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.

中文翻译：

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糖尿病持续时间对2型糖尿病老年人血糖控制与死亡风险之间关系的影响。

目的探讨糖尿病持续时间对血糖控制的影响，使用平均糖化血红蛋白（HbA1c）水平进行测量，以及不同年龄，性别和临床相关，合并症定义的亚组在2型糖尿病（T2D）老年人群中的死亡风险。方法我们研究了年龄较大（≥65岁）的T2D初级保健患者，他们在2005年至2013年间连续进行了三次年度HbA1c年度测量。主要暴露水平是所有三项HbA1c测量值的平均值。在第三次测量日期开始随访。个体平均HbA1c水平分为临床相关组（<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]和≥9％[≥75mmol / mol]）。我们使用多元Cox回归研究了血糖控制对全因死亡率危害的影响，并根据年龄，性别，使用伴随药物以及与年龄和疾病相关的合并症进行了调整。结果共纳入9734人。在7.3（4.6-8.7）年的中位（四分位间距）随访中，有3320人死亡。我们发现，平均HbA1c对全因死亡率的影响取决于糖尿病的持续时间（交互作用P <.001）。对于糖尿病持续时间短（<5年）的个体，血糖控制较差（HbA1c增加）会增加死亡风险，而对于长期糖尿病（≥5年）的个体，我们发现呈J型关联，即平均HbA1c在6.5％和7.9％[48和63 mmol / mol]之间的水平与最低的死亡风险相关。对于长期患有糖尿病的个体，既低（<6.5％[<48 mmol / mol]，危险比[HR] 1.21，95％置信区间[CI] 1.07-1.37，P = .002）和高平均HbA1c水平（≥ 9.0％[≥75mmol / mol]； HR 1.60、95％CI 1.28-1.99，P <.001）与死亡风险增加相关。我们还分别针对短期和长期糖尿病持续时间分别计算了全因死亡率的5年绝对风险，并发现了不同年龄段，性别和合并症人群的相似风险模式。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持续时间。在临床上特别重要，我们发现严格的血糖控制与糖尿病持续时间长（≥5年）的个体死亡风险增加相关。反过来，对于糖尿病持续时间短的人，严格的血糖控制与最低的死亡风险相关。这些结果表明，严格的血糖控制对糖尿病持续时间短的人群可能有益，而对糖尿病的暴露时间越长，目标人群就越不严格。