Changes in insulin sensitivity and secretion after sleeve gastrectomy

Background: Sleeve gastrectomy is indicated for the treatment of obesity and related co-morbidity including diabetes. The dynamic changes in insulin secretion and sensitivity after sleeve gastrectomy are unknown. Methods: Whole-body insulin sensitivity was measured by the euglycaemic hyperinsulinaemic clamp technique, and insulin secretion by C-peptide deconvolution after an oral glucose tolerance test (OGTT), before and 3, 6 and 12 months after sleeve gastrectomy in morbidly obese subjects. The time course of glucagon-like peptide (GLP) 1, as a marker of insulin secretion following OGTT, was also assessed. Results: Ten patients were included in the study. Median (range) baseline insulin sensitivity (M-value) increased from 84.0 (20.2-131.4) mmol per kg per min at baseline to 122.8 (99.0-179.3) mmol per kg per min at 12 months after surgery (P = 0.015). Fasting insulin sensitivity, measured by homeostatic model assessment of insulin resistance, which represents a surrogate index of hepatic insulin resistance, decreased from 3.3 (1.9-5.5) to 0.7 (0.5-1.1) mg/dl units/ml (P < 0.001). Total insulin secretion, measured as incremental area under the curve (AUC), after OGTT decreased from 360.4 (347.9-548.0) to 190.1 (10.1-252.0) mmol/l.180 min at 12 months (P = 0.011). The AUC for GLP-1 increased from 258.5 (97.5-552.6) to 5531.8 (4143.0-7540.9) pmol/l.180 min at 12 months after sleeve gastrectomy (P < 0.001). In multiple regression analysis, 51 per cent of the M-value variability was explained by GLP-1 secretion. Conclusion: Sleeve gastrectomy improved insulin sensitivity and reduced insulin secretion within 6 months after surgery. Although there was a correlation between insulin sensitivity and bodyweight, the major driver of the improvement in insulin sensitivity was GLP-1 secretion.