Roux-en-Y gastric bypass corrects hyperinsulinemia implications for the remission of type 2 diabetes.

CONTEXT Roux-en-Y gastric bypass (RYGB) has been shown to induce rapid and durable reversal of type 2 diabetes. OBJECTIVE The aim of the study was to investigate a possible mechanism for the remission of type 2 diabetes after RYGB. DESIGN A cross-sectional, nonrandomized, controlled study was conducted. Surgery patients were studied before RYGB and 1 wk and 3 months after surgery. SETTING This study was conducted at East Carolina University. SUBJECTS Subjects were recruited into three groups: 1) lean controls with no surgery [body mass index (BMI) < 25 kg/m²; n = 9], 2) severely obese type 2 diabetic patients (BMI > 35 kg/m²; n = 9), and 3) severely obese nondiabetic patients (BMI > 35 kg/m²; n = 9). INTERVENTION Intervention was RYGB. RESULTS One week after RYGB, diabetes was resolved despite continued insulin resistance (insulin sensitivity index was approximately 50% of lean controls) and reduced insulin secretion during an iv glucose tolerance test (acute insulin response to glucose was approximately 50% of lean controls). Fasting insulin decreased and was no different from lean control despite continued elevated glucose in the type 2 diabetic patients compared with lean. CONCLUSIONS After RYGB, fasting insulin decreases to levels like those of lean control subjects and diabetes is reversed (fasting blood glucose < 125 mg/dl). This leads us to propose that 1) exclusion of food from the foregut corrects hyperinsulinemia and 2) fasting insulin is dissociated from the influence of fasting glucose, insulin resistance, and BMI. The mechanisms for reversal of diabetes in the face of reduced insulin remain a paradox.

[1]  P. Schauer,et al.  Acute effects of gastric bypass versus gastric restrictive surgery on β-cell function and insulinotropic hormones in severely obese patients with type 2 diabetes , 2010, International Journal of Obesity.

[2]  A. Chetrit,et al.  Basal-State Hyperinsulinemia in Healthy Normoglycemic Adults Is Predictive of Type 2 Diabetes Over a 24-Year Follow-Up , 2009, Diabetes Care.

[3]  S. Salinari,et al.  First-Phase Insulin Secretion Restoration and Differential Response to Glucose Load Depending on the Route of Administration in Type 2 Diabetic Subjects After Bariatric Surgery , 2009, Diabetes Care.

[4]  M. Jensen,et al.  Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis. , 2009, The American journal of medicine.

[5]  D. Zheng,et al.  Mechanism for improved insulin sensitivity after gastric bypass surgery. , 2008, The Journal of clinical endocrinology and metabolism.

[6]  J. Teixeira,et al.  Effect of weight loss by gastric bypass surgery versus hypocaloric diet on glucose and incretin levels in patients with type 2 diabetes. , 2008, The Journal of clinical endocrinology and metabolism.

[7]  A. Mari,et al.  Mechanisms of Recovery From Type 2 Diabetes After Malabsorptive Bariatric Surgery , 2006, Diabetes.

[8]  J. Holst,et al.  Vildagliptin, a dipeptidyl peptidase-IV inhibitor, improves model-assessed beta-cell function in patients with type 2 diabetes. , 2005, The Journal of clinical endocrinology and metabolism.

[9]  R. DeFronzo,et al.  Pathogenesis of type 2 diabetes mellitus. , 2004, The Medical clinics of North America.

[10]  Andrea Tura,et al.  Assessing insulin secretion by modeling in multiple-meal tests: role of potentiation. , 2002, Diabetes.

[11]  G. Dohm,et al.  Involvement of protein kinase C in human skeletal muscle insulin resistance and obesity. , 2000, Diabetes.

[12]  G. Dohm,et al.  Dephosphorylation increases insulin-stimulated receptor kinase activity in skeletal muscle of obese Zucker rats , 1999, Molecular and Cellular Biochemistry.

[13]  W. Pories,et al.  The gastric bypass operation reduces the progression and mortality of non-insulin-dependent diabetes mellitus , 1997, Journal of Gastrointestinal Surgery.

[14]  W. Pories,et al.  Who Would Have Thought It? An Operation Proves to Be the Most Effective Therapy for Adult‐Onset Diabetes Mellitus , 1995, Annals of surgery.

[15]  W. Pories Why Does the Gastric Bypass Control Type 2 Diabetes Mellitus? , 1992, Obesity surgery.

[16]  G. Dohm,et al.  Is type II diabetes mellitus (NIDDM) a surgical disease? , 1992, Annals of surgery.

[17]  Jeppe Sturis,et al.  Estimation of Insulin Secretion Rates from C-Peptide Levels: Comparison of Individual and Standard Kinetic Parameters for C-Peptide Clearance , 1992, Diabetes.

[18]  G. Dohm,et al.  Surgical treatment of obesity and its effect on diabetes: 10-y follow-up. , 1992, The American journal of clinical nutrition.

[19]  R N Bergman,et al.  Assessment of insulin sensitivity in vivo. , 1985, Endocrine reviews.