Relationships of CRP and C-peptide with CV events and all-cause mortality in new onset T2DM

C-reactive protein, C-peptide, and risk of cardiovascular events and mortality after type 2 diabetes diagnosis: a Danish cohort study

Presented at the EASD annual meeting 2022 by: Alisa D. Kjaergaard, MD, PhD- Aarhus, Denmark

Introduction and methods

Previous studies have shown that high C-reactive protein (CRP) is associated with increased risk of CV events and all-cause mortality in the general (Danish) population. In patients with T2DM and a history of CVD, there was a relationship between CRP and MACE, but not for CRP and all-cause mortality. It is unknown what the relationship is between CRP and risk of MACE or all-cause mortality in individuals with recent-onset T2DM without a history of CV events.

Furthermore, high CRP is correlated with insulin resistance, which in its turn is associated with high risk of CV events. However, the joint effects of low-grade inflammation (CRP) and insulin resistance (C-peptide) on risk of CV events and all-cause mortality in individuals with T2DM are not known.

The aim of this study was to examine the relationship of CRP or CRP and C-peptide with CV events or all-cause mortality in individuals with recent T2DM diagnosis without a history of CV events.

For this study, data of a prospective national Danish cohort -DD2- were used. Patients were enrolled between 2010-2016 and followed until first CV event, death, migration or until 2018. Baseline CRP was measured in 7301 patients and baseline C-peptide in 5765 patients.

Outcomes were CV events consisting of MI, stroke, unstable angina, coronary revascularization, CV death) or all-cause mortality.

Main results

• High CRP levels (>3 mg/L) were associated with increased risk of CV events (HR 1.39, 95%CI:1.03-1.87) and all-cause mortality (HR 2.40, 95%CI:1.82-3.16) when compared to low levels (<1 mg/L).
• Patients with high CRP (>3 mg/L) and high C-peptide (≥1.47 nmol/L) had a high risk of CV events (aHR 1.61, 95%IC:1.10-2.23) followed by patients with low CRP (≤3 mg/L) and high C-peptide ((≥1.47 nmol/L levels) (aHR 1.54, 95%CI:1.09-2.18) and patients with high CRP (>3 mg/L) and low C-peptide (<1.47 nmol/L) (aHR 1.37, 95%CI:1.00-1.88) compared to patients with low CRP ((≤3 mg/L) and low C-peptide (<1.47 nmol/L).
• For all-cause mortality, patients with high CRP and high C-peptide had the highest risk (aHR 2.36, 95%CI:1.73-3.21) followed by patients with high CRP and low C-peptide (aRH 1.90, 95%CI:1.46-2.49) and patients with low CRP and high C-peptide (aHR 1.15, 95%CI:0.82-1.61) compared to patients with low CRP and low C-peptide.

Conclusion

This study showed that in a population of the DDE cohort consisting of individuals with recent onset T2DM and no history or CV events (a primary prevention setting) high CRP was a better marker of all-cause mortality than future CV events, whereas high C-peptide was a better marker of increased CV risk. These findings emphasize the importance of targeting insulin resistance for the prevention of CV events in patients with new onset T2DM.

• Our reporting is based on the information provided at the EASD annual meeting -