Comparison of effects of combined ACE inhibitor and low-dose thiazide diuretic with ACE inhibitor alone on insulin action in patients with hypertension and Type 2 diabetes: a double-blind crossover study.
OBJECTIVE
To establish the safety in terms of insulin sensitivity of a low dose thiazide/ACE inhibitor combination.


METHODS
We examined the effects on insulin sensitivity of captopril either alone or in combination with low-dose bendroflumethiazide (1.25 mg) in 15 hypertensive Type 2 diabetic patients. Insulin action was assessed using an isoglycaemic hyperinsulinaemic clamp in a double-blind, randomised, crossover study after a 6-week placebo run-in and following two 12-week treatment periods with captopril (C) (100 mg) alone or in combination with bendroflumethiazide (CB) (1.25 mg).


RESULTS
Blood pressure was lower following CB compare to C (138/83 vs. 144/85 mmHg; P < 0.05) and both were lower than baseline (153/92 mmHg; P < 0.01). CB resulted in a significant increase in fasting plasma glucose compared to C (9.6 +/- 2.6 vs. 8.5 +/- 1.6 mmol/l; P < 0.05). Exogenous glucose infusion rates required to maintain isoglycaemia during hyperinsulinaemia were lower after CB compared to C (25.1 +/- 13.3 vs. 34.2 +/- 16.8 micromol/kg/min; P < 0.01) as were isotopically determined glucose utilisation rates (29.0 +/- 12.4 vs. 36.6 +/- 17.3 micromol/kg/min; P < 0.05). There was no significant difference in fasting endogenous glucose production between treatments (CB 9.3 +/- 3.3 vs. C 8.6 +/- 1.6 micromol/kg/min), nor between suppression following insulin (CB 4.0 +/- 2.1 vs. C 4.3 +/- 3.1 micromol/kg/min).


CONCLUSIONS
Combination of low-dose bendroflumethiazide with captopril lowered blood pressure but resulted in deleterious effects on insulin action compared to captopril alone.
McLaughlin
D M
DM
Regional Centre for Endocrinology and Diabetes, Royal Victoria Hospital, Belfast, UK. darren.mclaughlin@setrust.hscni.net
Atkinson
A B
AB
Ennis
C N
CN
Browne
J
J
Hunter
S J
SJ
Sheridan
B
B
Bell
P M
PM
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001539:Bendroflumethiazide / Q000008:administration & dosage / Q000009:adverse effects; D002216:Captopril / Q000008:administration & dosage / Q000009:adverse effects; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D015309:Glucose Clamp Technique / Q000379:methods; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D008875:Middle Aged; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007328:Insulin; D001539:Bendroflumethiazide; D002216:Captopril