Nine hypertensive patients with body mass indexes between 24-27 kg/m2 and normal glucose tolerance with at least a postchallenge plasma insulin level greater than 360 pmol/L were recruited for a double blind, cross-over study with metformin (850 mg, twice daily) and placebo. Each treatment lasted 1 month. Before and after each treatment, hormone and substrate concentrations were determined, blood pressure was monitored over 24 h, and insulin sensitivity was measured by a euglycemic (4.7 mmol/L) hyperinsulinemic (450 pmol/L) clamp study. Renal cation excretion and erythrocyte membrane cation heteroexchange were measured. Metformin, compared to placebo, did not affect body weight (70 +/- 7 vs. 70 +/- 7 kg), fasting plasma glucose (4.8 +/- 0.1 vs. 4.8 +/- 0.1 mmol/L), total cholesterol (5.38+/0.33 vs. 5.48 +/- 0.38 mmol/L), or triglycerides (1.73 +/- 0.72 vs. 1.91 0.89 mmol/L). Nevertheless, after metformin treatment, the plasma high density lipoprotein cholesterol concentration increased (1.42 +/- 0.18 vs. 1.34 0.16 mmol/L), and the plasma insulin level dropped (62 +/- 10 vs. 88+/- 12 pmol/L; both P < 0.05). Insulin-mediated glucose disposal was higher after metformin treatment (26.1 +/- 2.4 vs. 19.3 +/- 2.3 micromol/min x kg; P < 0.01), whereas hepatic glucose production was completely suppressed. These positive metformin-induced metabolic effects were not associated with a significant change in mean daily blood pressure levels (141 +/- 6/89 +/- 3 vs. 142 +/- 7/90 +/- 3 mm Hg). Compared to placebo, metformin increased the excretion of sodium, potassium, and lithium by enhancing their glomerular filtration rate. Na+/Li+ countertransport was not affected by metformin. However, the apparent affinity for H+ of Na+/H+ exchange was increased, and the Hill coefficient was decreased. In conclusion, 1 month of metformin administration to patients with essential hypertension and normal glucose tolerance 1) reduces the basal plasma insulin concentration, 2) improves whole body insulin-mediated glucose utilization, and 3) improves plasma high density lipoprotein cholesterol levels. Despite these positive effects, metformin did not reduce arterial blood pressure.
Improvement of insulin sensitivity by metformin treatment does not lower blood presure of non-obese insulin-resistant hypertensive patients with normal glucose tolerance
DEL PRATO, STEFANO
1996-01-01
Abstract
Nine hypertensive patients with body mass indexes between 24-27 kg/m2 and normal glucose tolerance with at least a postchallenge plasma insulin level greater than 360 pmol/L were recruited for a double blind, cross-over study with metformin (850 mg, twice daily) and placebo. Each treatment lasted 1 month. Before and after each treatment, hormone and substrate concentrations were determined, blood pressure was monitored over 24 h, and insulin sensitivity was measured by a euglycemic (4.7 mmol/L) hyperinsulinemic (450 pmol/L) clamp study. Renal cation excretion and erythrocyte membrane cation heteroexchange were measured. Metformin, compared to placebo, did not affect body weight (70 +/- 7 vs. 70 +/- 7 kg), fasting plasma glucose (4.8 +/- 0.1 vs. 4.8 +/- 0.1 mmol/L), total cholesterol (5.38+/0.33 vs. 5.48 +/- 0.38 mmol/L), or triglycerides (1.73 +/- 0.72 vs. 1.91 0.89 mmol/L). Nevertheless, after metformin treatment, the plasma high density lipoprotein cholesterol concentration increased (1.42 +/- 0.18 vs. 1.34 0.16 mmol/L), and the plasma insulin level dropped (62 +/- 10 vs. 88+/- 12 pmol/L; both P < 0.05). Insulin-mediated glucose disposal was higher after metformin treatment (26.1 +/- 2.4 vs. 19.3 +/- 2.3 micromol/min x kg; P < 0.01), whereas hepatic glucose production was completely suppressed. These positive metformin-induced metabolic effects were not associated with a significant change in mean daily blood pressure levels (141 +/- 6/89 +/- 3 vs. 142 +/- 7/90 +/- 3 mm Hg). Compared to placebo, metformin increased the excretion of sodium, potassium, and lithium by enhancing their glomerular filtration rate. Na+/Li+ countertransport was not affected by metformin. However, the apparent affinity for H+ of Na+/H+ exchange was increased, and the Hill coefficient was decreased. In conclusion, 1 month of metformin administration to patients with essential hypertension and normal glucose tolerance 1) reduces the basal plasma insulin concentration, 2) improves whole body insulin-mediated glucose utilization, and 3) improves plasma high density lipoprotein cholesterol levels. Despite these positive effects, metformin did not reduce arterial blood pressure.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
