Low IGF-1 levels amplify cardio-kidney risk in MASLD patients, UK Biobank data shows

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global health concern, strongly linked to increased risk of cardiovascular disease (CVD) and chronic kidney disease (CKD). Despite its prevalence, the precise mechanisms driving these cardio-kidney outcomes (CKO) in MASLD patients are not fully understood, and current risk stratification methods may be insufficient. Insulin-like growth factor 1 (IGF-1) plays a crucial role in metabolic regulation and vascular function, but its long-term association with CKO in MASLD has remained unclear, representing a critical gap in understanding disease progression.

This prospective cohort study utilized data from 214,512 UK Biobank participants who were free of baseline cardiovascular or chronic kidney disease. Participants were categorized into four groups: no-MASLD and MASLD, further stratified by age- and sex-specific tertiles of serum IGF-1 (T1-T3, representing lowest to highest levels). The primary outcome was a composite CKO, while secondary outcomes included incident CKD and 3-point major adverse cardiovascular events (3P-MACE). Data was collected over a median 13-year follow-up period, and multivariable Cox models were used to assess associations.

Over a median 13-year follow-up, 20,395 composite cardio-kidney outcomes (CKOs) were recorded. MASLD significantly increased event rates across all IGF-1 tertiles (p < 0.001), with a notable interaction observed between MASLD status and IGF-1 levels (P for interaction = 0.014). In multivariable Cox models, MASLD remained independently associated with CKO risk, with the strongest association found in the lowest IGF-1 tertile (T1).