Insulin Sensitivity and Secretion Changes After Gastric Bypass in Normotolerant and Diabetic Obese Subjects

*Department of Computer and System Science, University of Rome "Sapienza" †Institute of Systems Analysis and Computer Science, National Research Council, Rome Italy ‡Department of Internal Medicine, Catholic University School of Medicine, Rome, Italy §Gastrointestinal Metabolic Surgery, Weill Cornell Medical College/New York-Presbyterian Hospital, New York, NY.
Annals of surgery (Impact Factor: 7.19). 03/2013; 257(3):462-8. DOI: 10.1097/SLA.0b013e318269cf5c
Source: PubMed

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.

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    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.
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