2型糖尿病海马胰岛素抵抗与认知功能障碍的研究进展

<正>全球糖尿病患者人数高达4.15亿,其中2型糖尿病(type 2 diabetes mellitus,T2DM)患者占90%以上~([1])。不仅是中老年人,越来越多的青年和儿童也面临T2DM威胁~([1])。T2DM主要是由于胰岛素抵抗和胰岛素分泌不足引起。目前导致胰岛素抵抗的原因尚未完全阐明,但认为与肥胖、不良饮食习惯、缺乏运动、年龄和遗传等危险因素有关。T2DM造     

辛伐他汀对糖尿病脑病大鼠认知功能障碍的影响及其机制研究

目的 探讨辛伐他汀糖尿病脑病大鼠认知功能的改善作用及可能机制。方法 采用高糖高脂饲料喂养联合腹腔注射链脲佐菌素(STZ)的方法建立糖尿病脑病大鼠模型,选取模型制备成功的大鼠随机分为模型组与辛伐他汀组(20 mg/kg),每组8只,另取同龄8只SD大鼠作为对照组,连续灌胃5周。测定大鼠空腹血糖水平;Morris水迷宫测定大鼠认知功能;HE染色观察大鼠脑组织海马病理损伤;Nissl染色观察大鼠海马神经元;ELISA检测大鼠脑组织白介素-1β(IL-1β)、IL-6和肿瘤坏死因子α(TNF-α)水平;Western blot检测大鼠脑组织中SIRT1、NLRP3、Caspase-1、ASC及IL-18蛋白表达。结果 与模型组相比,辛伐他汀组大鼠空腹血糖水平显著降低,认知功能显著改善,海马区病理性损伤减轻,海马尼氏体数量增加,IL-1β、IL-6和TNF-α水平降低,SIRT1蛋白表达水平升高,而NLRP3、Caspase-1、ASC及IL-18蛋白表达水平降低(P<0.05)。结论 辛伐他汀可通过调控SIRT1/NLRP3通路改善糖尿病脑病大鼠认知功能。     

海马与糖尿病认知功能障碍

<正>海马是学习、记忆的重要解剖基础和神经中枢,是近记忆回路的重要结构。海马与认知功能密切相关。而研究发现糖尿病患者广泛存在学习记忆功能减退等认知功能障碍,本文就海马与糖尿病认知功能障碍之间的关系作如下综述。     

胰岛素在糖尿病中的其它作用

胰岛素本身就是被免疫系统“误伤”而产生I型糖尿病的靶标。长期以来,人们一直认为,I型糖尿病的发生机体是因为免疫系统错误地把胰腺中生成胰岛素细胞识别为“外来者”,并因此破坏掉它们。但是究竟哪些分子是袭击的对象仍然还不清楚。目前,由美国科罗拉多大学健康科学中心的George Eisenbarth领导的小组,通过基因工程方法,让有糖尿病倾向的小鼠产生一种经过修正的胰岛素蛋白。这些小鼠没有发展为糖尿病,表明胰岛素的确是目标。更多的相关证据来自同一期的另一个研究。哈佛医学院David Hafler的研究小组发现在糖尿病人的胰腺淋巴节中存在…     

粘附分子与胰岛素依赖型糖尿病

最近研究表明粘附分子在胰岛素依赖型糖尿病发病中起重要作用。受淋巴细胞和内皮细胞表面选择性表达的粘附分子所调控的自身反应性淋巴细胞从血液移行到胰岛可能造成胰岛细胞损伤，导致胰岛炎，进而破坏胰岛β细胞形成胰岛素依赖型糖尿病。以粘附分子为基础的治疗方法在防治糖尿病中有广阔的应用前景。     

非胰岛素依赖型糖尿病患者的红细胞免疫功能

血管病变、感染为糖尿病（ＤＭ）常见的并发症。为了观察非胰岛素依赖型糖尿病（ＮＩＤＤＭ）患者的红细胞免疫功能 ,探讨其与血管病变、感染的关系 ,我们采用酵母菌花环试验 ,测定了４２例ＮＩＤＤＭ患者外周血ＲＢＣ Ｃ３ｂＲ花环率及ＲＢＣ ＩＣＲ花环率。１材料和方法１ .１材料研究对象 :按ＷＨＯ１９８５年诊断标准临床确诊为ＮＩＤＤＭ的患者４２例,年龄３１～７７岁,病程０．５～２１年,所有患者均无酮症酸中毒及心衰。对照组为２０例健康体检者 ,年龄３０～６４岁。主要试剂 :补体致敏及未致敏的冻干ＹＳ酵母菌体 ,购自第二军医…     

糖尿病脑病患者认知功能障碍的神经电生理学研究

目的 研究糖尿病脑病患者事件相关电位(ERP)的特征及早期评定患者有无认知功能障碍及严重程度的临床价值.方法 对39例糖尿病脑痛(DM&ICVD)患者、32例缺血性脑血管病(ICVD)患者及24例正常人进行事件相关电位检查及简易智能量表(MMSE)检测,将两组检测结果与正常对照组比较.结果 DM&ICVD组、ICVD组...     

老年2型糖尿病患者轻度认知功能障碍与胰岛素抵抗、 白介素-6的相关性研究

目的 探讨老年2型糖尿病患者轻度认知功能障碍与胰岛素抵抗、白介素-6的相关性。方法 选择我院2017年2月~2018年5月收治的老年2型糖尿病患者200例,根据是否存在轻度认知功能障碍分为观察组和对照组,各100例,所有患者进行空腹血糖（FBG）、空腹胰岛素（FINS）、白介素-6（IL-6）、糖化血红蛋白（HbA1c）、总胆固醇（TC）、甘油三脂（TG）、低密度脂蛋白胆固醇（LDL-C）测定,计算胰岛素抵抗指数（HOMA-IR）,比较两组各指标差异,Logistic回归分析老年2型糖尿病患者认知障碍的影响因素。结果 观察组患者的FBG（8.72±0.36）mmol/L、FINS（11.46±3.45）μU/ml、IL-6（14.78±2.34）pg/ml、HbA1c（8.56±1.46）%、TC（6.76±1.31）mmol/L、HOMA-IR（5.15±1.62）均高于对照组的FBG（7.14±0.46）mmol/L、FINS（6.91±1.56）μU/ml、IL-6（6.92±1.54）pg/ml、HbA1c（7.91±1.75）%、TC（6.12±1.54）mmol/L、HOMA-IR（4.16±1.50）,差异均有统计学意义（P＜0.05）;多因素Logistic回归分析显示,HOMA-IR、IL-6为老年2型糖尿病患者MCI发生的独立危险因素（P＜0.05）。结论 胰岛素抵抗、IL-6水平上升与老年2型糖尿病患者轻度MCI的发生存在相关性,可能是其主要危险因素,应早期干预。     

胰岛素作用与糖尿病视网膜病变患者的治疗原则

临床实践证明,对有胰岛素抵抗的NIDDM患者,用胰岛素控制血糖只有暂时和表面现象,并不能纠正机体的代谢紊乱,相反可能会因长期胰岛素积蓄导致代谢紊乱.     

由胰岛素信号通路筛选糖尿病药物作用靶点

胰岛素是维持血糖稳定的一种重要激素,通过效应细胞受体将胰岛素信号传递到细胞内,引发胞内一系列反应而发挥功能。随着对胰岛素信号通路的了解逐渐增多,已经从中筛选到一些用于治疗糖尿病的药物作用靶点,它们主要涉及增强靶细胞对胰岛素的敏感性和促进对葡萄糖的利用等环节。     

Differences in and correlations between cognitive abilities and brain volumes in healthy control,mild cognitive impairment,and Alzheimer disease groups

The purpose of this study is to investigate differences in and correlations between cognitive abilities and brain volumes in healthy control (HC), mild cognitive impairment (MCI), and Alzheimer's disease (AD) groups. The Korean Version of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD‐K), which is used to diagnose AD, was used to measure the cognitive abilities of the study subjects, and the volumes of typical brain components related to AD diagnosis—cerebrospinal fluid (CSF), gray matter (GM), and white matter (WM)—were acquired. Of the CERAD‐K subtests, the Boston Naming Test distinguished significantly among the HC, MCI, and AD groups. GM and WM volumes differed significantly among the three groups. There was a significant positive correlation between Boston Naming Test scores and GM and WM volumes. In conclusion, the Boston Naming Test and GM and WM brain volumes differentiated the three tested groups accurately, and there were strong correlations between Boston Naming Test scores and GM and WM volumes. These results will help to establish a test method that differentiates the three groups accurately and is economically feasible. Clin. Anat. 29:473–480, 2016. © 2016 Wiley Periodicals, Inc.     

Insomnia with objective short sleep duration is associated with cognitive impairment: a first look at cardiometabolic contributors to brain health

Study ObjectivesInsomnia with objective short sleep duration has been previously associated with adverse cardiometabolic health outcomes as well as poorer cognitive performance in otherwise noncognitively impaired adults. However, studies demonstrating an increased prevalence of cognitive impairment (CI) in this insomnia phenotype are lacking.MethodsWe analyzed data from Penn State Adult Cohort (N = 1,524; 48.9 ± 13.4 years; 53.4% women). Self-reported sleep difficulty was defined as normal sleep (n = 899), poor sleep (n = 453), and chronic insomnia (n = 172). Objective short sleep duration was defined as less than 6-h of sleep, based on in-lab, 8-h polysomnography. CI (n = 155) and possible vascular cognitive impairment (pVCI, n = 122) were ascertained using a comprehensive neuropsychological battery. Analyses adjusted for age, sex, race, education, body mass index, apnea/hypopnea index, smoking, alcohol, psychoactive medication, and mental and physical health problems.ResultsParticipants who reported poor sleep or chronic insomnia and slept objectively less than 6 hours were associated with a 2-fold increased odds of CI (OR = 2.06, 95% confidence limits [CL] = 1.15–3.66 and OR = 2.18, 95% CL = 1.07–4.47, respectively) and of pVCI (OR = 1.94, 95% CL = 1.01–3.75 and OR = 2.33, 95% CL = 1.07–5.06, respectively). Participants who reported poor sleep or chronic insomnia and slept objectively more than 6 hours were not associated with increased odds of either CI (OR = 0.72, 95% CL = 0.30–1.76 and OR = 0.75, 95% CL = 0.21–2.71, respectively) or pVCI (OR = 1.08, 95% CL = 0.42–2.74 and OR = 0.76, 95% CL = 0.16–3.57, respectively).ConclusionsInsomnia with objective short sleep duration is associated with an increased prevalence of CI, particularly as it relates to cardiometabolic health (i.e. pVCI). These data further support that this insomnia phenotype may be a more biologically severe form of the disorder associated with cardiovascular, cerebrovascular, and neurocognitive morbidity.     

糖尿病合并脑缺血再灌注导致学习记忆障碍大鼠模型的建立

目的建立糖尿病合并脑缺血再灌注导致学习记忆障碍大鼠模型。方法Wistar大鼠70只,分为正常对照组,糖尿病 假手术组,脑缺血组,糖尿病 脑缺血组。腹腔注射链脲佐菌素建立糖尿病模型,3d后双侧颈总动脉夹阻再灌注2次。术后1个月用跳台和Morris水迷宫判断其学习记忆能力,取海马组织,HE染色观察CA1区的细胞分布。结果电击后5min模型组的被动回避反应下台潜伏期明显缩短(P<0.01),24h后仍小于其他各组(P<0.05)。模型组学会主动回避反应的训练次数显著多于其他3组(P<0.001)。模型组在目标象限停留的时间最短(P<0.01),游泳的距离也最短(P<0.05)。结论糖尿病合并脑缺血再灌注可在短期内造成学习记忆障碍,糖尿病可加重脑缺血造成的脑损伤。     

胰岛素抵抗与血管内皮功能紊乱

大学附属省立医院内分泌科，合肥 230001)［摘要］ 内皮功能紊乱可导致具有胰岛素抵抗特征的心血管疾病。胰岛素抵抗是2型糖尿病、肥胖以及代谢综合征等一系列代谢紊乱疾病的标志之一，而这些代谢紊乱疾病具有内皮功能紊乱的特征。内皮功能紊乱和胰岛素抵抗之间形成恶性循环，相互促进，进而促使动脉粥样硬化的发生发展。     

Insulin Resistance Is an Important Risk Factor for Cognitive Impairment in Elderly Patients with Primary Hypertension

Purpose

Insulin resistance plays a role in the development of dementia and hypertension. We investigated a possible relationship between cognitive impairment and insulin resistance in elderly Chinese patients with primary hypertension.

Materials and Methods

One hundred and thirty-two hypertensive elderly patients (>60 years) were enrolled in this study, and assigned into either the cognitive impairment group (n=61) or the normal cognitive group (n=71). Gender, age, education, body mass index (BMI), waist hip ratio (WHR), total cholesterol (TC), triglyceride (TG), C-reactive protein (CRP), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), creatinine (Cr), fasting plasma glucose (FPG), fasting insulin (FINS), homeostasis model of assessment for insulin resistance index (HOMA-IR), systolic blood pressure, diastolic blood pressure, smoking history, atherosclerosis and the proportion of uncontrolled hypertension were compared between the two groups. Multi-factorial logistic regression analysis was performed.

Results

No significant differences were found in gender, age, TC, CRP, HDL-C, LDL-C, Cr, BP, smoking history, atherosclerosis and the proportion of uncontrolled hypertension between the two groups. The cognitive impairment group had lower education levels, and higher BMI, WHR, TG, FPG, FINS, and HOMA-IR levels than the control group. Logistic regression analysis revealed the levels of education, BMI, WHR, and HOMA-IR as independent factors that predict cognitive impairment in patients.

Conclusion

Our study demonstrates that poor education and increased BMI, WHR, and HOMA-IR are independent risk factors for cognitive impairment in elderly patients with hypertension. Insulin resistance plays an important role in the development of cognitive impairment in primary elderly hypertensive patients.     

胰岛素自身免疫性抗体对血清胰岛素测定的影响

目的 :了解胰岛素自身免疫性抗体(IAA)对血清胰岛素测定的影响。方法 :对29例IAA阳性的1型糖尿病患者去除IAA前后血清胰岛素浓度(用RIA测定)进行比较 ,另选29例IAA阴性的1型糖尿病患者作为对照。结果 :IAA阳性的糖尿病患者去除IAA前 ,胰岛素浓度高于IAA阴性组(分别为12.08±2.15、8.31±2.27 ,P<0.01) ;去除IAA后 ,IAA阳性组胰岛素明显下降(8.19±2.80,P<0.01) ,而IAA阴性组则无明显变化(8.24±2.50) ;血清IAA的存在可使血清胰岛素测定值升高4.44 %～72 % ;IAA阳性组去除IAA前后总体数差值的点估计为3.89μIu/ml,其95 %可信区间为3.03～4.75μIu/ml。IAA阳性组去除IAA前后胰岛素浓度的变化大小与IAA强弱呈直线相关。结论 :IAA存在对血清胰岛素的放射免疫分析有明显干扰 ,使结果假性升高     

Positive effects of combined cognitive and physical exercise training on cognitive function in older adults with mild cognitive impairment or dementia: A meta-analysis

Combined cognitive and physical exercise interventions have potential to elicit cognitive benefits in older adults with mild cognitive impairment (MCI) or dementia. This meta-analysis aims to quantify the overall effect of these interventions on global cognitive functioning in older adults with MCI or dementia. Ten randomized controlled trials that applied a combined cognitive-physical intervention with cognitive function as an outcome measure were included. For each study effect sizes were computed (i.e., post-intervention standardized mean difference (SMD) scores) and pooled, using a random-effects meta-analysis. The primary analysis showed a small-to-medium positive effect of combined cognitive-physical interventions on global cognitive function in older adults with MCI or dementia (SMD[95% confidence interval] = 0.32[0.17;0.47], p < 0.00). A combined intervention was equally beneficial in patients with dementia (SMD = 0.36[0.12;0.60], p < 0.00) and MCI (SMD = 0.39[0.15;0.63], p < 0.05). In addition, the analysis showed a moderate-to-large positive effect after combined cognitive-physical interventions for activities of daily living (ADL) (SMD = 0.65[0.09;1.21], p < 0.01)and a small-to-medium positive effect for mood (SMD = 0.27[0.04;0.50], p < 0.01). These functional benefits emphasize the clinical relevance of combined cognitive and physical training strategies.     

脑卒中后血管性认知功能损害的临床观察

目的:对脑卒中后血管性认知功能损害的情况及治疗效果进行初步观察。方法:采用开放、自身前后对照研究方法,比较简易智能量表(MMSE)对49例脑卒中后患者进行治疗及血管性认知功能测试。结果:随访49例,有不同程度认知障碍者39例(79.6%),其中30例为轻度认知障碍(76.9%)。治疗前MMSE(25.41±3.10)分,治疗后4周及12周时MMSE分别为(26.84±6.18)分和(28.16±3.60)分,治疗前后MMSE分值差异有高度显著性(P<0.001)。结论:脑卒中后1~3个月轻度血管性认知功能损害普遍存在,治疗效果显著。     

Elevated brain scyllo-inositol concentrations in patients with Alzheimer's disease

in vivo (1)H MRS reveals reduced N-acetylaspartate (NAA) and elevated myo-inositol (mI) in patients with mild Alzheimer's disease (AD) and patients with amnestic mild cognitive impairment (MCI). We are unaware of studies that have documented abnormal scyllo-inositol (sI) levels in patients with AD or patients with MCI, although a previous MRS study in older adults has indicated that sI is a peak of interest to measure in AD. Fifteen patients with mild AD, 26 patients with amnestic MCI, and 19 healthy older adults were recruited to this study. All underwent (1)H MRS of the posterior cingulate gyrus of the brain using a 3 T MRI scanner. Increases in the sI/creatine (Cr) ratio were observed in patients with mild AD (P < 0.05). The mI/Cr ratio was raised in patients with mild AD (P < 0.01) and MCI (P < 0.05). Reduced NAA/Cr was detected in patients with mild AD (P < 0.05). The sI/Cr ratio correlated negatively (r = -0.60, P < 0.05) with a measure of clock drawing in patients with mild AD, indicating that impaired cognitive ability in AD is associated with higher concentrations of sI/Cr. In vivo measurement of sI/Cr in the posterior cingulate gyrus of patients with mild AD revealed increases compared with cognitively healthy older adults. Further research on the mechanisms of sI increase in AD is needed. Future studies on the longitudinal course of sI/Cr in MCI and AD appear warranted.     

Endophenotypes in normal brain morphology and Alzheimer's disease: a review

Late-onset Alzheimer's disease is a common complex disorder of old age. Though these types of disorders can be highly heritable, they differ from single-gene (Mendelian) diseases in that their causes are often multifactorial with both genetic and environmental components. Genetic risk factors that have been firmly implicated in the cause are mutations in the amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2) genes, which are found in large multi-generational families with an autosomal dominant pattern of disease inheritance, the apolipoprotein E (APOE)ε4 allele and the sortilin-related receptor (SORL1) gene. Environmental factors that have been associated with late-onset Alzheimer's disease include depressive illness, various vascular risk factors, level of education, head trauma and estrogen replacement therapy. This complexity may help explain their high prevalence from an evolutionary perspective, but the etiologic complexity makes identification of disease-related genes much more difficult. The “endophenotype” approach is an alternative method for measuring phenotypic variation that may facilitate the identification of susceptibility genes for complexly inherited traits. The usefulness of endophenotypes in genetic analyses of normal brain morphology and, in particular for Alzheimer's disease will be reviewed as will the implications of these findings for models of disease causation. Given that the pathways from genotypes to end-stage phenotypes are circuitous at best, identifying endophenotypes more proximal to the effects of genetic variation may expedite the attempts to link genetic variants to disorders.