Plasma Levels of Fatty Acid-Binding Protein 4, Retinol-Binding Protein 4, High-Molecular-Weight Adiponectin, and Cardiovascular Mortality among Men with Type 2 Diabetes: A 22-Year Prospective Study

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Objective - To examine select adipokines, including fatty acid-binding protein 4, retinol-binding protein 4, and high-molecular-weight (HMW) adiponectin in relation to cardiovascular disease (CVD) mortality among patients with type 2 diabetes mellitus. Approach and Results - Plasma levels of fatty acid-binding protein 4, retinol-binding protein 4, and HMW adiponectin were measured in 950 men with type 2 diabetes mellitus in the Health Professionals Follow-up Study. After an average of 22 years of follow-up (1993-2015), 580 deaths occurred, of whom 220 died of CVD. After multivariate adjustment for covariates, higher levels of fatty acid-binding protein 4 were significantly associated with a higher CVD mortality: comparing extreme tertiles, the hazard ratio and 95% confidence interval of CVD mortality was 1.78 (1.22-2.59; P trend=0.001). A positive association was also observed for HMW adiponectin: the hazard ratio (95% confidence interval) was 2.07 (1.42-3.06; P trend=0.0002), comparing extreme tertiles, whereas higher retinol-binding protein 4 levels were nonsignificantly associated with a decreased CVD mortality with an hazard ratio (95% confidence interval) of 0.73 (0.50-1.07; P trend=0.09). A Mendelian randomization analysis suggested that the causal relationships of HMW adiponectin and retinol-binding protein 4 would be directionally opposite to those observed based on the biomarkers, although none of the Mendelian randomization associations achieved statistical significance. Conclusions - These data suggest that higher levels of fatty acid-binding protein 4 and HMW adiponectin are associated with elevated CVD mortality among men with type 2 diabetes mellitus. Biological mechanisms underlying these observations deserve elucidation, but the associations of HMW adiponectin may partially reflect altered adipose tissue functionality among patients with type 2 diabetes mellitus.


  • Gang Liu
  • Ming Ding
  • Stephanie E. Chiuve
  • Eric B. Rimm
  • Paul W. Franks
  • James B. Meigs
  • Frank B. Hu
  • Qi Sun
Enheter & grupper
Externa organisationer
  • Harvard University
  • Skåne University Hospital
  • Umeå University
  • Broad Institute

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Endokrinologi och diabetes
  • Kardiologi


Sidor (från-till)2259-2267
Antal sidor9
TidskriftArteriosclerosis, Thrombosis, and Vascular Biology
Utgåva nummer11
StatusPublished - 2016 nov 1
Peer review utfördJa