Association of circulatory PCSK-9 with biomarkers of redox imbalance and inflammatory cascades in the prognosis of diabetes and associated complications: a pilot study in the Indian population

Abstracts

Besides the profound role of proprotein convertase subtilisin/kexin type-9 (PCSK-9) in LDL-C regulation, its association with other metabolic complications cannot be disregarded. The co-existence of redox imbalance and inflammatory cascades has greatly reflected the etiology of hyperglycemia. Therefore, we studied the association of PCSK-9 with inflammation and oxidative stress biomarkers to predict its role in the prognosis of diabetes and its associated complications in the Indian population. This pilot study examined a total of n = 187 subjects: healthy controls (HC; n = 50), diabetic without complication (T2DM; n = 49), diabetic nephropathy (T2DM-N; n = 43), and diabetic dyslipidemic (T2DM-DL; n = 45) subjects. The relationship between circulatory PCSK-9 levels and inflammation and redox imbalance biomarkers has been explored. The significant positive association of elevated PCSK-9 level with the inflammatory (i.e. IL-1β, IL-6, TNF-α, and CRP) and oxidative stress marker (i.e. XOD, CD, LOOH, and MDA) was observed in T2DM-N and T2DM-DL subjects. Whereas single regression analysis depicted that PCSK-9 was inversely associated with the FRAP and PON-1 in T2DM-N and T2DM-DL subjects. Furthermore, no significant correlation was detected in both T2DM and HC subjects. We found a significant relationship between these prognostic biomarkers with an elevated level of PCSK-9 in T2DM-N and T2DM-DL subjects. PCSK-9 is a nontraditional biomarker in diabetes that may help identify patients at risk of developing secondary complications of diabetes in the Indian population. However, further large cohort validation studies are needed.

Keywords:

• PCSK-9
• diabetes mellitus and complications
• cytokines: IL-1 and IL-6
• PON-1 and XOD activity
• inflammation
• oxidative stress

Acknowledgments

The authors thank Prof. S.W. Akhtar, Honourable Chancellor, Integral University and IIMS&R, for providing the state-of-the-art research laboratory necessary for this work. The manuscript communication number (MCN) of this manuscript is IU/R&D/2023-MCN0002025, provided by Integral University.

Author contributions

Experimental hypothesis: M.S.K.; anthropometric and biochemical analysis: M.W. & S.S.A.; data analysis: M.W. & S.S.A.; figure & table preparation: M.W. & S.S.A.; manuscript writing: S.S.A. & M.W.; statistical analysis: M.W. & S.S.A.; revision & English editing: M.S.K. & S.S.A.

Ethical approval

The current clinical study was approved by the Institutional Ethical Committee, Integral Institute of Medical Sciences and Research (IIMS & R), Lucknow, U.P., India (Approval no. IEC/IIMS&R/2017/38).

Patient consent

All the participants of this study were aware of all the procedures and aims, and written informed consent was obtained from all participants.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

All the data supporting the findings are included in the article.

Additional information

Funding

The Authors are thankful to DST for infrastructural support to the Department of Biosciences, Integral University under the DST-FIST program, and the University Internal Grant (BRTF) of the Department of Biosciences for partially supporting this work. We are also thankful to the DHR, Ministry of Health & Family Welfare (MoHFW), Govt. of India for granting Young Scientist Fellowship to Dr. Sahir Sultan Alvi (File No.: 12014/13/2019-HR).