- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01386645
Effect of Dietary Glycemic Index on Beta-cell Function (GIdiet)
Study Overview
Status
Detailed Description
Type 2 diabetes is a major health problem in the United States affecting millions of people. It is caused by failure of the pancreatic beta-cells to secrete enough insulin resulting in high blood glucose levels. People with impaired glucose tolerance (IGT) and impaired fasting glucose have elevated glucose levels and are at increased risk for progressing to type 2 diabetes. The long-term objectives of this research are to better understand the factors that contribute to the loss of beta-cell function and impaired insulin secretion. High glucose levels have been shown to impair beta-cell function by causing oxidative stress, and oscillating high glucose levels increase oxidative stress even more than continuous high glucose. Diets containing foods with a high glycemic index (GI) increase the glycemic load (GL) of the diet and post-prandial glucose levels. Therefore, high GL (HGL) diets could be potentially damaging to the beta-cell by increasing glucose fluctuations and oxidative stress. Conversely, low GL (LGL) diets may be beneficial. The study explores the hypothesis that increased glycemic variability results in increased oxidative stress and thereby exacerbates beta-cell dysfunction in people with pre-diabetes.
Specific Aim 1: Determine if a HGL diet worsens and a LGL diet improves beta-cell function compared to a baseline control diet in subjects with pre-diabetes.
Specific Aim 2: Determine if increased glycemic variability on the HGL diet is associated with decreased beta-cell function and conversely if decreased glycemic variability on the LGL diet is associated with improved beta-cell function in subjects with pre-diabetes.
Specific Aim 3: Determine if oxidative stress induced by a HGL diet mediates decreases in beta-cell function by determining if 1) systemic markers of oxidative stress are associated with beta-cell function; 2) if the relationship between glycemic variability and beta-cell function is at least partially explained by oxidative stress; and 3) the anti-oxidant N-acetylcysteine (NAC) prevents decreases in beta-cell function on a HGL diet.
Study design: The study will be a randomized, parallel-design feeding study in men and women with pre-diabetes. Subjects will be randomly assigned to one of 3 separate arms (n=20/arm): 1) 4 weeks on a LGL diet (GI<35); 2) 4 weeks on a HGL diet (GI>70) + placebo twice daily; or 3) 4 weeks on a HGL diet (GI>70) + NAC 1200 mg twice daily. Subjects will be studied after a 2 week baseline control diet with a moderate glycemic load (GI 55-58) for comparison and all diets will be weight stable with the same macronutrient composition (55% carbohydrate/30% fat/15% protein). Beta-cell function will be assessed by both a frequently sampled intravenous glucose tolerance test and a meal test. Glycemic variability will be assessed by a Continuous Glucose Monitoring System and glycemic control by fructosamine. Markers of oxidative stress will be measured.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Washington
-
Seattle, Washington, United States, 98108
- VA Puget Sound Health Care System
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- impaired glucose tolerance (2 hour glucose 140-200 mg/dl after a standard 75 grams oral glucose tolerance test [OGTT]) or
- fasting glucose 100-115 mg/dl and 2 hour glucose > 100 mg/dl after a standard OGTT
Exclusion Criteria:
- diabetes or taking diabetes medications
- fasting glucose >115 mg/dl
- alanine aminotransferase (ALT) >1.5 times the upper limit of normal
- hematocrit <33%
- serum creatinine >1.5 men or >1.3 women
- multiple food allergies or intolerances
- other serious medical or inflammatory conditions
- pregnancy or lactation
- smoke or use tobacco
- take medications that affect insulin sensitivity and secretion (niacin, diabetes medications or glucocorticoids) or inflammation (anti-inflammatories such as ibuprofen, naprosyn, aspirin)
- significant gastroesophageal reflux (heartburn), swallowing problems or stomach ulcers, including those taking medication for these indications
- taking or having taken another investigational drug within the past 30 days
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Low GI diet
low glycemic index diet
|
Following a 2 week medium glycemic index control diet (glycemic index 50-55), subjects will be provided with a weight stable low glycemic index diet (glycemic index <35) for 4 weeks with all food provided by the Human Nutrition Lab
Other Names:
|
Placebo Comparator: High GI diet placebo
high glycemic index diet plus placebo
|
Following a 2 week medium glycemic index control diet (glycemic index 50-55), subjects will be provided with a weight stable high glycemic index diet (glycemic index >70) for 4 weeks, all food provided by the Human Nutrition Lab.
They will take placebo capsules (matching for active N-acetylcysteine (NAC) in arm 3) twice daily for the 4 weeks on the high GI diet.
The NAC vs. placebo arms (arms 2 and 3) will be double-blinded.
Other Names:
|
Active Comparator: High GI diet NAC
high glycemic index diet plus N-acetylcysteine
|
Following a 2 week medium glycemic index control diet (glycemic index 50-55), subjects will be provided with a weight stable high glycemic index diet (glycemic index >70) for 4 weeks, all food provided by the Human Nutrition Lab.
They will take N-acetylcysteine (NAC) two 600 mg capsules twice daily for the 4 weeks on the high GI diet.
The NAC vs. placebo arms (arms 2 and 3) will be double-blinded.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Disposition Index
Time Frame: 4 weeks
|
The disposition index generated from an intravenous glucose tolerance test (insulin sensitivity x the acute insulin response to intravenous glucose) is a measure of beta-cell function.
|
4 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Urine F2alpha Isoprostanes
Time Frame: 4 weeks
|
Fasting urine F2alpha isoprostane/Cr ratio.
Urine isoprostanes were measured by ELISA (Oxford Biomedical Research).
|
4 weeks
|
Glycemic Variability
Time Frame: 4 weeks
|
Glycemic variability as measured by the standard deviation (SD) of the glucose levels from the iPro continuous glucose monitoring system (CGMS)
|
4 weeks
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Kristina M Utzschneider, MD, VA Puget Sound Health Care System
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Glucose Metabolism Disorders
- Metabolic Diseases
- Endocrine System Diseases
- Diabetes Mellitus
- Hyperglycemia
- Prediabetic State
- Glucose Intolerance
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Protective Agents
- Respiratory System Agents
- Antioxidants
- Antidotes
- Free Radical Scavengers
- Expectorants
- Acetylcysteine
- N-monoacetylcystine
Other Study ID Numbers
- 1R01DK092568-01 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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