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J Nephropathol. Inpress.
doi: 10.34172/jnp.2025.27638
  Abstract View: 30

Original Article

Serum cathepsin D as a biomarker for vascular atherosclerosis in patients with diabetes mellitus; a case-control study

Israa Saad Salim* ORCID logo, Walaa Esmail Jasim ORCID logo, Ahmed Saadi Hassan ORCID logo

1 Department of Medical Laboratory Technology, College of Health and Medical Technology, Middle Technical University, Baghdad, Iraq
*Corresponding Author: Israa Saad Salim, Email: asosaad66@gmail.com

Abstract

Introduction: Diabetes mellitus represents a significant global health burden, with affected individuals facing a markedly increased risk of vascular disease. Atherosclerosis, the primary pathological process underlying most cardiovascular events, develops earlier and progresses more rapidly in diabetic patients compared to the general population. The identification of novel biomarkers for early atherosclerosis detection in diabetes remains a critical unmet need in preventive vascular diseases.

Objectives: This study aimed to evaluate the potential utility of cathepsin D as a biomarker for early atherosclerosis detection in diabetic patients.

Patients and Methods: This case-control study, conducted at Ghazi Al-Hariri hospital in Baghdad from February to July 2024, included 100 diabetic patients with vascular atherosclerosis and 50 healthy controls. Demographic and clinical data were collected through interviews and medical records, while blood samples were processed to measure serum cathepsin D and lipid profiles. The study outcomes were assessing the association between cathepsin D levels and the presence and severity of vascular atherosclerosis in diabetic patients, as well as evaluating the diagnostic accuracy of cathepsin D for identifying and stratifying atherosclerotic risk.

Results: The results demonstrated that higher cathepsin D concentrations were significantly associated with increased odds of vascular atherosclerosis in diabetic patients, with an unadjusted and adjusted odds ratio (OR) of 2.08 and 1.71, respectively. In terms of diagnostic utility, cathepsin D showed excellent discriminatory accuracy for identifying vascular atherosclerosis, with an area under the curve (AUC) of 0.940 (95% CI: 0.903–0.978). At a cut-off value of 9.45 ng/mL, cathepsin D achieved a sensitivity of 91% and specificity of 84%. Additionally, cathepsin D levels increased in parallel with the severity of atherosclerosis; diabetic patients at low, moderate, and high risk exhibited progressively higher mean concentrations, with all group differences reaching statistical significance.

Conclusion: In conclusion, the results demonstrated that elevated cathepsin D levels are significantly and independently associated with both the presence and severity of vascular atherosclerosis in diabetic patients. Cathepsin D also shows strong diagnostic accuracy, highlighting its potential as a valuable biomarker for early detection and risk assessment of vascular complications in this population.



Implication for health policy/practice/research/medical education:

This study establishes serum cathepsin D as a clinically relevant biomarker for vascular atherosclerosis in diabetic patients, demonstrating an independent association with atherosclerotic risk and progression. The findings highlight cathepsin D’s strong diagnostic accuracy in distinguishing diabetic individuals with atherosclerosis, supported by its capacity to reflect disease severity through stepwise elevation across low-, moderate-, and high-risk subgroups. Clinically, cathepsin D measurement could enhance early atherosclerosis detection in diabetes, enabling timely risk stratification and personalized interventions to mitigate cardiovascular morbidity. While further validation is needed, these results position cathepsin D as both a prognostic tool and a gateway to novel therapeutic approaches in diabetes-related cardiovascular disease (CVD).

Please cite this paper as: Salim IS, Jasim WE, Hassan AS. Serum cathepsin D as a biomarker for vascular atherosclerosis in patients with diabetes mellitus; a case-control study. J Nephropathol. 2025;x(x):e27638. DOI: 10.34172/jnp.2025.27638.

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Submitted: 02 Mar 2025
Revision: 21 Apr 2025
Accepted: 02 Nov 2025
ePublished: 01 Dec 2025
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