Serum melatonin levels and their relationship with inflammation and oxidative stress in patients with diabetic nephropathy: a cross-sectional case–control study

Diabetic nephropathy (DN), a major microvascular complication of type 2 diabetes mellitus (T2DM), is driven by oxidative stress and chronic inflammation. Melatonin, an endogenous indoleamine with potent antioxidant and anti-inflammatory properties, has been implicated in diabetic complications but its relationship with systemic inflammation and oxidative balance in DN remains incompletely characterised. This study aimed to evaluate serum melatonin levels in T2DM patients with and without nephropathy compared with healthy controls, and to assess associations with inflammatory indices (C-reactive protein, CRP; neutrophil-to-lymphocyte ratio, NLR) and total antioxidant/oxidant status (total antioxidant status, TAS; total oxidant status, TOS). This cross-sectional case–control study included 83 participants: 59 patients with T2DM (29 with DN and 30 without DN) and 24 healthy controls. Serum melatonin was measured by a validated enzyme-linked immunosorbent assay (ELISA). TAS and TOS were measured by an automated colorimetric method (Erel method). Inflammatory indices and renal-function markers were measured by standard methods. Receiver operating characteristic (ROC) curve analysis and multivariate logistic regression were used to evaluate predictive performance for DN. Serum melatonin was significantly lower in T2DM patients than controls (22.00 ± 15.56 vs. 42.88 ± 29.61 ng/L, p < 0.001), accompanied by reduced TAS (4.05 ± 3.94 vs. 7.87 ± 6.68 mmol/L, p < 0.001) and TOS (2.33 ± 2.43 vs. 8.50 ± 11.77 µmol/L, p = 0.002), and markedly elevated CRP ( p < 0.001). Within the diabetic cohort, neither TAS nor TOS differed significantly between DN and non-DN patients; serum melatonin was paradoxically marginally higher in the DN group ( p = 0.043), in the opposite direction to the conventionally hypothesised pattern. In contrast, DN patients had markedly higher urea and creatinine, lower albumin, and higher CRP ( p = 0.008). Melatonin correlated strongly and positively with TAS (ρ = 0.83) and TOS (ρ = 0.75). Urea provided the strongest discrimination for DN among the markers assessed (area under the curve, AUC, 0.805, 95% confidence interval, CI, 0.696–0.897), followed by estimated glomerular filtration rate (eGFR) (AUC 0.737); melatonin discriminated DN only modestly (AUC 0.666). Serum melatonin and total antioxidant capacity are concurrently reduced in T2DM, reflecting a coupled deficit of antioxidant defence. However, melatonin and TAS/TOS did not independently distinguish DN from non-DN diabetic patients; conventional renal-function markers and CRP were the dominant correlates of nephropathy. Melatonin appears to mark the global oxidative–metabolic burden of T2DM rather than nephropathy specifically.