Mitochondrial Methylation in Type 2 Diabetes

NCT04126551 | Completed

• 1 other identifier: 1901254125
• Study Type: observational
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

The overarching goal of this proposal is to determine whether DNA methylation of the mitochondrial DNA impairs mitochondrial function in insulin resistant states such as overweight/obesity and type 2 diabetes.

Conditions

Overweight; Obesity; Diabetes Mellitus, Type 2; Insulin Resistance

Outcome Measures

Primary Outcomes (1)

• Mitochondrial DNA methylation

  Mitochondrial DNA methylation and D-loop of mitochondria is altered in insulin resistant states such as overweight/obesity and type 2 diabetes

  3 years

Secondary Outcomes (1)

• Mitochondrial Function

  3 years

Study Arms (3)

Lean, healthy control

Lean, healthy control subjects. Volunteers will be matched for sex and age 21-55 years old. Ethnicities studied will be self-reported. We will attempt to match on race/ethnicities with equal numbers of non-Hispanic/Latinos and Hispanics/Latinos.

Other: Methylation status

Overweight/obese nondiabetic

Overweight/Obese nondiabetic subjects. Overweight and obesity will be defined using the standard body mass index cutoffs. Volunteers will be matched for sex and age 21-55 years old. Ethnicities studied will be self-reported. We will attempt to match on race/ethnicities with equal numbers of non-Hispanic/Latinos and Hispanics/Latinos.

Other: Methylation status

Type 2 diabetes

Participants with type 2 diabetes will be diagnosed accordingly to ADA criteria. Volunteers will be matched for sex and age 21-55 years old. Ethnicities studied will be self-reported. We will attempt to match on race/ethnicities with equal numbers of non-Hispanic/Latinos and Hispanics/Latinos.

Other: Methylation status

Interventions

Methylation status OTHER

Participants will be recruited, and muscle biopsies will be obtained for methylation analyses and measuring mitochondrial function

Lean, healthy control; Overweight/obese nondiabetic; Type 2 diabetes

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Three groups of volunteers will be studied: 1) lean, healthy volunteers, 2) overweight/obese volunteers without type 2 diabetes, and 3) volunteers with type 2 diabetes

You may qualify if:

• Subjects must be 21-55 years old
• Body Mass Index:
• Lean, healthy BMI ≤25; Overweight,non-diabetic BMI 25-29.9; Obese, non-diabetic BMI 30-50; Type 2 Diabetes (per the American Diabetes Association criteria)
• Subjects must be able to communicate meaningfully with the investigator and must be legally competent to provide written informed consent.
• Female subjects must be non-lactating and will be eligible only if they have a negative pregnancy test throughout the study period, and must agree to use acceptable birth control (hormonal contraceptives, barrier methods, have an intrauterine device, or surgical sterilization)
• Subjects must have the following laboratory values:
• Hematocrit ≥ 35 vol%
• Serum creatinine ≤ 1.6 mg/dl
• AST (SGOT) \< 2 times upper limit of normal
• ALT (SGPT) \< 2 times upper limit of normal
• Alkaline phosphatase \< 2 times upper limit of normal
• Triglycerides \< 150 mg/dl for nondiabetics
• Triglycerides \<300 for diabetics
• INR ≤ 1.3
• HbA1c ≤ 10

You may not qualify if:

• 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 must not be taking estrogens or other hormonal replacement therapy unless the subject has been on these agents on a stable dose for the prior three months. Subjects taking systemic glucocorticoids are excluded. Patients with type 2 diabetes will be excluded if they are taking thiazolidinediones.
• Subjects receiving Gemfibrozil must not also be receiving a statin.
• 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.
• Recent systemic or pulmonary embolus, untreated high-risk proliferative retinopathy, recent retinal hemorrhage, uncontrolled hypertension, systolic BP\>160, diastolic BP\>95, autonomic neuropathy, resting heart rate \>100, electrolyte abnormalities.

Sponsors & Collaborators

• University of Arizona: lead

Study Sites (1)

Clinical and Translational Research Center (CaTS)

Tucson, Arizona, 85724, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

DNA will be extracted from vastus lateralis skeletal muscle biopsies and blood samples

MeSH Terms

Conditions

Overweight; Obesity; Diabetes Mellitus, Type 2; Insulin Resistance

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism

Study Officials

• Dawn K Coletta, PhD

  University of Arizona

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: October 11, 2019
• First Posted: October 15, 2019
• Study Start: July 23, 2019
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: May 7, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)