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

Salinari, Serenella DSC*; Bertuzzi, Alessandro DSC; Guidone, Caterina MD; Previti, Elena MSC*; Rubino, Francesco MD§; Mingrone, Geltrude PhD

doi: 10.1097/SLA.0b013e318269cf5c
Original Articles

Objective: To elucidate the mechanisms of improvement/reversal of type 2 diabetes after Roux-en-Y gastric bypass (RYGB).

Methods: 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.

Results: 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 × 10−9: 104 ± 54 vs 228 ± 88; P < 0.05, preoperatively vs postoperatively; 242 ± 99 in controls). Insulin sensitivity by EHC (M × 102) was slightly but significantly improved in both normotolerant and diabetic subjects (1.46 ± 0.22 vs 1.37 ± 0.55 mmol·min−1·kg−1; P < 0.05 and 1.53 ± 0.23 vs 1.28 ± 0.62 mmol·min−1·kg−1; 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.

Conclusions: 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.

In diabetic subjects, the insulin secretion rate largely increased after Roux-en-Y gastric bypass (RYGB) only when glucose was administered orally and the first phase of insulin secretion was restored. Insulin sensitivity and incretion levels were increased. These mechanisms might explain the reversal of type 2 diabetes after RYGB.

*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.

Reprints: Serenella Salinari, DSC, Department of Computer and System Science, University of Rome “Sapienza,” Via Ariosto 25, 00185 Rome, Italy. E-mail:

Disclosure: The authors declare no conflicts of interest.

© 2013 Lippincott Williams & Wilkins, Inc.