Serum TNF-α and Its Association with Glycaemic Control in Type 2 Diabetes Mellitus: A Comparative Cross-Sectional Study

Abstract

Background: Chronic low-grade inflammation is increasingly recognized as an important component of the pathophysiology of type 2 diabetes mellitus (T2DM). Tumor necrosis factor-alpha (TNF-α), a pro-inflammatory cytokine implicated in insulin resistance, may be associated with worsening glycaemic control. This study compared serum TNF-α concentrations between individuals with T2DM and healthy controls and evaluated the association between TNF-α and glycated haemoglobin (HbA1c). Methods: This comparative case-control study included 120 participants, comprising 60 individuals with T2DM and 60 age- and sex-matched healthy controls. Clinical and biochemical parameters were recorded. HbA1c was measured by ion-exchange high-performance liquid chromatography, while serum TNF-α concentrations were determined using an enzyme-linked immunosorbent assay. TNF-α concentrations were compared between study groups and across HbA1c categories among participants with T2DM. Pearson correlation analysis was used to assess the relationship between TNF-α and HbA1c. Binary logistic regression was performed to identify variables associated with T2DM status. Receiver operating characteristic (ROC) analysis was used to evaluate the discriminatory performance of TNF-α, HbA1c, and their combined model. Results: Serum TNF-α concentrations were significantly higher in participants with T2DM than in controls (34.8 ± 9.6 vs. 13.7 ± 4.3 pg/mL; p<0.001). Among participants with T2DM, mean TNF-α concentrations increased progressively across HbA1c categories, from 21.4 ± 4.2 pg/mL in those with HbA1c of 6.5–7.5% to 45.6 ± 8.5 pg/mL in those with HbA1c >9.5% (p<0.001). TNF-α showed a strong positive correlation with HbA1c (r=0.712; p<0.001). In logistic regression, TNF-α, HbA1c, and BMI were independently associated with T2DM status. ROC analysis demonstrated AUCs of 0.903 for TNF-α, 0.958 for HbA1c, and 0.972 for the combined model. Conclusion: Serum TNF-α concentrations were elevated in T2DM and were positively associated with HbA1c and worsening glycaemic control. TNF-α may provide complementary information regarding inflammatory activity in T2DM; however, larger prospective and multicentre studies with independent validation are required before its clinical utility can be established. Keywords: Type 2 diabetes mellitus; tumour necrosis factor-alpha; HbA1c; glycaemic control; inflammation; insulin resistance.