Obesity, insulin resistance, and Alzheimer's disease.
Obesity, insulin resistance, and Alzheimer's disease.
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DOI：
10.1038/oby.2012.19
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发表时间：
2012-08
期刊：
影响因子：
6.9
通讯作者：
Schwartz, Robert S.
中科院分区：
文献类型：
--
作者：
Hildreth, Kerry L.;Van Pelt, Rachael E.;Schwartz, Robert S.
肥胖在我们的社会中已经达到流行病的比例，影响了超过三分之一的美国成年人，其中三分之二超重或肥胖（1）。年轻年龄组中超重和肥胖的趋势令人担忧; 20-39岁的男性中有27.5%和女性中有34.0%肥胖（1），2-19岁的儿童中有11.3%处于或高于2000年BMI年龄增长图表的第97百分位数（2）。大多数超重或肥胖的人也有胰岛素抵抗（3）。肥胖和胰岛素抵抗（IR）的不良健康后果已得到充分证实，特别是在心血管疾病和2型糖尿病（T2 DM）方面。最近，这些条件也与认知障碍和阿尔茨海默病（AD）的风险增加有关（4）。AD是痴呆症最常见的原因，也是美国65岁及以上人群的第五大死亡原因（5）。随着人口老龄化，美国受AD影响的患者数量预计将从目前的530万增加到2050年的1600万（5），这给患者、护理人员和医疗保健系统带来了巨大的货币和非货币成本。目前批准的AD治疗为一些患者提供了适度的症状获益，但不影响基础病理学。确定可改变的风险因素，以延迟或预防进展为临床痴呆和功能障碍，可能会对AD的患病率和相关费用产生巨大影响。虽然目前没有足够的证据将任何可改变的风险因素与AD紧密联系起来，但大量的经验证据支持几种心血管风险因素的作用，包括肥胖、高血压、血脂异常、糖尿病和IR（6）。所有这些因素都与AD的发生和进展有关，无论是单独还是总体（即代谢综合征）（7，8）。越来越多的文献表明，胰岛素调节异常是AD及其前驱症状轻度认知障碍的风险因素（4，9，10）。此外，IR代表了糖尿病发病过程中的临床前阶段，在此期间干预措施可能会产生最大效果。我们在这里集中讨论IR在AD发病机制中的潜在作用，并讨论了针对IR的干预措施作为预防或延迟AD进展的可能方法。
Obesity has reached epidemic proportions in our society, affecting over one-third of US adults, with two-thirds overweight or obese (1). Trends toward overweight and obesity among younger age groups are alarming; 27.5% of men and 34.0% of women ages 20–39 are obese (1), and 11.3% of children 2–19 years of age are at or above the 97th percentile for 2000 BMI-for-age growth charts (2). The majority of overweight or obese individuals are also insulin resistant (3). The adverse health consequences of obesity and insulin resistance (IR) are well-documented, particularly with respect to cardiovascular disease and type 2 diabetes mellitus (T2DM). More recently, these conditions have also been linked to an increased risk of cognitive impairment and Alzheimer’s disease (AD)(4). AD is the most common cause of dementia, and the fifth leading cause of death in the United States among those 65 and older (5). The number of patients affected by AD in the United States is projected to increase from 5.3 million currently, to 16 million in 2050 as the population ages (5), imposing extraordinary monetary and non-monetary costs on patients, caregivers, and the healthcare system. Currently approved therapies for AD provide modest symptomatic benefits to some patients, but do not affect the underlying pathology. Identification of modifiable risk factors to delay or prevent progression to clinical dementia and functional impairment could have a dramatic impact on the prevalence and costs associated with AD. Although there is currently insufficient evidence to firmly link any modifiable risk factor with AD, substantial empirical evidence supports a role for several cardiovascular risk factors, including obesity, hypertension, dyslipidemia, diabetes, and IR (6). All of these factors have been implicated in the development and progression of AD, both individually and in aggregate (ie, the metabolic syndrome)(7, 8). A growing body of literature has demonstrated insulin dysregulation as a risk factor for both AD and its prodrome, mild cognitive impairment (4, 9, 10). Furthermore, IR represents a preclinical stage on the path to diabetes during which efforts at intervention are likely to have maximal effect. We focus here on the potential role of IR in the pathogenesis of AD, and discuss interventions that target IR as possible approaches to prevent or delay progression of AD.
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影响因子：
3.7
作者：
Benedict, C;Hallschmid, M;Kern, W
通讯作者：
Kern, W
影响因子：
4
作者：
Baker, Laura D.;Frank, Laura L.;Craft, Suzanne
通讯作者：
Craft, Suzanne
影响因子：
8.3
作者：
Cardillo, C;Campia, U;Panza, JA
通讯作者：
Panza, JA
影响因子：
3
作者：
Choopani, S.;Moosavi, M.;Naghdi, N.
通讯作者：
Naghdi, N.
DOI：
10.1073/pnas.1015950108
发表时间：
2011-02-15
影响因子：
11.1
作者：
Erickson, Kirk I.;Voss, Michelle W.;Kramer, Arthur F.
通讯作者：
Kramer, Arthur F.