Protein biomarkers for the prediction of cardiovascular disease in type 2 diabetes

Diabetologia. 2015 Jun;58(6):1363-71. doi: 10.1007/s00125-015-3535-6. Epub 2015 Mar 5.

Abstract

Aims/hypothesis: We selected the most informative protein biomarkers for the prediction of incident cardiovascular disease (CVD) in people with type 2 diabetes.

Methods: In this nested case-control study we measured 42 candidate CVD biomarkers in 1,123 incident CVD cases and 1,187 controls with type 2 diabetes selected from five European centres. Combinations of biomarkers were selected using cross-validated logistic regression models. Model prediction was assessed using the area under the receiver operating characteristic curve (AUROC).

Results: Sixteen biomarkers showed univariate associations with incident CVD. The most predictive subset selected by forward selection methods contained six biomarkers: N-terminal pro-B-type natriuretic peptide (OR 1.69 per 1 SD, 95% CI 1.47, 1.95), high-sensitivity troponin T (OR 1.29, 95% CI 1.11, 1.51), IL-6 (OR 1.13, 95% CI 1.02, 1.25), IL-15 (OR 1.15, 95% CI 1.01, 1.31), apolipoprotein C-III (OR 0.79, 95% CI 0.70, 0.88) and soluble receptor for AGE (OR 0.84, 95% CI 0.76, 0.94). The prediction of CVD beyond clinical covariates improved from an AUROC of 0.66 to 0.72 (AUROC for Framingham Risk Score covariates 0.59). In addition to the biomarkers, the most important clinical covariates for improving prediction beyond the Framingham covariates were estimated GFR, insulin therapy and HbA1c.

Conclusions/interpretation: We identified six protein biomarkers that in combination with clinical covariates improved the prediction of our model beyond the Framingham Score covariates. Biomarkers can contribute to improved prediction of CVD in diabetes but clinical data including measures of renal function and diabetes-specific factors not included in the Framingham Risk Score are also needed.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Apolipoprotein C-III / blood
  • Area Under Curve
  • Biomarkers / blood*
  • Cardiovascular Diseases / complications*
  • Cardiovascular Diseases / diagnosis
  • Case-Control Studies
  • Diabetes Complications
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / diagnosis
  • Europe
  • Female
  • Glomerular Filtration Rate
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Insulin / therapeutic use
  • Interleukin-15 / blood
  • Interleukin-6 / blood
  • Logistic Models
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood
  • Peptide Fragments / blood
  • ROC Curve
  • Risk Factors
  • Troponin T / blood

Substances

  • Apolipoprotein C-III
  • Biomarkers
  • Glycated Hemoglobin A
  • Insulin
  • Interleukin-15
  • Interleukin-6
  • Peptide Fragments
  • Troponin T
  • hemoglobin A1c protein, human
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain