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

This study has been terminated.
(lack of funding)
Sponsor:
ClinicalTrials.gov Identifier:
NCT00382473
First Posted: September 29, 2006
Last Update Posted: April 25, 2014
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
University of Pittsburgh
  Purpose

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.

Condition Intervention
Diabetes Mellitus, Type 2 Overweight Behavioral: Aerobic exercise program - 8 weeks

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Mitochondrial Dysfunction in Type 2 Diabetes Mellitus and Capacity for Fat Oxidation During Exercise

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • The degree of improvement in fat oxidation during submaximal exercise obtained by indirect calorimetry after subjects have completed an eight week aerobic exercise program. [ Time Frame: 8 weeks ]

Secondary Outcome Measures:
  • The degree of improvement in muscle mitochondrial content after eight week exercise program. [ Time Frame: 8 weeks ]
  • The amount of improvement in muscle mitochondrial oxidative capacity after eight week exercise program. [ Time Frame: 8 weeks ]
  • Increase in fat oxidation from non-plasma sources after the eight week intervention. [ Time Frame: 8 weeks ]

Enrollment: 29
Study Start Date: September 2006
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: exercise Behavioral: Aerobic exercise program - 8 weeks
No drugs. Regular aerobic exercise in structured prescription format

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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   28 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00382473


Locations
United States, Pennsylvania
University of Pittsburgh, Montefiore Hospital
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
University of Pittsburgh
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
Principal Investigator: Frederico G Toledo, MD University of Pittsburgh
  More Information

Responsible Party: University of Pittsburgh
ClinicalTrials.gov Identifier: NCT00382473     History of Changes
Other Study ID Numbers: 0605115
First Submitted: September 28, 2006
First Posted: September 29, 2006
Last Update Posted: April 25, 2014
Last Verified: April 2014

Keywords provided by University of Pittsburgh:
Diabetes Mellitus, Type 2
Overweight
Fatty acid oxidation
Mitochondria
Exercise

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Overweight
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Body Weight
Signs and Symptoms