2型糖尿病男性患者血浆中脂肪酸结合蛋白4、视黄醇结合蛋白4、高分子量脂联素水平与心血管死亡率：一项22年的前瞻性研究
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.
作者信息
Liu Gang, Ding Ming, Chiuve Stephanie E, Rimm Eric B, Franks Paul W, Meigs James B, Hu Frank B, Sun Qi
机构信息
From the Department of Nutrition (G.L., M.D., S.E.C., E.B.R., P.W.F., F.B.H., Q.S.) and Department of Epidemiology (E.B.R., F.B.H.), Harvard T.H. Chan School of Public Health, Boston, MA; Division of Preventive Medicine (S.E.C.) and Channing Division of Network Medicine (E.B.R., F.B.H., Q.S.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Sweden (P.W.F.); Skåne University Hospital Malmö, Sweden (P.W.F.); Department of Public Health and Clinical Medicine, Faculty of Medicine, Umeå University, Sweden (P.W.F.); Division of General Internal Medicine, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston (J.B.M.); and Program in Medical and Population Genetics, Broad Institute, Cambridge, MA (J.B.M.).
出版信息
Arterioscler Thromb Vasc Biol. 2016 Nov;36(11):2259-2267. doi: 10.1161/ATVBAHA.116.308320. Epub 2016 Sep 8.
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.
目的
研究2型糖尿病患者中选定的脂肪因子，包括脂肪酸结合蛋白4、视黄醇结合蛋白4和高分子量（HMW）脂联素与心血管疾病（CVD）死亡率的关系。
方法与结果
在健康专业人员随访研究中，对950名2型糖尿病男性患者的血浆脂肪酸结合蛋白4、视黄醇结合蛋白4和HMW脂联素水平进行了测量。经过平均22年的随访（1993 - 2015年），发生了580例死亡，其中220例死于心血管疾病。在对协变量进行多变量调整后，较高水平的脂肪酸结合蛋白4与较高的心血管疾病死亡率显著相关：比较极端三分位数，心血管疾病死亡率的风险比和95%置信区间为1.78（1.22 - 2.59；P趋势 = 0.001）。对于HMW脂联素也观察到正相关：比较极端三分位数，风险比（95%置信区间）为2.07（1.42 - 3.06；P趋势 = 0.0002），而较高的视黄醇结合蛋白4水平与心血管疾病死亡率降低无显著关联，风险比（95%置信区间）为0.73（0.50 - 1.07；P趋势 = 0.09）。孟德尔随机化分析表明，HMW脂联素和视黄醇结合蛋白4的因果关系与基于生物标志物观察到的关系方向相反，尽管孟德尔随机化关联均未达到统计学显著性。
结论
这些数据表明，2型糖尿病男性患者中较高水平的脂肪酸结合蛋白4和HMW脂联素与心血管疾病死亡率升高有关。这些观察结果背后的生物学机制值得阐明，但HMW脂联素的关联可能部分反映了2型糖尿病患者脂肪组织功能的改变。
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