甲状腺功能正常2型糖尿病患者促甲状腺激素与血清同型半胱氨酸的相关性

查克熙; 杨敏; 刘冬梅

甲状腺功能正常2型糖尿病患者促甲状腺激素与血清同型半胱氨酸的相关性

Correlation between thyroid stimulating hormone and hyperhomocysteinemia in euthyroid type 2 diabetes mellitus patients

摘要

摘要: 目的：探讨甲状腺功能正常2型糖尿病（T2DM）患者促甲状腺激素（thyroid- stimulating hormone, TSH）与血清同型半胱氨酸（homocysteine, Hcy）的相关性，分析高同型半胱氨酸（hyperhomocysteinemia, HHcy）血症的危险因素。方法：选择2016年1月至2017年6月上海市第二人民医院内分泌科收治的甲状腺功能正常T2DM患者108例，其中男性56例、女性52例；年龄38～82岁，平均（64±10）岁。以同期在门诊进行健康体检者50例（年龄、性别均匹配）为对照组。测定身高、体质量，计算体质指数（BMI），空腹测定糖化血红蛋白（HbA1c）、血清生化指标、甲状腺功能、空腹C肽水平等，计算稳态模型评估胰岛素抵抗指数（HOMA-IR）、预估肾小球滤过率（eGFR）；酶循环法检测血清Hcy水平。甲状腺功能正常T2DM患者按TSH水平分为4组：G1组（TSH 0.3～0.99 mU/L），G2组（TSH 1.0～1.89 mU/L），G3组（TSH 1.9～2.49 mU/L），G4组（TSH 2.5～4.8 mU/L），并比较血清Hcy水平。结果：甲状腺功能正常T2DM组血清Hcy水平显著高于对照组［（15.4±4.5） vs （12.9±4.8） μmol/L，P<0.01］。偏相关分析显示，在校正年龄、性别、收缩压（SBP）、舒张压（DBP）、HbA1c、三酰甘油（TG）、总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）等相关因素后，甲状腺功能正常T2DM组血清Hcy水平与HOMA-IR、lgTSH显著正相关（r值分别为0.202、0.198，均P<0.05），与eGFR显著负相关（r值为-0.256，P<0.01），而与血清游离三碘甲状腺原氨酸（FT3）、游离甲状腺素（FT4）无明显相关性；对照组血清Hcy水平与FT3、FT4、lgTSH无明显相关性。甲状腺功能正常T2DM组血清Hcy水平随TSH升高出现逐步升高（P<0.05）。Logistic回归分析证实，男性发生高Hcy血症风险增加（OR=4.85，95%CI 1.92～12.23）；相对于G1组，G3组、G4组发生高Hcy血症的风险增加（OR=6.65，95%CI 1.50～29.54；OR=6.68，95%CI 1.93～23.14；均P<0.05）。结论：甲状腺功能正常T2DM患者血清Hcy水平升高，男性及正常高值的TSH是高Hcy血症的独立危险因素。

Abstract: Objective：To investigate the potential correlation between thyroid stimulating hormone and hyperhomocysteinemia (HHcy) in a cohort of euthyroid type 2 diabetes mellitus (T2DM), and explore other related risk factors for HHcy. Methods：From January 2016 to June 2017, 108 patients with euthyroid T2DM (56 males and 52 females) were enrolled in the Department of Endocrinology, the Second People’s Hospital. Fifty age- and gender-matched healthy volunteers were served as controls. Clinical characteristics such as body mass index (BMI), glycosylated hemoglobin (HbA1c), serum biochemistry parameters, thyroid function, fasting C-peptide were recorded. Fasting insulin resistance (HOMA-IR) was derived from C-peptide and estimated glomerular filtration (eGFR) was calculated using CKD-EPI formula. Serum homocysteine (Hcy) level was determined by enzymatic cycling assay. Euthyroid T2DM group was divided into 4 subgroups according to TSH levels: G1 (TSH 0.3-0.99 mU/L), G2(TSH 1.0-1.89 mU/L), G3 (TSH 1.9-2.49 mU/L), G4 (TSH 2.5-4.8 mU/L), and Hcy levels were compared among four subgroups. Differences of means between groups were compared by t-test or one-way ANOVA accordingly. The relationships between serum Hcy and other parameters were assessed by simple correlation analysis and logistic regression. Results：Serum Hcy levels was higher in euthyroid T2DM patients than that in controls (［15.4±4.5］ μmol/L vs ［12.9±4.8］ μmol/L, P<0.01). After adjusting for age, gender, and other confounding factors, across euthyroid T2DM subjects Hcy was positively correlated with HOMA-IR (r=0.215) and lgTSH (r=0.235, P<0.05), while negatively correlated with eGFR (r=-0.310, P<0.01). Hcy was not significantly associated with free thyroxine, free triiodothyronine, or lgTSH in normal control group. In euthyroid T2DM group, serum Hcy levels increased parallel with TSH (P<0.05). Based on logistic regression analysis, Hcy was associated with male gender (OR=4.85, 95%CI 1.92-12.23). The risk of HHcy increased significantly in G3 and G4 subgroups compared with G1 subgroups (OR=6.65, 95%CI 1.50-29.54; OR=6.68, 95%CI 1.93-23.14; all P<0.05). Conclusions：Serum homocysteine level is high in euthyroid T2DM patients. Male and a high normal TSH level may be independent risk factors for the presence of HHcy in euthyroid T2DM patients.

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