Effect of Dietary Glycemic Index on Beta-cell Function (GIdiet)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Seattle Institute for Biomedical and Clinical Research
Sponsor:
Collaborator:
VA Puget Sound Health Care System
Information provided by (Responsible Party):
Kristina Utzschneider, Seattle Institute for Biomedical and Clinical Research
ClinicalTrials.gov Identifier:
NCT01386645
First received: June 29, 2011
Last updated: August 27, 2014
Last verified: August 2014
  Purpose

The study will determine if increasing the highs and lows of blood glucose levels (glycemic variability) impairs insulin secretion in people with impaired glucose tolerance who are at risk for developing type 2 diabetes. Furthermore, the study will determine whether changes in beta-cell function are associated with glycemic variability and whether they are mediated by oxidative stress. To decrease or increase glycemic variability the study will provide subjects with special diets containing either low or high glycemic index foods respectively for 4 weeks. To determine if oxidative stress is a mediator, subjects on the high glycemic index diet will take either placebo or the anti-oxidant N-acetylcysteine. The study will address the hypothesis that increased glycemic variability results in increased oxidative stress and thereby exacerbates beta-cell dysfunction in individuals with impaired glucose tolerance. The findings may have important implications for the development of effective strategies aimed at the prevention and treatment of type 2 diabetes. In addition, understanding the contribution of dietary glycemic index to beta-cell dysfunction in subjects with pre-diabetes may have a significant public health impact, including changes to dietary counseling and promotion of healthier eating patterns.


Condition Intervention
Impaired Glucose Tolerance
Oxidative Stress
Prediabetes
Other: low glycemic index diet
Other: high glycemic index diet plus placebo
Drug: high glycemic index diet plus N-acetylcysteine

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: Effect of Dietary Glycemic Index on Beta-cell Function

Resource links provided by NLM:


Further study details as provided by Seattle Institute for Biomedical and Clinical Research:

Primary Outcome Measures:
  • disposition index [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • urine F2alpha isoprostanes [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Measure of oxidative stress

  • glycemic variability [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Glycemic variability as measured by the SD of the glucose levels from continuous glucose monitoring


Estimated Enrollment: 60
Study Start Date: July 2011
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Other Names:
  • Diet
  • N-acetylcysteine
  • NAC

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) 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 IGT.

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 IGT.

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 IGT.

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 IGT. 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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • impaired glucose tolerance (2 hour glucose 140-200 mg/dl after a standard 75 grams oral glucose tolerance test)

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01386645

Contacts
Contact: Tonya Johnson 206-277-5072 tonya.johnson2@va.gov
Contact: Kristina M Utzschneider, MD 206-277-3568 kutzschn@u.washington.edu

Locations
United States, Washington
VA Puget Sound Health Care System Recruiting
Seattle, Washington, United States, 98108
Contact: Tonya Johnson    206-277-5072 ext 6-5072      
Principal Investigator: Kristina M Utzschneider, MD         
Sponsors and Collaborators
Seattle Institute for Biomedical and Clinical Research
VA Puget Sound Health Care System
Investigators
Principal Investigator: Kristina M Utzschneider, MD VA Puget Sound Health Care System
  More Information

No publications provided

Responsible Party: Kristina Utzschneider, Associate Professor of Medicine, Seattle Institute for Biomedical and Clinical Research
ClinicalTrials.gov Identifier: NCT01386645     History of Changes
Other Study ID Numbers: 1R01DK092568-01
Study First Received: June 29, 2011
Last Updated: August 27, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Seattle Institute for Biomedical and Clinical Research:
impaired glucose tolerance
prediabetes
dietary glycemic index
beta-cell function
insulin secretion
oxidative stress
glycemic variability

Additional relevant MeSH terms:
Glucose Intolerance
Prediabetic State
Hyperglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Diabetes Mellitus
Endocrine System Diseases
Acetylcysteine
N-monoacetylcystine
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Expectorants
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antidotes

ClinicalTrials.gov processed this record on September 22, 2014