Effect of Metformin on Vascular and Mitochondrial Function in Type 1 Diabetes
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 23
- 试验地点
- 1
- 主要终点
- Insulin Sensitivity by Hyperinsulinemic Euglycemic Clamp
研究概览
简要总结
Insulin resistance (IR) is an important contributor to increased cardiovascular disease risk in type 1 diabetes (T1D). The purpose of this study is to measure the effect of metformin on insulin sensitivity, vascular function and compliance, and mitochondrial function in T1D. The long term goal is to identify novel non-glycemic approaches to managing cardiovascular disease risk in T1D. The results of this study may validate a novel approach to T1D treatment that could significantly improve current management of cardiovascular disease risk in this high risk population.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 25 Years 至 59 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 20-59 years of age,
- •Type 1 diabetes based on antibody-positivity, rapid persistent conversion to insulin requirement after diagnosis, absent C-peptide, or DKA at diagnosis, or a clinical course consistent with T1D,
- •HbA1c 6.0 - 9.5, and
- •Willing and able to commit to two 6 week-long periods of blinded medication followed by hyperinsulinemic euglycemic clamp, vascular testing, and muscle biopsies.
排除标准
- •Any comorbid condition associated with:
- •inflammation,
- •insulin Resistance, or
- •dyslipidemia including:
- •heart failure,
- •active or end stage liver disease,
- •kidney disease, or
- •rheumatological disease;
- •Tobacco use;
- •Pregnancy or women who are breastfeeding;
- •Steroid use;
- •Scheduled strenuous physical activity >3 days a week;
- •Angina, known CAD, or any other cardiovascular or pulmonary disease;
- •A history of COPD or asthma;
- •Presence of systolic blood pressure >190 at rest or >250 with exercise, or diastolic pressure >95 at rest or >105 with exercise;
- •Untreated thyroid disease;
- •Proteinuria (urine protein >200 mg/dl) or a creatinine > 1.5 mg/dl (males) or 1.4 mg/dL (females), suggestive of severe renal disease;
- •Severe Proliferative retinopathy;
- •Niacin treatment;
- •Administration of experimental agent for T1D within 30 days prior to screening;
- •Recent (prior 6 months) or current metformin or thiazolidenedione use;
- •Hypoglycemia unawareness or recurrent severe hypoglycemia (no symptoms of hypoglycemia with FSBS<40 and episodes of this severity >1 per week);
- •Weight instability (weight change >5% in last 6 months);
- •History of any organ transplant, including islet cell transplant;
- •Current or prior infection with HIV, hepatitis B or hepatitis C or hepatic -insufficiency (AST or ALT > 2x the upper limits of normal);
- •Any condition, medical or otherwise that would, in the opinion of the investigator, prevent complete participation in the study, or that would pose a significant hazard to the subject;
- •History of substance abuse within the 12 months prior to screening.
研究组 & 干预措施
Metformin
干预措施: Metformin (Drug)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Insulin Sensitivity by Hyperinsulinemic Euglycemic Clamp
时间窗: End of each 6 week intervention period
Determine the effect of metformin on insulin sensitivity in T1D. Reported measure is glucose infusion rate during hyperinsulinemic euglycemic clamp normalized to total body weight. For this measure, insulin was infused at 40 mU/m2 surface area. Blood sugar wass checked every 5 minutes and glucose infusion adjusted to maintain glucose level at 90 mg/dL for 2 hours. The glucose infusion rate for the final 30 minutes is reported as GIR (aka M-value or glucose disposal rate) in mg glucose/kg\*min. A higher value corresponds to greater sensitivity to insulin. There is no strictly defined normal range.
Flow-mediated Brachial Artery Dilation
时间窗: End of each 6 week intervention period
Measure of endothelial function by brachial ultrasound of the percent dilation after 5 minutes of occlusion.
次要结局
- Arterial Stiffness by PWV(End of each 6 week intervention period)
- Continuous Glucose Monitor Measures of Hypoglycemia(Last Week of each 6 Week Intervention Period (over 7 days))
- Metabolic Markers: Glucose, Triglycerides, Cholesterol(End of each 6 week intervention period)
- Metabolic Markers: Lactate(End of each 6 week intervention period)
- Arterial Stiffness by AI@75(End of each 6 week intervention period)
- Mitochondrial Measures: Protein Expression Levels of Electron Transport Chain Complexes(End of each 6 week intervention period)
- Inflammatory Marker: hsCRP(End of each 6 week intervention period)
- Metabolic Markers: Fatty Acids(End of each 6 week intervention period)
- Metabolic Markers: Glycerol(End of each 6 week intervention period)
- Metabolic Markers: Insulin(End of each 6 week intervention period)
- Vascular Markers: Endothelin-1 (pg/ml)(End of each 6 week intervention period)
- In Vivo Mitochondrial Function: Ratio of the Amount of ATP Generated Per Unit of Oxygen Consumed(End of each 6 week intervention period)
- Mitochondrial Measures: Oxygen Consumption(End of each 6 week intervention period)
- Heart Rate Variability(End of each 6 week intervention period)
- Continuous Glucose Monitor Measures of Mean Glucose(Last Week of each 6 Week Intervention Period (over 7 days))
- Metabolic Markers: Glucagon(End of each 6 week intervention period)
- Metabolic Markers: Adiponection(End of each 6 week intervention period)
- In Vivo Mitochondrial Function: Time Constants(End of each 6 week intervention period)
- In Vivo Mitochondrial Function: QMax, VPCr(End of each 6 week intervention period)
- In Vivo Mitochondrial Function: Oxidative Phosphorylation(End of each 6 week intervention period)
- In Vivo Mitochondrial Function:AnGly(End of each 6 week intervention period)
- Cardiac Function(End of each 6 week intervention period)