School of Pharmacy, University of Waterloo, Kitchener, ON, Canada.
School of Public Health Sciences, University of Waterloo, Waterloo, ON, Canada.
Int J Epidemiol. 2023 Jun 6;52(3):908-920. doi: 10.1093/ije/dyac168.
Previous studies have shown hypoglycaemia to be associated with an increased risk of dementia; however, there are several design challenges to consider. The objective of this study is to assess the association between hypoglycaemia and dementia while addressing these challenges using a lag period, exposure density sampling (EDS) and inverse probability of treatment weighting (IPTW).
This was a population-based cohort using data (1996-2018) from British Columbia, Canada. From a cohort of incident type 2 diabetes patients aged 40-70 years, we created a dynamic sub-cohort of hypoglycaemia-exposed (≥1 episode requiring hospitalization or a physician visit) and unexposed individuals using EDS, in which four unexposed individuals per one exposed were randomly selected into risk sets based on diabetes duration and age. Follow-up was until dementia diagnosis, death, emigration or 31 December 2018. Those diagnosed with dementia within 2 years of follow-up were censored. We adjusted for confounding using IPTW and estimated the hazard ratio (HR, 95% CI) of dementia using weighted conditional cause-specific hazards risk models with death as a competing risk.
Among 13 970 patients with incident type 2 diabetes, 2794 experienced hypoglycaemia. There were 329 dementia events over a median (interquartile range: IQR) follow-up of 5.03 (5.7) years. IPTW resulted in well-balanced groups with weighted incidence rates (95% CI) of 4.59 (3.52, 5.98)/1000 person-years among exposed and 3.33 (2.58, 3.88)/1000 person-years among unexposed participants. The risk of dementia was higher among those with hypoglycaemia (HR, 1.83; 95% CI 1.31, 2.57).
After addressing several methodological challenges, we showed that hypoglycaemia contributes to an increased risk of all-cause dementia among patients with type 2 diabetes.
先前的研究表明低血糖与痴呆风险增加有关，但在设计上存在一些挑战需要考虑。本研究旨在通过使用滞后期、暴露密度抽样（EDS）和逆概率治疗加权（IPTW）来评估低血糖与痴呆之间的关联，同时解决这些挑战。
这是一项基于人群的队列研究，使用了来自加拿大不列颠哥伦比亚省的 1996 年至 2018 年的数据。我们从年龄在 40-70 岁的 2 型糖尿病患者的队列中创建了一个低血糖暴露（≥1 次需要住院或看医生的发作）和未暴露个体的动态亚队列，其中每 1 个暴露个体随机选择 4 个未暴露个体进入风险集，根据糖尿病持续时间和年龄进行分组。随访至痴呆诊断、死亡、移民或 2018 年 12 月 31 日。随访 2 年内被诊断为痴呆的患者被删失。我们使用 IPTW 调整混杂因素，并使用加权条件因果风险模型估计痴呆的风险比（HR，95%置信区间），以死亡为竞争风险。
在 13970 例 2 型糖尿病患者中，有 2794 例发生低血糖。中位（四分位距：IQR）随访 5.03（5.7）年后，发生了 329 例痴呆事件。IPTW 使两组得到了很好的平衡，暴露组加权发生率（95%CI）为 4.59（3.52，5.98）/1000人年，未暴露组为 3.33（2.58，3.88）/1000人年。低血糖患者痴呆风险较高（HR，1.83；95%CI 1.31，2.57）。
在解决了一些方法学挑战后，我们表明 2 型糖尿病患者的低血糖与全因痴呆风险增加有关。
