LACK OF EFFECT OF LONG-TERM AMLODIPINE ON INSULIN SENSITIVITY AND PLASMA-INSULIN IN OBESE PATIENTS WITH ESSENTIAL-HYPERTENSION

To evaluate the effects of long-term treatment antihypertensive with t he dihydropyridine calcium antagonist amlodipine on insulin sensitivit y, plasma insulin, and lipoprotein metabolism in obese hypertensive pa tients. We measured the insulin sensitivity index (S(I)), determined b y the Minimal Model Method of Bergman, fasting plasma insulin and gluc ose concentrations, serum total triglyceride and lipoprotein cholester ol fractions, and blood pressure in 20 obese, non-diabetic patients wi th essential hypertension before and after 6 weeks of placebo and agai n after 6 months of amlodipine. Ten patients [mean body mass index (BM I) 30.2 kg . m-2] had been on prior treatment with a thiazide diuretic in low dosage and/or a beta-adrenoceptor blocker (group A), and 10 ma tched patients [BMI 31.8 kg . m-2] had been previously untreated (grou p B). Amlodipine was started in a dose of 5 mg and was increased to 10 mg once daily in 14 patients who were hypertensive after 8 weeks on t he lower dosage. At entry (before placebo), S(I) was slightly but not significantly lower in group A than B [2.7 vs. 3.6 x 10(-4) ml . muU-4 . min -1]; fasting plasma insulin was 13.6 vs. 12.9 muU . ml-1. After 6 weeks on placebo, S(I) averaged 3.7 in group A and 4.4 x 10(-4) muU . ml-1 . min-1 in group B; fasting plasma insulin was 14.6 vs. 15.1 m uU . ml-1, and glucose 5.5 vs. 5.5 mmol . l-1. After 6 months on amlod ipine there were no differences in S(I) [group A vs. group B, 5.2 vs. 3.8 x 10(-4) ml . muU-1 . min-1], fasting insulin [13.0 vs. 12.7 muU . ml-1], glucose [5.4 vs. 5.5 mmol . l-1], serum total triglycerides, a nd cholesterol or lipoprotein cholesterol fractions. Compared with pla cebo, amlodipine significantly reduced systolic and diastolic blood pr essures. Heart rate, body weight, and 24 h urinary sodium excretion we re unaltered. Long-term treatment with amlodipine does not affect insu lin sensitivity, circulating insulin or glucose, or lipoprotein metabo lism in obese, non-diabetic patients with essential hypertension.