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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

Liu, Gang; Ding, Ming; Chiuve, Stephanie E.; Rimm, Eric B.; Franks, Paul W. LU ; Meigs, James B.; Hu, Frank B. and Sun, Qi (2016) In Arteriosclerosis, Thrombosis, and Vascular Biology 36(11). p.2259-2267
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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
adipokines, adiponectin, cardiovascular disease, fatty acid-binding proteins, heart failure
in
Arteriosclerosis, Thrombosis, and Vascular Biology
volume
36
issue
11
pages
9 pages
publisher
American Heart Association
external identifiers
  • scopus:84986196627
  • wos:000387051500022
ISSN
1079-5642
DOI
10.1161/ATVBAHA.116.308320
language
English
LU publication?
yes
id
c27d1fbc-dd18-4788-873b-9a6401c21cab
date added to LUP
2016-11-14 11:00:02
date last changed
2017-10-29 04:53:57
@article{c27d1fbc-dd18-4788-873b-9a6401c21cab,
  abstract     = {<p>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.</p>},
  author       = {Liu, Gang and Ding, Ming and Chiuve, Stephanie E. and Rimm, Eric B. and Franks, Paul W. and Meigs, James B. and Hu, Frank B. and Sun, Qi},
  issn         = {1079-5642},
  keyword      = {adipokines,adiponectin,cardiovascular disease,fatty acid-binding proteins,heart failure},
  language     = {eng},
  month        = {11},
  number       = {11},
  pages        = {2259--2267},
  publisher    = {American Heart Association},
  series       = {Arteriosclerosis, Thrombosis, and Vascular Biology},
  title        = {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},
  url          = {http://dx.doi.org/10.1161/ATVBAHA.116.308320},
  volume       = {36},
  year         = {2016},
}