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Epigenetics and the Origin of Muscle Insulin Resistance in Humans

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ClinicalTrials.gov Identifier: NCT01726491
Recruitment Status : Completed
First Posted : November 15, 2012
Last Update Posted : January 16, 2018
Sponsor:
Information provided by (Responsible Party):
Lori R. Roust, Mayo Clinic

Study Description
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Brief Summary:
The investigators are trying to understand the role of DNA (deoxyribonucleic acid) methylation in insulin resistance in skeletal muscle and blood tissues. DNA methylation is a normal chemical process in the body that modifies DNA. By studying this, the investigators hope to better understand the causes of insulin resistance.

Condition or disease
Diabetes Mellitus Type 2 in Obese Obesity

Detailed Description:
Insulin resistance is defined as the decreased ability of insulin to perform its biological function in the muscle, liver and fat. Genetic and environmental factors are known to influence insulin sensitivity. It is not known how this is mediated. This study looks at the role of epigenetics (modifications of proteins associated with DNA and methylation of DNA) in alterations in insulin resistance. We will study lean healthy people, obese non-diabetic people and people with type 2 diabetes to characterize the DNA methylation patterns in muscle in each group. The second aim of the study is to see how a single bout of exercise affects the DNA methylation in the muscle. The third aim looks at the effect of 8 weeks of supervised exercise on the DNA methylation.

Study Design
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Study Type : Observational
Actual Enrollment : 46 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Epigenetics and the Origin of Muscle Insulin Resistance in Humans
Study Start Date : August 2012
Actual Primary Completion Date : November 21, 2016
Actual Study Completion Date : November 21, 2016

Resource links provided by the National Library of Medicine


Groups and Cohorts
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Group/Cohort
Insulin resistance epigenetics

This experiment will use the Infinium methylation assay to perform epigenome mapping and define patterns of DNA methylation in skeletal muscle and whole blood tissue of metabolically well-characterized lean healthy, obese nondiabetic, and type 2 diabetic volunteers. We will test the hypotheses that

(1) There is an increased methylation of genes involved in mitochondrial biogenesis and oxidative phosphorylation and altered methylation of promoters of genes coding for extracellular matrix and cytoskeletal proteins in insulin resistance, (2) The altered methylation patterns observed correspond to protein and mRNA expression changes, and (3) There are coordinated patterns of DNA methylation between the skeletal muscle and whole blood tissues in insulin resistance.
Single bout of exercise

This experiment will test the hypotheses in lean healthy, obese non-diabetic and type 2 diabetic volunteers that

  1. Increased methylation of the PGC-1α promoter predicts a decreased response of this gene to a single bout of exercise, and
  2. Altered methylation of promoters of nuclear encoded mitochondrial genes predicts a decreased response of this gene to a single bout of exercise.
Eight weeks of exercise

This experiment will test the hypothesis in lean healthy, obese non-diabetic and type 2 diabetic volunteers that

  1. There is decreased methylation of genes involved in mitochondrial biogenesis and oxidative phosphorylation, and the altered methylation corresponds to protein and mRNA (messenger ribonucleic acid) expression changes,
  2. There is altered methylation of genes involved in inflammation and cytoskeletal structure.


Outcome Measures
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Primary Outcome Measures :
  1. DNA methylation of genes in insulin resistance [ Time Frame: Baseline to visit 33 (approx 2 months) ]
    DNA methylation of genes involved in mitochondrial biogenesis, oxidative phosphorylation, extracellular matrix and cytoskeleton proteins in insulin resistance, with an acute episode of exercise, and with eight weeks of training exercise.


Secondary Outcome Measures :
  1. mRNA expression of genes [ Time Frame: Baseline to visit 33 approx 2 months ]
    mRNA expression of genes involved in mitochondrial biogenesis, oxidative phosphorylation, extracellular matrix and cytoskeletal signaling are altered in insulin resistance, with an acute episode of exercise and with 8 weeks of exercise training.


Biospecimen Retention:   Samples With DNA
thigh muscle biopsies bloodsamples

Eligibility Criteria
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Ages Eligible for Study:   21 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Three groups of volunteers will be studied: 1) lean, healthy volunteers, 2)obese volunteers without type 2 diabetes, and 3) volunteers with type 2 diabetes.
Criteria

Volunteers must be:

  • 21 - 55 years old
  • must be non-lactating, non-pregnant
  • not taking medications known to affect glucose or if taking them, on stable doses.
  • free of significant heart or lung disease
Contacts and Locations
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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): NCT01726491


Locations
United States, Arizona
Mayo Clinic in Arizona
Scottsdale, Arizona, United States, 85259
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Lori Roust, MD Mayo Clinic
Principal Investigator: Dawn K Coletta, Ph.D. Mayo Clinic
More Information
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Responsible Party: Lori R. Roust, Consultant in Endocrinology, Mayo Clinic
ClinicalTrials.gov Identifier: NCT01726491     History of Changes
Other Study ID Numbers: 11-007028
First Posted: November 15, 2012    Key Record Dates
Last Update Posted: January 16, 2018
Last Verified: January 2018

Keywords provided by Lori R. Roust, Mayo Clinic:
Insulin resistance
Exercise
Type 2 diabetes mellitus
Obesity
Epigenetic studies

Additional relevant MeSH terms:
Diabetes Mellitus
Insulin Resistance
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
 Hyperinsulinism
Insulin, Globin Zinc
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs