Clinical Trials Logo

Clinical Trial 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.


Clinical Trial 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 Design


Related Conditions & MeSH terms


NCT number NCT01386645
Study type Interventional
Source Seattle Institute for Biomedical and Clinical Research
Contact
Status Completed
Phase N/A
Start date July 2011
Completion date August 1, 2019

See also
  Status Clinical Trial Phase
Recruiting NCT05354245 - Using a Complex Carbohydrate Mixture to Steer Fermentation and Improve Metabolism in Adults With Overweight and Prediabetes (DISTAL) N/A
Completed NCT03644524 - Heat Therapy and Cardiometabolic Health in Obese Women N/A
Recruiting NCT06007404 - Understanding Metabolism and Inflammation Risks for Diabetes in Adolescents
Recruiting NCT06115265 - Ketogenic Diet and Diabetes Demonstration Project N/A
Completed NCT03188263 - Morning Light Treatment to Improve Glucose Metabolism N/A
Recruiting NCT03821961 - 18F-FDOPA PET/CT Imaging in Patients Undergoing Metabolic Surgery N/A
Completed NCT04303468 - Intervention With a GABA Supplement in Prediabetics N/A
Recruiting NCT06094231 - Treating Patients With Renal Impairment and Altered Glucose MetAbolism With TherapeutIc Carbohydrate Restriction and Sglt2-Inhibiton - a Pilot Study N/A
Completed NCT03675360 - Low-Carbohydrate Dietary Pattern on Glycemic Outcomes Trial N/A
Completed NCT01910051 - Explorative Assessment of Biomarkers in Overweight and Obese Subjects
Completed NCT03527368 - The Time-Restricted Intake of Meals Study N/A
Not yet recruiting NCT06453278 - (DDS) in India: a Screening Tool to Identify Prediabetes and Undiagnosed Type 2 Diabetes in Dental Settings
Suspended NCT03240978 - Exercise Intervention for the Prevention of Prediabetes in Overweight Chinese N/A
Completed NCT03865342 - Prevention of Diabetes Using Mobile-enabled, Virtual Delivery of the National Diabetes Prevention Program N/A
Completed NCT02899390 - Diabetes Prevention Program in Adults of the Yaqui Tribe of Hermosillo, Sonora at Risk of Diabetes N/A
Recruiting NCT01972113 - Vitamin K and Glucose Metabolism in Children at Risk for Diabetes (Vita-K 'n' Kids Study) N/A
Completed NCT01436916 - Oral Cholecalciferol in Prevention of Type 2 Diabetes Mellitus Phase 4
Completed NCT01432509 - Prospective Follow-up of a Cohort of Pre-diabetics in the North of France (DiabeNord) N/A
Completed NCT00990184 - Study to Evaluate the Effects of Colesevelam on Insulin Sensitivity and ß-Cell Function in Subjects With Impaired Fasting Glucose (Prediabetes) Phase 3
Completed NCT00886340 - A Lifestyle Change Program to Prevent Type 2 Diabetes Phase 2