Minor Long-Term Changes In Weight Have Beneficial Effects On Insulin Sensitivity And Beta-Cell Function In Obese Subjects

Aim: To evaluate the long-term effect of changes in body composition induced by weight loss on insulin sensitivity (S-I), non-insulin mediated glucose disposal, glucose effectiveness (S-G) and beta-cell function.Design: Glucose metabolism was evaluated before and after participation in a two-year weight loss trial of Orlistat vs. placebo, combined with an energy and fat restricted diet.Subjects: Twelve obese patients (11 women, 1 man), age 45.8+/-10.5 years, body weight (BW) 99.7+/-13.3 kg, BMI 35.3+/-2.8 kg/m(2).Measurements: At inclusion and 2 years later an oral glucose tolerance test (OGTT) and a frequently sampled intravenous glucose tolerance test (FSIGT) were performed. Body composition was estimated by a dual-energy X-ray absorptiometry (DXA) whole body scanning.Results: The patients obtained varying changes in BW ranging from a weight loss of 17.8 kg to a weight gain of 6.0 kg. Corresponding changes in fat mass (FM) varied from a 40% reduction to a 19% increase. A significant decrease in both fasting (p=0.038) and 2 h (p=0.047) blood glucose at OGTT was found. The improvement in insulin sensitivity (SI) estimated by means of Bergmans Minimal Model, was significantly and linearly correlated to change in total FM (r=-0.83, p=0.0026). A multiple regression analysis showed that changes in truncal FM was the strongest predictor of change in S-I explaining 67% of the variation. First phase insulin response (AIRg) remained unchanged whereas insulin disposition index increased significantly (p=0.044). At inclusion five patients had impaired glucose tolerance of which four, who lost weight, were normalized at the retest 2 years later.Conclusion: In obese subjects long-term minimal or moderate changes in weight were found to be linearly associated with changes in insulin sensitivity. In obese subjects with impaired glucose tolerance even a minor weight loss was able to normalize glucose tolerance.