Mitochondrial Dysfunction in Diabetes

Not Applicable

Completed

• Conditions: Obese; Diabetes
• Interventions: Behavioral: Exercise and muscle biopsies

• Registration Number: NCT01724502
• Lead Sponsor: Mayo Clinic

Brief Summary

The purpose of this study is to determine whether insulin resistance is accompanied by "exercise resistance". Investigators will use mass spectrometry and proteomics analysis to test the hypothesis is that a bout of exercise that increases mitochondrial protein abundance in lean, healthy individuals is less effective in insulin resistant patients.

Detailed Description

The investigators' prior research has focused on defining the changes in expression of nuclear encoded mitochondrial genes that predict changes in insulin sensitivity in skeletal muscle, with the goal of defining the molecular mechanisms underlying the connection between mitochondrial dysfunction and insulin resistance in skeletal muscle.

Three groups of subjects will be studied: lean, healthy control subjects (n=12) obese non-diabetic subjects (n=12) and patients with type 2 Diabetes Mellitus (n=12) for a total of 36 subjects. Twenty subjects have completed the study at Arizona State University; the remaining 16 subjects will be accrued at the Mayo Clinic in Arizona.

Subjects will come to the Mayo Clinic 4 times. On Study Day 1 Subjects will be screened with a medical history \& physical and a 75 g oral glucose tolerance test to determine if they are eligible for the study. On Study Day 2, subjects will report to the clinic after an overnight fast, undergo a euglycemic clamp (using deuterated glucose) to determine insulin sensitivity, and in addition have a muscle biopsy (basal biopsy for comparison). On Study Day 3, subjects will report to the clinic after an overnight fast, and undergo a Volume Oxygen Maximum (VO_2 max) determination. On Study Day 4, subjects will report to the clinic after an overnight fast to perform an exercise bout with muscle biopsy 30 minutes after the end of exercise. This will be followed by an overnight fast, and an additional muscle biopsy at 24 hours post exercise.

Study Timeline

• Study Start: 2012-09
• Study First Submitted: 2012-11-07
• Study First Submitted QC: 2012-11-07
• Study First Posted: 2012-11-09
• Primary Completion: 2014-03
• Study Completion: 2014-03
• Status Verified: 2014-05
• Last Update Submitted: 2014-05-08
• Last Update Posted: 2014-05-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Healthy Control Subjects	Exercise and muscle biopsies	All subjects on this arm will undergo exercise and muscle biopsies.
Obese Non-Diabetic Subjects	Exercise and muscle biopsies	All subjects on this arm will undergo exercise and muscle biopsies.
Type 2 Diabetic Subjects	Exercise and muscle biopsies	All subjects on this arm will undergo exercise and muscle biopsies.

Primary Outcome Measures

Name	Time	Method
Protein Concentration of Mitochondria	Study Day 4 (30 min after exercise) and (24 hours after exercise)	Protein concentration will be determined from muscle biopsies by the method of Lowry. 75 micrograms of muscle lysate proteins will be separated on a 10% Sodium Dodecyl Sulfate Polyacrylamide Gel, and then visualized with Coomassie stain. The gel lane will be cut into cubes, digested with trypsin and cleaned, then protein abundance will be determined using spectral counting.

Trial Locations

Locations (1)

Mayo Clinic in Arizona; 🇺🇸 Scottsdale, Arizona, United States