A comparison of the effects of low- and conventional-dose thiazide diuretic on insulin action in hypertensive patients with NIDDM |
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| Authors: | R Harper C N Ennis A P Heaney B Sheridan M Gormley A B Atkinson G D Johnston P M Bell |
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| Institution: | (1) Sir George E. Clark Metabolic Unit, Royal Victoria Hospital, Belfast, UK, GB;(2) Regional Endocrine Laboratory, Royal Victoria Hospital, Belfast, UK, GB;(3) Mater Infirmorum Hospital, Belfast, UK, GB;(4) Department of Therapeutics and Pharmacology, The Queen's University of Belfast, Belfast, UK, GB |
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| Abstract: | 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 HbA1 c 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 μmol · kg− 1· min− 1, p < 0.05) and suppressed to a lesser extent following insulin (4.0 ± 0.7 vs 2.0 ± 0.4 μmol · 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. Diabetologia (1995) 38: 853–859]
Received: 6 September 1994 and in revised form: 29 December 1994 |
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| Keywords: | Insulin resistance hypertension non-insulin-dependent diabetes mellitus thiazide diuretic |
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