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

Abstract

s 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.