Comparative Assessment of Fasting and Stimulated C-peptide Levels as Discriminatory Markers of Coronary Artery Disease in Type 2 Diabetes Mellitus: A Cross-Sectional Study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) significantly increases the risk of coronary artery disease (CAD), a leading cause of mortality in this population. Early identification of high-risk individuals using reliable biomarkers is crucial for effective prevention. Previous studies have reported that elevated serum C-peptide has been associated with an increased risk of CAD. C-peptide can be assessed under both fasting and stimulated conditions; however, the relative discriminative ability of these measures to identify CAD remains uncertain. This study was therefore undertaken to evaluate the association of fasting and stimulated C-peptide (SCP) levels with the presence of CAD in patients with T2DM and to compare their relative performance in identifying CAD. MATERIALS AND METHODS: This cross-sectional study was conducted at Government Medical College, Kannur, Kerala, India. It included patients with T2DM of five to 15 years' duration. Patients receiving insulin therapy, with chronic liver disease, an estimated glomerular filtration rate (eGFR) < 45 ml/min/1.73 m², or critical illness were excluded. Clinical, anthropometric, and biochemical parameters, including fasting C-peptide (FCP) and SCP, were assessed. Blood samples for FCP were obtained following a minimum of eight hours of overnight fasting, while SCP samples were collected 90 minutes after administration of a standardized liquid meal. CAD was identified from prior medical records or diagnostic evaluations, with screening performed in those without known CAD. Data were analyzed using IBM SPSS Statistics software, version 24 (IBM Corp., Armonk, NY, USA). Group comparisons were performed using independent-samples t-tests, while logistic regression was employed to identify factors associated with CAD. Receiver operating characteristic (ROC) curve analysis was used to find the optimal C-peptide cut-off values for identifying CAD. A p-value ≤ 0.05 was considered statistically significant. RESULTS: A total of 282 patients with T2DM (148 males, 134 females; mean age 53.9 ± 7.3 years; mean diabetes duration 8.7 ± 1.9 years) were included. CAD was present in 65 patients (23.1%), comprising 44 with angiographically confirmed disease and 21 with myocardial infarction (four patients with ST-segment elevation myocardial infarction (STEMI) and 17 patients with non-ST-segment elevation myocardial infarction (NSTEMI)). Patients with CAD had significantly higher FCP levels (2.30 ± 0.77 vs. 1.84 ± 0.59 ng/mL; t = 5.04, p < 0.001) and SCP levels (5.24 ± 1.39 vs. 4.04 ± 1.16 ng/mL; t = 6.96, p < 0.001) compared to those without CAD. Logistic regression analysis demonstrated that SCP showed a stronger independent association with CAD, with each unit increase corresponding to nearly a twofold increase in odds. Receiver operating characteristic (ROC) curve analysis showed moderate diagnostic performance for FCP (cut-off ≥ 2.15 ng/mL: sensitivity 64.6%, specificity 72.4%, accuracy 70.6%), whereas SCP exhibited superior discriminatory ability (cut-off ≥ 4.91 ng/mL: sensitivity 73.8%, specificity 84.3%, accuracy 81.8%). CONCLUSIONS: In patients with T2DM, elevated FCP and SCP levels are significantly associated with CAD, with SCP demonstrating a stronger association and superior discriminative ability. These findings highlight its potential as a useful biomarker for earlier identification of high-risk individuals, although confirmation in multicenter prospective studies is warranted.