Serum Complement C3 and C4 Levels in Patients with Type 2 Diabetes Mellitus in Al-Najaf Province, Iraq: A Case-Control Study

Abstract

Background: Type 2 diabetes mellitus (T2DM) is an abnormal long-term metabolic condition in which people have high blood-sugar levels, low-grade inflammation, and abnormal immune system activity. The complement system, namely, complement components C3 and C4, might be potentially involved in metabolic inflammation and insulin resistance. Random blood sugar (RBS) and glycemic parameters levels may also give some clues about changes in inflammation and metabolism in these patients with T2DM. Objective: To compare the levels of complement C3, complement C4, C-reactive protein (CRP), and RBC level between patients with T2DM and apparently healthy subjects in Al-Najaf Province, Iraq and investigate association between these biomarkers. Methods: A case-control study was conducted at the Diabetes Unit, Al-Sadr Teaching Hospital, Al-Najaf, Iraq, from October 2024 to April 2025. The study enrolled 35 patients with T2DM and 30 apparently healthy controls. Demographic data, including age and sex, were recorded. Serum C3, C4, CRP, and RBS levels were measured and compared between groups. Spearman’s correlation analysis, multivariable logistic regression, and receiver operating characteristic (ROC) curve analysis were performed. A p-value of < 0.05 was considered statistically significant. Results: Patients with T2DM were significantly older than controls (54.43±11.62 vs. 36.03±2.82 years; p<0.001), while sex distribution was comparable between groups (p = 0.730). RBS was markedly higher in patients with T2DM than in controls (291.31 ± 63.62 vs. 107.40±3.89 mg/dL; p<0.001). Similarly, T2DM patients had significantly higher serum CRP (9.07±7.54 vs. 0.67± 0.79 mg/dL; p < 0.001), C3 (1.53±0.57 vs. 1.10±0.25 g/L; p < 0.001), and C4 levels (0.47±0.34 vs. 0.25±0.07 g/L; p = 0.016). Among patients with T2DM, CRP correlated positively with C3 (rs = 0.336,  p = 0.048) and C4 (rs = 0.564,  p < 0.001), while C3 was strongly correlated with C4 (rs = 0.653, p < 0.001). In multivariable logistic regression, age (adjusted odds ratio = 1.438, 95%  confidence  interval: 1.073–1.926;  p = 0.015) and CRP (adjusted odds ratio = 2.406,  95%  confidence  interval: 1.110–5.217; p = 0.026) were independently associated with T2DM. CRP demonstrated excellent discriminatory performance for T2DM, with an area under the ROC curve of 0.937 (95% confidence interval: 0.884–0.990; p < 0.001). Conclusion: Patients with T2DM had significantly elevated serum C3, C4, CRP, and RBS levels compared with healthy controls. The positive correlations of CRP with C3 and C4 support an association between complement components and systemic inflammation in T2DM. Although C3 and C4 were elevated in the patient group, they were not independently associated with T2DM after adjustment for age and CRP. CRP showed the strongest discriminatory ability among the evaluated biomarkers. Larger, age-matched prospective studies are needed to clarify the potential clinical and