#767 Sarcopenia-related markers derived from creatinine and cystatin C, GDF-15 and adverse outcomes in people with diabetes

Abstract Background and Aims Protein catabolism and chronic inflammation are key drivers of sarcopenia and frailty in individuals with diabetes and chronic kidney disease (CKD). The difference between cystatin C-based and creatinine-based estimated glomerular filtration rates (eGFRcys and eGFRcr, respectively), termed eGFRdiff, along with growth differentiation factor-15 (GDF-15), have emerged as promising markers of metabolic and inflammatory dysregulation. Lower eGFRdiff and elevated GDF-15 levels are associated with sarcopenia, frailty, CKD progression and mortality. However, the interplay between eGFRdiff and GDF-15 and their respective impacts on adverse outcomes, such as a kidney event and mortality in diabetes, remains unclear. Method A total of 638 Japanese individuals with diabetes were stratified into tertiles based on eGFRdiff. Serum GDF-15 levels were measured using enzyme-linked immunosorbent assays. Spearman's correlation coefficients were used to assess relationships between eGFRdiff, GDF-15 and kidney function markers, including eGFRcr, eGFRcys and the urinary albumin-to-creatinine ratio (UACR). Multivariate ordered logistic regression was used to evaluate the association between eGFRdiff and GDF-15. Cox proportional hazards models with restricted cubic splines, adjusted for confounders, were used to examine associations of eGFRdiff and GDF-15 with adverse outcomes, including a kidney event (≥30% decline in eGFRcr), mortality and composite outcomes. Results The mean age of patients was 65 years and 53.9% were male. Over a median follow-up of 5.4 years, 75 patients (11.8%) experienced a kidney event, 44 (6.9%) died and 112 (17.6%) reached composite outcomes. GDF-15 was weakly but significantly negatively correlated with eGFRdiff (r = –0.35). Both markers showed weak-to-moderate correlations with kidney function markers: eGFRcr (GDF-15: r = –0.26; eGFRdiff: r = –0.14), eGFRcys (GDF-15: r = –0.45; eGFRdiff: r = 0.54) and UACR (GDF-15: r = 0.28; eGFRdiff: r = –0.23). Multivariate regression confirmed an independent inverse association between eGFRdiff and GDF-15. Lower eGFRdiff and higher GDF-15 levels independently predicted adverse outcomes after adjustment for clinical variables. Conclusion Both eGFRdiff and GDF-15 were independently associated with adverse outcomes in individuals with diabetes. Although eGFRdiff was more strongly linked to a kidney event, GDF-15 showed a stronger association with mortality. These findings underscore the potential utility of these markers in risk stratification for diabetes-related complications.