The Role of the Duodenum in the Pathogenesis of Insulin Resistance and Type 2 Diabetes Mellitus

Inclusion Criteria: Inclusion criteria for lean, healthy control subjects: 1. Fasting plasma glucose (FPG) \< 100 2. Age 18 to 55 3. BMI 18.5 to 24.9 kg/m2 4. Stable weight for prior 3 months Inclusion criteria for prediabetic individuals: 1. Based on American Diabetes Association criteria of FPG \> 100 and \<126 2. Age 18 to 55 3. BMI 35 to 60 kg/m2 4. Stable weight for prior 3 months Inclusion criteria for diabetic individuals: 1. Diagnosis of type 2 diabetes mellitus (T2DM) for \< 5 years 2. Hemoglobin A1c \< 8% 3. Age 18 to 55 4. BMI 35 to 60 kg/m2 5. Stable weight for prior 3 months Exclusion Criteria: Exclusion criteria for all study subjects: 1. Use of any of the following medications: Thiazolidinediones, dipeptidyl-peptidase IV (DPP-IV) inhibitors (e.g., sitagliptin), GLP-1 analogs (e.g., exenatide). 2. Subjects with T2DM who are unable to maintain adequate glycemic control (i.e., having a fasting blood glucose that exceeds 250mg/dL on two consecutive tests) while temporarily discontinuing their oral diabetes medications for the study and in whom the study physician determines insulin therapy would not be appropriate. 3. Females with a positive pregnancy test 5\. Prior gastric, duodenal, proximal jejunal surgery or pancreas resection 6. Known malabsorptive disorder 7. History of cancer in past 5 years 8. Renal insufficiency defined by serum creatinine \> 1.5 mg/dl 9. Hepatic enzyme elevations of greater than twice the upper limits of normal 10. Current use of warfarin or clopidogrel 11. Intercurrent infections 12. Contraindication to nasogastric or nasojejunal feeding tube (e.g., deviated nasal septum, prior upper gastrointestinal bleed, or history of easy bleeding) 13. Residence outside the greater Nashville, TN area