Beneficial effects of a long-term oral L-arginine treatment added to a hypocaloric diet and exercise training program in obese, insulin-resistant type 2 diabetic patients.
Am J Physiol Endocrinol Metab. 2006 Nov;291(5):E906-12. Epub 2006 Jun 13. PMID: 16772327
Diabetology, Endocrinology and Metabolic Disease Unit, Fondazione Centro San Raffaele del Monte Tabor, Milan, Italy.
Because chronic L-arginine supplementation improves insulin sensitivity and endothelial function in nonobese type 2 diabetic patients, the aim of this study was to evaluate the effects of a long-term oral L-arginine therapy on adipose fat mass (FM) and muscle free-fat mass (FFM) distribution, daily glucose levels, insulin sensitivity, endothelial function, oxidative stress, and adipokine release in obese type 2 diabetic patients with insulin resistance who were treated with a combined period of hypocaloric diet and exercise training. Thirty-three type 2 diabetic patients participated in a hypocaloric diet plus an exercise training program for 21 days. Furthermore, they were divided into two groups in randomized order: the first group was also treated with L-arginine (8.3 g/day), and the second group was treated with placebo. Although in the placebo group body weight, waist circumference, daily glucose profiles, fructosamine, insulin, and homeostasis model assessment index significantly decreased, L-arginine supplementation further decreased FM (P<0.05) and waist circumference (P<0.0001), preserving FFM (P<0.03), and improved mean daily glucose profiles (P<0.0001) and fructosamine (P<0.03). Moreover, change in area under the curve of cGMP (second messenger of nitric oxide; P<0.001), superoxide dismutase (index of antioxidant capacity; P<0.01), and adiponectin levels (P<0.02) increased, whereas basal endothelin-1 levels (P<0.01) and leptin-to-adiponectin ratio (P<0.05) decreased in the L-arginine group. Long-term oral L-arginine treatment resulted in an additive effect compared with a diet and exercise training program alone on glucose metabolism and insulin sensitivity. Furthermore, it improved endothelial function, oxidative stress, and adipokine release in obese type 2 diabetic patients with insulin resistance.