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临床试验/NCT01561664
NCT01561664已完成不适用

Relations Between Obesity and Insulin Resistance: Role of Inflammation Regulatory Mechanisms in Obese Patients Without Associated Comorbidity

University Hospital, Montpellier2 个研究点 分布在 1 个国家目标入组 30 人开始时间: 2011年11月最近更新:
适应症
干预措施

试验速览

阶段
不适用
状态
已完成
入组人数
30
试验地点
2
主要终点
TLR regulation

研究概览

简要总结

Insulin resistance is one of the main mechanisms involved in metabolic diseases. inflammation has been implicated in its pathogenesis, due to innate immunity activation by free fatty acids, lipopolysaccharides (LPS) and lactate. Free fatty acids, LPS and lactate activate innate immunity in squelettal muscle and adipose tissue via Toll-like receptor 2/4, NFkB, IRF3 (Interferon Responsive Factor 3) and cytokines secretion (TNFa, IFN g, IL1b, IL6), chemokines secretion (MCP1) and leukotrienes (LTB4). Feed back mechanisms involved in TLR signaling pathways as RLI (ribonuclease L inhibitor)/ABCE1, have never been studied in inflammation due to obesity. RLI inhibits an endoribonuclease, RNase L, which has been recently implicated in TLR signaling The purpose of this study is to analyse the role of RLI and RNase L in TLR regulation, and its potential implication in the link between obesity, inflammation and insulin resistance in adipose tissue and squeletal muscle in humans.

详细描述

The investigators working hypothesis is that RNase L and RLI contribute to chronic inflammation regulation and to insulin response through TLR 4 pathway regulation in obesity. The investigators main purpose is to compare innate immunity activation pathway between insulin sensitive, insulin resistant obese patients and control patients. Insulin sensitive and insulin resistant obese patients will be distinguish thanks to the HOMA ir index. The investigators second objectives are to evaluate if the degree of inflammation in adipose tissue and squeletal muscle is correlated to insulin sensitivity measured by hyperinsulinemic euglycemic clamp and to characterise inflammatory pathway and regulation pathway. A special focus will be given to the leukotrienes and their potential role in insulin resistance pathogenesis. The investigators will have two approaches:- characterisation of subjects with normal weight, of obese insulin sensitive and obese insulin resistant through a metabolic evaluation, an inflammatory characterisation and a measure of insulin sensitivity at the systemic level, in adipose tissue and in squeletal muscle.- an in vitron approach with human myoblast and adipocytes culture, extracted from the investigators patients: characterisation of inflammation, innate immunity.

研究设计

研究类型
Interventional
分配方式
Non Randomized
干预模型
Parallel
盲法
None

入排标准

年龄范围
50 Years 至 65 Years(Adult, Older Adult)
性别
All
接受健康志愿者

入选标准

  • Age between 50 and 65 years old
  • Men/ menopausal women
  • BMI <25 kg/m2 for the control group, BMI >30 kg/m2 for the obese group
  • Non diabetic patients
  • HOMAIR <3 for the insulin sensitive obese group
  • Non smoking
  • Without any inflammatory disease
  • Without any first degrees relative with diabetes
  • Without any treatment that could interfere with insulin sensitivity
  • without any infection

排除标准

  • 未提供

研究组 & 干预措施

overweight insulin resistant

Experimental

overweight patients insulin resistant responding to the study criteria

干预措施: muscle and fat biopsy (Other)

volunteers

Active Comparator

not overweight Volunteers responding to the study criteria

干预措施: muscle and fat biopsy (Other)

overweight patients insulin sensitive

Experimental

overweight patients insulin sensitive responding to the study criteria

干预措施: muscle and fat biopsy (Other)

结局指标

主要结局

TLR regulation

时间窗: 2 years

analyse the role of RLI and RNase L in TLR regulation, and its potential implication in the link between obesity, microinflammation and insulin resistance in adipose tissue and squelettal muscle in humans.

次要结局

未报告次要终点

研究者

申办方类型
Other
责任方
Sponsor

研究点 (2)

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