Zinc–Copper Imbalance and Lipid Peroxidation Mark Glycaemic Control in Type 2 Diabetes Mellitus

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Abstract

Background: Oxidative stress and trace element imbalance are implicated in the pathogenesis of type 2 diabetes mellitus (T2DM). Zinc serves as an antioxidant and insulin cofactor, whereas dysregulated copper may amplify oxidative damage. This study investigated serum zinc, copper, their ratio (Zn/Cu), and lipid peroxidation markers across glycaemic control states. Methods: In this cross-sectional study (January–May 2025), 110 adults were classified as normoglycaemic (n = 40), well-controlled T2DM (HbA1c ≤ 7.0%, n = 35), or poorly controlled T2DM (HbA1c > 7.0%, n = 35). Serum zinc and copper were measured by flame atomic absorption spectrophotometry; malondialdehyde (MDA) by TBARS assay; and 8-iso-prostaglandin F₂α (8-iso-PGF₂α) by ELISA. MANCOVA adjusted for age, sex, BMI, blood pressure, diabetes duration, and waist circumference. Discriminant analysis was performed to identify biomarkers distinguishing glycaemic groups. Results: Poor glycaemic control was linked to significantly higher 8-iso-PGF₂α, MDA, and copper levels, and lower zinc and Zn/Cu ratios (p < 0.001). The Zn/Cu ratio and copper exhibited the largest effect sizes. Strong correlations were observed between oxidative stress indices and trace element levels (p < 0.001). Discriminant analysis correctly classified 88.7% of participants, identifying Zn/Cu ratio and 8-iso-PGF₂α as key discriminators. Conclusion: Glycaemic dysregulation in T2DM is strongly associated with oxidative stress and trace element imbalance. The Zn/Cu ratio demonstrates potential as a biomarker for metabolic risk stratification and individualised disease monitoring. Clinical trial number: Not applicable.’

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