Prevention of Pediatric NAFLD in Hispanic Children

西班牙裔儿童 NAFLD 的预防

• 批准号: 10552057
• 负责人: MIRIAM B. VOS
• 金额: $ 57.61万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-05 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10552057
• 关键词: 9 year old; Address; Adipose tissue; Adult; Affect; Age; Alanine; Biochemical; Biological Markers; Body Composition; Cardiovascular Diseases; Chemosensitization; Child; Child Psychology; Clinical; Clinical Trials; Complex; Consumption; Counseling; Development; Diabetes Mellitus; Diet; Dietary Intervention; Dietary Sugars; Dietary intake; Disease; Dyslipidemias; Ethnic Origin; Family; Fatty Liver; Fatty acid glycerol esters; Feces; First Degree Relative; Food; Future; Genetic; Genetic Polymorphism; Guidelines; Health; Health Promotion; Hepatic; Hispanic; Home; Home visitation; Hour; Image; Inflammation; Insulin Resistance; Intervention; Intervention Studies; Intramuscular; Juice; Lipids; Liver; Liver Cirrhosis; Liver diseases; Longitudinal Studies; Magnetic Resonance Imaging; Malignant neoplasm of liver; Metabolic Pathway; Metabolic dysfunction; Methods; Minority; Mission; Monitor; Morbidity - disease rate; National Institute of Nursing Research; Non-Insulin-Dependent Diabetes Mellitus; Nursing Research; Nutritional Study; Obesity; Obesity associated liver disease; Observational Study; Onset of illness; Overweight; Pancreas; Patient Recruitments; Pattern; Pediatric Research; Phase; Physiological; Plasma; Prevention; Prevention strategy; Prevention trial; Primary Prevention; Puberty; Randomized; Recording of previous events; Reduce health disparities; Research; Risk; Role; Site; Testing; Time; Transferase; United States; Urine; Visceral; adipokines; behavior change; chemokine; diabetes risk; disorder prevention; fatty acid oxidation; follow-up; genetic testing; genetic variant; health care disparity; health disparity; high risk; high risk population; improved; innovation; insulin sensitivity; lifetime risk; lipid biosynthesis; lipid metabolism; liver inflammation; liver transplantation; metabolome; metabolomics; mortality; multidisciplinary; non-alcoholic fatty liver disease; pediatric non-alcoholic fatty liver disease; prepuberty; prevent; primary health center; primary outcome; programs; randomized trial; randomized, clinical trials; research facility; response; secondary outcome; subcutaneous; sugar; treatment as usual; trial comparing

Abstract Nonalcoholic fatty liver disease (NAFLD) is an obesity-associated liver disease that affects an estimated 7 million children in the United States. It is the most common reason for liver transplantation in adults and increases long term risk of diabetes and cardiovascular disease. NAFLD disproportionately affects Hispanic children and is an exceptionally important health disparity. The proposed studies will address prevention of NAFLD in children because current treatments are only partially effective, and no cure exists for the disease. A unique physiologic opportunity exists in children in that NAFLD appears to have a narrow time of onset in children, during early puberty. In a recently completed randomized clinical diet provision trial comparing a very low free sugar diet to usual care, we demonstrated improved hepatic steatosis, liver inflammation and rate of de novo lipogenesis in children who already have NAFLD. However, it is unknown if providing a low free sugar diet (LFSD) in pre-pubertal children can help prevent hepatic steatosis and NAFLD onset as they age into puberty. The central study supporting the 3 aims is a 1 year randomized prevention trial with a 1 year follow-up observational study in children who are pre-pubertal at baseline and who are known to be in a high-risk group for developing NAFLD because of Hispanic ethnicity and a first degree relative with NAFLD or type 2 diabetes. The intervention will replace typical drinks and food high in (non-dairy) sugars with low or no sugar foods using our established methods including 1) provision of food for the entire family 2) facilitated grocery shopping 3) home visits 4) behavior change counseling and, 5) frequent monitoring. Hispanic children age 7-9 years, Tanner stage 1, who are at high risk of NAFLD by family history will be randomized to LFSD intervention or usual care with matching for contact hours. The primary outcome is hepatic steatosis by MRI-PDFF at 1 year. Aim 1 tests whether the intervention protects against increase in hepatic steatosis at 1 year and NAFLD onset at 2 years. Aim 2 tests gene variants associated with NAFLD, baseline anthropometrics and insulin sensitivity modifiers of the impact of LFSD on change in hepatic steatosis at 1 year. Aim 3 explores biochemical and lipid metabolism mechanisms underlying hepatic steatosis and LFSD. In summary, this trial will generate evidence regarding the potential for using free sugar restriction as a NAFLD prevention strategy for children at increased risk of NAFLD. The findings will have sustained and significant implications for health promotion in Hispanic children, reduce health disparities, and inform future prevention efforts for children at increased risk of NAFLD.

摘要 非酒精性脂肪性肝病（NAFLD）是一种肥胖相关的肝病， 据估计，美国有700万儿童。这是肝脏最常见的原因 在成年人中移植，并增加糖尿病和心血管疾病的长期风险。 NAFLD不成比例地影响西班牙裔儿童，是一个非常重要的健康问题。 差距拟议的研究将解决儿童NAFLD的预防问题，因为目前 治疗方法只是部分有效，而且没有治愈这种疾病的方法。一种独特的生理 儿童中存在机会，因为NAFLD在儿童中的发病时间似乎较短， 在青春期早期在最近完成的一项随机临床饮食供应试验中， 非常低的游离糖饮食，我们证明改善肝脂肪变性，肝脏 已经患有NAFLD的儿童的炎症和新生脂肪生成率。但 尚不清楚为青春期前儿童提供低游离糖饮食（LFSD）是否有助于预防 肝脂肪变性和NAFLD的发病。中心研究支持3 aims是一项为期1年的随机预防试验，在儿童中进行了为期1年的随访观察性研究 在基线时处于青春期前，并且已知处于发展的高风险组 NAFLD，因为西班牙裔种族和一级亲属与NAFLD或2型糖尿病。 干预措施将取代典型的饮料和食物高（非乳制品）低糖或无糖 使用我们既定的方法，包括1）为整个家庭提供食物2） 便利的杂货店购物3）家访4）行为改变咨询，5）经常 监测. 7-9岁的西班牙裔儿童，坦纳1期，NAFLD的高风险， 家族史将随机分配至LFSD干预或常规护理，并匹配接触 小时主要结局是1年时通过MRI-PDFF评估的肝脂肪变性。目标1测试是否 干预可防止1年时肝脂肪变性增加和2年时NAFLD发作。 目的2测试与NAFLD、基线人体测量学和胰岛素相关的基因变异 LFSD对1年时肝脂肪变性变化影响的敏感性调节剂。Aim 3探索 肝脂肪变性和LFSD的生化和脂质代谢机制。在 总之，这项试验将产生关于使用游离糖限制的可能性的证据。 作为NAFLD风险增加的儿童的NAFLD预防策略。调查结果将有 对西班牙裔儿童健康促进的持续和重大影响， 我们的研究报告显示了这些差异，并为未来针对NAFLD风险增加的儿童的预防工作提供了信息。