engleski

Metabolic effects of ramipril in non-insulin dependent diabetics with essential hypertension

The effect of ramipril in comparison with atenolol and placebo on glucose and lipid metabolism was studied in non-insulin dependent diabetics, well controlled individually with diet and glibenclamide during a 2-month period, with mild (90-104 mm Hg) and moderate (105-114 mm Hg) essential hypertension. The effects of ramipril on specific insulin binding to erythrocyte receptors, glucose utilization and relationship between ramipril dosage and insulin binding and glucose utilization were assessed. The possible need of glibenclamide dose reduction in well controlled patients on glibenclamide therapy during the administration of ramipril was also assessed. Seventy patients were treated with 2.5 mg/day of ramipril (group A, 20 patients), 5.0 mg/day of ramipril (group B, 20 patients), 50 mg/day of atenolol (group C, 20 patients) or placebo (group D, 10 patients), and compared. Blood glucose by the GOD-Pap method, HbA1c by fast protein lipid chromatograpy method (FPLC), lipids by CHOD-Pap method, CHOD-Pap method with PEG precipitation and enzymatic methods, specific insulin binding% by I121-labeled insulin, and metabolized glucose by glucose clamp test were measured before and after the treatment. Baseline fasting blood glucose, postprandial blood glucose and HbA1c were similar in all groups and did not change significantly with treatment. Differences in the mean values of specific insulin binding before and after 6 weeks of treatment in groups A, B, C and D were +1.13± 1.54, +0.28± 2.61, -0.14± 1.83 and -1.50± 1.53, respectively. The difference in specific insulin binding% between group A and group D was statistically significant (p<0.05). Differences in the mean values of metabolized glucose in mg/kg/min before and after the treatment in groups A, B, C and D were +0.36± 1.31, +0.88± 1.18, +0.33± 1.22 and -0.19± 0.59, respectively. The difference in metabolized glucose between group B vs. group C and group D was statistically significant (p<0.05). There was no clinically or statistically significant difference in specific insulin binding% and metabolized glucose in mg/kg/min between groups A and B. The baseline dose of glibenclamide (9.56± 5.56) was similar in all the four groups and did not change significantly after the treatment. It was concluded that 6 weeks of treatment with ramipril in hypertensive NIDDM subjects 1) had no effect on the glucose and lipid metabolism ; 2) induced a significant increase in specific insulin binding% at a dose of 2.5 mg vs. placebo, and a significant increase in metabolized glucose at a dose of 5.0 mg vs. atenolol and placebo ; 3) entailed no significant dose-dependent (2.5 vs. 5.0 mg/day) difference in specific insulin binding% and metabolized glucose in mg/kg/min ; and 4) suggested no need of glibenclamide dose reduction in well controlled patients on glibenclamide therapy.

diabetes mellitus; hypertension; ramipril; metabolic effects

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