MERCURY AND ARSENIC EXPOSURE AS POTENTIATORS OF OXIDATIVE DNA DAMAGE AND METABOLIC DYSFUNCTION IN TYPE 2 DIABETES MELLITUS: A CASE–CONTROL STUDY IN EDO SOUTH, NIGERIA

Abstract

Background: Type 2 Diabetes Mellitus (T2DM) is increasingly recognized as a multifactorial metabolic disorder driven not only by genetic predisposition and lifestyle factors, but also by environmental toxicants capable of disrupting cellular metabolism and redox homeostasis. In Sub-Saharan Africa, rapid urbanization, industrial pollution, artisanal mining activities, contaminated water systems, and unsafe waste disposal practices have intensified human exposure to heavy metals such as mercury (Hg), arsenic (As), lead (Pb), and cadmium (Cd). These toxicants are known to induce oxidative stress, mitochondrial dysfunction, inflammatory activation, and pancreatic β-cell injury, yet their contribution to diabetes pathogenesis remains insufficiently characterized in Nigerian populations.

Objective: This study investigated the association between heavy metal exposure, oxidative DNA damage, inflammatory activation, and antioxidant defense responses among individuals with T2DM in Edo South, Nigeria.

 Methods: A hospital-based case–control study was conducted involving 240 participants comprising 140 clinically diagnosed T2DM patients and 100 apparently healthy controls. Serum concentrations of oxidative DNA damage biomarker 8-hydroxy-2′-deoxyguanosine (8-OHdG), inflammatory cytokines (TNF-α, IL-6, hs-CRP), antioxidant enzymes (SOD, CAT, GPX), lipid peroxidation marker malondialdehyde (MDA), adiponectin, and heavy metals (Hg, As, Pb, Cd) were quantified using standard biochemical and toxicological techniques. Comparative analyses were performed using Student’s t-test, while Pearson correlation and multivariate linear regression were employed to identify independent predictors of fasting blood sugar (FBS).

 Results: T2DM patients demonstrated significantly elevated oxidative DNA damage, with serum 8-OHdG levels markedly higher than controls (5.74 \pm 0.81 ng/mL vs. 1.62 \pm 0.56 ng/mL; p < 0.001). Inflammatory biomarkers including hs-CRP, TNF-α, and IL-6 were also significantly increased, indicating persistent low-grade systemic inflammation. Marked elevations in antioxidant enzymes (SOD, CAT, GPX) were observed in diabetic subjects, suggesting an adaptive compensatory response to excessive reactive oxygen species (ROS) generation. Furthermore, MDA levels were significantly elevated, confirming enhanced lipid peroxidation and oxidative injury.

 Heavy metal profiling revealed that 60.7% of T2DM participants exhibited elevated mercury concentrations, while 50% demonstrated elevated arsenic levels; in contrast, all controls remained within normal reference ranges. Multivariate regression analysis identified mercury exposure (β= -0.52 = -0.52, p < 0.001), GPX activity (β= -2.63, p < 0.001), and age (β= -0.45, p < 0.001) as significant independent predictors of glycemic dysregulation.

 Conclusion: This study provides compelling evidence that environmental heavy metal exposure particularly mercury and arsenic is strongly associated with oxidative DNA damage, chronic inflammation, and metabolic dysfunction in T2DM patients in Edo South, Nigeria. The findings support the emerging concept that environmental toxicants constitute important non-traditional drivers of diabetes pathogenesis. Integrating environmental health surveillance, toxicological screening, and oxidative stress management into diabetes care may improve disease prevention and therapeutic outcomes in vulnerable populations.