Epigenetics of Muscle Insulin Resistance

Obesity Clinical Trial

Official title:

Epigenetics and the Origin of Muscle Insulin Resistance in Humans Aims 1-3

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03259984
• Other study ID #: 1612045470
• Status: Completed
• Start date: November 2016
• Est. completion date: November 2, 2018

Study information

• Verified date: October 2019
• Source: University of Arizona
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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. The investigators 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 72
• Est. completion date: November 2, 2018
• Est. primary completion date: November 2, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 55 Years

Eligibility

Inclusion Criteria

1. Age 21-55

2. BMI: Lean, BMI less than or equal to 25; Obese, BMI between 30- 50; type 2 diabetic, BMI between 30- 50.

3. Subjects must be able to communicate meaningfully with the investigator and must be legally competent to provide written informed consent.

4. Subjects may be of either sex with age as described in each protocol. Female subjects must be non-lactating and will be eligible only if they have a negative pregnancy test throughout the study period.

5. Subjects must range in age as described in each specific protocol.

6. Subjects must have the following laboratory values:

1. Hematocrit = 35 vol%

2. Serum creatinine = 1.6 mg/dl

3. AST (SGOT) < 2 times upper limit of normal

4. ALT (SGPT) < 2 times upper limit of normal

5. Alkaline phosphatase < 2 times upper limit of normal

6. Triglycerides < 150 mg/dl for nondiabetics

7. Triglycerides <300 for diabetics

8. INR = 1.3

Exclusion Criteria

1. Subjects must not be receiving any of the following medications: thiazide or furosemide diuretics, beta-blockers, or other chronic medications with known adverse effects on glucose tolerance levels unless the patient has been on a stable dose of such agents for the past three months before entry into the study. Subjects may be taking a stable dose of estrogens or other hormonal replacement therapy, if the subject has been on these agents for the prior three months. Subjects taking systemic glucocorticoids are excluded. Patients with type 2 diabetes will be excluded if they are taking thiazolidinediones, but may be taking sulfonylureas or other medications known to work through effects on insulin secretion.

2. Subjects receiving Gemfibrozil must not also be receiving a statin.

3. Subjects with a history of clinically significant heart disease (New York Heart Classification greater than grade II; more than non-specific ST-T wave changes on the EKG), peripheral vascular disease (history of claudication), or pulmonary disease (dyspnea on exertion of one flight or less; abnormal breath sounds on auscultation) will not be studied.

4. Recent systemic or pulmonary embolus, untreated high-risk proliferative retinopathy, recent retinal hemorrhage, uncontrolled hypertension, systolic BP>180, diastolic BP>105, autonomic neuropathy, resting heart rate >100, electrolyte abnormalities.

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Insulin Resistance
• Obesity

Locations

Country	Name	City	State
United States	University of Arizona	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
University of Arizona

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	DNA methylation of genes in insulin resistance	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.	9 months
Secondary	mRNA expression of genes	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.	9 months