Oxidative Stress, Systemic Inflammation, and Insulin Resistance Across the Glycaemic Spectrum: A Cross-Sectional Biochemical Association Study

Abstract

Background: Oxidative stress, systemic inflammation, and insulin resistance are frequently co-reported
across the glycaemic spectrum, yet the concurrent inter-relationships among these perturbations remain
incompletely characterised in integrated observational analyses. Objectives: This cross-sectional study
aimed to characterise concurrent associations among surrogate markers of oxidative stress
(malondialdehyde [MDA] and reduced glutathione [GSH]), systemic inflammation (high-sensitivity C
reactive protein [hs-CRP]), glycaemic dysregulation (fasting blood glucose [FBG], HbA1c, HOMA-IR),
lipid parameters, and mineral homeostasis in a cohort of 75 adult participants stratified by glycaemic
status. Methods: Participants (n = 75; males = 35, females = 40; mean age 48.2 ± 11.1 years) were
classified as normoglycaemic (n = 30), prediabetic (n = 19), or diabetic (n = 26) per ADA 2023 criteria.
Twenty-one biochemical parameters were measured. Between-group differences were assessed by
Kruskal-Wallis and Mann-Whitney U tests with Bonferroni correction. Bivariate associations were
examined by Pearson and Spearman correlation analyses; multiple linear regression and principal
component analysis (PCA) were applied as exploratory multivariate approaches. Results: Significant
progressive differences were observed across glycaemic strata for all key biomarkers (all Bonferroni
corrected p < 0.001). FBG demonstrated strong positive associations with HbA1c (r = 0.974), HOMA-IR
(r = 0.933), MDA (r = 0.927), and hs-CRP (r = 0.945). HOMA-IR was inversely associated with HDL-C
(r = −0.828) and positively associated with TG (r = 0.915), MDA (r = 0.936), and hs-CRP (r = 0.954).
MDA and GSH showed a strong inverse association (r = −0.951, p < 0.001). Exploratory PCA identified
a dominant first component (PC1) explaining 68.9% of total variance, with substantial co-loadings from
FBG, HOMA-IR, MDA, and hs-CRP. In regression modelling, FBG, HOMA-IR, and hs-CRP were
independently associated with HbA1c (Adj. R² = 0.952, p < 0.001).