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The Role of the Duodenum in the Pathogenesis of Insulin Resistance and Type 2 Diabetes Mellitus
This study is not yet open for participant recruitment.
Verified by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), June 2008
Sponsored by: National Center for Research Resources (NCRR)
Information provided by: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier: NCT00568620
  Purpose

In parallel with the increasing prevalence of obesity worldwide, type 2 diabetes mellitus (T2DM) has reached epidemic proportions. Despite a multitude of available therapies, only bariatric surgery (e.g., roux-en-Y gastric bypass (GBP)) has proven to be an effective long term treatment modality for morbid obesity. Moreover, the majority of T2DM patients who undergo GBP experience normalization of their blood glucose and are able to discontinue their anti-diabetes medications soon after the procedure. The insulin resistant state commonly seen in non-diabetic obese subjects also improves after GBP. Evidence from recent animal studies suggests that the rapid return to euglycemia seen in T2DM patients after GBP might in part result from excluding the duodenum from the flow of nutrients. With the use of enteral feeding tubes, we hope to better understand the factors in the human gut that may predispose obese individuals to the development of insulin resistance and T2DM.


Condition Intervention
Insulin Resistance and Type 2 Diabetes
Procedure: Glucose tolerance test via nasogastric feeding tube
Procedure: Glucose tolerance test via nasojejunal feeding tube

MedlinePlus related topics: Diabetes Obesity
Drug Information available for: Insulin Dextrose
U.S. FDA Resources
Study Type: Interventional
Study Design: Basic Science, Randomized, Single Blind (Subject), Crossover Assignment
Official Title: The Role of the Duodenum in the Pathogenesis of Insulin Resistance and Type 2 Diabetes Mellitus

Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Primary Outcome Measures:
  • Insulin sensitivity [ Time Frame: 3 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incretin effect [ Time Frame: 3 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: June 2008
Estimated Study Completion Date: December 2009
Estimated Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental Procedure: Glucose tolerance test via nasogastric feeding tube
50 g glucose tolerance test on day 1; 50 g glucose tolerance test with 30 mL oil on day 2; Intravenous glucose tolerance test on day 3
Procedure: Glucose tolerance test via nasogastric feeding tube
50 g glucose tolerance test on day 1; 50 g glucose tolerance test with 30 mL oil on day 2; intravenous glucose tolerance test on day 3
2: Experimental Procedure: Glucose tolerance test via nasojejunal feeding tube
50 g glucose tolerance test on day 1; 50 g glucose tolerance test with 30 mL oil on day 2; intravenous glucose tolerance test on day 3

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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

  Contacts and Locations
No Contacts or Locations Provided
  More Information

Responsible Party: Vanderbilt University Medical Center ( James Isbell, MD )
Study ID Numbers: IRB#070770, GCRC #1710
Study First Received: December 4, 2007
Last Updated: June 6, 2008
ClinicalTrials.gov Identifier: NCT00568620  
Health Authority: United States: Federal Government

Study placed in the following topic categories:
Hyperinsulinism
Metabolic Diseases
Diabetes Mellitus, Type 2
Diabetes Mellitus
Endocrine System Diseases
Endocrinopathy
Insulin Resistance
Metabolic disorder
Glucose Metabolism Disorders
Insulin

ClinicalTrials.gov processed this record on January 15, 2009