Limited Adipose Tissue Expandability as a Risk Factor for Development of Type 2 Diabetes: the Role of Preadipocytes
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Adipogenic capacity of preadipocytes
研究概览
简要总结
The goal of the study is to analyze deviations in adipogenic potential and metabolic properties of preadipocytes in subjects with genetic predisposition to type 2 diabetes, and thus identify factors that underlie hypertrophic growth of adipose tissue associated with the development of this disease.
详细描述
Adipose tissue (AT) expands in response to excessive energy intake by hyperplasia or hypertrophy. While hyperplasia is associated with preservation of insulin sensitivity, hypertrophic AT exerts a number of metabolic defects. The mechanisms by which hyperplasia is suppressed at the expense of AT hypertrophy remain unknown, but it is expected that the hypertrophy of adipocytes is primarily driven by insufficient recruitment and differentiation of available preadipocytes. The limitation of hyperplasia occurs already in non-obese healthy subjects who are genetically predisposed to Type 2 Diabetes. Using these and control subjects, the LIMEX project aims to analyze the mechanisms of AT expandability. The project will combine in vivo characterization of AT and in vitro studies on human preadipocytes derived from AT biopsies obtained during clinical study. In vitro, proliferation, adipogenesis and lipogenesis of adipose cells will be monitored and these properties will be related to the degree of AT hypertrophy in vivo, insulin sensitivity and genetic predisposition to metabolic complications.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 30 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •healthy non-obese men
- •subject has genetic predisposition for T2DM- i.e. two first-degree relatives (parents, siblings) or one first-degree relative and two second-degree relatives with type 2 diabetes (grandparents, uncle, aunt) diagnosed with T2DM OR
- •subject without any family history of T2DM.
排除标准
- •any prior history of obesity
- •elevated triglyceride concentration (above 1.7 mmol/l)
- •hypertension
- •thyroid or other endocrine disease
- •drug abuse
结局指标
主要结局
Adipogenic capacity of preadipocytes
时间窗: 3 months from the establishment of the cell culture
proliferation assays, messenger ribonucleic acid (mRNA) gene expression
次要结局
- Insulin sensitivity(3 hours investigation of the subject at the start of the study)
- Glucose tolerance(2 hours investigation of the subject at the start of the study)
- Lipid metabolism(3 months from the establishment of the cell culture)
研究者
Vladimir Stich
Professor, MUDr
Charles University, Czech Republic