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DC22-1353 Supplemental_DD2_CRP_CVE_death_REVISED_16DEC2022.docx (803.13 kB)

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

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posted on 2023-03-17, 17:27 authored by Anne Gedebjerg, Mette Bjerre, Alisa Devedzic Kjaergaard, Jens Steen Nielsen, Jørgen Rungby, Ivan Brandslund, Michael Mæng, Henning Beck-Nielsen, Allan Vaag, Henrik Toft Sørensen, Troels Krarup Hansen, Reimar Wernich Thomsen

  

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.

 

Funding

A.P. Møller Foundation

Aarhus University

Augustinus Foundation

Bønnelycke Foundation

Danielsen Foundation

Danish Agency for Science

Danish Diabetes Academy

Diabetesforeningen

Hertz Foundation

Hjerteforeningen

Novo Nordisk A/S

Novo Nordisk Fonden

Sundhedsstyrelsen

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