Unraveling the Role of Mitochondrial DNA Methylation in Type 2 Diabetes
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Mitochondrial DNA methylation
研究概览
简要总结
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.
详细描述
To determine whether differences in human skeletal muscle DNA methylation patterns in the mitochondrial and nuclear genome can explain the lower abundance of ETC and OXPHOS mRNA and protein observed in insulin resistant skeletal muscle of overweight/obese and type 2 diabetic participants. To determine whether patterns of human skeletal muscle DNA methylation in the mitochondrial and nuclear genome are predictive of ETC function. We will isolate skeletal muscle mitochondria from metabolically well-characterized lean insulin sensitive, overweight/obese insulin resistant nondiabetic and obese insulin resistant type 2 diabetic volunteers, and functionally evaluate each ETC complex (I - IV) and complex V (ATP synthase).
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 21 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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.
结局指标
主要结局
Mitochondrial DNA methylation
时间窗: 3 years
Mitochondrial DNA methylation and D-loop of mitochondria is altered in insulin resistant states such as overweight/obesity and type 2 diabetes
次要结局
- Mitochondrial Function(3 years)
研究者
Dawn K Coletta
Associate Professor of Medicine
University of Arizona