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.

Arterioscler Thromb Vasc Biol
Authors
Abstract

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.

Year of Publication
2016
Journal
Arterioscler Thromb Vasc Biol
Volume
36
Issue
11
Pages
2259-2267
Date Published
2016 Nov
ISSN
1524-4636
DOI
10.1161/ATVBAHA.116.308320
PubMed ID
27609367
PubMed Central ID
PMC5083188
Links
Grant list
R01 ES021372 / ES / NIEHS NIH HHS / United States
R01 DK058845 / DK / NIDDK NIH HHS / United States
R00 HL098459 / HL / NHLBI NIH HHS / United States
K24 DK080140 / DK / NIDDK NIH HHS / United States
R01 ES022981 / ES / NIEHS NIH HHS / United States
U01 DK078616 / DK / NIDDK NIH HHS / United States
UM1 CA167552 / CA / NCI NIH HHS / United States
R01 HL035464 / HL / NHLBI NIH HHS / United States