Increased Risk for Type 2 Diabetes Among Adolescents With Fatty Liver

This study evaluated risk for type 2 diabetes among more than 1 million adolescents in Israel with and without nonalcoholic fatty liver disease.

Among adolescents with normal glucose levels, evidence of nonalcoholic fatty liver disease (NAFLD) is associated with an approximately 3-fold increased risk for type 2 diabetes (T2D) in young adulthood, according to study results published in the Journal of Clinical Endocrinology and Metabolism.

Previous studies have provided variable rates of T2D in youths diagnosed with NAFLD. The objective of the current study was to determine the long-term risk for T2D among adolescents with NAFLD.

The nationwide, population-based study included more than 1 million adolescents from Israel, who were examined before military service during 1997 to 2011 and had normal glucose levels. Investigators followed all participants until December 31, 2016, for a mean duration follow-up of 10.9 plus or minus 3.9 years in the NAFLD group vs 13.3 plus or minus 4.3 years in the control group.

The study sample included 633 participants (81.8% men; mean age, 17.5±0.5 years) with a diagnosis of NAFLD according to a biopsy or radiographic tests. The control group included 1,025,163 participants (56.8% men; mean age, 17.3±0.5 years) without NAFLD.

During follow-up, 12 (1.9%) of 633 patients with NAFLD were diagnosed with T2D compared with 2917 (0.3%) control participants (adjusted hazard ratio [aHR] 10.4; 95% CI, 5.9-18.3). The observed association was limited to adolescents who were overweight and obese, as all patients with NAFLD and diabetes had high body mass index (BMI) at baseline. After further adjustment for BMI, the risk for T2D was attenuated (aHR 2.5; 95% CI, 1.4-4.4).

The increased risk for T2D associated with NAFLD remained consistent in an analysis that included only adolescents without dyslipidemia or hypertension (aHR 2.8; 95% CI, 1.5-5.1).

To better temporally explore the association between adolescent NAFLD and T2D, the outcome was set as T2D onset by age 30 years. The analysis revealed the risk for T2D by age 30 years remained elevated for adolescents with NAFLD (aHR 2.1; 95% CI, 1.02-4.53).

Compared with a sex-, birth year-, and baseline BMI-matched control group, the risk for incident T2D was 3-fold greater among patients with high BMI and NAFLD (aHR 3; 95% CI, 1.5-5.7).

The study had several limitations, including lack of laboratory or radiographic systematic screening for NAFLD; use of self-reported data on alcohol consumption, which made it impossible to exclude some NAFLD cases that were, in fact, alcoholic steatohepatitis; unavailable detailed histopathology and imaging data; missing lifestyle data that can affect risk for NAFLD and T2D; and relatively limited sample size.

“In the absence of effective pharmaceutical treatment for NAFLD, these findings emphasize the importance of aggressive reduction of other risk factors, especially excessive BMI, together with promotion of physical exercise and tight medical follow-up starting at youth,” concluded the researchers.


Bardugo A, Bendor CD, Zucker I, et al. Adolescent nonalcoholic fatty liver disease and type 2 diabetes in young adulthood. Published online Oct 19, 2020. J Clin Endocrinol Metab. doi: 10.1210/clinem/dgaa753