Diabetes Care：雌酮水平可预测男性糖尿病发病风险

雌激素可减少绝经妇女和临床前鼠源性模型的糖尿病风险。但是，对于雌二醇和雌酮与男性糖尿病的关系所知甚少。为了确定血循环中雌二醇和雌酮水平与弗雷明汉心脏研究(FHS)中社区居住男性的糖尿病风险的关系，来自美国波士顿大学数学系的Guneet Kaur Jasuja博士等人进行了一项研究，研究发现，雌酮是预测男性糖尿病比较敏感的风险标志物。研究结果在线发表于2013年5月20日的美国《糖尿病治疗》(Diabetes Care)杂志上。

第七次检查时(1998-2001)，研究人员评价FHS参与者的后代男性(n=1,458)雌二醇和雌酮水平与糖尿病的横断面关系；第7次检查时的激素水平与糖尿病发病率的预期相关性于6.8年后(第8次检查时)进行评价。2型糖尿病定义为：空腹血糖值>125mg/dL，使用糖尿病治疗药物或二者兼有。采用液相色谱串联质谱法测定雌二醇、雌酮和睾酮水平，并计算游离的雌二醇和雌酮水平。

结果显示，在横断面研究模型中，每横断面雌酮和雌二醇倍增，雌酮和雌二醇升高的男性存在糖尿病的可能性分别升高40%和62%。第7次检查时，游离雌酮与空腹血糖受损相关(横断面危险比1.28[95% CI 1.02-1.62]，P=0.04)。现有糖尿病风险随着总的和游离的雌酮和雌二醇四分位数的升高而增高，糖尿病发病风险也随着雌酮四分位数的升高而增高。在多变量纵向分析中，第7次检查时总的或游离的雌酮水平升高2倍与第8次检查时发生糖尿病的可能性分别升高77%和93%相关。

研究表明，虽然雌二醇和雌酮都与男性糖尿病具有横断面相关性，但是在纵向分析中，雌酮是较雌二醇更为敏感的糖尿病发病风险标志物。

Circulating Estrone Levels Are Associated Prospectively With Diabetes Risk in Men of the Framingham Heart Study.
Abstract
OBJECTIVEIn postmenopausal women and preclinical murine models, estrogen administration reduces diabetes risk; however, the relationship of estradiol and estrone to diabetes in men is poorly understood. We determined the relationship between circulating estradiol and estrone levels and diabetes risk in community-dwelling men of the Framingham Heart Study (FHS).METHODSCross-sectional relationships of estradiol and estrone levels with diabetes were assessed at examination 7 (1998-2001) in FHS generation 2 men (n = 1,458); prospective associations between hormone levels at examination 7 and incident diabetes were assessed 6.8 years later at examination 8. Type 2 diabetes mellitus was defined as fasting glucose >125 mg/dL, medication use, or both. Estradiol, estrone, and testosterone levels were measured with liquid chromatography tandem mass spectrometry, and free estradiol and estrone were calculated.RESULTSIn cross-sectional models, men with elevated estrone and estradiol had 40% and 62% increased likelihoods of existing diabetes per cross-sectional doubling of estrone and estradiol levels, respectively. Free estrone (cross-sectional odds ratio 1.28 [95% CI 1.02-1.62], P = 0.04) was associated with impaired fasting glucose at examination 7. There was an increase in risk of existing diabetes with increasing quartiles of total and free estrone and estradiol and an increase in risk of incident diabetes with increasing quartiles of estrone levels. In multivariate longitudinal analyses, a twofold increase in total or free estrone levels at examination 7 was associated with 77 and 93% increases, respectively, in odds of incident diabetes at examination 8.CONCLUSIONSAlthough both estradiol and estrone exhibit cross-sectional associations with diabetes in men, in longitudinal analyses estrone is a more sensitive marker of diabetes risk than estradiol.