Lifcourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora Colorado.
Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Colorado.
J Clin Endocrinol Metab. 2020 Sep 1;105(9):e3437-50. doi: 10.1210/clinem/dgaa467.
Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in developed nations. There are currently no accurate biomarkers of NAFLD risk in youth.
Identify sex-specific metabolomics biomarkers of NAFLD in a healthy cohort of youth.
DESIGN/SETTING: This prospective study included 395 participants of the EPOCH cohort in Colorado, who were recruited 2006-2009 ("T1 visit") and followed for 5 years ("T2 visit"). We entered 767 metabolites measured at T1 into a reduced rank regression model to identify the strongest determinants of hepatic fat fraction (HFF) at T2, separately for boys and girls. We compared the capacity of metabolites versus conventional risk factors (overweight/obesity, insulin, alanine transaminase, aspartate transaminase) to predict NAFLD (HFF ≥5%) and high HFF (fourth vs first quartile) using area under the receiver operating characteristic curve (AUC).
Prevalence of NAFLD was 7.9% (8.5% of boys, 7.1% of girls). Mean ± SD HFF was 2.5 ± 3.1%. We identified 13 metabolites in girls and 10 metabolites in boys. Metabolites were in lipid, amino acid, and carbohydrate metabolism pathways. At T1, the metabolites outperformed conventional risk factors in prediction of high HFF but not NAFLD. At T2, the metabolites were superior to conventional risk factors as predictors of high HFF (AUC for metabolites vs conventional risk factors for boys: 0.9565 vs 0.8851, P = 0.02; for girls: 0.9450 vs 0.8469, P = 0.02) with similar trends for NAFLD, although the differences were not significant.
The metabolite profiles identified herein are superior predictors of high HFF when assessed 5 years prior and concurrently in a general-risk setting.
非酒精性脂肪性肝病（NAFLD）是发达国家慢性肝病的主要原因。目前，青少年 NAFLD 风险尚无准确的生物标志物。
确定健康青少年人群中 NAFLD 的性别特异性代谢组学生物标志物。
设计/设置：本前瞻性研究纳入了科罗拉多州 EPOCH 队列的 395 名参与者，他们于 2006-2009 年（“T1 访视”）招募，并随访 5 年（“T2 访视”）。我们将 T1 时测量的 767 种代谢物输入降秩回归模型，以分别确定男孩和女孩 T2 时肝脂肪分数（HFF）的最强决定因素。我们比较了代谢物与传统危险因素（超重/肥胖、胰岛素、丙氨酸转氨酶、天冬氨酸转氨酶）预测 NAFLD（HFF≥5%）和高 HFF（第四四分位与第一四分位）的能力，采用接受者操作特征曲线下面积（AUC）。
NAFLD 的患病率为 7.9%（男孩 8.5%，女孩 7.1%）。平均±SD HFF 为 2.5±3.1%。我们在女孩中鉴定出 13 种代谢物，在男孩中鉴定出 10 种代谢物。代谢物存在于脂质、氨基酸和碳水化合物代谢途径中。在 T1 时，代谢物在预测高 HFF 方面优于传统危险因素，但不能预测 NAFLD。在 T2 时，代谢物作为高 HFF 的预测因子优于传统危险因素（男孩代谢物与传统危险因素的 AUC 为 0.9565 与 0.8851，P=0.02；女孩为 0.9450 与 0.8469，P=0.02），NAFLD 也有类似趋势，但差异无统计学意义。
在一般风险环境中，在评估前 5 年和同期进行评估时，本文确定的代谢物谱是高 HFF 的更好预测因子。
