The role of postprandial releases of insulin and incretin hormones in meal-induced satiety - effect of obesity and weight reduction

BACKGROUND: Previous studies have indicated that the secretion of the intestinal satiety hormone glucagon-like peptide-1 (GLP-1) is attenuated in obese subjects. OBJECTIVE: To compare meal-induced response of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) in obese and lean male subjects, to investigate the effect of a major weight reduction in the obese subjects, and to look for an association between these hormones and ad libitum food intake. METHOD: Plasma concentrations of intestinal hormones and appetite sensations were measured prior to, and every 30 min for 180 min after, ingestion of a 2.5 MJ solid test meal. Gastric emptying was estimated scintigraphically. An ad libitum lunch was served 3h after the test meal. SUBJECTS: Nineteen non-diabetic obese (body mass index (BMI) 34.1 -43.8 kg/m(2)) and 12 lean (BMI 20.4-24.7 kg/m(2)) males. All obese subjects were re-examined after a mean stabilised weight loss of 18.8 kg (95% CI 14.4 -23.2). RESULTS: Total area under the GLP-1 response curve (AUC(total.GLP-1)) was lower in obese before and after the weight loss compared to lean subjects (P < 0.05), although weight loss improved the response from 80 to 88% of that of the lean subjects (P = 0.003). The GIP response was similar in obese and lean subjects. However, after the weight loss both AUC(total.GIP) and AUC(incremental),(GIP) were lowered (P < 0.05). An inverse correlation was observed between AUC(incremental, GIP) and energy intake at the subsequent ad libitum meal in all groups. In lean subjects ad libitum energy intake was largely predicted by the insulin response to the preceding meal (r(2) = 0.67, P = 0.001). CONCLUSION: Our study confirmed previous findings of a reduced postprandial GLP-1 response in severely obese subjects. Following weight reduction, GLP-1 response in the obese subjects apparently rose to a level between that of obese and lean subjects. The data suggests that postprandial insulin and GIP responses are key players in short-term appetite regulation.