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.
OBJECTIVE
It has been suggested that the adverse metabolic effects of antihypertensive 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 diuretics, the adverse effects of thiazides on insulin sensitivity may be eliminated. We examined the effects on insulin sensitivity of captopril either alone 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 placebo run-in and following two 12-week treatment periods with captopril (C) (100 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 < 0.001). CB resulted in a significant increase in fasting plasma glucose compared to C (9.7+/-0.8 vs. 8.5+/-0.6 mmol/; P < 0.05). Exogenous glucose infusion rates required to maintain isoglycaemia during hyperinsulinaemia were lower after CB compared to C (22.3+/-2.4 vs. 27.4+/-4.2 mol x kg(-1) x min(-1); P < 0.05). Suppression of endogenous glucose production was reduced after CB compared to baseline (4.0+/-0.6 vs. 2.4+/-0.5 mol x kg(-1) x min(-1); P< 0.05).


CONCLUSIONS
Combination of bendrofluazide with captopril lowered blood pressure but resulted in deleterious effects on insulin action compared to captopril alone.
Hunter
S J
SJ
Sir George E. Clark Metabolic Unit, Royal Victoria Hospital, Belfast, Northern Ireland, UK.
Wiggam
M I
MI
Ennis
C N
CN
Whitehead
H M
HM
Sheridan
B
B
Atkinson
A B
AB
Bell
P M
PM
D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001581:Benzothiadiazines; D001794:Blood Pressure; D002216:Captopril / Q000008:administration & dosage / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D004232:Diuretics; D004311:Double-Blind Method; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D049993:Sodium Chloride Symporter Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*
D000959:Antihypertensive Agents; D001581:Benzothiadiazines; D004232:Diuretics; D007328:Insulin; D010919:Placebos; D049993:Sodium Chloride Symporter Inhibitors; D002216:Captopril