Mean HbA1c, HbA1c variability, and mortality in people with diabetes aged 70 years and older: a retrospective cohort study
Mean HbA1c, HbA1c variability, and mortality in people with diabetes aged 70 years and older: a retrospective cohort study
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DOI：
10.1016/s2213-8587(18)30048-2
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发表时间：
2018-06-01
影响因子：
44.5
通讯作者：
Sinclair, Alan J.
中科院分区：
文献类型：
--
作者：
Forbes, Angus;Murrells, Trevor;Sinclair, Alan J.
背景近年来，由于担心更严格的目标与死亡率的增加相关，针对老年人的血糖控制目标已被修订。我们的目标是调查老年糖尿病患者的血糖控制(平均HbA(1c))和变异性(HbA(1c)随时间的变异性)与死亡率之间的关系。方法我们使用健康改善网络数据库进行了一项为期5年的回溯性队列研究，其中包括英国587家初级保健机构的数据。研究对象包括年龄在70岁及以上的1型或2型糖尿病患者。主要结果是达到全因死亡的时间。我们的主要暴露变量是平均糖化血红蛋白(1c)和随时间变化的糖化血红蛋白(1c)。观察包括4年的磨合期(从2003年开始)作为基线，并有5年的随访(从2007年到2012年)。我们在三个模型中评估了平均HBA(1c)：2003-06年的基线平均HbA(1c)(模型1)、整个随访期的平均值(模型2)和随时间变化的年度更新平均值(模型3)。根据2003-2012年间HbA(1c)变化达到或超过0.5%(5.5 mm o l/m ol)的次数计算变异性分数(从0[低]到100[高])，或根据每个模型的年平均值变化计算到死亡率点，每个模型至少有6个读数。结果队列由54 803人组成，其中17 680人在观察期内死亡，其中28 017人死亡8614人(30.7%)，26 786人死亡9066人(33.8%)。总死亡率为每1000人年77人(女性为每1000人年73人，男性为每1000人年80人)。数据显示死亡风险在两性中呈J型分布，随着HbA(1c)值大于8%(·莫罗/摩尔)和小于6%(42mmoL/摩尔)而显著增加，尽管在模型1中，对于HbA(1c)值在8%(·莫罗/摩尔)到小于8.5%(<；69 mmol/摩尔)的男性和在模型1和模型3中，对于HbA(1c)值分别小于6%(42 mmol/摩尔)的男性，超额死亡风险并不显著。在所有模型中，死亡率随着HbA(1c)变异性的增加而显著增加(总体上和性别)。在模型2 HBA(1c)测量中，比较血糖变异性评分大于80到100的患者与血糖变异性评分为0到20的患者的调整后风险比，女性为2.47(95%可信区间2.08-2.93)，男性为2.21(1.87-2.61)。将平均糖化血红蛋白(1c)模型与血糖变异性分数进行拟合，改变了风险分布；这一观察结果在模型2分析中最为明显，其中只有糖化血红蛋白(1c)值在女性大于9.5%(80 mm o l/m ol)和男性大于9%(75 m ol/m ol)时，风险显著增加才明显。解释血糖控制水平低和高都与死亡风险增加相关，变异性水平似乎也是一个重要因素，这表明在中等范围内稳定的血糖水平与较低的风险相关。用糖化血红蛋白(1c)随时间变化来评估血糖变异性，可能是了解老年糖尿病患者死亡风险的一个重要因素。版权所有(C)2018爱思唯尔有限公司。保留所有权利。
Background Glycaemic targets for older people have been revised in recent years because of concern that more stringent targets are associated with increased mortality. We aimed to investigate the association between glycaemic control (mean HbA(1c)) and variability (variability of HbA(1c) over time) and mortality in older people with diabetes.Methods We did a 5-year retrospective cohort study using The Health Improvement Network database, which includes data from 587 UK primary care practices. We included patients of either sex who were aged 70 years and older with type 1 or type 2 diabetes. The primary outcome was time to all-cause mortality. Our primary exposure variables were mean HbA(1c) and variability of HbA(1c) over time. The observation included a 4-year run-in period (from 2003) as a baseline, with a 5-year follow-up (from 2007 to 2012). We assessed mean HbA(1c) in three models: a baseline mean HbA(1c) for 2003-06 (model 1), the mean across the whole follow-up period (model 2), and a time-varying yearly updated mean (model 3). A variability score (from 0 [low] to 100 [high]) was calculated on the basis of number of changes in HbA(1c) of 0.5% (5.5 mmol/mol) or more from 2003 to 2012 or to the point of mortality, based on changes in the annual mean as per each model with a minimum of six readings.Findings The cohort consisted of 54 803 people, of whom 17 680 (8614 [30.7%] of 28 017 women and 9066 [33.8%] of 26 786 men) died during the observation period. The overall mortality rate was 77 per 1000 person-years (73 per 1000 person-years for women and 80 per 1000 person-years for men). The data showed a J-shaped distribution for mortality risk in both sexes, with significant increases with HbA(1c) values greater than 8% (64 mmol/mol) and less than 6% (42 mmol/mol), although excess mortality risk was non-significant in model 1 for men at HbA(1c) values of 8% (64 mmol/mol) to less than 8.5% (< 69 mmol/mol) and in models 1 and 3 for both sexes assessed individually at HbA(1c) values less than 6% (42 mmol/mol). Mortality increased substantially with increasing HbA(1c) variability in all models (overall and for both sexes). For the model 2 HbA(1c) measure, the adjusted hazard ratios comparing patients with a glycaemic variability score of more than 80 to 100 with those with a score of 0 to 20 were 2.47 (95% CI 2.08-2.93) for women and 2.21 (1.87-2.61) for men. Fitting the mean HbA(1c) models with the glycaemic variability score altered the risk distribution; this observation was most marked in the model 2 analysis, in which a significant increased risk was only apparent with HbA(1c) values greater than 9.5% (80 mmol/mol) in women and 9% (75 mmol/mol) in men.Interpretation Both low and high levels of glycaemic control were associated with an increased mortality risk, and the level of variability also seems to be an important factor, suggesting that a stable glycaemic level in the middle range is associated with lower risk. Glycaemic variability, as assessed by variability over time in HbA(1c), might be an important factor in understanding mortality risk in older people with diabetes. Copyright (C) 2018 Elsevier Ltd. All rights reserved.