Elevated Serum Cathepsin D Correlates with TNF-α, Insulin, and Myocardial Infarction in Type 2 Diabetes

Abstract

Background: Cathepsin D, a lysosomal enzyme, has a clear role in the metabolic and inflammatory processes associated with conditions such as type 2 diabetes mellitus and myocardial infarction (MI), particularly in the context diabetic complications. Objective: To evaluate serum cathepsin D levels in T2DM patients with MI and assess associations with TNF α, insulin, and other metabolic/inflammatory parameters. Methods: Case-control study: This study included 120 participants divided into three equal groups (40 participants): 40 control groups, 40 individuals with type 2 diabetes and insulin resistance, and 40 individuals with diabetes who had suffered a MI. Results: Cathepsin D levels were significantly elevated in G3 (374 ± 118 ng/L) vs. G2 (291 ± 41.6 ng/L) and G1 (233.6 ± 55.8 ng/L; p < 0.001). Strong positive correlations existed between cathepsin D and TNF-α (r = 0.514, p < 0.05) and insulin (r = 0.554, p < 0.05). ROC analysis indicated high diagnostic accuracy for MI in diabetics: cathepsin D (AUC 0.94, sensitivity 88%, specificity 88%) and TNF-α (AUC 0.93, sensitivity 92%, specificity 80%). All metabolic (RBS, HbA1c%, insulin) and inflammatory markers (CRP, TNF-α) were significantly higher in G2 and G3 vs. G1 (p < 0.001).  Conclusion: Serum cathepsin D is significantly elevated in T2DM patients with MI and correlates strongly with TNF-α and insulin resistance. These findings support its potential as a biomarker for cardiovascular risk stratification in diabetic populations.