Abstract
BACKGROUND: Soluble CD36 (sCD36), the circulating form of the scavenger receptor CD36, plays a key role in lipid accumulation and inflammation during the progression of diabetic kidney disease (DKD), and has been proposed as a promising non-invasive biomarker. The renoprotective effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) may involve modulation of sCD36. This study aimed to evaluate the impact of GLP-1RA and insulin treatment on sCD36 levels and their association with renal function in DKD patients. METHODS: This single-center, prospective observational cohort study enrolled 191 patients with type 2 diabetes and early-stage DKD, who were stratified into three groups based on treatment regimen: control group (n = 63), insulin group (n = 71), and GLP-1RA group (n = 57). All patients received standard care with metformin, with the insulin and GLP-1RA groups receiving additional respective treatments for 12 weeks. Clinical parameters including sCD36, urinary albumin-to-creatinine ratio (UACR), lipid profile, glycemic markers, and islet function indices were assessed at baseline and post-treatment. Intra- and inter-group comparisons were performed using paired tests and analysis of covariance. Generalized linear regression models were applied to assess the relationship between sCD36 and renal function. RESULTS: Baseline sCD36 and UACR levels were comparable across the three groups (P > 0.05). After 12 weeks, sCD36 levels significantly declined in the GLP-1RA group (median: 195.20 ng/mL, IQR: 160.45-314.75), compared to the insulin group (364.60 ng/mL, IQR: 279.10-394.10) and control group (386.10 ng/mL, IQR: 323.60-471.30) (P < 0.001). The GLP-1RA group also showed the most marked reduction in UACR (P < 0.001). Regression analysis demonstrated a significant positive association between sCD36 and UACR levels both before and after treatment (P < 0.001), and the change in sCD36 (ΔsCD36) was positively correlated with the improvement in UACR, suggesting a link to reduced renal lipotoxicity and inflammation. CONCLUSION: GLP-1RAs significantly reduce sCD36 and UACR levels in patients with early DKD, outperforming insulin in renoprotection. These findings raise the possibility that GLP-1RAs may exert renoprotective effects through modulation of CD36-related pathways, although direct mechanistic validation was not performed in this study.sCD36 may serve as a useful biomarker for monitoring DKD progression and therapeutic response, though further multicenter and long-term studies are needed to confirm its clinical utility.