ESPE Yearbook of Paediatric Endocrinology

Diabetes Care. 2024 Dec 1;47(12):2196-2204. doi: 10.2337/dc24-1236

Brief Summary: Using data from >10,000 children in the Swedish Childhood Obesity Treatment Register (BORIS) and >59,000 general population comparators, the authors found that metabolic dysfunction–associated steatotic liver disease (MASLD, formerly known as NAFLD) in children with obesity increases the risk of youth-onset T2D. MASLD was associated with a 2.7-fold increased risk of developing T2D, independent of other risk factors. Notably, the combination of MASLD and dysglycemia had a synergistic effect, conferring a 9-fold increased risk. Importantly, a reduction in BMI SDS through obesity treatment significantly reduced this risk in individuals who responded to treatment.

Comment: MASLD and T2D are strongly associated in adults, with each condition increasing the risk of the other; the prevalence of MASLD exceeds 70% among people with T2D, and MASLD is a major predictor for the development of T2D, with a twofold higher incidence of diabetes observed in those with MASLD. Overweight, obesity, and insulin resistance are key shared risk factors. The risk of developing diabetes rises in parallel with the severity of hepatic steatosis and fibrosis, and improvement or resolution of MASLD is associated with a reduction in diabetes risk. Both conditions are driven by insulin resistance, adipose tissue dysfunction, and chronic low-grade inflammation, which promote hepatic lipid accumulation, mitochondrial dysfunction, and hepatocellular injury. The coexistence of MASLD and T2D amplifies the risk of both liver-related and extrahepatic complications, including cardiovascular disease and malignancy.

Similarly, this study now provides compelling longitudinal data linking pediatric MASLD to a markedly higher risk of youth-onset T2D, especially when coupled with non-diabetes range dysglycemia. Because youth-onset T2Dis a generally more aggressive disease than in adults, and since MASLD is at higher risk for progression in adolescents than adults, early identification and integrated management of these metabolic perturbations and others (renal hyperfiltration, OSA, dyslipidemia, polycystic ovary syndrome etc.) should be standard practice in pediatric obesity and diabetes care to prevent full-blown metabolic decompensation.

Key Message: Routine identification and management of MASLD should be standard practice in pediatric obesity care, as it identifies children at highest risk of youth-onset T2D, other metabolic dysfunction, and long-term cardiorenal disease.

References: 1. Cusi K, Abdelmalek MF, Apovian CM, et al. Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in People With Diabetes: The Need for Screening and Early Intervention. A Consensus Report of the American Diabetes Association. Diabetes Care. 2025;48(7):1057-1082. doi: 10.2337/dci24-0094.2. Comprehensive Medical Evaluation and Assessment of Comorbidities: Standards of Care in Diabetes-2025. Diabetes Care. 2025;48(Supplement_1):S59-S85. doi: 10.2337/dc25-S004.3. Qi X, Li J, Caussy C, Teng GJ, Loomba R. Epidemiology, Screening, and Co-Management of Type 2 Diabetes Mellitus and Metabolic Dysfunction-Associated Steatotic Liver Disease. Hepatology (Baltimore, Md.). 2024;:01515467-990000000-00875. doi: 10.1097/HEP.0000000000000913.4. Duell PB, Welty FK, Miller M, et al. Nonalcoholic Fatty Liver Disease and Cardiovascular Risk: A Scientific Statement From the American Heart Association. Arteriosclerosis, Thrombosis, and Vascular Biology. 2022;42(6):e168-e185. doi: 10.1161/ATV.0000000000000153.