Effect of Dietary Glycemic Index on Beta-cell Function

NCT01386645 | Completed Results

• 1 other identifier: 1R01DK092568-01
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

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 and/or impaired fasting glucose 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 and/or impaired fasting glucose. 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.

Conditions

Impaired Glucose Tolerance; Oxidative Stress; Prediabetes; Impaired Fasting Glucose

Keywords

impaired glucose tolerance; prediabetes; dietary glycemic index; beta-cell function; insulin secretion; oxidative stress; glycemic variability

Outcome Measures

Primary Outcomes (1)

• Disposition Index

  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 Outcomes (2)

• Urine F2alpha Isoprostanes

  4 weeks

• Glycemic Variability

  4 weeks

Study Arms (3)

Low GI diet

ACTIVE COMPARATOR

low glycemic index diet

Other: low glycemic index (LGI) diet

High GI diet placebo

PLACEBO COMPARATOR

high glycemic index diet plus placebo

Other: high glycemic index (HGI) diet plus placebo (PLAC)

High GI diet NAC

ACTIVE COMPARATOR

high glycemic index diet plus N-acetylcysteine

Drug: high glycemic index diet plus N-acetylcysteine

Interventions

low glycemic index (LGI) diet OTHER

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

Also known as: LGI

Low GI diet

high glycemic index (HGI) diet plus placebo (PLAC) OTHER

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.

Also known as: HGI/PLAC

High GI diet placebo

high glycemic index diet plus N-acetylcysteine DRUG

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.

Also known as: Diet, N-acetylcysteine, NAC

High GI diet NAC

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Seattle Institute for Biomedical and Clinical Research: lead
• VA Puget Sound Health Care System: collaborator

Study Sites (1)

VA Puget Sound Health Care System

Seattle, Washington, 98108, United States

Location

MeSH Terms

Conditions

Glucose Intolerance; Prediabetic State

Interventions

Diet; Acetylcysteine

Condition Hierarchy (Ancestors)

Hyperglycemia; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Diabetes Mellitus; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Limitations and Caveats

Some of the iPro CGMS devices failed to record or were dislodged. Thus, the number of participants with useable data for the CGMS variability data is less than the total enrolled.

Results Point of Contact

• Title: Kristina Utzschneider
• Organization: VA Puget Sound Hlthcare System

kutzschn@uw.edu

206-277-3568

Study Officials

• Kristina M Utzschneider, MD

  VA Puget Sound Health Care System

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2011
• First Posted: July 1, 2011
• Study Start: July 1, 2011
• Primary Completion: August 1, 2019
• Study Completion: August 1, 2019
• Last Updated: August 12, 2020
• Results First Posted: August 12, 2020

Record last verified: 2020-08

Locations

US (1)