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Oxidative Stress Biomarkers and Systemic Inflammatory Indices in Metabolic Dysfunction-Associated Steatotic Liver Disease with Type 2 Diabetes Mellitus: A Comparative and Longitudinal Analysis

Year: 2026

Type: article

Abstract: Metabolically dysfunction-associated steatotic liver disease (MASLD) complicated by type 2 diabetes mellitus (T2DM) represents a clinically aggressive phenotype associated with accelerated hepatic fibrosis progression. The interplay among oxidative stress, systemic inflammation, and the risk of hepatic fibrosis in this context remains incompletely characterised. We conducted a single-centre observational study enrolling 110 adult MASLD patients, stratified into two groups: Group 1 (G1, n = 20), patients with concurrent T2DM, followed longitudinally at three successive time points, and Group 2 (G2, n = 90), non-diabetic controls. Serum oxidative stress biomarkers were assessed using malondialdehyde (MDA) and 8-isoprostaglandin F2α (8-iso-PGF2α). Systemic inflammatory status was quantified through the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR). Hepatic fibrosis risk was estimated using the FIB-4 index. Diabetic MASLD patients exhibited significantly elevated levels of 8-iso-PGF2α (p = 0.014) and NLR (p = 0.016) compared with controls, indicating greater oxidative membrane damage and systemic neutrophilic inflammation. A robust inverse correlation between PLR and FIB-4 was observed across all analytical strata (combined cohort: Spearman r = −0.680, p < 0.001). MLR emerged as the only independent predictor of MDA in G1 (β = 841.78, p = 0.013). Longitudinal analysis demonstrated biomarker stability over time, except for a significant increase in ALT from T1 to T2 (p_adj = 0.014). These findings support the clinical utility of routinely available haematological inflammatory ratios and lipid peroxidation biomarkers for phenotypic characterisation of MASLD in the diabetic context, highlighting the need for larger prospective studies with histological validation.

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms27125432