A LONG-TERM COMPARISON BETWEEN ENALAPRIL AND CAPTOPRIL ON INSULIN SENSITIVITY IN NORMOTENSIVE NON-INSULIN-DEPENDENT DIABETIC VOLUNTEERS

Background: There are conflicting reports about the effects of angiote nsin converting enzyme inhibitors on insulin sensitivity and glycaemic control. In addition, the chronic effects of ACEI on insulin sensitiv ity in normotensive but insulin resistant individuals have been contro versial. Aim: To determine the long-term effects of low-dose captopril or enalapril on insulin sensitivity and lipid parameters in normotens ive non-insulin dependent diabetic volunteers. Methods: Twenty-eight n ormotensive non-insulin dependent diabetes mellitus subjects on diet a lone or diet plus oral hypoglycaemic agents were randomized in a singl e-blind cross-over study to receive either captopril (12.5 mg daily) o r enalapril (5 mg daily). Initially, captopril was compared with enala pril for 28 days with a 28-day washout period between drug regimens. F or the long-term study, the subjects then remained on the second ACEI for a further II months. Insulin sensitivity was measured using the is oglycaemic hyperinsulinaemic clamp (insulin infusion rate 20 mIU/kg/mi n) at the start and completion of each part of the cross-over study an d then at 3, 6 and 12 months of drug therapy. Fasting glucose, insulin , HbA(1), lipids and lipoproteins were measured at the start of each c lamp. Results: No first or second order carry-over effects were demons trated between the ACEIs. No differences were detected between enalapr il and captopril on insulin sensitivity at any of the time points. Sta tistically significant hypotension was avoided, and at doses used the ACEIs did not modify any parameters of glycaemic control over the 12-m onth study period. There were no significant alterations in plasma cho lesterol, triglycerides, HDL cholesterol or Apo AI levels during the s tudy. Conclusions: Long-term low-dose ACEIs (captopril/enalapril) do n ot modify insulin sensitivity, glycaemic control or lipids in normoten sive non-insulin dependent diabetic subjects.