Back to resultsThe Role of the Duodenum in the Pathogenesis of Insulin Resistance and Type 2 Diabetes Mellitus
Primary Purpose
Insulin Resistance and Type 2 Diabetes
Status
Completed
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Placement of nasogastric feeding tube
Nasojejunal feeding tube
Sponsored by
About this trial
This is an interventional basic science trial for Insulin Resistance and Type 2 Diabetes
Eligibility Criteria
Inclusion Criteria:
Inclusion criteria for lean, healthy control subjects:
- Fasting plasma glucose (FPG) < 100
- Age 18 to 55
- BMI 18.5 to 24.9 kg/m2
- Stable weight for prior 3 months
Inclusion criteria for prediabetic individuals:
- Based on American Diabetes Association criteria of FPG > 100 and <126
- Age 18 to 55
- BMI 35 to 60 kg/m2
- Stable weight for prior 3 months
Inclusion criteria for diabetic individuals:
- Diagnosis of type 2 diabetes mellitus (T2DM) for < 5 years
- Hemoglobin A1c < 8%
- Age 18 to 55
- BMI 35 to 60 kg/m2
- Stable weight for prior 3 months
Exclusion Criteria:
Exclusion criteria for all study subjects:
- Use of any of the following medications: Thiazolidinediones, dipeptidyl-peptidase IV (DPP-IV) inhibitors (e.g., sitagliptin), GLP-1 analogs (e.g., exenatide).
- 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.
- 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
1: Nasogastric feeding tube
2: Placement of nasojejunal feeding tube
Arm Description
Outcomes
Primary Outcome Measures
Insulin sensitivity
Secondary Outcome Measures
Incretin effect
Full Information
NCT ID
NCT00568620
First Posted
December 4, 2007
Last Updated
October 31, 2016
Sponsor
Vanderbilt University
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
1. Study Identification
Unique Protocol Identification Number
NCT00568620
Brief Title
The Role of the Duodenum in the Pathogenesis of Insulin Resistance and Type 2 Diabetes Mellitus
Official Title
The Role of the Duodenum in the Pathogenesis of Insulin Resistance and Type 2 Diabetes Mellitus
Study Type
Interventional
2. Study Status
Record Verification Date
October 2016
Overall Recruitment Status
Completed
Study Start Date
May 2008 (undefined)
Primary Completion Date
June 2012 (Actual)
Study Completion Date
September 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Vanderbilt University
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Insulin Resistance and Type 2 Diabetes
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
Participant
Allocation
Randomized
Enrollment
19 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1: Nasogastric feeding tube
Arm Type
Experimental
Arm Title
2: Placement of nasojejunal feeding tube
Arm Type
Experimental
Intervention Type
Procedure
Intervention Name(s)
Placement of nasogastric feeding tube
Intervention Description
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
Intervention Type
Procedure
Intervention Name(s)
Nasojejunal feeding tube
Intervention Description
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
Primary Outcome Measure Information:
Title
Insulin sensitivity
Time Frame
3 days
Secondary Outcome Measure Information:
Title
Incretin effect
Time Frame
3 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Inclusion criteria for lean, healthy control subjects:
Fasting plasma glucose (FPG) < 100
Age 18 to 55
BMI 18.5 to 24.9 kg/m2
Stable weight for prior 3 months
Inclusion criteria for prediabetic individuals:
Based on American Diabetes Association criteria of FPG > 100 and <126
Age 18 to 55
BMI 35 to 60 kg/m2
Stable weight for prior 3 months
Inclusion criteria for diabetic individuals:
Diagnosis of type 2 diabetes mellitus (T2DM) for < 5 years
Hemoglobin A1c < 8%
Age 18 to 55
BMI 35 to 60 kg/m2
Stable weight for prior 3 months
Exclusion Criteria:
Exclusion criteria for all study subjects:
Use of any of the following medications: Thiazolidinediones, dipeptidyl-peptidase IV (DPP-IV) inhibitors (e.g., sitagliptin), GLP-1 analogs (e.g., exenatide).
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.
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
12. IPD Sharing Statement
Citations:
PubMed Identifier
27279247
Citation
Tamboli RA, Sidani RM, Garcia AE, Antoun J, Isbell JM, Albaugh VL, Abumrad NN. Jejunal administration of glucose enhances acyl ghrelin suppression in obese humans. Am J Physiol Endocrinol Metab. 2016 Jul 1;311(1):E252-9. doi: 10.1152/ajpendo.00082.2016. Epub 2016 Jun 7.
Results Reference
derived
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The Role of the Duodenum in the Pathogenesis of Insulin Resistance and Type 2 Diabetes Mellitus
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