School of Medicine Publications
Document Type
Article
Publication Date
4-13-2026
Abstract
Background: Proprotein convertase subtilisin kexin/type-9 (PCSK-9) regulates cholesterol homeostasis through lysosomal degradation of LDL-R and also acts as a pleiotropic mediator of inflammation. Emerging evidence links PCSK-9 to diabetes pathogenesis. Given the genetic diversity and distinct lifestyle of the Indian population, investigating role of PCSK-9 in Indian type-2 diabetes mellitus (T2DM) patients is crucial. Notably, its association with ApoCIII and chemokines such as CXCL2 and MCP-1 remains unexplored.
Results: A total of 187 participants were included: Heathy control (HC; n = 50), T2DM (n = 49), T2DM with nephropathy (T2DM-N; n = 43), and T2DM with dyslipidaemia (T2DM-DL; n = 45). Plasma PCSK-9, apolipoprotein CIII (ApoCIII), C-X-C motif chemokine ligand 2 (CXCL2), and Monocyte chemoattractant protein-1 (MCP-1) levels were quantified using ELISA. PCSK-9, ApoCIII, CXCL2, and MCP-1 were significantly elevated among diabetic groups when compared to HC subjects. A significant correlation was observed between PCSK-9 and higher levels of ApoCIII, CXCL2, and MCP-1, whereas no such association was observed in HC. Moreover, receiver operating characteristics (ROC) curve analysis demonstrated diagnostic accuracy of the studied biomarkers for predicting diabetes. PCSK-9 showed an area under curve (AUC) of 0.9863 (sensitivity 97%, specificity 100%), CXCL-2 an AUC of 0.9841 (sensitivity 92%, specificity 100%), ApoCIII an AUC of 0.9598 (sensitivity 84%, specificity 96%), and MCP-1 an AUC of 1.00 (sensitivity 100%, specificity 100%).
Conclusion: Elevated PCSK-9 levels showed significant association with ApoCIII, CXCL2, and MCP-1, suggesting a possible interplay between lipid metabolic and inflammatory pathways in T2DM. This study opens new avenues for utilizing PCSK-9 as a non-traditional biomarker in chronic diabetes management, risk stratification, treatment optimization, and personalized medicine. However, to generalize these findings, larger cohorts and multicentric studies are warranted.
Recommended Citation
Waiz, M., Alvi, S. S., Ahmad, P., Sheeha, B. B., Puri, P., Ahmad, I., ... & Khan, M. S. (2026). Prognostic significance and interplay of circulatory PCSK-9–ApoCIII–chemokine axis in type 2 diabetes and its complications: a pilot study in North Indian patients. The Egyptian Journal of Internal Medicine, 38(1), 39. https://doi.org/10.1186/s43162-026-00624-z
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Publication Title
The Egyptian Journal of Internal Medicine
DOI
10.1186/s43162-026-00624-z
Academic Level
faculty
Mentor/PI Department
Immunology and Microbiology
Comments
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.