Adolescent nonalcoholic fatty liver disease and type 2 diabetes in young adulthood

Aya Bardugo, Cole D. Bendor, Inbar Zucker, Miri Lutski, Tali Cukierman-Yaffe, Estela Derazne, Ofri Mosenzon, Dorit Tzur, Zivan Beer, Orit Pinhas-Hamiel, Michal Ben-Ami, Boris Fishman, Dana Ben-Ami Shor, Itamar Raz, Arnon Afek, Hertzel C. Gerstein, Hans Ulrich Häring, Amir Tirosh, Zohar Levi, Gilad Twig

Research output: Contribution to journalArticlepeer-review


Context: The long-term risk of type 2 diabetes in adolescents with nonalcoholic fatty liver disease (NAFLD) is unclear. Objective: To assess type 2 diabetes risk among adolescents with NAFLD. Design and Setting: A nationwide, population-based study of Israeli adolescents who were examined before military service during 1997-2011 and were followed until December 31, 2016. Participants: A total of 1 025 796 normoglycemic adolescents were included. Interventions: Biopsy or radiographic tests were prerequisite for NAFLD diagnosis. Data were linked to the Israeli National Diabetes Registry. Main Outcome Measures: Type 2 diabetes incidence. Results: During a mean follow-up of 13.3 years, 12 of 633 adolescents with NAFLD (1.9%; all with high body mass index [BMI] at baseline) were diagnosed with type 2 diabetes compared with 2917 (0.3%) adolescents without NAFLD. The hazard ratio (HR) for type 2 diabetes was 2.59 (95% confidence interval [CI], 1.47-4.58) for the NAFLD vs. the non-NAFLD group after adjustment for BMI and sociodemographic confounders. The elevated risk persisted in several sensitivity analyses. These included an analysis of persons without other metabolic comorbidities (adjusted HR, 2.75 [95% CI, 1.48-5.14]) and of persons with high BMI; and an analysis whose outcome was type 2 diabetes by age 30 years (adjusted HR, 2.14 [95% CI, 1.02-4.52]). The results remained significant when a sex-, birth year-, and BMI-matched control group was the reference (adjusted HR, 2.98 [95% CI, 1.54-5.74]). Conclusions: Among normoglycemic adolescents, NAFLD was associated with an increased adjusted risk for type 2 diabetes, which may be apparent before age 30 years.

Original languageEnglish
Pages (from-to)E34-E44
JournalJournal of Clinical Endocrinology and Metabolism
Issue number1
StatePublished - 1 Jan 2021


  • Adolescence
  • Adolescent
  • Non-alcoholic fatty liver disease
  • Type 2 diabetes
  • Young adults


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