Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California; Department of Gastroenterology, Rady Children's Hospital, San Diego, California.
Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland; Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland.
Clin Gastroenterol Hepatol. 2023 May;21(5):1261-1270. doi: 10.1016/j.cgh.2022.05.028. Epub 2022 Jun 13.
BACKGROUND & AIMS: Type 2 diabetes (T2D) is a growing problem in children. Children with NAFLD are at potentially high risk for developing T2D; however, the incidence of T2D in this population is unknown. This study aimed to determine the incidence of T2D in children with NAFLD and identify associated risk factors.
Children with NAFLD enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network were followed longitudinally. Incidence of T2D was determined by using clinical history and fasting laboratory values. Cumulative incidence curves were developed for time to T2D. A Cox regression multivariable model was constructed using best subsets Akaike's Information Criteria selection.
This study included 892 children with NAFLD and with a mean age of 12.8 years (2.7) followed for 3.8 years (2.3) with a total 3234 person-years at risk. The incidence rate of T2D was 3000 new cases per 100,000 person-years at risk. At baseline, 63 children had T2D, and during follow-up, an additional 97 children developed incident T2D, resulting in a period prevalence of 16.8%. Incident T2D was significantly higher in females versus males (hazard ratio [HR], 1.8 [1.0-2.8]), associated with BMI z-score (HR, 1.8 [1.0-3.0]), and more severe liver histology including steatosis grade (HR, 1.3 [1.0-1.7]), and fibrosis stage (HR, 1.3 [1.0-1.5]).
Children with NAFLD are at high risk for existing and incident T2D. In addition to known risk factors for T2D (female and BMI z-score), severity of liver histology at the time of NAFLD diagnosis was independently associated with T2D development. Targeted strategies to prevent T2D in children with NAFLD are needed.
2 型糖尿病（T2D）在儿童中日益增多。患有非酒精性脂肪性肝病（NAFLD）的儿童有发生 T2D 的潜在高风险；然而，该人群中 T2D 的发病率尚不清楚。本研究旨在确定患有 NAFLD 的儿童中 T2D 的发病率，并确定相关的危险因素。
在非酒精性脂肪性肝炎临床研究网络中入组的患有 NAFLD 的儿童进行了纵向随访。通过临床病史和空腹实验室值来确定 T2D 的发病率。为 T2D 时间开发了累积发病率曲线。使用最佳子集 Akaike 信息准则选择构建了 Cox 回归多变量模型。
本研究纳入了 892 名患有 NAFLD 的儿童，平均年龄为 12.8 岁（2.7），随访时间为 3.8 年（2.3），总风险人数为 3234 人年。T2D 的发病率为每 10 万人年 3000 例新发病例。基线时有 63 例患有 T2D，随访期间又有 97 例儿童发生 T2D，因此时期患病率为 16.8%。与男性相比，女性的 T2D 发病率明显更高（风险比[HR]，1.8[1.0-2.8]），与 BMI z 分数（HR，1.8[1.0-3.0]）相关，更严重的肝脏组织学包括脂肪变性分级（HR，1.3[1.0-1.7]）和纤维化分期（HR，1.3[1.0-1.5]）。
患有 NAFLD 的儿童既有 T2D 的现有风险，也有 T2D 的发病风险。除了 T2D 的已知危险因素（女性和 BMI z 分数）外，NAFLD 诊断时肝脏组织学的严重程度与 T2D 的发生也独立相关。需要针对患有 NAFLD 的儿童制定预防 T2D 的靶向策略。
