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. 2023 May;21(5):1261-1270.
doi: 10.1016/j.cgh.2022.05.028. Epub 2022 Jun 13.

Incidence of Type 2 Diabetes in Children With Nonalcoholic Fatty Liver Disease

Kimberly P Newton  1 , Laura A Wilson  2 , Nancy A Crimmins  3 , Mark H Fishbein  4 , Jean P Molleston  5 , Stavra A Xanthakos  6 , Cynthia Behling  7 , Jeffrey B Schwimmer  8 ; Nonalcoholic Steatohepatitis Clinical Research Network
Collaborators, Affiliations

Incidence of Type 2 Diabetes in Children With Nonalcoholic Fatty Liver Disease

Kimberly P Newton et al. Clin Gastroenterol Hepatol. 2023 May.

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.

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Conflict of interest statement

Conflict of Interest Disclosures:

Kimberly P. Newton MD: No conflicts of interest to disclose.

Laura Wilson ScM: No conflicts of interest to disclose.

Nancy A. Crimmins MD, MS: No conflicts of interest to disclose.

Mark Fishbein MD: No conflicts of interest to disclose.

Jean Molleston MD: Research involvement with Gillead, 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. Consultant for Merck.

Figures

Figure 1.
Figure 1.. Flow diagram showing participants evaluated and included in study
Figure 2.
Figure 2.. Cumulative incidence of type 2 diabetes
Cumulative incidence curves of type 2 diabetes over 10 years by (A) sex, (B) steatosis grade < 33% versus ≥ 33%, (C) lobular inflammation grade 0–4 versus > 4, (D) ballooning grade none/few versus many, (E) Not NASH/borderline versus definite NASH, and (F) fibrosis stage < 2 versus fibrosis stage 2–4.
See this image and copyright information in PMC

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