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. Issue 11 (November 2016)

• Record Type: Journal Article
• Authors: Liu, Gang; Ding, Ming; Chiuve, Stephanie E.; Rimm, Eric B.; Franks, Paul W.; Meigs, James B.; Hu, Frank B.; Sun, Qi
• Is Part Of: Arteriosclerosis, thrombosis, and vascular biology. Volume 36:Issue 11(2016)
• Publication Date: 2016-11
• Subjects: adipokines -- adiponectin -- cardiovascular disease -- fatty acid–binding proteins -- heart failure; Arteriosclerosis -- Periodicals; Thrombosis -- Periodicals; Blood-vessels -- Pathophysiology -- Periodicals; Electronic journals; 616.13
• DOI: 10.1161/ATVBAHA.116.308320
• Languages: English
• ISSNs: 1079-5642

Abstract

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. Abstract : Supplemental Digital Content is available in the text.