@article{0eb4fc5abf3048bab292271eec66095b,
title = "Incidence of Type 2 Diabetes in Children With Nonalcoholic Fatty Liver Disease",
abstract = "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. Methods: 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. Results: 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]). Conclusions: 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.",
keywords = "Gender, Hispanic, Obesity, Steatohepatitis",
author = "{Nonalcoholic Steatohepatitis Clinical Research Network} and Newton, {Kimberly P.} and Wilson, {Laura A.} and Crimmins, {Nancy A.} and Fishbein, {Mark H.} and Molleston, {Jean P.} and Xanthakos, {Stavra A.} and Cynthia Behling and Schwimmer, {Jeffrey B.} and Donna Garner and Paula Hertel and Alicia Lawson and Yen Pham and Nicole Triggs and Kristin Bramlage and April Carr and Meghan McNeill and Marialena Mouzaki and Stavra Xanthakos and Adina Alazraki and Rebecca Cleeton and Maria Cordero and Saul Karpen and Miriam Vos and Laura Carr and Cummings, {Oscar W.} and Kathryn Harlow and Ann Klipsch and Wendy Morlan and Emily Ragozzino and Cindy Sawyers and Angela Anthony and Theresa Cattoor and Janet Freebersyser and Jain, {Ajay K.} and Susan Torretta and Janis Durelle and Goyal, {Nidhi P.} and Patricia Ugalde-Nicalo and Andrew Wang and Niviann Blondet and Kara Cooper and Randolph Otto and Matthew Yeh and Melissa Young and Kleiner, {David E.} and Doo, {Edward C.} and Sherry Hall and Hoofnagle, {Jay H.} and Sherker, {Averell H.} and Rebecca Torrance",
note = "Funding Information: Funding The Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), United States (grants U01DK061713, U01DK061718, U01DK061728, U01DK061731, U01DK061732, U01DK061734, U01DK061737, U01DK061738, U01DK061730, U24DK061730). Additional support is received from the National Center for Advancing Translational Sciences (NCATS), United States (grants UL1TR000439, UL1TR000077, UL1TR000436, UL1TR000150, UL1TR000424, UL1TR000006, UL1TR000448, UL1TR000040, UL1TR000100, UL1TR000004, UL1TR000423, UL1TR000058, UL1TR000454). TONIC: The TONIC trial was conducted by the NASH CRN and supported in part by the Intramural Research Program of the National Cancer Institute, United States and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, United States. The vitamin E and matching placebo were provided by Pharmavite through a Clinical Trial Agreement with the NIH. CyNCh: The CyNCh trial was conducted by the NASH CRN, United States and supported in part by the Intramural Research Program of the National Cancer Institute and by a Collaborative Research and Development Agreement (CRADA), United States between NIDDK and Raptor Pharmaceuticals. Conflicts of interest These authors disclose the following: Jean P. Molleston, MD: research involvement with Gilead, Mirum, Albireo, AbbVie, and Cystic Fibrosis Foundation, not related to current project. Stavra A. Xanthakos, MD: research funding from TargetRWE and Axcella Health, not related to current project; consultant for Intercept Pharmaceuticals related to pediatric NAFLD trials/treatment. Cynthia Behling MD, PhD: consultant for Pfizer. Jeffrey B. Schwimmer, MD: research grants to UC San Diego from Intercept Pharmaceuticals, Genfit, Seraphina Therapeutics; and consultant for Merck. The remaining authors disclose no conflicts. Funding Information: Funding The Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN ) is supported by the National Institute of Diabetes and Digestive and Kidney Diseases ( NIDDK ), United States (grants U01DK061713, U01DK061718, U01DK061728, U01DK061731, U01DK061732, U01DK061734, U01DK061737, U01DK061738, U01DK061730, U24DK061730). Additional support is received from the National Center for Advancing Translational Sciences ( NCATS ), United States (grants UL1TR000439, UL1TR000077, UL1TR000436, UL1TR000150, UL1TR000424, UL1TR000006, UL1TR000448, UL1TR000040, UL1TR000100, UL1TR000004, UL1TR000423, UL1TR000058, UL1TR000454). TONIC: The TONIC trial was conducted by the NASH CRN and supported in part by the Intramural Research Program of the National Cancer Institute, United States and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, United States. The vitamin E and matching placebo were provided by Pharmavite through a Clinical Trial Agreement with the NIH. CyNCh: The CyNCh trial was conducted by the NASH CRN, United States and supported in part by the Intramural Research Program of the National Cancer Institute and by a Collaborative Research and Development Agreement (CRADA), United States between NIDDK and Raptor Pharmaceuticals. Publisher Copyright: {\textcopyright} 2022 AGA Institute",
year = "2022",
doi = "10.1016/j.cgh.2022.05.028",
language = "English (US)",
journal = "Clinical Gastroenterology and Hepatology",
issn = "1542-3565",
publisher = "W.B. Saunders Ltd",
}