C-reactive Protein, C-peptide, and Risk of First-time Cardiovascular Events and Mortality in Early Type 2 Diabetes: A Danish Cohort Study

Objective: We investigated the relationship between high-sensitivity C-reactive protein (hsCRP), a marker of low-grade inflammation, alone or in combination with C-peptide, a marker of hyperinsulinemia/insulin resistance, and risk for cardiovascular events (CVEs) and mortality in patients recently diagnosed with type 2 diabetes (T2D).

Research Design and Methods: We measured serum hsCRP (n=7301) and C-peptide (n=5765) in patients with recent-onset T2D in the prospective Danish DD2 cohort study. Patients with no prior CVE (n=6,407) were followed until first myocardial infarction, stroke, coronary revascularization, or cardiovascular death, and all patients (n=7,301) were followed for all-cause mortality. We computed adjusted hazard ratios (aHRs) by Cox regression and tested for interaction between hsCRP and C-peptide.

Results: During follow-up (median=4.8 years), high (>3 mg/L) versus low (<1 mg/L) hsCRP was associated with increased CVE risk (aHR=1.45; 95% CI 1.07–1.96), and with even greater risk of all-cause mortality (2.47 [1.88–3.25]). Compared to patients with low hsCRP (≤3 mg/L) and low C-peptide (<1470 pmol/L), those with high levels of both biomarkers had the highest CVE (1.61 [1.10–2.34]) and all-cause mortality risk (2.36 [1.73–3.21]). Among patients with high C-peptide, risk of CVE did not differ by low or high hsCRP, whereas risk of all-cause mortality did.

Conclusions: The finding of high hsCRP as a stronger prognostic biomarker of all-cause mortality than of CVE may facilitate improved early detection and prevention of deadly diseases besides CVE. Conversely, elevated C-peptide as a strong CVE biomarker supports the need to target hyperinsulinemia/insulin resistance in T2D CVE prevention.