2型糖尿病患者糖化血红蛋白（HbA1c）与全因死亡率的关系呈J形：观察性研究的荟萃分析
The HbA1c and all-cause mortality relationship in patients with type 2 diabetes is J-shaped: a meta-analysis of observational studies.
作者信息
Arnold Luke W, Wang Zhiqiang
机构信息
Centre for Chronic Disease, The University of Queensland School of Medicine, Royal Brisbane and Women's Hospital, Herston QLD 4029, Australia.
出版信息
Rev Diabet Stud. 2014 Summer;11(2):138-52. doi: 10.1900/RDS.2014.11.138. Epub 2014 Aug 10.
BACKGROUND
Low blood glucose and HbA1c levels are recommended in the literature on management of diabetes. However, data have shown that low blood glucose is associated with serious adverse effects for the patients and the recommendation has been criticized. Therefore, this article revisits the relationship between HbA1c and all-cause mortality by a meta-analysis of observational studies.
AIM
The aim of this study is to determine whether there is a J- or U-shaped non-linear relationship between HbA1c and all-cause mortality in type 2 diabetes patients, implying an increased risk to premature all-cause mortality at high and low levels of HbA1c.
METHODS
A comprehensive literature search was conducted using PubMed, Medline, and Cochrane Library databases with strict inclusion/exclusion criteria. The published adjusted hazard ratios (HR) with 95% confidence intervals of all-cause mortality for each HbA1c category and per study were analyzed. Fractional polynomial regression was used with random effect modeling to assess the non-linear relationship of the HR trends between studies. Seven eligible observational studies with a total of 147,424 participants were included in the study.
RESULTS
A significant J-shaped relationship was observed between HbA1c and all-cause mortality. Crude relative risk for all-cause mortality identified a decreased risk per 1% increase in HbA1c below 7.5% (58 mmol/mol) (0.90, CI 0.86-0.94) and an increased risk per 1% increase in HbA1c above 7.5% (58 mmol/mol) (1.04, CI 1.01-1.06). Observational studies revealed a J-shaped relationship between HbA1c and all-cause mortality, equivalent to an increased risk of mortality at high and low HbA1c levels.
CONCLUSIONS
This increased mortality at high and low HbA1c levels has significant implications on investigating optimum clinical HbA1c targets as it suggests that there are upper and lower limits for creating a 'security zone' for diabetes management.
背景
糖尿病管理文献推荐较低的血糖和糖化血红蛋白（HbA1c）水平。然而，数据显示低血糖会给患者带来严重不良反应，该推荐因此受到批评。因此，本文通过对观察性研究进行荟萃分析，重新审视HbA1c与全因死亡率之间的关系。
目的
本研究的目的是确定2型糖尿病患者的HbA1c与全因死亡率之间是否存在J型或U型非线性关系，这意味着HbA1c处于高水平和低水平时，过早全因死亡风险会增加。
方法
使用PubMed、Medline和Cochrane图书馆数据库进行全面的文献检索，设定严格的纳入/排除标准。分析每项研究中每个HbA1c类别全因死亡率的已发表调整风险比（HR）及95%置信区间。采用分数多项式回归和随机效应模型评估各研究间HR趋势的非线性关系。该研究纳入了7项符合条件的观察性研究，共147,424名参与者。
结果
观察到HbA1c与全因死亡率之间存在显著的J型关系。全因死亡率的粗相对风险显示，HbA1c低于7.5%（58 mmol/mol）时，每增加1%，风险降低（0.90，CI 0.86 - 0.94）；HbA1c高于7.5%（58 mmol/mol）时，每增加1%，风险增加（1.04，CI 1.01 - 1.06）。观察性研究揭示了HbA1c与全因死亡率之间的J型关系，即HbA1c处于高水平和低水平时死亡风险增加。
结论
HbA1c处于高水平和低水平时死亡率增加，这对研究最佳临床HbA1c目标具有重要意义，因为这表明糖尿病管理的“安全区”存在上限和下限。
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