Effect of Dietary Glycemic Index on Beta-cell Function (GIdiet)
|ClinicalTrials.gov Identifier: NCT01386645|
Recruitment Status : Active, not recruiting
First Posted : July 1, 2011
Last Update Posted : April 17, 2018
|Condition or disease||Intervention/treatment||Phase|
|Impaired Glucose Tolerance Oxidative Stress Prediabetes Impaired Fasting Glucose||Other: low glycemic index diet Other: high glycemic index diet plus placebo Drug: high glycemic index diet plus N-acetylcysteine||Not Applicable|
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 :||Interventional (Clinical Trial)|
|Actual Enrollment :||53 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Primary Purpose:||Basic Science|
|Official Title:||Effect of Dietary Glycemic Index on Beta-cell Function|
|Study Start Date :||July 2011|
|Estimated Primary Completion Date :||July 2018|
|Estimated Study Completion Date :||December 2018|
Active Comparator: Low GI diet
low glycemic index diet
Other: 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 Name: Diet
Placebo Comparator: High GI diet placebo
high glycemic index diet plus placebo
Other: 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 Name: Diet
Active Comparator: High GI diet NAC
high glycemic index diet plus N-acetylcysteine
Drug: 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.
- 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
- urine F2alpha isoprostanes [ Time Frame: 4 weeks ]Measure of oxidative stress
- glycemic variability [ Time Frame: 4 weeks ]Glycemic variability as measured by the SD of the glucose levels from continuous glucose monitoring
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01386645
|United States, Washington|
|VA Puget Sound Health Care System|
|Seattle, Washington, United States, 98108|
|Principal Investigator:||Kristina M Utzschneider, MD||VA Puget Sound Health Care System|