性激素结合球蛋白可能是2型糖尿病患者非酒精性脂肪性肝病的一个新标记物

目的分析2型糖尿病患者血清性激素结合球蛋白（SHBG）的影响因素，评估血清SHBG是否可作为非酒精性脂肪性肝病（NAFLD）的血清标记物。方法选择2009年9月至2012年8月南京鼓楼医院内分泌科诊治的2型糖尿病患者281例，根据腹部B超分为有NAFLD组和无NAFLD组。清晨空腹抽血检测肝酶、血脂、血糖、胰岛素、甲状腺功能及性激素，利用多元线性回归及非条件logistic回归分析血清SHBG与代谢指标及脂肪肝患病率的关系。结果有NAFLD组125例，男85例，女40例，平均年龄（57±12）岁；无NAFLD组156例，男85例，女71例，平均年龄（61±13）岁。有脂肪肝组血清SHBG显著低于无脂肪肝组（26±9）比（44±6）nmol／L，t=-10．42，P〈0．05]。多元线性回归分析显示，血清SHBG与年龄、高密度脂蛋白胆固醇（HDL—C）独立正相关（p=0．316、0．200，均P〈0．05），与腰围、甘油三酯（TG）、稳态模型胰岛素抵抗指数（HOMA—IR）及促甲状腺素独立负相关（β=0．175、-0．243、-0．163、-0．205，均P〈0．05）。按血清SHBG水平由低到高四等分将患者分成4组，随着SHBG的递增，年龄、HDL—C逐渐递增（趋势P均〈0．05），而体质指数（BMI）、腰围、丙氨酸转氨酶（ALT）、谷氨酰转肽酶（GGT）、TG、空腹血糖（FPG）、空腹胰岛素（FINS）及HOMA．IR逐渐递减（趋势P均〈0．05）。将SHBG第一分位患脂肪肝的比值比（OR）设为1．00，随着SHBG四分位数的递增，经全因子校正后，第二至第四分位的OR（95％G，）分别为0．39（0．14。0．88）、0．20（0．07～0．57）、0．08（0．02～0．26）（趋势P〈0．05）。结论2型糖尿病患者的血清SHBG水平与年龄、腰围、HDL．C、TG及HOMA—IR显著相关；低水平SHBG是2型糖尿病合并NAFLD的独立危险因素，可能是评估脂肪肝的一项重要血清标记物。

Sex hormone-binding globulin is probably a new marker for nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus

Objective To investigate the association of serum sex hormone-binding globulin （SHBG） with metabolic variables in type 2 diabetic patients, and to evaluate whether serum SHBG could be a biomarker of nonalcoholic fatty liver disease （NAFLD）. Methods Total of 281 type 2 diabetic patients treated in Nanjing Drum Tower Hospital from September 2009 to August 2012 were included in the study. The patients were assigned to the NAFLD group and non-NAFLD group according to the result of liver ultrasound. Fasting blood draw were taken to detect liver enzymes, lipids, insulin levels, thyroid function and sex hormones. The correlations between serum SHBG levels and metabolic parameters as well as the prevalence of NAFLD were analyzed by using multiple linear regression or unconditional multinomial logistic regression analysis. Results There were 125 subjects in NAFLD group （male 85, female 40, age （57 ± 12） yrs） and 156 in non-NAFLD group （male 85,female 71 ,age （61 ± 13） yrs）, respectively. Serum SHBG levels in NAFLD group were significantly lower than that in non-NAFLD group （ （26 ± 9） vs （44 ± 6） nmol/L,t = - 10.42, P 〈 0. 05 ）. In the multiple linear regression model with SHBG as the dependent variable, age and high density lipoprotein cholesterol （HDL-C） were positively associated with SHBG （ n =0. 316,0. 200, all P 〈 0. 05 ）, while waist circumference, triglycerides （TG）, homeostasis model assessment of insulin resistance （HOMA-IR） and thyrotropin were inversely associated with SHBG （13 = -0. 175, -0. 243, -0. 163, -0. 205, all P 〈 0. 05 ）. The patients were divided into 4 groups according to SHBG quartiles. With the increased quartiles of serum SHBG, the age and HDL-C in the patients increased （ all P for trend 〈 0. 05 ） , while the body mass index （ BMI）, waist circumference, alanine aminotransferase （ALT） , gamma-glutamyl transpeptidase （GGT） , TG, fasting plasma glucose （ FPG）, fasting insulin （ Fins ） and HOMA-IR changed in a decreased trend （ all P for trend 〈 O. 05 ）. Besides, the proportion of NAFLD also decreased significantly with increased quartiles of SHBG （ P for trend 〈 0.05 ）. In the fully adjusted model,when compared with the first quartile of SHBG （reference, 1.00）,the odds ratio （OR） and 95% confidence interval （CI） for NAFLD across increasing quartiles of SHBG were 0. 39 （0. 14 -0. 88 ） ,0. 20 （0. 07 - 0. 57 ） and 0. 08 （ 0. 02 - 0. 26 ）, respectively （ P for trend 〈 0.05 ）. Conclusions Serum SHBG level in type 2 diabetic patients is significantly associated with age, waist circumference, HDL-C, TG and HOMA-IR. Low serum SHBG is an independent risk factor for the presence of NAFLD and might be an important bio-marker of NAFLD in type 2 diabetic patients.