Fructose Metabolism Effects on the Liver: Unraveling the Role of Defective Intestinal GNG in Individuals With Obesity
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Fru-GNG
研究概览
简要总结
This study will test the hypothesis that within a defined range of fructose intake, the ability to convert fructose to glucose (via gluconeogenesis) in the small intestine plays a protective role for the liver, shielding it from the deleterious effects of fructose. We will investigate whether this protective effect of the intestine is impaired in individuals with obesity.
详细描述
Qualified participants will undergo a sugar tolerance test at baseline and then randomized to undergo four separate outpatient tracer/feeding studies in a crossover fashion. After an overnight fast, a six-hour fed tracer study will be initiated, during which participants will consume liquid meals containing stable isotopes at regular intervals and receive other isotopes intravenously. Meal composition will differ only by fructose content (High vs. Low) and tracer (oral vs. intravenous 13C-labeled fructose). Blood and urine samples will be collected frequently throughout the study. Each visit will be performed approximately three weeks apart. Vital signs and anthropometrics will be measured at each clinic visit.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 20 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •BMI 30 to 38 kg/m2 (obese group) or BMI 19 to 25 kg/m2 (lean group)
排除标准
- •Pregnancy or lactation within the past six months;
- •Type 1 or 2 diabetes mellitus (including fasting glucose ≥126 mg/dL, HgbA1c ≥6.5%);
- •History of liver disease or AST and ALT 2x above the upper limit of normal;
- •Fasting triglyceride > 300 mg/dl; total cholesterol levels above the 95th percentile for age and sex;
- •Hemoglobin (Hgb) <12.5g/d or hematocrit<3x Hgb value;
- •Report of HIV or hepatitis B or C infection;
- •History of cancer, other than basal cell or squamous cell carcinoma or kidney disease stage 3 or higher or patients currently on dialysis;
- •Use of any anti-diabetic medications or hypolipidemic agents in the past six months;
- •History of surgical procedure for obesity;
- •Change in body weight >5% in the past six months (by self-report);
- •History of other conditions known to affect insulin sensitivity and lipid metabolism (e.g., polycystic ovary syndrome), history of galactosemia, hereditary fructose intolerance, or who test positive for fructose malabsorption at screening;
- •Known intolerance to acetaminophen.
研究组 & 干预措施
High fructose meals, oral 13C fructose
Liquid meals will be fed, containing 55% total carbohydrate (16% fructose), 30% fat, 15% protein, and a tracer amount of 13C fructose.
干预措施: High fructose meal (Other)
High fructose meals, oral 13C fructose
Liquid meals will be fed, containing 55% total carbohydrate (16% fructose), 30% fat, 15% protein, and a tracer amount of 13C fructose.
干预措施: 13C labeled fructose, oral (Other)
High Fructose Meals, IV 13C Fructose
Liquid meals will be fed, containing 55% total carbohydrate (16% fructose), 30% fat, 15% protein. A tracer amount of 13C fructose will be administered intravenously.
干预措施: High fructose meal (Other)
High Fructose Meals, IV 13C Fructose
Liquid meals will be fed, containing 55% total carbohydrate (16% fructose), 30% fat, 15% protein. A tracer amount of 13C fructose will be administered intravenously.
干预措施: 13C labeled fructose, intravenous (Other)
Low fructose meals, oral fructose tracer
Liquid meals will be fed, containing 55% total carbohydrate (6% fructose), 30% fat, 15% protein, and a tracer amount of 13C fructose.
干预措施: Low fructose meal (Other)
Low fructose meals, oral fructose tracer
Liquid meals will be fed, containing 55% total carbohydrate (6% fructose), 30% fat, 15% protein, and a tracer amount of 13C fructose.
干预措施: 13C labeled fructose, oral (Other)
Low fructose meals, IV 13C fructose tracer
Liquid meals will be fed, containing 55% total carbohydrate (6% fructose), 30% fat, 15% protein. A tracer amount of 13C fructose will be administered intravenously.
干预措施: Low fructose meal (Other)
Low fructose meals, IV 13C fructose tracer
Liquid meals will be fed, containing 55% total carbohydrate (6% fructose), 30% fat, 15% protein. A tracer amount of 13C fructose will be administered intravenously.
干预措施: 13C labeled fructose, intravenous (Other)
结局指标
主要结局
Fru-GNG
时间窗: 6 hours
Total amount of fructose converted to glucose
Fru-hGNG
时间窗: 6 hours
Amount of fructose converted to glucose in the liver
Fru-iGNG
时间窗: 6 hours
Amount of fructose converted to glucose in the intestine
De novo lipogenesis (DNL)
时间窗: 6 hours
Percent of newly synthesized palmitate
次要结局
未报告次要终点
研究者
Jean-marc Schwarz
Professor
Touro University, California