title: Combined effects of sex hormone-binding globulin and sex hormones on risk of incident type 2 diabetes.
abstract: BACKGROUND
  The aim of the present study was to investigate the combined effects of sex hormone-binding globulin (SHBG) and sex hormones on the risk of type 2 diabetes (T2D).
  
  
  METHODS
  A nested case-control study of Chinese participants in the Environment, Inflammation and Metabolic Diseases Study (2008-13) was performed. Of the 3510 subjects free of diabetes, 145 men and 87 women developed diabetes over the 5-year follow-up. One age- and sex-matched control subject was selected for each case. Baseline concentrations of SHBG, estradiol, testosterone, and dehydroepiandrosterone sulfate (DHEA-S) were divided into tertiles and subjects were classified as having low, intermediate and high levels accordingly.
  
  
  RESULTS
  After multivariate adjustment, men with low SHBG levels had a fourfold greater risk of T2D than men with high SHBG levels. Conversely, men with high estradiol levels had a fourfold greater risk of T2D than men with low estradiol levels. Men with low SHBG + high estradiol had a 20-fold greater risk of T2D than men with high SHBG + low estradiol (odds ratio [OR] 20.23; 95% confidence interval [CI] 4.62-51.33). These risk associations in men were not observed for testosterone or DHEA-S, alone or in combination with SHBG. Compared with low SHBG, the risk of T2D decreased with increasing SHBG tertile (OR 0.92 [95% CI 0.21-4.53], 0.14 [95% CI 0.10-0.74]; Ptrend  = 0.043) after multivariate adjustment in women. Estradiol, testosterone, and DHEA-S levels showed no association with T2D in women.
  
  
  CONCLUSIONS
  Low SHBG in conjunction with high estradiol has an additive detrimental effect on the risk of T2D in men.
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Jinbo
authors.initials: J
authors.lastname: Hu
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Aiping
authors.initials: A
authors.lastname: Zhang
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Shumin
authors.initials: S
authors.lastname: Yang
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Richa
authors.initials: R
authors.lastname: Goswami
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Huang
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Hospital of Chongqing University, Chongqing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Cheng
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Qianna
authors.initials: Q
authors.lastname: Zhen
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Qifu
authors.initials: Q
authors.lastname: Li
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000453:epidemiology; D004958:Estradiol / Q000097:blood*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D012307:Risk Factors; D012738:Sex Hormone-Binding Globulin / Q000032:analysis*; D013739:Testosterone / Q000097:blood*
chemical_list: D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate
keywords: 2型糖尿病; combined effects; sex hormone-binding globulin; sex hormones; type 2 diabetes; 性激素; 性激素结合球蛋白; 联合作用