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. doi: 10.1152/ajpendo.00002.2006. Epub 2006 Jun 13.


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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Arginine / administration & dosage*
  • Blood Glucose / metabolism
  • Blood Pressure
  • Body Weight / drug effects
  • Combined Modality Therapy
  • Diabetes Mellitus, Type 2 / diet therapy
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diet, Reducing*
  • Energy Intake
  • Exercise*
  • Female
  • Fructosamine / blood
  • Humans
  • Insulin / blood
  • Insulin Resistance
  • Male
  • Middle Aged
  • Obesity / diet therapy
  • Obesity / drug therapy*
  • Triglycerides / blood


  • Blood Glucose
  • Insulin
  • Triglycerides
  • Fructosamine
  • Arginine