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.
Authors: Liu, Gang; Ding, Ming; Chiuve, Stephanie E; Rimm, Eric B; Franks, Paul W; Meigs, James B; Hu, Frank B; Sun, Qi
Published In Arterioscler Thromb Vasc Biol, (2016 Nov)
Abstract: 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.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.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.
PubMed ID: 27609367
MeSH Terms: Adiponectin/blood*; Adiponectin/genetics; Adult; Aged; Biomarkers/blood; Cardiovascular Diseases/blood*; Cardiovascular Diseases/diagnosis; Cardiovascular Diseases/genetics; Cardiovascular Diseases/mortality*; Cause of Death; Chi-Square Distribution; Diabetes Mellitus, Type 2/blood*; Diabetes Mellitus, Type 2/diagnosis; Diabetes Mellitus, Type 2/genetics; Diabetes Mellitus, Type 2/mortality*; Fatty Acid-Binding Proteins/blood*; Fatty Acid-Binding Proteins/genetics; Genetic Predisposition to Disease; Humans; Linear Models; Male; Mendelian Randomization Analysis; Middle Aged; Molecular Weight; Multivariate Analysis; Polymorphism, Single Nucleotide; Prognosis; Proportional Hazards Models; Prospective Studies; Retinol-Binding Proteins, Plasma/analysis*; Retinol-Binding Proteins, Plasma/genetics; Risk Assessment; Risk Factors; Sex Factors; Time Factors; United States/epidemiology