TY - JOUR
T1 - Incidence of Type 2 Diabetes in Children With Nonalcoholic Fatty Liver Disease
AU - Nonalcoholic Steatohepatitis Clinical Research Network
AU - Newton, Kimberly P.
AU - Wilson, Laura A.
AU - Crimmins, Nancy A.
AU - Fishbein, Mark H.
AU - Molleston, Jean P.
AU - Xanthakos, Stavra A.
AU - Behling, Cynthia
AU - Schwimmer, Jeffrey B.
AU - Garner, Donna
AU - Hertel, Paula
AU - Lawson, Alicia
AU - Pham, Yen
AU - Triggs, Nicole
AU - Bramlage, Kristin
AU - Carr, April
AU - McNeill, Meghan
AU - Mouzaki, Marialena
AU - Xanthakos, Stavra
AU - Alazraki, Adina
AU - Cleeton, Rebecca
AU - Cordero, Maria
AU - Karpen, Saul
AU - Vos, Miriam
AU - Carr, Laura
AU - Cummings, Oscar W.
AU - Harlow, Kathryn
AU - Klipsch, Ann
AU - Morlan, Wendy
AU - Ragozzino, Emily
AU - Sawyers, Cindy
AU - Anthony, Angela
AU - Cattoor, Theresa
AU - Freebersyser, Janet
AU - Jain, Ajay K.
AU - Torretta, Susan
AU - Durelle, Janis
AU - Goyal, Nidhi P.
AU - Ugalde-Nicalo, Patricia
AU - Wang, Andrew
AU - Blondet, Niviann
AU - Cooper, Kara
AU - Otto, Randolph
AU - Yeh, Matthew
AU - Young, Melissa
AU - Kleiner, David E.
AU - Doo, Edward C.
AU - Hall, Sherry
AU - Hoofnagle, Jay H.
AU - Sherker, Averell H.
AU - Smith, Michael
N1 - 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:
© 2022 AGA Institute
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - Gender
KW - Hispanic
KW - Obesity
KW - Steatohepatitis
UR - http://www.scopus.com/inward/record.url?scp=85135499014&partnerID=8YFLogxK
U2 - 10.1016/j.cgh.2022.05.028
DO - 10.1016/j.cgh.2022.05.028
M3 - Article
C2 - 35709934
AN - SCOPUS:85135499014
SN - 1542-3565
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
ER -