Effects of Metformin on Hepatic Free Fatty Acid Metabolism in Patients Diagnosed With Type 2 Diabetes: A C11 PET Study
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 36
- 主要终点
- Hepatic Fatty Acid Oxidation
研究概览
简要总结
Background: Metformin treatment has beneficial effects on both glucose and lipid metabolism. Whereas there is general agreement that the blood glucose lowering effect of metformin results from inhibition of hepatic gluconeogenesis, it is less clear exactly how the drug lowers blood triglyceride concentration. There are indications that it enhances hepatic free fatty acid (FFA) oxidation thus diminishing substrate for reesterification and resecretion as very-low-density-lipoprotein (VLDL) triglycerides (TG). However, the liver is not easily accessible for sampling in humans and data on the clinical effects of metformin in the liver are therefore lacking. This may change due to the increasing use of the positron emission tomography (PET) technique. Using PET isotopes (11C or 18F) coupled to either palmitate or a fatty acid analogue, it is possible to non-invasively measure hepatic fatty acid handling.
Aim: To determine how 3 months metformin treatment (1000 mg twice daily) affects hepatic lipid and glucose metabolism in patients with newly diagnosed type 2 diabetes.
Design: Randomized, placebo controlled, double-blind parallel study with patients receiving either metformin or placebo. A control group of BMI and age-matched non-diabetic individuals will receive metformin for 3 months.
Hypothesis: Metformin lowers VLDL-TG secretion and circulating triglycerides by increasing hepatic fatty acid oxidation
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 50 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Recently diagnosed type 2 diabetes
- •Age 50-70 years
排除标准
- •Insulin treatment
- •NASH (non alcoholic steatohepatitis)
- •HbA1C>8.5 %
- •Chronic or acute pancreatitis
- •Alcohol or medicine abuse
- •Allergy towards metformin
- •Claustrophobia
- •Severe obesity (weight >130 kilogram)
研究组 & 干预措施
Placebo
Placebo
干预措施: Placebo (Drug)
Healthy controls
Healthy controls receiving 1000 mg metformin twice daily for 3 months
干预措施: Metformin (Drug)
Metformin
Metformin "Sandoz", 1000 mg twice daily for 3 months
干预措施: Metformin (Drug)
结局指标
主要结局
Hepatic Fatty Acid Oxidation
时间窗: 90 days
Hepatic fatty acid oxidation assessed by dynamic C11-palmitate PET
Hepatic Fatty Acid Reesterification
时间窗: 90 days
Hepatic fatty acid reesterification assessed by C11-palmitate PET
Hepatic Fatty Acid Uptake
时间窗: 90 days
Hepatic fatty acid uptake assessed by C11-palmitate PET
VLDL-TG Secretion
时间窗: 90 days
Hepatic VLDL-TG secretion assessed by \[1-14C\] VLDL tracer
Whole Body Glucose Rd
时间窗: 90 days
Whole body basal glucose metabolism assessed by \[3-3H\]glucose tracer kinetics
次要结局
- Fatty Acid Turnover(90 days)
- VLDL-TG Oxidation(90 days)
研究者
Lars Christian Gormsen
Senior Registrar, MD PhD
Aarhus University Hospital