Epigenetics and the Origin of Muscle Insulin Resistance in Humans

Sponsor

Mayo Clinic (Other)

Overall Status

Completed

CT.gov ID

NCT01726491

Collaborator

(none)

Enrollment

Location

51.7

Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

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	Intervention/Treatment	Phase
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

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 :

Aug 1, 2012

Actual Primary Completion Date :

Nov 21, 2016

Actual Study Completion Date :

Nov 21, 2016

Arms and Interventions

Arm	Intervention/Treatment
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 Increased methylation of the PGC-1α promoter predicts a decreased response of this gene to a single bout of exercise, and 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 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, There is altered methylation of genes involved in inflammation and cytoskeletal structure.

Outcome Measures

Primary Outcome Measures

DNA methylation of genes in insulin resistance [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

mRNA expression of genes [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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