pFIB scores for paediatric MASLD fibrosis are associated with risk of youth-onset type 2 diabetes in children with obesity

Abstract Aims/hypothesis Youth-onset type 2 diabetes is an aggressive phenotype of metabolic disease, yet tools to identify children with obesity at highest short-term risk are limited. We evaluated whether the paediatric liver fibrosis risk scores (pFIB) pFIB-c and pFIB-6, originally developed for metabolic dysfunction-associated steatotic liver disease (MASLD) fibrosis risk stratification, identify individuals at increased risk of incident type 2 diabetes. Methods A cohort study was conducted using the Swedish Childhood Obesity Treatment Register (BORIS, 2005–2020) linked with national registers, from which type 2 diabetes was ascertained. We included 4856 children with obesity (aged 12.0 years at baseline) and 23,758 general population comparators. The pFIB-c and pFIB-6 scores were calculated as published. Time-to-event analysis yielding HR was performed using Cox regression and flexible parametric survival models. Results Among children with obesity, 12.4% had a pFIB-6 ≥4. A high pFIB-6 score increased the risk for type 2 diabetes at 9–19 years of age (adjusted HR 3.05 [95% CI 2.17, 4.28]). The incidence rate (95% CI) per 10,000 person-years was 1.02 (0.61, 1.72) in the general population comparators, 45.5 (37.8, 54.7) in individuals with obesity and a pFIB-6 <4, and 161.7 (122.2, 213.9) when the pFIB-6 was ≥4. In contrast, neither score, measured at paediatric age, predicted type 2 diabetes risk at 20–25 years of age. Among individual score components, elevated alanine aminotransferase (ALT) and HOMA-IR were most strongly associated with type 2 diabetes risk. In an independent cohort, higher pFIB-6 scores were associated with greater adipose tissue insulin resistance. Conclusions/Interpretation A liver-derived composite risk score identifies a subgroup of adolescents with obesity at markedly increased short-term risk of type 2 diabetes. These findings suggest that integrating hepatic and metabolic variables may improve early risk stratification in paediatric obesity and help identify individuals who may benefit from intensified monitoring during adolescence.