A double blind comparison of the effects of amlodipine and enalapril on insulin sensitivity in hypertensive patients

Abstract

This study compares the effects of a calcium channel blocker (amlodipine) and an angiotensin converting enzyme inhibitor (enalapril) on in vivo insulin sensitivity in patients with essential hypertension. Forty-six patients with mild and moderate hypertension were studied. After a 2-week single-blind placebo phase, they were randomly assigned to double-blind therapy with either amlodipine (2.5 to 10 mg/day) or enalapril (5 to 40 mg/day) for 16 weeks. Both groups were comparable in terms of demographic characteristics, degree of obesity, metabolic parameters, and arterial blood pressure. Insulin sensitivity was measured at baseline and at week 16 during the active phase using euglycemic hyperinsulinemic clamps. Arterial blood pressure decreased similarly in both groups. Whole body glucose uptake (M-value) increased with amlodipine from 3.63 +/- 0.32 (mean +/- SEM) to 3.97 +/- 0.31 mg/kg/min (P = .02). A similar tendency was observed with enalapril: from 3.59 +/- 0.32 to 3.94 +/- 0.30 mg/kg/min (P = .09). A trend to lower steady-state insulin level during the second clamp (compared to baseline) was observed in both groups. The clamp-derived insulin sensitivity index (that corrects for steady-state insulin levels and glucose levels during the clamp) increased similarly in both groups: from 1.15 +/- 0.11 to 1.39 +/- 0.13 with amlodipine (P = .03) and from 1.25 +/- 0.13 to 1.49 +/- 0.16 with enalapril (P = .01). LDL cholesterol decreased with amlodipine (mean change, -11.3 mg/dL, P = .004). Amlodipine and enalapril were associated with increments in insulin sensitivity. Amlodipine provided an additional benefit with decreased low density lipoprotein cholesterol levels.

Correlations of high-sensitivity C-reactive protein and atherosclerosis in Japanese type 2 diabetic patients

“…All these patients were being treated with one or more antihypertensive drugs, including ACE inhibitors, angiotensin II receptor blockers, and calcium channel antagonists, prior to enrollment. In this regard, all of these three drug classes have been reported to improve insulin resistance (40,41) and aortic stiffness (42,43). In addition, 33 and 31% of our patients with high HSCRP and low HSCRP respectively had been diagnosed with dyslipidemia.…”

Insulin Receptor Substrate-2 (Irs2) in Endothelial Cells Plays a Crucial Role in Insulin Secretion

“…In addition to the amelioration of insulin secretion through the increased islet blood flow induced by an ACE inhibitor, as seen in this study, the blockade of the RAS during the development of diabetes has been attributed to improvements in peripheral insulin sensitivity and b-cell dysfunction (30,31). ACE inhibitors have been shown to improve whole-body and skeletal muscle insulin resistance in hypertensive subjects with or without type 2 diabetes (32)(33)(34)(35)(36)(37)(38)(39)(40). The reduction of angiotensin II-mediated vascular resistance by ACE inhibition may improve insulin-stimulated glucose transport activity in skeletal muscle (41).…”

Diabetic retinopathy is associated with insulin resistance and cardiovascular autonomic dysfunction in type 2 diabetic patients

“…First, subjects in this study population had essential hypertension, which was treated with one or more antihypertensive drugs. These characteristics of the patients' backgrounds have been reported to affect insulin resistance 36,37 and sympathetic nerve function. 38,39 Nonetheless, the results indicate that DR in diabetic patients is related to cardiac depression and insulin resistance.…”