Serum IGF-1 and the Risk of Cardio-Kidney Outcomes in Metabolic Dysfunction-Associated Steatotic Liver Disease

초록

Background Metabolic dysfunction-associated steatotic liver disease (MASLD) increases cardiovascular and kidney disease risk. Insulin-like growth factor 1 (IGF-1) regulates metabolic and vascular function, but its role in long-term cardio-kidney outcomes (CKO) in MASLD remains unclear. This study examined the association between MASLD, IGF-1 levels and CKO. Methods In this prospective cohort study, we used data from 214 512 UK Biobank participants without baseline cardiovascular or chronic kidney disease (CKD). Participants were categorized into four groups: no-MASLD and MASLD stratified by age- and sex-specific tertiles of serum IGF-1 (T1-T3). The primary outcome was a composite CKO; secondary outcomes were incident CKD and 3-point major adverse cardiovascular events (3P-MACE). Results Over a median 13-year follow-up, 20 395 CKOs occurred. MASLD increased event rates across all IGF-1 tertiles (p < 0.001), with a significant interaction observed between MASLD and IGF-1 levels (P for interaction = 0.014). In multivariable Cox models, MASLD remained independently associated with CKO risk, strongest in the lowest IGF-1 tertile (T1: adjusted hazards ratio [aHR], 1.24 [95% CI: 1.18-1.30] vs. no-MASLD). Similar trends were observed for incident CKD (T1: aHR, 1.35 [95% CI: 1.22-1.49]) and 3P-MACE (T1: aHR, 1.26 [95% CI: 1.18-1.35]). Subgroup analyses indicated consistent associations across sex, BMI and diabetes, with stronger effects in participants < 65 years and markedly greater CKD risk among those with baseline albuminuria. Conclusion MASLD independently predicted CKO, particularly among individuals with low IGF-1 levels. Incorporating IGF-1 into clinical evaluations may improve risk stratification beyond conventional metabolic factors.

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