Circulating biomarkers in glucose dysregulation: impact of age adjustment on NGAL, FGF23, SCUBE-1, cystatin C, and MMP-9

Abstract Objectives Diabetes and prediabetes are associated with metabolic, inflammatory, and vascular alterations that may contribute to chronic complications. The objective of this study was to investigate whether circulating biomarkers reflecting inflammation, endothelial dysfunction, and extracellular matrix remodeling (NGAL, FGF23, SCUBE-1, cystatin C, and MMP-9) are altered across the spectrum of glucose dysregulation, and to evaluate their relationship with urinary albumin-to-creatinine ratio (UACR), a widely used clinical marker of renal involvement. Methods This cross-sectional study included 84 participants: 28 with type 2 diabetes mellitus, 28 with prediabetes, and 28 healthy controls. Serum biomarker levels were measured using ELISA. Because baseline age differed among groups, ANCOVA was performed to adjust for age. Results In unadjusted analyses, FGF23 (p=0.007) and SCUBE-1 (p=0.002) levels were higher in both dysglycemic groups than in controls, and MMP-9 levels increased progressively across groups (p<0.001). NGAL and cystatin C levels did not differ significantly. After age adjustment, only MMP-9 remained significant (p<0.001), whereas FGF23 (p=0.110) and SCUBE-1 (p=0.071) lost significance. No significant associations were found between UACR and any biomarkers. Conclusions After adjustment for age, only MMP-9 remained significantly associated with the spectrum of glucose dysregulation (p<0.001), whereas the apparent associations observed for FGF23 and SCUBE-1 were attenuated and lost statistical significance. These findings suggest that extracellular matrix remodeling, reflected by circulating MMP-9 levels, may represent an early age-independent biological process associated with dysglycemia.