Epigenetics and the Origin of Muscle Insulin Resistance in Humans

NCT ID: NCT01726491

Last Updated: 2018-01-16

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 46 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2012-08-31
• Study Completion Date: 2016-11-21

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.

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.

Conditions

Diabetes Mellitus Type 2 in Obese; Obesity

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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.

No interventions assigned to this group

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.

No interventions assigned to this group

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.

No interventions assigned to this group

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Lori R. Roust

Consultant in Endocrinology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lori Roust, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Dawn K Coletta, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic in Arizona

Scottsdale, Arizona, United States

Countries

United States

Other Identifiers

11-007028

Identifier Type: -

Identifier Source: org_study_id