Laboratory for Molecular Cardiology, Department of Cardiology, Copenhagen University Hospital, Copenhagen, Denmark.
Laboratory for Molecular Cardiology, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
Diabetes Obes Metab. 2020 Feb;22(2):231-242. doi: 10.1111/dom.13891. Epub 2019 Nov 18.
AIM: To investigate the effect of diabetes duration on glycaemic control, measured using mean glycated haemoglobin (HbA1c) level, and mortality risk within different age, sex and clinically relevant, comorbidity-defined subgroups in an elderly population with type 2 diabetes (T2D). METHODS: We studied older (≥65 years) primary care patients with T2D, who had three successive annual measurements of HbA1c taken between 2005 and 2013. The primary exposure was the mean of all three HbA1c measurements. Follow-up began on the date of the third measurement. Individual mean HbA1c levels were categorized into clinically relevant groups (<6.5% [<48 mmol/mol]; 6.5%-6.9% [48-52 mmol/mol]; 7%-7.9% [53-63 mmol/mol]; 8%-8.9% [64-74 mmol/mol]; and ≥9% [≥75 mmol/mol]). We used multiple Cox regression to study the effect of glycaemic control on the hazard of all-cause mortality, adjusted for age, sex, use of concomitant medication, and age- and disease-related comorbidities. RESULTS: A total of 9734 individuals were included. During a median (interquartile range) follow-up of 7.3 (4.6-8.7) years, 3320 individuals died. We found that the effect of mean HbA1c on all-cause mortality depended on the duration of diabetes (P for interaction <.001). For individuals with short diabetes duration (<5 years), the risk of death increased with poorer glycaemic control (increasing HbA1c), whereas for individuals with longstanding diabetes (≥5 years), we found a J-shaped association, where a mean HbA1c level between 6.5% and 7.9% [48 and 63 mmol/mol] was associated with the lowest risk of death. For individuals with longstanding diabetes, both low (<6.5% [<48 mmol/mol]; hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.07-1.37, P = .002) and high mean HbA1c levels (≥9.0% [≥75 mmol/mol]; HR 1.60, 95% CI 1.28-1.99, P < .001) were associated with an increased risk of death. We also calculated 5-year absolute risks of all-cause mortality, separately for short and long diabetes duration, and found similar risk patterns across different age groups, sex and comorbidity strata. CONCLUSIONS: In elderly individuals with T2D, the effect of glycaemic control (measured by HbA1c) on all-cause mortality depended on the duration of diabetes. Of particular clinical importance, we found that strict glycaemic control was associated with an increased risk of death among individuals with long (≥ 5 years) diabetes duration. Conversely, for individuals with short diabetes duration, strict glycaemic control was associated with the lowest risk of death. These results indicate that tight glycemic control may be beneficial in people with short duration of diabetes, whereas a less stringent target may be warranted with longer diabetes exposure.
目的:研究不同年龄、性别和临床相关合并症定义亚组的 2 型糖尿病(T2D)老年人群中,糖尿病病程对糖化血红蛋白(HbA1c)平均水平所代表的血糖控制情况以及死亡率风险的影响。
方法:我们研究了≥65 岁的 T2D 初级保健患者,这些患者在 2005 年至 2013 年期间连续三年接受了 HbA1c 三次年度测量。主要暴露因素是所有三次 HbA1c 测量的平均值。随访从第三次测量的日期开始。个体平均 HbA1c 水平被分为具有临床意义的组(<6.5%[<48mmol/mol];6.5%-6.9%[48-52mmol/mol];7%-7.9%[53-63mmol/mol];8%-8.9%[64-74mmol/mol];和≥9%[≥75mmol/mol])。我们使用多 Cox 回归分析研究了血糖控制对全因死亡率的危害效应,调整了年龄、性别、同时使用药物以及与年龄和疾病相关的合并症。
结果:共纳入了 9734 名个体。在中位数(四分位距)7.3(4.6-8.7)年的随访期间,有 3320 人死亡。我们发现 HbA1c 平均水平对全因死亡率的影响取决于糖尿病的病程(P 交互<.001)。对于病程较短(<5 年)的个体,血糖控制越差(HbA1c 升高),死亡风险越高,而对于病程较长(≥5 年)的个体,我们发现存在 J 形关联,HbA1c 水平在 6.5%至 7.9%[48 至 63mmol/mol]之间与死亡风险最低相关。对于病程较长的个体,HbA1c 水平较低(<6.5% [<48mmol/mol];危险比[HR] 1.21,95%置信区间[CI] 1.07-1.37,P=0.002)和较高(≥9.0% [≥75mmol/mol];HR 1.60,95%CI 1.28-1.99,P<.001)与死亡风险增加相关。我们还分别针对病程较短和较长的个体计算了全因死亡率的 5 年绝对风险,在不同年龄组、性别和合并症分层中发现了相似的风险模式。
结论:在患有 T2D 的老年个体中,血糖控制(通过 HbA1c 测量)对全因死亡率的影响取决于糖尿病的病程。具有重要临床意义的是,我们发现对于病程较长(≥5 年)的个体,严格的血糖控制与死亡风险增加相关。相反,对于病程较短的个体,严格的血糖控制与最低的死亡风险相关。这些结果表明,在病程较短的个体中,严格的血糖控制可能是有益的,而对于较长的糖尿病暴露,可能需要更宽松的目标。
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