Comparative Study of Subcutaneous and Visceral Adipose Tissue in Patients Affected by Cushing Syndrome Versus 2 Controls Population
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Comparison between visceral adipose tissue of Cushing patients and that of normal weight controls.
研究概览
简要总结
The purpose of this trial is to investigate the impact of cortisol on adipose tissue functions, distribution and morphology. Patient with endogenous blood cortisol excess exhibit changes in adipose tissue, with fat gain in the upper trunk, face and neck leading to visceral obesity and features of the metabolic syndrome. The aims of this study will be
- to compare the pattern of gene expression between visceral and subcutaneous adipose tissue in Cushing patients requiring an adrenalectomy as cortisol adenoma treatment;
- to compare these patterns of gene expression with those of two control populations:1/ healthy metabolic subjects having a partial nephrectomy, 2/obese patients with similar degree of insulin resistance.
详细描述
Cushing's syndrome is a rare disease resulting from chronic exposure to glucocorticoids (endogenous or iatrogenic) with abnormal fat distribution (lipodystrophy). Glucocorticoids regulate the functions of adipose tissue (AT) targeting adipocyte differentiation as well as anabolic, catabolic and secretory pathways of the adipocyte. However, the mechanisms by which glucocorticoids differentially disrupt the development or metabolism of AT between deep and superficial deposits remain unknown. Among the main effectors of the glucocorticoid signaling pathway, 11 beta-hydroxysteroid deshydrogenase (11beta-HSD1) , that regenerate cortisol from cortisone, is likely a key step in the biological effect of glucocorticoids in AT. Identifying these mechanisms of action of glucocorticoids on different fat depots requires the comparison with fatty deposits derived from two types of control populations: 1/ normal weight individuals without inflammatory or metabolic disorder (controls1); 2/individuals obese matched for the level of insulin resistance (controls2).
Hypothesis: Excess glucocorticoids cause abnormal fat distribution via a direct effect on the various deposits of AT, leading secondarily to insulin resistance.
Primary endpoint: To compare gene expression of glucocorticoid signaling between the visceral AT (VAT) of Cushing patients with that of controls1 (matched for age and sex).
Secondary endpoints:
- For patients with Cushing and controls1, to compare their respective subcutaneous AT (SCAT) and VAT for:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Cases: Adults with Cushing's syndrome secondary to adrenal adenoma.
- •Controls1: Adults with normal weight: BMI <25, having partial nephrectomy
- •Controls2 adults with common obesity treated by bariatric surgery, BMI> 35kg/m2
排除标准
- •Diabetes, renal or hepatic impairment, pregnancy, menopause, HIV or HCV, Cushing's syndrome due to other causes than cortisol adenoma
研究组 & 干预措施
Cushing group
AT biopsy during partial nephrectomy
干预措施: analyze the role of glucocorticoid in AT distribution. (Other)
Controls1
normal weight metabolic healthy patients having partial nephrectomy with small AT Biopsy.
干预措施: analyze the role of glucocorticoid in AT distribution. (Other)
Controls2
obese individuals already included and having biopsies of VAT and SCAT stocked.
干预措施: analyze the role of glucocorticoid in AT distribution. (Other)
结局指标
主要结局
Comparison between visceral adipose tissue of Cushing patients and that of normal weight controls.
时间窗: 1 day (gene expression will be tested on AT withdraw the day of surgical adrenalectomy)
Comparison of glucocorticoid pathway genes expression between visceral adipose tissue of Cushing patients and that of normal weight controls matched on sex and age.
次要结局
- comparison between SCAT and VAT from Cushing patients(1 day (gene expression will be tested on AT withdraw the day of surgical adrenalectomy))
- Comparison of the respective SCAT and VAT between Cushing patients and normal weight controls.(1 day (gene expression will be tested on AT withdraw the day of surgical adrenalectomy))
- Comparison of the respective SCAT and VAT between Cushing patients and obese controls.(1 day (gene expression will be tested on AT withdraw the day of surgical adrenalectomy))