The effect of metformin and insulin on sympathetic nerve activity, norepinephrine spillover and blood pressure in obese, insulin resistant, normoglycemic, hypertensive men.

To evaluate the effect of metformin on insulin sensitivity and to further examine the relationship between insulin resistance, sympathetic nerve activity and blood pressure, 6 obese insulin resistant, normoglycemic hypertensive men were investigated (age 49 +/- 2 years, BMI 27.6 +/- 1.2, mean +/- SEM). The study had a placebo controlled, double blind, cross over design with 6 weeks' metformin treatment (850 mg b.i.d) vs placebo. Blood pressure was measured weekly. At the end of each treatment period, glucose infusion rate (GIR), muscle sympathetic nerve activity (MSA) and renal and total body norepinephrine (NE) kinetics (radioisotope dilution) were examined during euglycemic hyperinsulinemic clamp. Fasting insulin was 13 +/- 3 and 10 +/- 2 mU/l and fasting glucose 5.3 +/- 0.2 and 5.1 +/- 0.1 mmol/l after placebo and metformin treatment, respectively (ns). GIR during the last hour of the insulin clamp was 3.7 +/- 0.6 vs 3.6 +/- 0.6 mg/kg x min (ns). Resting MSA, total body and right renal NE spillover did not differ significantly after placebo and metformin treatment. Systolic and diastolic blood pressures were 151 +/- 10/95 +/- 5 mmHg after placebo and 146 +/- 5/94 +/- 5 mmHg after metformin treatment (ns). Thus metformin treatment did not have any significant effect on insulin sensitivity, blood pressure or sympathetic activity in this small group of patients. Renal plasma flow and MSA increased significantly during the insulin clamp, whereas renal NE and total body NE spillover remained unchanged, suggesting nonuniform regional sympathetic nerve responses to acute hyperinsulinemia.