The WELL Study (Wellness Education for Liver Health Study): Reducing liver disease in genetically predisposed adults

WELL 研究（肝脏健康健康教育研究）：减少有遗传倾向的成年人的肝病

• 批准号: 10112901
• 负责人: Laura Saslow
• 金额: $ 11.7万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-01 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10112901
• 关键词: Adherence; Adult; Behavioral; Body Weight; Body Weight decreased; Body mass index; Carbohydrates; Cirrhosis; Clinical; Clinical Trials; Data; Deposition; Diet; Disease; Disease Outcome; Dropout; Education; Evidence based intervention; Fatty Liver; Fatty acid glycerol esters; Feedback; Fibrosis; Formulation; Future; Genetic; Genetic Predisposition to Disease; Genomics; Genotype; Glucose; Goals; Grant; Guidelines; Health; Hepatitis C; Hypertension; Individual; Inflammation; Insulin Resistance; Intervention; Interview; Life Style; Lipids; Liver; Liver Fibrosis; Liver diseases; Magnetic Resonance Imaging; Medical Care Costs; Methods; National Institute of Diabetes and Digestive and Kidney Diseases; Non-Insulin-Dependent Diabetes Mellitus; Participant; Patients; Pharmaceutical Preparations; Pilot Projects; Polycystic Ovary Syndrome; Population; Prediabetes syndrome; Prevalence; Primary carcinoma of the liver cells; Protons; Randomized Controlled Trials; Research; Research Project Grants; Research Support; Resources; Risk; Risk Factors; STEM research; Serum; Structure; Testing; Time; Weight; acceptability and feasibility; arm; base; density; dietary; dietary adherence; high risk; improved; insulin sensitivity; intrahepatic; liver transplantation; modifiable risk; mortality; non-alcoholic fatty liver disease; nonalcoholic steatohepatitis; personalized medicine; preference; programs; satisfaction; treatment strategy

ABSTRACT No medications are currently available for treatment of nonalcoholic fatty liver disease (NAFLD), an increasingly prevalent disease afflicting about 25% of US adults. NAFLD is caused by excessive fat deposition in the liver (steatosis); can progress to nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, hepatocellular carcinoma, liver transplantation, and increased liver-related and all-cause mortality. We have preliminary data that (1) insulin resistance is the strongest modifiable risk factor for developing NAFLD, and (2) individuals genetically predisposed to NAFLD by carrying PNPLA3 rs738409-GG show about a two-fold increased risk of developing NAFLD and a six-fold risk of nonalcoholic steatohepatitis (NASH) when combined with insulin resistance. Despite being at high risk of liver disease, rs738409-GG individuals with insulin resistance are not being especially targeted to help them improve their insulin sensitivity and thus likely improve their NAFLD outcomes. The PI and others have shown that very low-carbohydrate diets (VLCD) are more effective at reducing insulin resistance than many other types of diets, in addition to being effective for weight loss, lowering overall inflammation, and reducing intrahepatic lipid content. We hypothesize that a very low- carbohydrate diet and behavioral support program may be able to achieve NAFLD reversal in adults with steatosis and/or mild fibrosis, especially in a high-risk subpopulation, rs738409-GG individuals. To prepare to test this we will conduct a preliminary exploration of the needs and preferences of individuals with NAFLD for a VLCD program. Then we will adapt our materials based on this feedback. Finally, we will conduct a pilot feasibility and acceptability trial of a 4-month VLCD program in 30 PNPLA3 rs738409 GG adults with NAFLD. This R03 builds off of the PI’s current K01 with NIDDK, which is optimizing a 12-month VLCD program with adults with type 2 diabetes. We anticipate that the research stemming from this grant will lead to future R-level grants at the National Institute of Diabetes and Digestive and Kidney Diseases, as it will provide support for a multicenter randomized controlled trial.

抽象的 目前尚无治疗非酒精性脂肪肝病（NAFLD）的药物，这是一种 越来越普遍的疾病折磨了约25％的美国成年人。 NAFLD是由脂肪沉积过多引起的 在肝脏中（脂肪变性）；可以发展为非酒精性脂肪性肝炎（NASH），纤维化，肝硬化，肝细胞 癌，肝移植以及肝脏相关和全因死亡率增加。我们有初步数据 （1）胰岛素抵抗是开发NAFLD的强大可修改风险因素，（2）个体 通过携带PNPLA3 RS738409-GG显示出遗传上偏见的NAFLD，显示出增加了两倍的风险 与胰岛素结合使用时，发展NAFLD和非酒精性脂肪性肝炎（NASH）的六倍 反抗。尽管患有肝病的风险很高，但具有胰岛素抵抗性的卢比的卢比范围不是 特别针对帮助他们提高胰岛素敏感性，因此可能会改善其NAFLD 结果。 PI和其他人表明，非常低碳水化合物饮食（VLCD）在 除了有效减肥外，还比许多其他类型的饮食降低胰岛素耐药性， 降低整体炎症，并减少ep膜内脂质含量。我们假设一个非常低的 碳水化合物饮食和行为支持计划可能能够实现成年人的NAFLD 脂肪变性和/或轻度纤维化，尤其是在高风险亚群中，rs738409-gg个体。准备 对此进行测试，我们将对NAFLD的个人的需求和偏好进行初步探索 VLCD程序。然后，我们将根据此反馈调整材料。最后，我们将进行飞行员 4个月VLCD计划在30 pnpla3 rs738409 gg成年人的可行性和可接受性试验。 该R03与NIDDK建立在PI当前K01的基础上，NIDDK正在优化12个月的VLCD程序 患有2型糖尿病的成年人。我们预计这项赠款的研究将导致未来的R级 国家糖尿病和消化系统和肾脏疾病的赠款，因为它将为 多中心随机对照试验。