Integrated Evaluation of Serum Oxidative Stress Markers and Histopathological Grading in Predicting Early Organ Damage in Type 2 Diabetes Mellitus

Abstract

Background: Type 2 diabetes mellitus (T2DM) is a persistent metabolic illness linked with an advancement of microvascular and macrovascular issues. Oxidative stress has a critical role in the pathogenesis of diabetic organ injury, but its combination with histopathological grading to predict early remains underdeveloped.

Objective: To assess the relationship between serum oxidative stress markers and histopathological grading in accurately forecasting early organ damage in T2DM patients.

Methods: This cross-sectional clinical study was conducted from June 2024 to June 2025 at Gujranwala Medical College, Gujranwala, Pakistan, and Khawaja Muhammad Safdar Medical College, Sialkot, Pakistan. One hundred and twenty (120) T2DM patients (35–65 years old) were recruited by non-probability consecutive sampling. The ELISA was used to measure serum levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH). The tissue biopsies were histopathologically graded using standard criteria (Grade I–III). The statistical analysis involved the use of SPSS version 26, with p < 0.05 being significant.

Results: The average age of the participants was 53.1 ± 9.2 years, and 56.7% were males. The mean HbA1c level was 9.2 ± 1.5%. Elevated MDA levels (4.9 ± 1.3 nmol/mL) and reduced antioxidant markers SOD (2.0 ± 0.7 U/mL) and GSH (3.1 ± 1.0 µmol/L) were observed. The histopathological changes were 31.7% Grade I, 43.3% Grade II, and 25.0% Grade III. The increase in MDA (3.3 ± 0.9 to 6.1 ± 1.4 nmol/mL) and the corresponding decrease in SOD and GSH levels (p < 0.001) corresponded with increasing grades. There was a high positive correlation between MDA and tissue damage (r = +0.71) and negative correlations for SOD (r = −0.57) and GSH (r = −0.62). Early organ damage in 61.7% of patients was mostly the kidneys (38.3%) and the liver (23.3%).

Conclusion: Histopathological severity is closely linked with serum oxidative stress markers, which can be used as quality early predictors of organ damage in T2DM. Biochemical analysis combined with histological analysis is a promising method of early diagnosis and risk stratification.