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
(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.
(Less)
- author
- Liu, Gang ; Ding, Ming ; Chiuve, Stephanie E. ; Rimm, Eric B. ; Franks, Paul W. LU ; Meigs, James B. ; Hu, Frank B. and Sun, Qi
- organization
- publishing date
- 2016-11-01
- 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
- Lippincott Williams & Wilkins
- external identifiers
-
- pmid:27609367
- wos:000387051500022
- scopus:84986196627
- 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
- 2024-06-01 19:24:59
@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}},
keywords = {{adipokines; adiponectin; cardiovascular disease; fatty acid-binding proteins; heart failure}},
language = {{eng}},
month = {{11}},
number = {{11}},
pages = {{2259--2267}},
publisher = {{Lippincott Williams & Wilkins}},
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}},
doi = {{10.1161/ATVBAHA.116.308320}},
volume = {{36}},
year = {{2016}},
}