Prevention of Pediatric NAFLD in Hispanic Children

摘要 非酒精性脂肪性肝病(NAFLD)是一种与肥胖相关的肝病，影响 据估计，美国有700万儿童。这是肝病最常见的原因。 成人器官移植会增加患糖尿病和心血管疾病的长期风险。 非酒精性脂肪肝对西班牙裔儿童的影响不成比例，是一种特别重要的健康问题 贫富差距。拟议的研究将解决儿童NAFLD的预防问题，因为目前 治疗只有部分有效，而且这种疾病还没有治愈的方法。一种独特的生理学 儿童中存在机会，因为NAFLD在儿童中的发病时间似乎很短， 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给平时的照顾，我们表现出改善肝脏脂肪变性，肝脏 已经患有非酒精性脂肪肝的儿童的炎症和新生脂肪生成率。然而，它 在青春期前儿童中提供低游离糖饮食(LFSD)是否有助于预防 随着年龄的增长进入青春期，肝脏脂肪变性和非酒精性脂肪肝的发病。中央研究支持3个 AIMS是一项为期一年的随机预防试验，对儿童进行为期一年的跟踪观察研究 他们处于青春期前的基线水平，并且是已知的高危人群 非酒精性脂肪肝是因为西班牙裔种族，并且是非酒精性脂肪肝或2型糖尿病的一级亲属。 干预措施将用低糖或不含糖取代典型的高(非乳制品)糖饮料和食物 使用我们既定方法的含糖食品，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)频繁 监控。7-9岁的西班牙裔儿童，Tanner阶段1，他们是NAFLD的高危人群 家族史将随机分为LFSD干预或与接触者匹配的常规护理 几个小时。1年后的主要结果是MRI-PDFF显示的肝脏脂肪变性。AIM 1测试是否 干预可防止1年后肝脏脂肪变性增加和2年后NAFLD发病。 AIM 2检测与NAFLD、基线人体测量学和胰岛素相关的基因变异 LFSD对1年后肝脏脂肪变性影响的敏感性修饰物。《目标3》探索 肝脏脂肪变性和LFSD的生化和脂代谢机制。在……里面 总结，这项试验将产生关于使用游离糖限制的可能性的证据 作为预防NAFLD的一项战略，用于增加NAFLD风险的儿童。调查结果将会有 对西班牙裔儿童健康促进的持续和重大影响，降低健康 在这方面，儿童基金会将继续关注差距，并为今后预防罹患非酒精性脂肪肝风险增加的儿童提供信息。

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.