of diabetes mellitus in those with impaired fasting glucose. 6 Large observational studies demonstrate that thiazide diuretics and most ␤-blockers increase the incidence of new-onset diabetes mellitus compared with renin-angiotensin system (RAS) blockers or calcium channel blockers. 7 To further support this observation, a network-based meta-analysis of hypertensive agents showed that RAS blockers were the agents least likely to be associated with the development of diabetes mellitus, whereas thiazides had a higher incidence of diabetes mellitus compared with placebo.…”