Petersen Irene, Nicolaisen Sia Kromann, Ricciardi Federico, Sharma Manuj, Thomsen Reimar W, Baio Gianluca, Pedersen Lars
Department of Primary Care and Population Health, University College London, London, UK.
Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark.
Clin Epidemiol. 2020 Jun 3;12:569-577. doi: 10.2147/CLEP.S251704. eCollection 2020.
Individuals with type 2 diabetes (T2D) have a twofold increased risk for cardiovascular events (CVE), and CVE is responsible for nearly 80% of the mortality. Current treatment guidelines state that individuals should immediately initiate antidiabetic treatment and cardiovascular risk-factor management from T2D diagnosis. However, the evidence base is sparse, and randomized trials are unlikely to be conducted. We examined the impact of being eligible for T2D treatment, as determined by the threshold of HbA ≥6.5% (≥48 mmol/mol), on all-cause mortality and CVE. We hypothesised that individuals who were just above this threshold had a lower risk of CVE and all-cause mortality than individuals just below.
We used the regression discontinuity design (RDD), a quasi-experimental design, comparing rates of all-cause mortality and CVE in people just below and just above the eligibility for treatment threshold. We included Danish healthcare records from 43,070 individuals aged 40-80 years with no previous T2D record and the first record of HbA in the range of 6.0-7.0% (42-53 mmol/mol) between 2006 and 2014. In total, 36,360 individuals had the first record of HbA between 6.0% and 6.4% (42-47 mmol/mol), and 6710 individuals had a first record between 6.5% and 7.0% (48-53 mmol/mol). Individuals with a measurement just above 6.5% (48 mmol/mol) had a 21% lower rate of death or CVE, compared to those just below (hazard ratio: 0.79 (95% CI 0.69-0.90)). Few individuals received early metformin treatment. However, the chance of metformin treatment initiation within 3 months was substantially higher for individuals with an HbA measurement above (14%) than below (1%) the threshold.
Individuals with first record of HbA measure just above treatment threshold experienced a 21% lower rate of death or CVE than those just below. Lifestyle modifications and cardiovascular risk-factor management may contribute to this reduced rate.
2型糖尿病（T2D）患者发生心血管事件（CVE）的风险增加两倍，且CVE导致近80%的死亡率。当前治疗指南指出，个体应在T2D诊断时立即启动抗糖尿病治疗和心血管危险因素管理。然而，证据基础薄弱，且不太可能进行随机试验。我们研究了根据糖化血红蛋白（HbA）≥6.5%（≥48 mmol/mol）这一阈值确定的符合T2D治疗条件对全因死亡率和CVE的影响。我们假设，刚好高于此阈值的个体发生CVE和全因死亡的风险低于刚好低于该阈值的个体。
我们采用回归断点设计（RDD），这是一种准实验设计，比较刚好低于和刚好高于治疗阈值合格标准的人群的全因死亡率和CVE发生率。我们纳入了来自丹麦医疗记录的43070名40 - 80岁且既往无T2D记录、2006年至2014年间首次HbA记录在6.0 - 7.0%（42 - 53 mmol/mol）范围内的个体。总共有36360名个体的首次HbA记录在6.0%至6.4%（42 - 47 mmol/mol）之间，6710名个体的首次记录在6.5%至7.0%（48 - 53 mmol/mol）之间。与刚好低于该阈值的个体相比，测量值刚好高于6.5%（48 mmol/mol）的个体死亡或发生CVE的发生率低21%（风险比：0.79（95%置信区间0.69 - 0.90））。很少有个体接受早期二甲双胍治疗。然而，HbA测量值高于阈值（14%）的个体在3个月内开始使用二甲双胍治疗的可能性远高于低于阈值（1%）的个体。
首次HbA测量值刚好高于治疗阈值的个体死亡或发生CVE的发生率比刚好低于该阈值的个体低21%。生活方式改变和心血管危险因素管理可能有助于降低这一发生率。
