Insulin sensitivity, glucose effectiveness, and β-cell function in obese males with essential hypertension: Investigation of the effects of treatment with a calcium channel blocker (diltiazem) or an angiotensin-converting enzyme inhibitor (quinapril)

Abstract

It has been suggested that hyperinsulinemia secondary to insulin resistance may be a pathogenetic factor common to obesity, non-insulin-dependent diabetes mellitus (NIDDM), and hypertension. Furthermore, β-blockers and thiazide diuretics have been shown to be capable of increasing insulin resistance and thus of inducing NIDDM in predisposed individuals. We used the minimal model approach (MMA) to glucose metabolism and insulin kinetics to compare peripheral insulin sensitivity and β-cell function in hypertensive and normotensive obese men. The hypertensive group consisted of 37 obese men with mild to moderate hypertension; following a drug-free period of 4 weeks, 20 of these subjects received diltiazem and 17 quinapril over the 12-week study period. The normotensive (control) group contained 17 obese men without microalbuminuria, dyslipidemia, or a family history of essential hypertension or NIDDM. Before and at the end of the 12-week study period, subjects underwent frequently sampled intravenous glucose tolerance (FSIGT) tests. The results were used to estimate an insulin sensitivity index (S 1), a glucose effectiveness index (S G), and β-cell sensitivity to glucose indices during first- and second-phase insulin secretion (Φ 1 and Φ 2) using the minimal models of glucose metabolism and insulin kinetics. No significant differences in S l or S G were detected between the hypertensive and control groups. Twelve weeks' treatment with diltiazem led to a slight but significant increase in Φ 1; however, neither diltiazem nor quinapril had significant effects on S l or S G. We conclude that men with obesity and hypertension have no greater insulin resistance than those with obesity alone, suggesting that hypertension is not generally associated with any significant increase in insulin resistance. Treatment with diltiazem or quinapril does not have undesirable effects on glucose metabolism. However, treatment with diltiazem led to a significant increase in β-cell sensitivity to glucose; this is of particular interest, given the importance of Φ 1 for peripheral glucose uptake.