Insulin metabolism and the risk of Alzheimer disease The Rotterdam Study
Insulin metabolism and the risk of Alzheimer disease The Rotterdam Study
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DOI：
10.1212/wnl.0b013e3181ffe4f6
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发表时间：
2010-11-30
期刊：
影响因子：
9.9
通讯作者：
Breteler, M. M. B.
中科院分区：
文献类型：
--
作者：
Schrijvers, E. M. C.;Witteman, J. C. M.;Breteler, M. M. B.
目的：糖尿病与阿尔茨海默病（Alzheimer disease，AD）的发病风险增加有关，但其作用机制仍存在争议。可能的病理生理机制是葡萄糖毒性和胰岛素对淀粉样蛋白代谢的直接影响。大多数研究的随访时间较短，糖尿病对AD风险的长期影响尚不清楚。我们研究空腹血糖、胰岛素水平和胰岛素抵抗是否与AD的风险相关，以及这种风险是否随着时间的推移而恒定。方法：这项研究是基于鹿特丹研究的3,139名参与者，这是一项以人群为基础的队列研究。所有受试者均无痴呆，无糖尿病史，基线时测量空腹血糖和胰岛素水平。胰岛素抵抗估计与稳态模型评估。我们调查了空腹血糖，胰岛素和胰岛素抵抗是如何与AD的风险在3个不同的阶层根据时间到事件，使用考克斯比例风险models.Results：在随访期间，211名参与者开发AD，其中71人在3年内的基线。胰岛素水平和胰岛素抵抗与基线3年内AD的高风险相关。3年后，风险不再增加。葡萄糖与AD的高风险无关。结论：我们的研究结果表明，胰岛素代谢影响AD的临床表现仅在3年内。神经病学（R）2010;75：1982-1987
Objective: Diabetes mellitus has been associated with an increased risk of Alzheimer disease (AD), but how it exerts its effect remains controversial. Possible pathophysiologic mechanisms are glucose toxicity and a direct effect of insulin on amyloid metabolism. Most studies had short follow-up, and longer-term effects of diabetes on AD risk are unknown. We investigated whether fasting glucose and insulin levels and insulin resistance are associated with the risk of AD and whether this risk is constant over time.Methods: The study was based on 3,139 participants of the Rotterdam Study, a population-based cohort study. All subjects were free from dementia, did not have a history of diabetes, and had fasting levels of glucose and insulin measured at baseline. Insulin resistance was estimated with the homeostasis model assessment. We investigated how fasting glucose, insulin, and insulin resistance are related to the risk of AD in 3 different strata according to time-to-event, using Cox proportional hazards models.Results: During follow-up, 211 participants developed AD, 71 of them within 3 years of baseline. Levels of insulin and insulin resistance were associated with a higher risk of AD within 3 years of baseline. After 3 years, the risk was no longer increased. Glucose was not associated with a higher risk of AD. There was no interaction of APOE epsilon 4 carriership and insulin metabolism on the risk of AD.Conclusions: Our findings suggest that insulin metabolism influences the clinical manifestation of AD only within 3 years. Neurology (R) 2010;75:1982-1987