Association of serum galectin-3 levels and LGALS3 gene expression across albuminuria categories in patients with type 2 diabetes mellitus: A cross-sectional study

Abstract

Diabetic kidney disease (DKD) remains the leading cause of end-stage kidney disease worldwide because conventional markers, such as urinary albumin and the estimated glomerular filtration rate, are not sensitive enough to detect renal stress until significant damage has occurred. Galectin-3 (Gal-3), a β-galactoside-binding lectin encoded by the galectin-3 (LGALS3) gene, is implicated in renal fibrosis, macrophage-driven inflammation, and advanced glycation end-product signaling, making it a biologically plausible candidate biomarker.Methods. This cross-sectional study enrolled 90 adults with type 2 diabetes mellitus (T2DM), stratified by urinary albumin-to-creatinine ratio (UACR) into A1 (UACR < 30 mg/g), A2 (UACR 30–300 mg/g), and A3 (UACR > 300 mg/g) categories (n = 30 each), along with 30 age- and sex-matched healthy controls. Serum Gal-3 was measured by sandwich enzyme-linked immunosorbent assay (ELISA), and LGALS3 messenger RNA expression in peripheral blood mononuclear cells (PBMCs) was quantified by reverse transcription quantitative polymerase chain reaction. Discriminative performance was assessed using receiver operating characteristic (ROC) analysis, and the independent statistical association of Gal-3 was evaluated using multivariate logistic regression.Results. Serum Gal-3 was significantly elevated in normoalbuminuric T2DM patients compared to that in healthy controls (21.2 ± 3.6 vs 17.6 ± 3.8 ng/mL; p = 0.003) and rose progressively across albuminuria categories (A1 to A3; one-way analysis of variance [ANOVA] p < 0.001). The LGALS3 mRNA expression increased simultaneously. Serum Gal-3 showed good cross-sectional discriminative ability for any category of albuminuria A2/A3 vs A1; area under the curve 0.84, 95% CI 0.77–0.91, and remained independently associated with albuminuria after multivariate adjustment (odds ratio 1.42 per ng/mL; 95% CI 1.18–1.71; p < 0.001).Conclusion. Serum Gal-3 and LGALS3 expression levels are significantly associated with albuminuria in T2DM and may serve as complementary markers. However, future longitudinal validation studies are required to establish whether Gal-3 has a predictive value for the progression of diabetic kidney disease.