Epigenetics and the Origin of Muscle Insulin Resistance in Humans
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Purpose
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.
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Diabetes Mellitus Type 2 in Obese Obesity |
| Study Type: | Observational |
| Study Design: | Observational Model: Cohort Time Perspective: Prospective |
| Official Title: | Epigenetics and the Origin of Muscle Insulin Resistance in Humans |
- DNA methylation of genes in insulin resistance [ Time Frame: Baseline to visit 33 (approx 2 months) ] [ Designated as safety issue: No ]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.
- mRNA expression of genes [ Time Frame: Baseline to visit 33 approx 2 months ] [ Designated as safety issue: No ]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
| Estimated Enrollment: | 72 |
| Study Start Date: | August 2012 |
| Estimated Study Completion Date: | August 2017 |
| Estimated Primary Completion Date: | August 2017 (Final data collection date for primary outcome measure) |
| Groups/Cohorts |
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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. |
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Single bout of exercise
This experiment will test the hypotheses in lean healthy, obese non-diabetic and type 2 diabetic volunteers that
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Eight weeks of exercise
This experiment will test the hypothesis in lean healthy, obese non-diabetic and type 2 diabetic volunteers that
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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.
Eligibility| Ages Eligible for Study: | 21 Years to 55 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
| Sampling Method: | Non-Probability Sample |
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.
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| Contact: Roxane R McLaughlin, RN | 480-301-4142 | mclaughlin.roxane@mayo.edu |
| Contact: Jennifer Early, RN | 480-301-4142 | early.jennifer@mayo.edu |
| United States, Arizona | |
| Mayo Clinic in Arizona | Recruiting |
| Scottsdale, Arizona, United States, 85259 | |
| Contact: Roxane McLaughlin, RN 480-301-4142 mclaughlin.roxane@mayo.edu | |
| Contact: Jennifer Early, RN 480-301-4142 early.jennifer@mayo.edu | |
| Principal Investigator: | Lori Roust, MD | Mayo Clinic |
| Principal Investigator: | Dawn K Coletta, Ph.D. | Mayo Clinic |
More Information
No publications provided
| Responsible Party: | Lori R. Roust, Consultant in Endocrinology, Mayo Clinic |
| ClinicalTrials.gov Identifier: | NCT01726491 History of Changes |
| Other Study ID Numbers: | 11-007028 |
| Study First Received: | November 8, 2012 |
| Last Updated: | November 9, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Mayo Clinic:
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Insulin resistance Exercise Type 2 diabetes mellitus Obesity Epigenetic studies |
Additional relevant MeSH terms:
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Diabetes Mellitus Diabetes Mellitus, Type 2 Insulin Resistance Obesity Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases Hyperinsulinism Overnutrition |
Nutrition Disorders Overweight Body Weight Signs and Symptoms Insulin Hypoglycemic Agents Physiological Effects of Drugs Pharmacologic Actions |
ClinicalTrials.gov processed this record on June 17, 2013