Dietary Omega-3 Fatty Acids as a Therapeutic Strategy in Insulin Resistant Humans
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Insulin Sensitivity by Hyperinsulinemic-euglycemic Clamp at Baseline and 6 Month Follow up
研究概览
简要总结
This study is being done to understand the effects of dietary omega-3 fats on insulin sensitivity in adult men and women.
详细描述
Dietary omega-3 polyunsaturated fatty acids (n-3 PUFA), which include eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish oil, prevent insulin resistance in rodents, but data in humans is ambiguous. No existing studies have systematically evaluated the influence of n-3 PUFAs on insulin sensitivity and beta cell function in insulin resistant, non-diabetic humans. The Investigators hypothesize that 6 months of oral supplementation of purified EPA/DHA (3.9g/day) will significantly improve hepatic and peripheral insulin sensitivity and beta cell responsiveness in insulin-resistant, non-diabetic individuals. Based on recent work in mice, the investigators also hypothesize that EPA/DHA will increase the content and function of mitochondria in skeletal muscle, measured using a combination of in vivo and in vitro methods. Overall, the investigators hypothesize that EPA+DHA supplementation will improve hepatic and peripheral insulin sensitivity in insulin resistant humans, and this improvement will be associated with mitochondrial biogenesis and attenuated lipid accumulation in skeletal muscle and liver.
A sub-study was added in which participants receiving dietary omega-3 fatty acids or placebo supplements underwent abdominal subcutaneous adipose tissue biopsies to measure the content of total, pro- (M1) and anti- (M2) inflammatory macrophages (immunohistochemistry), crown-like structures (immunohistochemistry), and senescent cells (β-galactosidase staining), as well as a two-step euglycemic, pancreatic clamp with a stable-isotope labeled precursor ((U-13C)palmitate) infusion to determine the insulin concentration needed to suppress palmitate flux by 50% (IC50(palmitate)f).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Omega-3
Patients in this group will receive oral supplementation with EPA+DHA (3.9grams/day) for 6 months.
干预措施: Omega-3 (Drug)
Placebo
Patients in this group will be supplemented with placebo capsules containing ethyl oleate.
干预措施: placebo (Drug)
结局指标
主要结局
Insulin Sensitivity by Hyperinsulinemic-euglycemic Clamp at Baseline and 6 Month Follow up
时间窗: Baseline, after 6 months of treatment
A 2-stage insulin clamp will be performed with titration of dextrose to maintain euglycemia. D2 glucose will be infused to evaluate hepatic glucose production at baseline and in response to insulin. Hyperinsulinemic-euglycemic clamp technique: The plasma insulin concentration is acutely raised and maintained by a continuous infusion of insulin. Meanwhile, the plasma glucose concentration is held constant at basal levels by a variable glucose infusion. When the steady-state is achieved, the glucose infusion rate (GIR) equals glucose uptake by all the tissues in the body and is therefore a measure of tissue insulin sensitivity.
次要结局
- Mitochondrial Function Determined by Muscle Biopsy at Baseline and 6 Month Follow up(Baseline, after 6 months of treatment)
- Beta Cell Function From Insulin Secretion Following Ingestion of a Mixed Meal at Baseline and 6 Month Follow up(baseline, after 6 months of treatment)
- Insulin Concentration Needed to Suppress Palmitate Appearance Rates (IC50(Palmitate)f)(approximately after 6 months of treatment)
- Senescent Cells(approximately after 6 months of treatment)
- Immunohistochemistry Assessments of Macrophage Burden(approximately after 6 months of treatment)
- Macrophage Crown-like Structures(approximately after 6 months of treatment)
研究者
Ian R. Lanza
Assistant Professor of Medicine
Mayo Clinic