CRP, C-Peptide, and Risk of First-Time Cardiovascular Events and Mortality in Early Type 2 Diabetes: A Danish Cohort Study

Anne Gedebjerg, Mette Bjerre, Alisa Devedzic Kjaergaard, Jens Steen Nielsen, Jørgen Rungby, Ivan Brandslund, Michael Maeng, Henning Beck-Nielsen, Allan Vaag, Henrik Toft Sørensen, Troels Krarup Hansen, Reimar Wernich Thomsen

Research output: Contribution to journalArticlepeer-review

Abstract

We investigated the relationship between hs-CRP, a marker of low-grade inflam-mation, 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 In patients with recent-onset T2D, we measured serum hs-CRP (n = 7,301) and C-peptide (n = 5,765) in the prospective Danish Centre for Strategic Research in Type 2 Diabetes 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 com-puted adjusted hazard ratios (aHRs) by Cox regression and tested for the interaction between hs-CRP and C-peptide. RESULTS During follow-up (median 4.8 years), high (>3 mg/L) versus low (<1 mg/L) hs-CRP 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 with patients with low hs-CRP (£3 mg/L) and low C-peptide (<1,470 pmol/L), those with high lev-els 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 CVEs did not differ by low or high hs-CRP, whereas risk of all-cause mortality did. CONCLUSIONS The finding of high hs-CRP as a stronger prognostic biomarker of all-cause mortality than of CVEs may facilitate improved early detection and prevention of deadly diseases besides CVEs. Conversely, elevated C-peptide as a strong CVE biomarker sup-ports the need to target hyperinsulinemia/insulin resistance in T2D CVE prevention.

Original languageEnglish
Pages (from-to)1037-1045
Number of pages9
JournalDiabetes Care
Volume46
Issue number5
DOIs
Publication statusPublished - 2023 May

Bibliographical note

Funding Information:
acknowledge Sia Kromann Nicolaisen (Department of Clinical Epidemiology, Aarhus University Hospital and Department of Clinical Medicine, Aarhus University, Aarhus, Denmark) for assistance with data management. Funding. The DD2 is supported by the Danish Agency for Science (grants 09-067009 and 09-075724), the Danish Health and Medicines Authority (Sundhedsstyrelsen), the Danish Diabetes Association (Diabetesforeningen), and an unrestricted donation from Novo Nordisk A/S. Project partners are listed at https://www.DD2.nu. The work of A.G. was supported by the Danish Diabetes Academy, which is funded by an unrestricted grant from Novo Nordisk Fonden, and the Danish Heart Foundation (Hjerteforenin-gen grant 15-R99-A5866-22891) and Aarhus University. In addition, A.G. has received funding from the Danielsen Foundation, Augustinus Foundation, A.P. Møller Foundation, Hertz Foundation, and Bønnelycke Foundation.

Funding Information:
The funding sources had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Duality of Interest. M.M. has received lecture and advisory board fees from Novo Nordisk and has received a research grant from Bayer. The Department of Clinical Epidemiology, Aarhus University Hospital, receives funding for other studies from companies in the form of research grants to (and administered by) Aarhus University. None of these studies has any relation to the current study. No other potential conflicts of interest relevant to this article were reported. Author Contributions. J.S.N., J.R., H.B.-N., A.V., and H.T.S. participated in the design of the overall DD2 project and cohort study and data collection. A.G., M.B., A.D.K., M.M., H.T.S., T.K.H., and R.W.T. participated in the design of the current study. A.G., M.B., M.M., H.T.S., T.K.H., and R.W.T. conceived of the current study. A.G. and A.D.K. performed the statistical analyses. A.G., H.T.S., and R.W.T. drafted the manuscript. J.R., H.B.-N., A.V., and H.T.S. participated in conceiving and designing the parent DD2 project cohort study. M.B. was responsible for hs-CRP measurements. I.B. was responsible for the biobank and the other biochemical analyses. All authors contributed substantially to the study, revised the manuscript for intellectual content, and approved the final version to be submitted. A.G. and R.W.T. are the guarantors of this work and, as such, had full access to all data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Prior Presentation. Parts of this study were presented in oral form at the 58th European Association for the Study of Diabetes Annual Meeting, Stockholm, Sweden, 19–23 September 2022.

Funding Information:
The DD2 is supported by the Danish Agency for Science (grants 09-067009 and 09-075724), the Danish Health and Medicines Authority (Sundhedsstyrelsen), the Danish Diabetes Association (Diabetesforeningen), and an unrestricted donation from Novo Nordisk A/S. Project partners are listed at https://www.DD2.nu. The work of A.G. was supported by the Danish Diabetes Academy, which is funded by an unrestricted grant from Novo Nordisk Fonden, and the Danish Heart Foundation (Hjerteforeningen grant 15-R99-A5866-22891) and Aarhus University. In addition, A.G. has received funding from the Danielsen Foundation, Augustinus Foun-dation, A.P. Møller Foundation, Hertz Foundation, and Bønnelycke Foundation. The funding sources had no role in study de-sign, data collection, data analysis, data inter-pretation, or writing of the report. M.M. has received lecture.

Publisher Copyright:
© 2023 by the American Diabetes Association.

Subject classification (UKÄ)

  • Endocrinology and Diabetes

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