Comparison of effects of captopril used either alone or in combination with a thiazide diuretic on insulin action in hypertensive Type 2 diabetic patients: a double-blind crossover study

Aims It has been suggested that the adverse metabolic effects of antihypert ensive therapy offset some of the benefits of blood pressure reduction. It has also been suggested that angiotensin converting enzyme (ACE) inhibitors reduce insulin resistance and that, if used together with thiazide diureti cs, the adverse effects of thiazides on insulin sensitivity may be eliminat ed. We examined the effects on insulin sensitivity of captopril either alon e or in combination with bendrofluazide in 11 hypertensive Type 2 diabetic patients. Methods Insulin action was assessed using an isoglycaemic hyperinsulinaemic clamp in a double-blind, randomized, crossover study after a 6-week placeb o run-in and following two 12-week treatment periods with captopril (C) (10 0 mg) alone or in combination with bendrofluazide (CB) (2.5 mg). Results Blood pressure was lower following CB compared to C (128/82 vs. 144 /88 mmHg; P<0.005) and both were lower than baseline (162/101 mmHg; P < 0.0 01). CB resulted in a significant increase in fasting plasma glucose compar ed to C (9.7 +/- 0.8 vs. 8.5 +/- 0.6 mmol/l; P < 0.05). Exogenous glucose i nfusion rates required to maintain isoglycaemia during hyperinsulinaemia we re lower after CB compared to C (22.3 +/- 2.4 vs. 27.4 +/- 4.2 mol.kg(-1).m in(-1); P<0.05). Suppression of endogenous glucose production was reduced a fter CB compared to baseline (4.0 +/- 0.6 vs. 2.4 +/- 0.5 mol.kg(-1).min(-1 ); P < 0.05). Conclusions Combination of bendrofluazide with captopril lowered blood pres sure but resulted in deleterious effects on insulin action compared to capt opril alone.