A COMPARISON OF THE EFFECTS OF LOW-DOSE AND CONVENTIONAL-DOSE THIAZIDE DIURETIC ON INSULIN ACTION IN HYPERTENSIVE PATIENTS WITH NIDDM

In conventional doses, thiazide diuretics impair glucose tolerance and decrease insulin sensitivity, making them an unpopular choice for tre ating diabetic patients with hypertension. However, use of low-dose th iazide diuretics may avoid the adverse metabolic effects seen with con ventional doses. In a double-blind, randomised crossover study we asse ssed peripheral and hepatic insulin action in 13 hypertensive non-insu lin-dependent diabetic patients after a 6-week placebo run-in and foll owing two 12-week treatment periods with either low (1.25 mg) or conve ntional (5.0 mg) dose bendrofluazide. There were no differences betwee n doses in their effects on systolic and diastolic blood pressure. Ben drofluazide 1.25 mg had significantly less effect on serum potassium, uric acid, fasting glucose and HbA(1c) concentrations than the 5.00 mg dose. Exogenous glucose infusion rates required to maintain euglycaem ia were significantly different between doses (p < 0.05) with conventi onal-dose bendrofluazide worsening peripheral insulin resistance compa red to baseline (23.8 +/- 2.9 vs 27.3 +/- 3.5 mu mol . kg(-1) . min(-1 ), p < 0.05) and low-dose bendrofluazide producing no change compared to baseline (26.8 +/- 3.6 vs 27.3 +/- 3.5 mu mol . kg(-1) . min(-1), p = NS). Postabsorptive endogenous glucose production was higher on tre atment with bendrofluazide 5.0 mg compared to 1.25 mg (11.7 +/- 10.5 v s 10.2 +/- 0.3 mu mol . kg(-1) . min(-1), p < 0.05) and suppressed to a lesser extent following insulin (4.0 +/- 0.7 vs 2.0 +/- 0.4 mu mol . kg(-1) . min(-1), p < 0.05). Treatment with bendrofluazide 5.0 mg inc reased postabsorptive endogenous glucose production compared to baseli ne (11.7 +/- 0.5 vs 10.6 +/- 0.4 mu mol . kg(-1) . min(-1), p < 0.05) whereas bendrofluazide 1.25 mg did not (10.2 +/- 0.3 vs 10.6 +/- 0.4 m u mol . kg(-1) min(-1), p = NS). At a dose of 1.25 mg bendrofluazide i s as effective as conventional doses but has less adverse metabolic ef fects. In contrast to conventional doses which worsen both hepatic and peripheral insulin resistance, low-dose bendrofluazide has no effect on insulin action in non-insulin-dependent diabetic subjects.