Pathophysiologic Mechanisms Leading to Intrahepatic Fat Accumulation in Obese Youth
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 260
- 试验地点
- 1
- 主要终点
- Lactate synthesis
研究概览
简要总结
The main aim of the study is to discover the mechanisms underlying the pathophysiology of NAFLD in obese youth.
详细描述
Nonalcoholic fatty liver disease (NAFLD) is the most common hepatic disease in pediatrics, affecting about 30% of obese youth. The term NAFLD defines a wide spectrum of disease severity ranging from simple intrahepatic fat accumulation without liver injury (steatosis) to nonalcoholic steatohepatitis (NASH), fibrosis and cirrhosis.
A 20-year retrospective study has shown that subjects who develop NAFLD during their youth have about 13 times higher mortality rate for end-stage liver disease than healthy subjects of similar age and gender. NAFLD is highly prevalent among Hispanic youth, while non-Hispanic Black (NHB) youth are protected against intrahepatic fat accumulation even in the presence of severe obesity and insulin resistance. Understanding the pathophysiology underlying these differences could shed new light on the mechanisms leading to NAFLD in obese youth.
Preliminary data suggest that Hispanic and NHB obese youth might have a different ability to metabolize carbohydrates (CHO) through glycolysis, with Hispanics showing higher glycolysis than NHB. Therefore, Hispanics might experience a higher rated tricyclic acid cycle (TCA) and hepatic de novo lipogenesis (DNL).
In the present study, the investigators aim to address the following questions:
- Is the different susceptibility between Hispanics and NHB in developing NAFLD due to a higher capability of Hispanics to metabolize CHO through glycolysis, TCA cycle and DNL?
- Do these metabolic changes anticipate the onset of the disease in Hispanic youth?
- Are the higher rates of glycolysis, TCA and DNL driven by high but not pathologic changes in glucose levels over time?
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 12 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Good general health, taking no medication on a chronic basis;
- •age 12 to 18 years, in puberty (girls and boys: Tanner stage II-V);
- •BMI >85th for obese cohort;
排除标准
- •Baseline creatinine >1.0 mg; pregnancy;
- •the presence of endocrinopathies (e.g. Cushing syndrome);
- •cardiac or pulmonary or other significant chronic illness;
- •adolescents with a psychiatric disorder or with substance abuse;
- •monogenic obesity syndromes;
- •use of drugs affecting intrahepatic fat content (e.g.; liraglutide, fish oil, etc.).
结局指标
主要结局
Lactate synthesis
时间窗: 60 months
lactate synthesis will be measured during an oral glucose tolerance test by measuring lactate. Synthetic rates will be measured by using a mathematical model.
次要结局
未报告次要终点