YKL-40, cardiovascular events, and mortality in individuals recently diagnosed with type 2 diabetes: A Danish cohort study

Diabetes Res Clin Pract. 2025 Jan:219:111970. doi: 10.1016/j.diabres.2024.111970. Epub 2024 Dec 22.

Abstract

Aims: We investigated the association of the inflammatory biomarker YKL-40 with cardiovascular events (CVEs) and mortality in individuals with type 2 diabetes.

Methods: We followed 11,346 individuals recently diagnosed with type 2 diabetes for up to 14 years. Baseline YKL-40 levels (measured in 9,010 individuals) were grouped into percentiles (0-33 %, 34-66 %, 67-90 %, and 91-100 %) and analyzed continuously (per 1 SD log increment), with comparisons to CRP (measured in 9,644 individuals). Cox regression assessed associations with atrial fibrillation (AF), ischemic stroke (IS), venous thromboembolism (VTE), myocardial infarction (MI), heart failure (HF), peripheral artery disease (PAD), and all-cause, cardiovascular, and cancer mortality.

Results: Adjusted HRs (95% CIs) for the highest (91-100%) versus the lowest (0-33%) YKL-40 percentile category were 1.31 (1.04-1.66) for AF, 1.43 (0.98-2.07) for IS, 1.07 (0.65-1.76) VTE, 0.88 (0.52-1.48) for MI, 1.66 (1.19-2.31) for HF, 1.66 (1.12-2.48) for PAD, and 2.18 (1.85-2.56) for all-cause, 1.64 (1.07-2.50) for cardiovascular, and 2.73 (2.05-3.63) for cancer mortality. Each 1 SD log increase in YKL-40 and CRP levels similarly increased CVE risks, with CRP being superior for MI and cardiovascular mortality.

Conclusions: YKL-40 is a prognostic biomarker for most CVEs, and even more so for all-cause mortality, primarily driven by cancer-related causes.

Keywords: C-Reactive Protein; Cardiovascular Diseases; Chitinase-3-Like Protein 1; Cohort Studies; Diabetes Mellitus, Type 2; Insulin Resistance; Mortality.

MeSH terms

  • Aged
  • Biomarkers* / blood
  • C-Reactive Protein / analysis
  • C-Reactive Protein / metabolism
  • Cardiovascular Diseases* / blood
  • Cardiovascular Diseases* / mortality
  • Chitinase-3-Like Protein 1* / blood
  • Cohort Studies
  • Denmark / epidemiology
  • Diabetes Mellitus, Type 2* / blood
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / mortality
  • Female
  • Humans
  • Male
  • Middle Aged

Substances

  • Chitinase-3-Like Protein 1
  • CHI3L1 protein, human
  • Biomarkers
  • C-Reactive Protein