Mitochondrial Dysfunction in Type 2 Diabetes Mellitus and Capacity for Fat Oxidation During Exercise

NCT ID: NCT00382473

Last Updated: 2014-04-25

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-09-30
• Study Completion Date: 2010-12-31

Brief Summary

The purpose of this study is to compare the effects of an 8-week aerobic training program upon fat oxidation in vivo and markers of skeletal muscle mitochondrial content and oxidative capacity in sedentary obese subjects with and without type 2 diabetes. We will also investigate if mitochondrial content in muscle predicts success of weight loss.

The specific aims are:

• To compare systemic fat oxidation rates;
• To measure mitochondrial content in muscle before and after aerobic training;
• To determine if decreased mitochondrial content is also associated with decreased mitochondrial oxidative capacity;
• To measure non-plasma fatty acid oxidation in vivo during submaximal exercise conditions both prior and after aerobic training;
• To determine whether increases in fat oxidation due to physical activity predict weight loss success when a reduced calorie diet is added to a physical activity program.

Detailed Description

During prolonged moderate-intensity exercise, skeletal muscle gradually increases its metabolic reliance on fat oxidation. In healthy subjects, this adaptation is enhanced by aerobic training and is associated with increased mitochondrial capacity in muscle. Whether or not subjects with type-2 diabetes (T2DM) respond to exercise training with similar metabolic and mitochondrial adaptations is yet to be demonstrated. Skeletal muscle mitochondrial oxidative capacity has been shown to be deficient in T2DM, suggesting a compromised physiologic reserve that might have implications for the metabolic plasticity of muscle during exercise.

This study will test the hypothesis that fat oxidation rates during exercise are poorly responsive to training in T2DM, being correlated to the degree of muscle mitochondrial adaptation. The effects of a 16-week intervention (8 weeks of exercise intervention followed by 10-12 weeks of weight loss intervention) on systemic fat oxidation during exercise and mitochondrial capacity will be compared between 3 sedentary subject groups; 15 lean subjects, 15 overweight subjects with T2DM, and 15 overweight subjects without diabetes. The first aim is to compare the degree of improvement in fat oxidation during submaximal exercise obtained by indirect calorimetry. The second and third aims are, respectively, to compare the degree of improvement in mitochondrial content and oxidative capacity in muscle biopsy samples. The fourth aim is to determine whether fat oxidation from non-plasma sources is increased by the intervention. The final aim is to examine whether improvements in fat oxidation predict degree off success in a subsequent weight loss program.

The results of this study will be relevant to the understanding of the mechanisms by which exercise training confers metabolic improvements in T2DM. In addition, this study will address whether perturbations in mitochondria could explain why obese individuals with T2DM might have difficulty with fat disposal.

Conditions

Diabetes Mellitus, Type 2; Overweight

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

exercise

Group Type: EXPERIMENTAL

Aerobic exercise program - 8 weeks

Intervention Type: BEHAVIORAL

No drugs. Regular aerobic exercise in structured prescription format

Interventions

Aerobic exercise program - 8 weeks

No drugs. Regular aerobic exercise in structured prescription format

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

Men and women, aged 28-55 year-old, in general good health and with no contraindications to exercise. We are recruiting three groups of subjects: Group 1: overweight/obese adults with type 2 diabetes, with a BMI between 28-40. Group 2: overweight/obese adults without type 2 diabetes, with a BMI between 28-40. Group 3: adults without type 2 diabetes, with a BMI equal or less than 25 (not overweight/obese.)

Exclusion Criteria

Any condition that does not permit exercise; current participation in a regular physical activity; uncontrolled blood pressure; treatment with any of the following medications: insulin, any weight-loss drug, oral glucocorticoids, or any drugs that affect muscle and fat metabolism such as niacin, fibrates, and beta blockers

• Minimum Eligible Age: 28 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

University of Pittsburgh

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Frederico G Toledo, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

University of Pittsburgh, Montefiore Hospital

Pittsburgh, Pennsylvania, United States

Countries

United States

Other Identifiers

0605115

Identifier Type: -

Identifier Source: org_study_id