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: 8.33). 03/2013; 257(3):462-8. DOI: 10.1097/SLA.0b013e318269cf5c
Source: PubMed


: 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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    • "AUC-insulin level within 5 min was also significantly higher in GK-S group, indicating improvement of first-phase insulin secretion following RYGB surgery (Figure 1A-iii,iv). These findings indicate that pancreatic β-cell secretory function is improved after RYGB surgery, in agreement with previous reports (Salinari et al., 2013). "
    Journal of Molecular Cell Biology 10/2014; 6(6). DOI:10.1093/jmcb/mju042 · 6.77 Impact Factor
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    • "GB achieves long-term weight loss, decreases mortality [1], and rapidly normalizes hyperglycemia [2], permitting dosage reduction and/or withdrawal of diabetes medication. These effects are likely related to both the marked reduction in peripheral insulin resistance [3] and increased incretin and insulin secretion [4], which occur even prior to sustained weight loss [5–7]. "
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    ABSTRACT: In severely obese type 2 diabetes patients, gastric bypass surgery (GB) reduces body mass index (BMI) and hemoglobin A1c (HbA1c) and allows reduced doses of insulin and other medications. Data regarding the effects of GB on severely obese patients with type 1 diabetes are limited. Severely obese women with type 1 diabetes (n = 9) were studied immediately before and after GB (7.7 ± 5.8 weeks, mean ± SD). On average, GB reduced mean BMI by 11 % and mean HbA1c by 0.9 % (from 8.0 to 7.1 %), with a parallel 38 % decrease in basal insulin requirements (expressed per kilogram of body weight). GB rapidly decreased BMI, HbA1c, and insulin requirements in severely obese women with type 1 diabetes. However, physiologic insulin replacement remains necessary in patients with type 1 diabetes.
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    ABSTRACT: Diabesity is a term often used to indicate the association of type-2 diabetes mellitus (T2DM) with obesity; the prevalence of both conditions is rapidly increasing worldwide and has reached epidemic proportions. Insulin resistance represents the major determinant of T2DM, which becomes manifest once relative β-cell failure ensues and insulin secretion is no longer sufficient to compensate for insulin resistance. In recent years, gastrointestinal surgery has emerged as the most effective option for the treatment of obesity and diabetes, with level-1 evidence of diabetes remission. Restrictive gastric operations such as gastric banding can improve insulin resistance in proportion to weight loss, while gastrointestinal bypass procedures, such as roux-en-y gastric-bypass (RYGB) and biliopancreatic diversion (BPD), can improve glucose homeostasis even before a significant weight loss is reached, suggesting weight-independent mechanisms of action. Studies comparing RYGB to BPD show that RYGB primarily enhances insulin secretion and reduces hepatic glucose output, whereas BPD rapidly improves glycemia primarily through the normalization of insulin sensitivity. Given the fact that BPD involves a significantly longer bypass of the proximal intestine than RYGB, these data suggest that the exclusion of a greater length of small bowel from the transit of food may cause broader and more profound influence on insulin sensitivity.
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