目的：最新研究显示亚临床甲减(subclinical hypothyroidism，SCH)与心血管疾病的发生是正相关的。但其与慢性肾脏病(chronic kidney diseases，CKD)之间的关系尚不明确。在本研究中，我们首先进行病例对照研究，然后通过meta分析来探讨SCH和CKD之间的关系，并对TSH与CKD间进行剂量–效应分析。方法：在这项以医院为基础的病例对照研究中，我们纳入了从2011年1月至2015年12月期间在北京同仁医院就诊的3 150名甲状腺功能正常的2型糖尿病患者和525名有亚临床甲减的2型糖尿病患者。所有关于SCH与CKD之间关系研究的英文文献均是在2016年1月通过MEDLINE、EMBASE和谷歌学术数据库检索获得的。研究数据采用STATA13.0软件进行meta分析，最终筛选出5项观察性研究。结果：本研究表明，与甲状腺功能正常的2型糖尿病患者相比，SCH患者更容易罹患CKD(OR 1.26；95%CI：1.05~1.52)。累积证据表明SCH和CKD(OR 1.81；95%CI：1.43~2.29)之间有显著的关联性。在TSH正常范围内，与低水平血清TSH相比，高水平血清TSH的CKD合并OR为1.68(95%CI：1.45~1.94)；剂量–效应的荟萃分析显示CKD的发病风险与TSH的非线性升高相关(P=0.04)；CKD发病风险与血清TSH间呈剂量–效应线性递增关系(合并OR 1.09；95%CI：1.03~1.16；TSH每升高1 mIU/L)。结论：目前证据表明，在2型糖尿病患者中，SCH可能是CKD发生的危险因素；血清TSH升高与CKD发病风险间呈非线性关系。
Relationship between chronic kidney disease and subclinical hypothyroidism in T2DM subjects: a case-control and dose-response analysis
Objective: Update evidence indicated a positive association between subclinical hypothyroidism (SCH) and cardiovascular diseases. But the relationship to chronic kidney diseases (CKD) remains unclear. In this paper, we first performed a case-control study, and then supplied an accumulated evidence to ascertain the relationship between SCH and CKD. Methods: In this hospital-based, case-control study, we recruited 3 220 type 2 diabetic patients with euthyroid and 525 type 2 diabetic patients with SCH participants from January 2011 to December 2015 in Beijing, China. All English reports were searched in Medline, EMBASE and Google scholar databases for relevant studies on the relationship between SCH and CKD through Jan 2016. Meta-analysis was performed using STATA13.0 software. Five observational studies reporting the risk of SCH on the incidence of CKD were enrolled. Results: Our case-control study indicated that SCH was associated with CKD versus the euthyroid [odds ratio (95% CI): 1.26 (1.05~1.52)]. Accumulated evidence showed a significant relationship between SCH and CKD (summary OR 1.81; 95% CI: 1.43~2.29). The summary OR for incident CKD was1.68 (95% CI: 1.45~1.94) for the highest versus lowest TSH categories. Association between a nonlinear trend for TSH elevation with CKD was marginally significant by a dose-response meta-analysis (P=0.04). Dose-response linear increment of CKD events was explored (summary OR 1.09; 95% CI: 1.03~1.16 per incremental increased in TSH of 1 mIU/L). Conclusion: The present evidence suggested that SCH is probably a significant risk factor of CKD. Nonlinear trend is shown between TSH elevation and CKD.