Summary
In conventional doses, thiazide diuretics impair glucose tolerance and decrease insulin sensitivity, making them an unpopular choice for treating diabetic patients with hypertension. However, use of low-dose thiazide diuretics may avoid the adverse metabolic effects seen with conventional doses. In a double-blind, randomised crossover study we assessed peripheral and hepatic insulin action in 13 hypertensive non-insulin-dependent diabetic patients after a 6-week placebo run-in and following two 12-week treatment periods with either low (1.25 mg) or conventional (5.0 mg) dose bendrofluazide. There were no differences between doses in their effects on systolic and diastolic blood pressure. Bendrofluazide 1.25 mg had significantly less effect on serum potassium, uric acid, fasting glucose and HbA1c concentrations than the 5.00 mg dose. Exogenous glucose infusion rates required to maintain euglycaemia were significantly different between doses (p < 0.05) with conventional-dose bendrofluazide worsening peripheral insulin resistance compared to baseline (23.8±2.9 vs 27.3±3.5 μmol · 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 μmol · kg-1 · min-1, p = NS). Postabsorptive endogenous glucose production was higher on treatment with bendrofluazide 5.0 mg compared to 1.25 mg (11.7 ±0.5 vs 10.2±0.3 μol · kg-1 · min-1 p < 0.05) and suppressed to a lesser extent following insulin (4.0±0.7 vs 2.0±0.4 μ±mol · kg-1 · min-1, p < 0.05). Treatment with bendrofluazide 5.0 mg increased postabsorptive endogenous glucose production compared to baseline (11.7±0.5 vs 10.6±0.4 μmol · kg-1 · min-1, p<0.05) whereas bendrofluazide 1.25 mg did not (10.2±0.3 vs 10.6±0.4 μmol · kg-1 · min-1 p = NS). At a dose of 1.25 mg bendrofluazide is as effective as conventional doses but has less adverse metabolic effects. 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.
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Abbreviations
- EGP:
-
Endogenous glucose production
- Ra :
-
rate of glucose appearance
- Rd :
-
rate of glucose disappearance
- NIDDM:
-
non-insulin-dependent diabetes mellitus
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Harper, R., Ennis, C.N., Heaney, A.P. et al. A comparison of the effects of low- and conventional-dose thiazide diuretic on insulin action in hypertensive patients with NIDDM. Diabetologia 38, 853–859 (1995). https://doi.org/10.1007/s001250050363
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DOI: https://doi.org/10.1007/s001250050363