DISPARATE EFFECTS OF INSULIN REDUCTION WITH DILTIAZEM ON SERUM DEHYDROEPIANDROSTERONE-SULFATE LEVELS IN OBESE HYPERTENSIVE MEN AND WOMEN

Evidence suggests that amelioration of hyperinsulinemic insulin resist ance in men with calcium channel blockers of the dihydropyridine class is associated with a fall in serum insulin and a rise in serum dehydr oepiandrosterone sulfate (DHEA-S) concentrations. The present study wa s conducted to determine whether 1) the nondihydropyridine calcium cha nnel blocker diltiazem also reduces circulating insulin levels in huma ns, and 2) a reduction in circulating insulin with a calcium channel b locker is associated with a rise in serum DHEA-S concentrations in wom en as well as men. Ten obese hypertensive men and 13 obese hypertensiv e postmenopausal women were studied. Subjects were assessed at baselin e and after the oral administration of diltiazem (60 mg, three times d aily) for 18 days. Diltiazem treatment was associated with reductions in fasting serum insulin levels in both the men (from 91 +/- 14 to 56 +/- 12 pmol/L; P < 0.03) and women (from 92 +/- 20 to 48 +/- 9 pmol/L; P = 0.05). Serum glucose levels did not change in either group. In me n, concurrent with the fall in serum insulin levels, serum DHEA-S leve ls rose from 4.05 +/- 1.06 to 6.91 +/- 1.32 mu mol/L (P < 0.04), and s erum DHEA levels rose from 14.4 +/- 3.0 to 24.3 +/- 4.6 nmol/L (P = 0. 05) with diltiazem treatment, whereas serum cortisol did not change. I n contrast, diltiazem administration in the women was not associated w ith any change in serum DHEA-S, DHEA, or cortisol levels. These observ ations suggest that the action of calcium channel blockers to fewer fa sting serum insulin levels is not specific for the dihydropyridine cla ss and applies to both men and women. Furthermore, the finding of a se x-based disparity in DHEA-S and DHEA responses to insulin reduction su ggests that the metabolism of these steroids may be regulated differen tly in men than in women.