Effects of low dose versus conventional dose thiazide diuretic on insulin action in essential hypertension

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Abstract
Objective: To see whether low dose thiazide diuretics given to patients with essential hypertension might avoid the adverse metabolic consequences seen with conventional doses. Design: Double blind randomised crossover study of two 12 week treatment periods with either low dose (1.25 mg) or conventional dose (5.0 mg) bendrofluazide given after a six week placebo run in period. Setting: Outpatient clinics serving the greater Belfast area. Subjects: 16 white non-diabetic patients (9 male) under 65 with essential hypertension recruited from general practices within the greater Belfast area. Main outcome measures: Systolic and diastolic blood pressure and peripheral and hepatic insulin action. Results: One man failed to complete the study. There were no differences between doses in their effects on systolic and diastolic blood pressure. Bendrofluazide 1.25 mg had substantially less effect20on serum potassium concentration than the 5.0 mg dose. There were no intertreatment differences in fasting glucose, insulin, cholesterol, and triglyceride concentrations. Bendrofluazide 5.0 mg significantly increased postabsorptive endogenous glucose production compared with baseline (mean 10.9 (SD 1.2) v 10.0 (0.8) μmol/kg/min), whereas bendrofluazide 1.25 mg did not. Postabsorptive endogenous glucose20production was significantly higher with bendrofluazide 5.0 mg compared with 1.25 mg (10.9 (1.2) v 9.9 (0.8) μmol/kg/min) but was suppressed to a similar extent after insulin (bendrofluazide 5.0 mg202.8 (1.5) μmol/kg/min v bendrofluazide 1.25 mg 2.2 (1.5) μmol/kg/min). Exogenous glucose infusion rates required to maintain euglycaemia were not significantly different between doses and were20similar to baseline. Conclusions: Bendrofluazide 1.25 mg is as effective as conventional doses but has less adverse metabolic effect. In contrast with conventional doses, how dose bendrofluazide has no effect on hepatic insulin action. There is no difference between low and conventional doses of bendrofluazide in their effect on peripheral insulin sensitivity.