Abstract
BACKGROUND: The relationships between body size changes and the risk of hypertension and metabolic dysfunction-associated steatotic liver disease (MASLD) are still unclear. This study examined the independent and combined influences of child and adult body size on the risk of adulthood hypertension and MASLD. METHODS: We included 226,420 participants from the UK Biobank who were free of hypertension and liver diseases. Child-to-adult body size categories were identified based on self-reported childhood body size and measured BMI in adulthood. Cox proportional hazard regression models were applied to assess the associations between body size categories and the incidence of hypertension and MASLD. Mediation analyses to address the effect of anthropometric measures and metabolic risk factors were also performed. RESULTS: After a median follow-up of approximately 13 years, 28,662 individuals had developed hypertension (N = 27,624) and/or MASLD (N = 1,692). Low body size in childhood increased the risk of adulthood hypertension and MASLD, regardless of adult body size. Individuals with low child body size and high adult body size exhibited the highest risk for both hypertension (HR 2.01, P < 0.001) and MASLD (HR 3.28, P < 0.001). Individuals who had high child body size but average body size in adulthood had risks of the two diseases that were similar to those of persons who had an average body size consistently (all P > 0.05). Body size changes influenced hypertension through significant natural direct effects and indirect effects via anthropometric and metabolic factors, while their impact on MASLD was primarily mediated by these factors without significant direct effects. CONCLUSIONS: Childhood leanness exacerbates the risk of hypertension and MASLD in adulthood. Within the follow-up period, normal adult body size would mitigate the detrimental effects of childhood obesity. Thus, attention should be given to reinforcing weight management in children by implementing evidence-based strategies.