INSULIN SENSITIVITY, GLUCOSE EFFECTIVENESS, AND BETA-CELL FUNCTION INOBESE MALES WITH ESSENTIAL-HYPERTENSION - INVESTIGATION OF THE EFFECTS OF TREATMENT WITH A CALCIUM-CHANNEL BLOCKER (DILTIAZEM) OR AN ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR (QUINAPRIL)

It has been suggested that hyperinsulinemia secondary to insulin resis tance may be a pathogenetic factor common to obesity, non-insulin-depe ndent diabetes mellitus (NIDDM), and hypertension. Furthermore, beta-b lockers and thiazide diuretics have been shown to be capable of increa sing insulin resistance and thus of inducing NIDDM in predisposed indi viduals. We used the minimal model approach (MMA) to glucose metabolis m and insulin kinetics to compare peripheral insulin sensitivity and b eta-cell function in hypertensive and normotensive obese men. The hype rtensive group consisted of 37 obese men with mild to moderate hyperte nsion; following a drug-free period of 4 weeks, 20 of these subjects r eceived diltiazem and 17 quinapril over the 12-week study period. The normotensive (control) group contained 17 obese men without microalbum inuria, dyslipidemia, or a family history of essential hypertension or NIDDM. Before and at the end of the 12-week study period, subjects un derwent frequently sampled intravenous glucose tolerance (FSIGT) tests . The results were used to estimate an insulin sensitivity index (S-I) , a glucose effectiveness index (S-G), and beta-cell sensitivity to gl ucose indices during first- and second-phase insulin secretion (Phi(1) and Phi(2)) using the minimal models of glucose metabolism and insuli n kinetics. No significant differences in S-I or S-G were detected bet ween the hypertensive and control groups. Twelve weeks' treatment with diltiazem led to a slight but significant increase in Phi(1); however , neither diltiazem nor quinapril had significant effects on S-I or S- G. We conclude that men with obesity and hypertension have no greater insulin resistance than those with obesity alone, suggesting that hype rtension is not generally associated with any significant increase in insulin resistance. Treatment with diltiazem or quinapril does not hav e undesirable effects on glucose metabolism. However, treatment with d iltiazem led to a significant increase in beta-cell sensitivity to glu cose; this is of particular interest, given the importance of Phi(1) f or peripheral glucose uptake. Copyright (C) 1997 by W.B. Saunders Comp any.