Serum Cortisol, Insulin Resistance, and Oxidative Stress Biomarkers in Patients with Type 2 Diabetes Mellitus: A Case-Control Study from Ankara, Turkey

Abstract

Background: Type 2 Diabetes Mellitus (T2DM) is a leading cause of global morbidity, affecting 537 million adults in 2021. In Turkey, T2DM prevalence has reached 15.2% of the adult population (TURDEP-II). The interplay between hypothalamic-pituitary-adrenal (HPA) axis dysregulation, insulin resistance, and oxidative stress constitutes a critical pathophysiological circuit in T2DM, yet simultaneous quantification with effect size analysis in a Turkish clinical cohort has not been reported.

Hypothesis: We hypothesized that T2DM patients exhibit significantly elevated serum cortisol and HOMA-IR (H1), and significantly elevated MDA with depleted SOD and catalase (H2), compared with healthy controls.

Objective: To simultaneously quantify serum cortisol, fasting insulin, HOMA-IR, MDA, SOD, and catalase in 45 T2DM patients versus 40 healthy controls at Ankara City Hospital, and to evaluate the mechanistic interplay between HPA axis hyperactivation, insulin resistance, and oxidative antioxidant depletion.

Methods: A prospective case-control study (January–October 2024). T2DM confirmed per ADA 2023 criteria (FPG ≥ 7.0 mmol/L or HbA1c ≥ 6.5%). Cortisol and insulin: ECLIA (Roche Cobas e602; intra-assay CV 2.8% and 3.1% respectively). MDA: TBARS (CV 4.2%); SOD: NBT reduction (CV 3.8%); catalase: H₂O₂ spectrophotometry (CV 4.6%). Statistics: independent t-test; Cohen's d; G*Power 3.1.9; SPSS v26.

Results: Both hypotheses confirmed. T2DM patients showed elevated cortisol (28.6 ± 2.1 vs. 14.2 ± 1.3 µg/dL; P = 3.12×10⁻¹¹; d = 2.18), HOMA-IR (5.8 ± 0.4 vs. 1.9 ± 0.2; P = 4.20×10⁻¹⁵; d = 2.84), MDA (4.12 ± 0.18 vs. 2.04 ± 0.11 nmol/mL; P = 1.80×10⁻¹³; d = 2.61), depleted SOD (78.4 ± 4.2 vs. 132.6 ± 5.1 U/mL; P = 2.30×10⁻¹²; d = 2.39) and catalase (31.7 ± 2.1 vs. 58.3 ± 2.4 U/mg protein; P = 4.10×10⁻¹³; d = 2.54). Post-hoc power > 99.9%.

Conclusion: T2DM patients in Ankara demonstrate HPA axis hyperactivation (cortisol d = 2.18) coupled with profound insulin resistance (HOMA-IR d = 2.84) and antioxidant exhaustion (MDA–SOD–catalase d = 2.39–2.61). The cortisol→IRS-1 serine phosphorylation→PI3K-Akt impairment cascade constitutes the primary mechanistic bridge between hypercortisolaemia and insulin resistance in this cohort. These findings support cortisol-targeting and antioxidant-adjunctive strategies in Turkish T2DM management.