Prevention of Pediatric NAFLD in Hispanic Children

西班牙裔儿童 NAFLD 的预防

基本信息

批准号：
10383660
负责人：
MIRIAM B. VOS
金额：
$ 58.54万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
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/10383660
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 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 Health Care Primary Prevention Puberty Randomized Randomized Clinical Trials Recording of previous events Reduce health disparities Research Risk Role Site Testing Time Transferase United States Urine Visceral adipokines base behavior change beta-Chemokines 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 outcome programs randomized trial research facility response secondary outcome subcutaneous sugar treatment as usual trial comparing

项目摘要

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.

抽象的非酒精性脂肪肝病（NAFLD）是一种与肥胖相关的肝病，影响了美国估计有700万儿童。这是肝脏的最常见原因成人的移植并增加了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，并且是一个非常重要的健康差距。拟议的研究将解决儿童中NAFLD的预防治疗仅是部分有效的，并且没有治愈该疾病的治疗方法。独特的生理学 NAFLD的儿童中存在机会在青春期初期。在最近完成的随机临床饮食供应试验中我们表现出非常低的自由糖饮食，以治疗通常的护理，我们证明了肝脂肪变性的改善，肝脏已经患有NAFLD的儿童的炎症和从头脂肪形成率。但是，它尚不清楚是否在前儿童中提供低糖饮食（LFSD）可以帮助防止肝脂肪变性和NAFLD发作时，它们会衰老。支持3的中央研究 AIMS是一项为期1年的随机预防试验，对儿童进行了1年的随访观察研究他们是基线前的普伯塔尔（Pubertal） NAFLD是由于西班牙裔种族和具有NAFLD或2型糖尿病的一级亲戚。干预措施将取代典型的饮料和较高（非乳制）糖的饮料和食物使用我们既定的方法，包括1）为整个家庭提供食物2）促进的杂货店购物3）家庭访问4）行为改变咨询和5）经常监视。西班牙裔儿童7-9岁，坦纳阶段1，他们处于NAFLD的高风险家族史将被随机分配给LFSD干预措施或通常的护理，并进行匹配以进行联系小时。主要结果是MRI-PDFF在1年的肝脂肪变性。 AIM 1测试是否干预措施可预防1年肝脂肪变性的增加，并在2年的NAFLD发作时增加。 AIM 2测试与NAFLD相关的基因变异，基线人类学和胰岛素 LFSD对1年肝脂肪变化变化的影响的敏感性修饰符。 AIM 3探索肝脂肪变性和LFSD的生化和脂质代谢机制。在摘要，该试验将为使用免费糖限制的潜力提供证据作为针对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的健康促进的持续和重要影响，减少健康差异，并为儿童的未来预防工作提供了增加的NAFLD风险。