Joseph Magagnoli, Tammy H Cummings, James W Hardin, Jayakrishna Ambati, S Scott Sutton
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One AChEi, galantamine, also directly agonizes α7nAChRs, potentially enhancing its anti-inflammatory properties.</p><p><strong>Objective: </strong>This study aimed to investigate the association between AChEi use, particularly galantamine, and T2DM risk in AD patients.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of Veterans Health Administration (VA) data, examining early- and late-onset AD patients receiving galantamine or other AD medications. Propensity score matching was used to balance groups and minimize confounding. Cox proportional hazard models assessed T2DM risk for galantamine, other AChEis and memantine.</p><p><strong>Results: </strong>A total of 40 065 AD patients were included in the study. Among early-onset AD patients, galantamine use significantly reduced T2DM risk (hazard ratio [HR] = 0.80, 95% confidence interval [CI]: 0.66-0.98). Memantine also showed a protective effect (HR = 0.82, 95% CI: 0.69-1) in this group. Neither galantamine nor memantine influenced T2DM risk in late-onset AD. Other AD medications showed no association with T2DM risk.</p><p><strong>Conclusion: </strong>Galantamine use was associated with a lower risk of T2DM in early-onset AD patients, potentially due to enhanced anti-inflammatory effects through both AChE inhibition and direct α7nAChR agonism. Memantine also demonstrated a protective effect. These findings suggest potential new applications for existing AD medications in T2DM prevention, particularly in early-onset AD patients. 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引用次数: 0
摘要
背景：慢性炎症是 2 型糖尿病（T2DM）发病的关键因素。胆碱能抗炎途径（CAP）通过激活巨噬细胞上的α7烟碱乙酰胆碱受体（α7nAChRs），抑制促炎细胞因子，从而减轻炎症反应。乙酰胆碱酯酶抑制剂（AChEis）主要用于治疗阿尔茨海默病（AD），可通过 CAP 发挥抗炎作用。其中一种乙酰胆碱酯酶抑制剂加兰他敏还能直接激动α7nAChRs，从而增强其抗炎特性：本研究旨在调查 AChEi（尤其是加兰他敏）的使用与 AD 患者 T2DM 风险之间的关联：我们对退伍军人健康管理局（VA）的数据进行了回顾性分析，研究了接受加兰他敏或其他AD药物治疗的早期和晚期AD患者。我们采用倾向评分匹配法来平衡各组，并最大限度地减少混杂因素。Cox 比例危险模型评估了加兰他敏、其他 AChEis 和美金刚的 T2DM 风险：研究共纳入了 40 065 名 AD 患者。在早发AD患者中，使用加兰他敏可显著降低T2DM风险（危险比[HR] = 0.80，95%置信区间[CI]：0.66-0.98）。美金刚也显示出对该组患者的保护作用（HR = 0.82，95% CI：0.69-1）。加兰他敏和美金刚均不影响晚发型AD患者的T2DM风险。结论：使用加兰他敏和美金刚均不会影响晚发型AD患者的T2DM风险：结论：使用加兰他敏可降低早发AD患者的T2DM风险，这可能是由于通过抑制乙酰胆碱酯酶和直接激动α7nAChR增强了抗炎作用。美金刚也显示出保护作用。这些研究结果表明，现有的抗多发性硬化药物在预防 T2DM 方面可能会有新的应用，尤其是在早期发病的多发性硬化患者中。还需要进一步的研究，包括针对不同人群的随机对照试验，以证实这些结果及其内在机制。
Targeting the cholinergic anti-inflammatory pathway for type 2 diabetes prevention: A retrospective cohort study.
Background: Chronic inflammation is a key factor in type 2 diabetes mellitus (T2DM) development. The cholinergic anti-inflammatory pathway (CAP) reduces inflammation by activating α7 nicotinic acetylcholine receptors (α7nAChRs) on macrophages, suppressing proinflammatory cytokines. Acetylcholinesterase inhibitors (AChEis), primarily used for Alzheimer's disease (AD), may exert anti-inflammatory effects through the CAP. One AChEi, galantamine, also directly agonizes α7nAChRs, potentially enhancing its anti-inflammatory properties.
Objective: This study aimed to investigate the association between AChEi use, particularly galantamine, and T2DM risk in AD patients.
Methods: We conducted a retrospective analysis of Veterans Health Administration (VA) data, examining early- and late-onset AD patients receiving galantamine or other AD medications. Propensity score matching was used to balance groups and minimize confounding. Cox proportional hazard models assessed T2DM risk for galantamine, other AChEis and memantine.
Results: A total of 40 065 AD patients were included in the study. Among early-onset AD patients, galantamine use significantly reduced T2DM risk (hazard ratio [HR] = 0.80, 95% confidence interval [CI]: 0.66-0.98). Memantine also showed a protective effect (HR = 0.82, 95% CI: 0.69-1) in this group. Neither galantamine nor memantine influenced T2DM risk in late-onset AD. Other AD medications showed no association with T2DM risk.
Conclusion: Galantamine use was associated with a lower risk of T2DM in early-onset AD patients, potentially due to enhanced anti-inflammatory effects through both AChE inhibition and direct α7nAChR agonism. Memantine also demonstrated a protective effect. These findings suggest potential new applications for existing AD medications in T2DM prevention, particularly in early-onset AD patients. Further research, including randomized controlled trials with diverse populations, is needed to confirm these results and the underlying mechanisms.
期刊介绍：
Diabetes, Obesity and Metabolism is primarily a journal of clinical and experimental pharmacology and therapeutics covering the interrelated areas of diabetes, obesity and metabolism. The journal prioritises high-quality original research that reports on the effects of new or existing therapies, including dietary, exercise and lifestyle (non-pharmacological) interventions, in any aspect of metabolic and endocrine disease, either in humans or animal and cellular systems. ‘Metabolism’ may relate to lipids, bone and drug metabolism, or broader aspects of endocrine dysfunction. Preclinical pharmacology, pharmacokinetic studies, meta-analyses and those addressing drug safety and tolerability are also highly suitable for publication in this journal. Original research may be published as a main paper or as a research letter.
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