Mechanisms of Diabetes Relapse After Bariatric Surgery

The mechanisms of type 2 diabetes (T2DM) remission after gastric bypass surgery (GBP) are unclear. The levels of the gut hormones incretins and their effect on insulin secretion, which is impaired in T2DM, markedly increase after GBP. The anatomical changes of GBP, rather than weight loss, seem to be responsible for the changes of incretins. The objective of this proposal is to investigate the different mechanisms by which GBP, laparoscopic adjustable gastric banding (LAGB) and vertical sleeve gastrectomy (VSG) affect glucose control. We wish to understand the role of weight loss versus changes in gut peptides in the short and long term in morbidly patients with T2DM after GBP, LAGB or VSG.

AIM 1: Will study the short term changes of incretins levels and effect in obese individuals with T2DM after GBP, LAGB or VSG, before and 1 month after GBP or before and after equivalent weight loss after LAGB or VSG.

AIM 2: Will study the long-term (12 and 24 months after surgery) changes in the incretin effect on insulin secretion, in patients with T2DM after GBP, LAGB or VSG.

AIM 3: Will study the changes of insulin secretion to IV glucose (AIRg) and insulin sensitivity (Si), measured by the minimal model, in patients with T2DM after GBP, VSG or LAGB, before and at 24 months after the surgery, at weight stability under condition of controlled diet.

Inclusion criteria

Post GBP, LAGB or VSG Subjects

• Must be able to attend 4 study visits at St. Luke's Roosevelt Hospital Center in Manhattan, New York City
• History of Type 2 Diabetes before surgery

Inclusion criteria

• 35 < BMI < 50
• Non-Smoker
• Total Body Weight < 300 LBS
• 30<Age<60
• HbA1c < 9%
• Resting Blood Pressure < 160/100 mmHg
• Beta Blockers discontinued 2 weeks prior
• Fasting Triglyceride Concentration < 600 mg/dl (patient can be on dyslipidemia medications)
• Without recent (within last 6 months) CHD history (prior history of angioplasty or coronary artery bypass surgery with normal stress test ok)

Exclusion criteria

• Patients with abnormal thyroid, renal function, known malabsorption syndrome or a seizure disorder requiring anti epileptic therapy, and/or elevation of liver enzymes three times above the normal limit.
• Patients should not have significant secondary complications from diabetes that would preclude undergoing gastric by-pass surgery. This would include significant psychiatric, renal or neurological, or known active coronary artery disease.
• Any abnormality during the maximum exercise stress test that indicates it would be unsafe to undergo bariatric surgery.
• Currently pregnant or nursing.
• Known cardiovascular disease
• Patient with current mucosal (gastrointestinal, respiratory, urogenital) or skin (cellulitis) infection
• HbA1c >9% and diabetes diagnosed more than 6 years prior to enrollment, or patients taking insulin or TZD (Avandia, Actos, Exenatide, DPP-IV inhibitors etc.) at the time of enrollment.
• Patients diagnosed with intestinal conditions such as chronic diarrhea, diverticulitis, or irritable bowel syndrome. These clinical conditions would interfere with the collection and interpretation of the H2 breath test.
• Any other condition which, in the opinion of the investigators, may make the candidate unsuitable for participation in this study.