Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan; Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei City, Taiwan.
Division of Gastroenterology, Department of Internal Medicine, Taipei Beitou Health Management Hospital, Taipei, Taiwan.
Prog Neuropsychopharmacol Biol Psychiatry. 2017 Oct 3;79(Pt B):77-83. doi: 10.1016/j.pnpbp.2017.06.002. Epub 2017 Jun 3.
Epidemiological evidence reveals that patients with type 2 diabetes mellitus (T2DM) have an increased risk of neurodegenerative diseases (NDs), including dementia and Parkinson's disease (PD). The effects of metformin exposure on dementia and PD risk in patients with T2DM are unknown. We evaluated the effects of metformin exposure on the risk of dementia and PD in patients with T2DM. We performed a cohort study by using Taiwan's National Health Insurance Research Database. We recruited 4651 patients in the metformin cohort and a comparable number of nonmetformin controls by using propensity score matching. Multivariate Cox proportional hazards regression was used to estimate the effects of metformin on the risk of dementia and PD after adjustment for several confounding factors. During the 12-year follow-up, the metformin cohort exhibited a higher risk of PD than the nonmetformin cohort (hazard ratio [HR]: 2.27, 95% confidence interval [CI]=1.68-3.07). The metformin cohort had an increased risk of all-cause dementia (HR: 1.66, 95% CI=1.35-2.04). Moreover, metformin exposure increased the risk of Alzheimer's disease (HR: 2.13, 95% CI=1.20-3.79) and vascular dementia (HR: 2.30, 95% CI=1.25-4.22). The effects of exposure duration and dosage on dementia and PD occurrence were also observed. Long-term metformin exposure in patients with T2DM may lead to the development of NDs, including dementia and PD. Additional large-scale, prospective controlled trials are required to confirm the observed association in patients with T2DM.
流行病学证据表明，2 型糖尿病（T2DM）患者发生神经退行性疾病（NDs）的风险增加，包括痴呆和帕金森病（PD）。二甲双胍暴露对 T2DM 患者痴呆和 PD 风险的影响尚不清楚。我们评估了二甲双胍暴露对 T2DM 患者痴呆和 PD 风险的影响。我们使用台湾全民健康保险研究数据库进行了一项队列研究。通过倾向评分匹配，我们招募了 4651 名二甲双胍队列患者和数量相当的非二甲双胍对照组。多变量 Cox 比例风险回归用于估计二甲双胍在调整了几个混杂因素后对痴呆和 PD 风险的影响。在 12 年的随访期间，二甲双胍队列的 PD 风险高于非二甲双胍队列（风险比 [HR]：2.27，95%置信区间 [CI]=1.68-3.07）。二甲双胍队列发生全因痴呆的风险增加（HR：1.66，95% CI=1.35-2.04）。此外，二甲双胍暴露增加了阿尔茨海默病（HR：2.13，95% CI=1.20-3.79）和血管性痴呆（HR：2.30，95% CI=1.25-4.22）的风险。还观察到暴露持续时间和剂量对痴呆和 PD 发生的影响。T2DM 患者长期二甲双胍暴露可能导致 NDs 的发生，包括痴呆和 PD。需要进一步的大规模、前瞻性对照试验来证实 T2DM 患者中观察到的相关性。
