Longitudinal Multi-Omic Profiles to Reveal Mechanisms of Obesity-Mediated Insulin Resistance
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 110
- 试验地点
- 2
- 主要终点
- Change from baseline on the magnetic-resonance based measurement of intrahepatic lipid deposition
研究概览
简要总结
This 12-week controlled diet and weight intervention study seeks to define the molecular pathways that link excess body weight to the development of insulin resistance (IR). Blood, adipose and stool are sampled at three timepoints; baseline, peak weight (4 weeks) and post weight loss to monitor changes in cellular processes. Additionally, direct insulin sensitivity testing, and radiological measurement of visceral fat and intrahepatic fat content is measured at three timepoints to correlate clinical indices with cellular changes.
详细描述
Obesity has become an epidemic worldwide. Metabolic/cardiovascular complications of obesity are likely related to the fact that obese individuals tend to be insulin resistant (IR). While insulin- mediated glucose uptake (IMGU) correlates with adipose tissue mass, not all obese individuals are IR, and metabolic and cardiovascular profiles of those who are IR vs insulin sensitive (IS) differ significantly. Why one individual who reaches a BMI of 30 kg/m2 will develop IR and another with similar BMI and activity level remains IS is unclear. Furthermore, while insulin sensitivity improves with weight loss, this response varies as well. Given that fat mass per se does not fully explain the obesity contribution to IMGU, itis likely that differential adipocyte function plays a role. With this study, our purpose is to employ an integrated omics strategy to identify analyte/pathway signatures in blood and adipose tissue that characterize IR versus IS states and expand our biological knowledge of the mechanisms underlying IR.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 35 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age 35-65
- •BMI 25-35 kg/m2
- •Stable body weight
- •Nondiabetic
排除标准
- •Patients with;
- •major organ disease
- •history of liposuction or bariatric surgery
- •active eating or psychiatric disorder
- •pregnancy or lactation, heavy alcohol use
- •recent change in weight (over the past 12 weeks)
- •use of weight loss medication, statins, or oral steroids
- •Clinical screening exclusions;
- •hematocrit < 33%
- •fasting glucose >/= 126 mg/dL
- •blood pressure >160/100 mmHg
结局指标
主要结局
Change from baseline on the magnetic-resonance based measurement of intrahepatic lipid deposition
时间窗: Post-weight loss (8 weeks)
Compare measurement of liver fat content via magnetic resonance spectroscopy (MRS) after 8 week diet and weight intervention
Change from baseline in plasma inflammatory cytokine levels in serum samples as measured by Luminex immunoassay
时间窗: Peak Weight (4 weeks)
Compare intra-personal levels of plasma inflammatory cytokines as measured by Luminex immunoassay after 4 week diet and weight intervention
Change from baseline on the 2-stage Steady State Plasma Glucose test
时间窗: Peak weight (4 weeks)
Compare direct measurement of insulin sensitivity after 4 week diet and weight intervention
Change from baseline on the radiographic measurement of visceral to subcutaneous (V:S) fat ratio
时间窗: Post-weight loss (8 weeks)
Compare measurement of abdominal V:S fat volume via computed tomography (CT) after 8 week diet and weight intervention
Measurement of markers of lipid and carbohydrate metabolism and inflammation from adipose mRNA
时间窗: Baseline
Compare adipose tissue transcripts such as known MODY transcription factors, defensin chemokine receptors, and platelet activation factors measured by PCR between participants identified as Insulin sensitive (IS) and Insulin resistant (IR) using the 2-stage Steady State Plasma Glucose test.
Quantification of plasma inflammatory cytokine levels in serum samples by Luminex immunoassay
时间窗: Baseline
Compare plasma inflammatory cytokine levels in serum samples as measured by Luminex immunoassay between participants identified as Insulin Sensitive (IS) and Insulin Resistant (IR) using the 2-stage Steady State Plasma Glucose test.
Change from peak weight on the 2-stage Steady State Plasma Glucose test
时间窗: Post-weight loss (8 weeks)
Compare direct measurement of insulin sensitivity after 8 week diet and weight intervention
次要结局
未报告次要终点
研究者
Tracey McLaughlin
Professor of Medicine
Stanford University