Insulin Sensitivity and Secretion Changes After Gastric Bypass in Normotolerant and Diabetic Obese Subjects
ABSTRACT : To elucidate the mechanisms of improvement/reversal of type 2 diabetes after Roux-en-Y gastric bypass (RYGB).
: Fourteen morbidly obese subjects, 7 with normal glucose tolerance and 7 with type 2 diabetes, were studied before and 1 month after RYGB by euglycemic hyperinsulinemic clamp (EHC), by intravenous glucose tolerance test (IVGTT) and by oral glucose tolerance test (OGTT) in 3 different sessions. Intravenous glucose tolerance test IVGTT and OGTT insulin secretion rate (ISR) and sensitivity were obtained by the minimal model. Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) were measured. Six healthy volunteers were used as controls.
: Total ISR largely increased in diabetic subjects only when glucose was administered orally (37.8 ± 14.9 vs 68.3 ± 22.8 nmol; P < 0.05, preoperatively vs postoperatively). The first-phase insulin secretion was restored in type 2 diabetic after the IVGTT (Φ1 × 10: 104 ± 54 vs 228 ± 88; P < 0.05, preoperatively vs postoperatively; 242 ± 99 in controls). Insulin sensitivity by EHC (M × 10) was slightly but significantly improved in both normotolerant and diabetic subjects (1.46 ± 0.22 vs 1.37 ± 0.55 mmol·min·kg; P < 0.05 and 1.53 ± 0.23 vs 1.28 ± 0.62 mmol·min·kg; P < 0.05, respectively). Quantitative insulin sensitivity check index was improved in all normotolerant (0.32 ± 0.02 vs 0.30 ± 0.02; P < 0.05) and diabetic subjects (0.33 ± 0.03 vs 0.31 ± 0.02; P < 0.05). GIP and GLP-1 levels increased both at fast and after OGTT mainly in type 2 diabetic subjects.
: The large increase of ISR response to the OGTT together with the restoration of the first-phase insulin secretion in diabetic subjects might explain the reversal of type 2 diabetes after RYGB. The large incretin secretion after the oral glucose load might contribute to the increased ISR.
SourceAvailable from: Dariush Elahi[Show abstract] [Hide abstract]
ABSTRACT: Background Bariatric surgery is the most effective treatment for the reduction of body weight and resolution of type 2 diabetes mellitus (T2DM). Objectives To longitudinally assess hormonal and tissue responses after RYGB. Setting University Hospital, United States. Methods Eight patients (five with T2DM) were studied before and after RYGB. A standardized test meal (STM) was administered before and at 3, 6, 9,12,and 15 months. Separately, a 2 hr. hyperinsulinemic-euglycemic clamp (E-clamp) and a 2 hr. hyperglycemic clamp (H-clamp) were performed before and at 1, 3, 6, and 12 months. Glucagon-like peptide-1 (GLP-1) was infused during the last hour of the H-clamp. Body composition was assessed with DXA methodology. Results Enrollment BMI was 49±3 kg/m2 (X±SE). STM glucose and insulin responses were normalized by 3 and 6 months. GLP-1 level increased dramatically at 1, 3 and 6 months, normalizing by 12 and 15 months. Insulin sensitivity (M of E-clamp) increased progressively at 3-12 months as fat mass decreased. The insulin response to glucose alone fell progressively over 12 months but the glucose clearance/metabolism (M of H-clamp) did not change significantly until 12 months. In response to GLP-1 infusion, insulin levels fell progressively throughout the 12 months. Conclusions The early hypersecretion of GLP-1 leads to hyperinsulinemia and early normalization of glucose levels. The GLP-1 response normalizes within one year after surgery. Enhanced peripheral tissue sensitivity to insulin starts at three months, and is associated to fat mass loss. β-cell sensitivity improves at 12 months, and after loss of ≈33% of excess body weight. There is a tightly controlled feedback loop between peripheral tissue sensitivity, β-cell and L-cell (GLP-1) responses.Surgery for Obesity and Related Diseases 08/2014; 10(6). DOI:10.1016/j.soard.2014.07.011 · 4.94 Impact Factor
Journal of Molecular Cell Biology 10/2014; 6(6). DOI:10.1093/jmcb/mju042 · 8.43 Impact Factor
Diabetes 07/2014; 63(7):2225-8. DOI:10.2337/db14-0402 · 8.47 Impact Factor