The Oxidation-Inflammatory Axis in Type 2 Diabetes Mellitus: Environmental Heavy Metal Exposure as a Potential Co-Factor in a Nigerian Hospital Cohort

Abstract

Background: Type 2 Diabetes Mellitus (T2DM) prevalence in Sub-Saharan Africa has risen markedly over recent decades, suggesting that environmental factors beyond traditional metabolic risk factors may contribute to disease pathogenesis. This study investigates the concurrent presence of heavy metal exposure, oxidative DNA damage, systemic inflammation, and dysregulated antioxidant responses in a Nigerian cohort with T2DM.

 Methods: A hospital-based case–control study was conducted at Irrua Specialist Teaching Hospital, Edo State, Nigeria (August 2023–February 2025). Participants included 140 adults with confirmed T2DM and 100 non-diabetic controls without metabolic disorders. We measured oxidative DNA damage (8-hydroxy-2′-deoxyguanosine [8-OHdG]), pro-inflammatory cytokines (tumour necrosis factor-α [TNF-α], interleukin-6 [IL-6], high-sensitivity C-reactive protein [hs-CRP]), antioxidant enzymes (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPX]), lipid peroxidation (malondialdehyde [MDA]), and trace metal concentrations (mercury [Hg], arsenic [As], lead [Pb], cadmium [Cd]) via inductively coupled plasma mass spectrometry (ICP-MS).

 Results: T2DM patients exhibited significantly elevated 8-OHdG (5.74 ± 0.81 vs. 1.62 ± 0.56 ng/mL; p < 0.001; Cohen's d = 2.1). Heavy metal analysis revealed markedly elevated mercury in 60.7% of T2DM cases versus 0% of controls, and elevated arsenic in 50% of cases versus 0% of controls (p < 0.001, Fisher's exact test). Multivariate linear regression identified SOD (β = −0.90, p < 0.001), GPX (β = −1.80, p < 0.001), mercury exposure (β = −42.3, p < 0.001), and adiponectin (β = 2.1, p = 0.012) as significant predictors of fasting blood sugar in the T2DM group (F[7,132] = 9.2, p < 0.001, R²adj = 0.32).

 Conclusions: These findings describe an oxidative-inflammatory phenotype in T2DM that is associated with elevated environmental heavy metal burdens, particularly mercury and arsenic. The data suggest that toxicological screening may be warranted in T2DM patients from high-exposure settings and merit further investigation into potential therapeutic targets.