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

Gedebjerg, Anne ; Bjerre, Mette ; Kjaergaard, Alisa Devedzic ; Nielsen, Jens Steen ; Rungby, Jørgen ; Brandslund, Ivan ; Maeng, Michael ; Beck-Nielsen, Henning ; Vaag, Allan LU and Sørensen, Henrik Toft , et al. (2023) In Diabetes Care 46(5). p.1037-1045
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... (More)

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.

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publication status
published
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Diabetes Care
volume
46
issue
5
pages
9 pages
publisher
American Diabetes Association
external identifiers
  • pmid:36930691
  • scopus:85159419602
ISSN
0149-5992
DOI
10.2337/dc22-1353
language
English
LU publication?
yes
additional info
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.
id
82e190ae-d8ba-4d11-9891-0a07d4279f50
date added to LUP
2024-01-15 10:34:39
date last changed
2024-04-15 21:28:27
@article{82e190ae-d8ba-4d11-9891-0a07d4279f50,
  abstract     = {{<p>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 (&gt;3 mg/L) versus low (&lt;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 (&lt;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.</p>}},
  author       = {{Gedebjerg, Anne and Bjerre, Mette and Kjaergaard, Alisa Devedzic and Nielsen, Jens Steen and Rungby, Jørgen and Brandslund, Ivan and Maeng, Michael and Beck-Nielsen, Henning and Vaag, Allan and Sørensen, Henrik Toft and Hansen, Troels Krarup and Thomsen, Reimar Wernich}},
  issn         = {{0149-5992}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{1037--1045}},
  publisher    = {{American Diabetes Association}},
  series       = {{Diabetes Care}},
  title        = {{CRP, C-Peptide, and Risk of First-Time Cardiovascular Events and Mortality in Early Type 2 Diabetes : A Danish Cohort Study}},
  url          = {{http://dx.doi.org/10.2337/dc22-1353}},
  doi          = {{10.2337/dc22-1353}},
  volume       = {{46}},
  year         = {{2023}},
}