Increased risk of type 2 diabetes in Alzheimer disease
Increased risk of type 2 diabetes in Alzheimer disease
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DOI：
10.2337/diabetes.53.2.474
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发表时间：
2004-02-01
期刊：
影响因子：
7.7
通讯作者：
Butler, PC
中科院分区：
文献类型：
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作者：
Janson, J;Laedtke, T;Butler, PC
阿尔茨海默病和2型糖尿病的特点是随着年龄增长、遗传易感性和胰岛和大脑中相似的病理特征（阿尔茨海默病的淀粉样蛋白来源于大脑中的淀粉样蛋白，2型糖尿病的胰岛淀粉样蛋白来源于胰腺中的胰岛淀粉样多肽）患病率增加。越来越多的证据表明，大脑和胰腺中淀粉样蛋白沉积的前体分别与阿尔茨海默病和2型糖尿病的发病机制有关。鉴于这些相似之处，我们质疑是否存在一个共同的潜在机制，即易患胰岛和大脑淀粉样蛋白。为了解决这个问题，我们首先在一项基于社区的对照研究中检查了2型糖尿病的患病率，该研究是梅奥诊所阿尔茨海默病患者登记处（ADPR），该研究跟踪了阿尔茨海默病患者和未患阿尔茨海默病的对照组。除了这项临床研究，我们还对来自同一社区的尸检病例进行了病理研究，以确定阿尔茨海默病患者的胰岛淀粉样蛋白患病率是否增加，2型糖尿病患者的脑淀粉样蛋白患病率是否增加。纳入ADPR的患者（阿尔茨海默病患者n = 100，非阿尔茨海默病患者对照组n = 138）根据空腹血糖浓度（FPG）分为非糖尿病（FPG < 110 mg/dl）、空腹血糖受损（IFG, FPG 110-125 mg/dl）和2型糖尿病（FPG > 126 mg/dl）。并比较了阿尔茨海默病与非阿尔茨海默病对照者10年FPG的平均斜率。从105人的尸检标本中（首先，28例阿尔茨海默病患者与21例非阿尔茨海默病患者对照，其次，35例2型糖尿病患者与21例非2型糖尿病对照）检查了胰岛和脑淀粉样蛋白的存在。2型糖尿病（35%对18%，P < 0.05）和IFG（46%对24%，P < 0.01）在阿尔茨海默病患者中比非阿尔茨海默病患者更普遍，因此81%的阿尔茨海默病患者同时患有2型糖尿病或IFG。阿尔茨海默病患者FPG随年龄增长的斜率大于非阿尔茨海默病患者（P < 0.01）。与非阿尔茨海默病对照组相比，阿尔茨海默病患者胰岛淀粉样蛋白出现频率更高（P < 0.05），范围更广（P < 0.05）。然而，弥漫性和神经性斑块在2型糖尿病患者中并不比对照组更常见。在2型糖尿病患者中，2型糖尿病持续时间与弥漫性斑块（P < 0.001）和神经性斑块的密度相关（P < 0.01）。在这个来自明尼苏达州东南部的社区队列中，2型糖尿病和IFG在阿尔茨海默病患者中比在对照组中更常见，因为2型糖尿病的病理标志是胰岛淀粉样蛋白。然而，在2型糖尿病患者中，脑斑块的形成并没有增加，尽管当它存在时，它在一定程度上与糖尿病的持续时间相关。这些数据支持了阿尔茨海默病患者更容易患2型糖尿病的假设，以及这些疾病中导致脑细胞和β细胞损失的过程之间可能存在联系。中国糖尿病杂志（英文版），2004。
Alzheimer disease and type 2 diabetes are characterized by increased prevalence with aging, a genetic predisposition, and comparable pathological features in the islet and brain (amyloid derived from amyloid beta protein in the brain in Alzheimer disease and islet amyloid derived from islet amyloid polypeptide in the pancreas in type 2 diabetes). Evidence is growing to link precursors of amyloid deposition in the brain and pancreas with the pathogenesis of Alzheimer disease and type 2 diabetes, respectively. Given these similarities, we questioned whether there may be a common underlying mechanism predisposing to islet and cerebral amyloid. To address this, we first examined the prevalence of type 2 diabetes in a community-based controlled study, the Mayo Clinic Alzheimer Disease Patient Registry (ADPR), which follows patients with Alzheimer disease versus control subjects without Alzheimer disease. In addition to this clinical study, we performed a pathological study of autopsy cases from this same community to determine whether there is an increased prevalence of islet amyloid in patients with Alzheimer disease and increased prevalence of cerebral amyloid in patients with type 2 diabetes. Patients who were enrolled in the ADPR (Alzheimer disease n = 100, non-Alzheimer disease control subjects n = 138) were classified according to fasting glucose concentration (FPG) as nondiabetic (FPG < 110 mg/dl), impaired fasting glucose (IFG, FPG 110-125 mg/dl), and type 2 diabetes (FPG > 126 mg/dl). The mean slope of FPG over 10 years in each case was also compared between Alzheimer disease and non-Alzheimer disease control subjects. Pancreas and brain were examined from autopsy specimens obtained from 105 humans (first, 28 cases of Alzheimer disease disease vs. 21 non-Alzheimer disease control subjects and, second, 35 subjects with type 2 diabetes vs. 21 non-type 2 diabetes control subjects) for the presence of islet and brain amyloid. Both type 2 diabetes (35% vs. 18%; P < 0.05) and IFG (46% vs. 24%; P < 0.01) were more prevalent in Alzheimer disease versus non-Alzheimer disease control subjects, so 81% of cases of Alzheimer disease had either type 2 diabetes or IFG. The slope of increase of FPG with age over 10 years was also greater in Alzheimer disease than non-Alzheimer disease control subjects (P < 0.01). Islet amyloid was more frequent (P < 0.05) and extensive (P < 0.05) in patients with Alzheimer disease than in non-Alzheimer disease control subjects. However, diffuse and neuritic plaques were not more common in type 2 diabetes than in control subjects. In cases of type 2 diabetes when they were present, the duration of type 2 diabetes correlated with the density of diffuse (P < 0.001) and neuritic plaques (P < 0.01). In this community cohort from southeast Minnesota, type 2 diabetes and IFG are more common in patients with Alzheimer disease than in control subjects, as is the pathological hallmark of type 2 diabetes, islet amyloid. However, there was no increase in brain plaque formation in cases of type 2 diabetes, although when it was present, it correlated in extent with duration of diabetes. These data support the hypothesis that patients with Alzheimer disease are more vulnerable to type 2 diabetes and the possibility of linkage between the processes responsible for loss of brain-cells and beta-cells in these diseases. Diabetes 53: 474-481,2004.