Serum sLOX-1 and 25-Hydroxyvitamin D3 Across the Glycemic Spectrum: Associations with Metabolic and Microvascular Parameters in Prediabetes and Type 2 Diabetes

Background/Objectives: Oxidative endothelial injury and vitamin D deficiency have independently been implicated in diabetic vascular complications, yet their distribution across the glycemic spectrum, from normoglycemia through prediabetes to established type 2 diabetes, has not been systematically characterised. This study aimed to evaluate serum soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) and 25-hydroxyvitamin D3 [25(OH)D3] levels across the glycemic spectrum and to examine their associations with microvascular complications and metabolic parameters in prediabetic individuals and patients with type 2 diabetes mellitus (T2DM). Methods: In this prospectively recruited cross-sectional study, 80 adults were enrolled: 26 healthy controls, 27 prediabetic individuals, and 27 T2DM patients. Serum sLOX-1 was quantified by enzyme-linked immunosorbent assay (ELISA) and 25(OH)D3 by liquid chromatography–tandem mass spectrometry (LC-MS/MS). Between-group comparisons were performed using the Kruskal–Wallis test with Dunn’s post hoc correction. Spearman’s rank correlation and binary logistic regression were applied to examine associations with metabolic and microvascular parameters. Results: Serum sLOX-1 was significantly elevated in both prediabetic (median 10.75 ng/mL; p = 0.0397) and T2DM (8.83 ng/mL; p = 0.0209) groups compared to controls (3.50 ng/mL) in unadjusted analyses. After adjustment for age and body mass index (BMI) by quantile regression, the elevation persisted in the prediabetic group (adjusted ratio of medians = 2.91, p = 0.040) but was substantially attenuated and no longer significant in the T2DM group (ratio = 1.81, p = 0.265). Serum 25(OH)D3 was significantly lower in the T2DM group than in prediabetic individuals (12.11 vs. 22.69 ng/mL; p = 0.0024) but did not decline progressively across the glycemic spectrum; vitamin D deficiency (<20 ng/mL) was present in 78% of T2DM patients. In binary logistic regression (five predictors, events per variable (EPV) = 5.4), 25(OH)D3 (odds ratio (OR) = 0.922, p = 0.020) and log-transformed urinary albumin-to-creatinine ratio (logUACR; OR = 4.014, p = 0.001) were independently associated with T2DM status after adjustment for age and waist circumference, while sLOX-1 was not significant (OR = 1.058, p = 0.136). In unadjusted analyses, sLOX-1 correlated positively with waist circumference and glycated hemoglobin (HbA1c); both associations were no longer statistically significant after age adjustment. Conclusions: These findings show that sLOX-1 is elevated at the prediabetic stage independently of age and BMI, whereas the elevation in established T2DM was not robust to covariate adjustment. Lower 25(OH)D3 concentrations were associated with T2DM status in logistic regression, but this association was not significant when the reference group was restricted to normoglycaemic controls, indicating that the finding reflects the contrast between T2DM and prediabetic groups rather than a generalised pattern across the glycaemic spectrum. The two biomarkers were not significantly correlated with one another. Given the cross-sectional design, low EPV, and exploratory nature of all analyses, prospective validation in larger age-matched cohorts is required.