《胰岛素抵抗对缺血性脑卒中患者认知功能的影响及不良功能预后分析.docx》由会员分享，可在线阅读，更多相关《胰岛素抵抗对缺血性脑卒中患者认知功能的影响及不良功能预后分析.docx（111页珍藏版）》请在taowenge.com淘文阁网|工程机械CAD图纸|机械工程制图|CAD装配图下载|SolidWorks_CaTia_CAD_UG_PROE_设计图分享下载上搜索。
1、110缩略词表英文缩写英文全称中文全称ABAbdominal obesity腹型肥胖ACEAngiotensin converting enzyme血管紧张素转移酶ADAlzheimer disease阿尔茨海默病ADAAmerican Diabetes Association 美国糖尿病协会ANG IIAngiotension II血管紧张素IIASSAtherosclerotic stroke动脉粥样硬化性脑卒中ATCIAtherosclerotic cerebral infarction动脉粥样硬化性脑梗死BBBBlood brain barrier血脑屏障BGBlood glucose
2、血糖BMIBody mass index体重指数CACatecholamine儿茶酚胺CASCarotid artery stenosis颈动脉狭窄CBFCerebral blood flow脑血流量CETPCholesterol ester transporter protein胆固醇酯转运蛋白ChoCholine胆碱复合物CICognitive impairment认知功能障碍CMCarbohydrate metabolism糖代谢CCVDCardio-cerebrovascular disease心脑血管疾病缩略词表英文缩写英文全称中文全称CSVDCerebral small vesse
3、l disease脑小血管病DMDiabetes mellitus糖尿病DTIDiffusion Tensor Imaging弥散张量成像ETEndothelins内皮素FAFractional anisotropy异性分数FBGFasting blood glucose空腹血糖FINSFastinginsulin空腹胰岛素GluGlucose葡萄糖GlutGlucosetransporterproteins葡萄糖转运蛋白GPOGlycerol phosphate oxidase甘油磷酸氧化酶GTGlucose tolerance糖耐量HDL-CHigh-densitylipoproteinc
4、holesterol高密度脂蛋白胆固醇HISHyperinsulinemia 高胰岛素血症1H-MRSHydrogen proton magnetic resonance spectroscopy氢质子磁共振波谱分析HPLHyperlipidemia高脂血症HTCHypertriglyceridemia高甘油三酯血症缩略词表英文缩写英文全称中文全称HUAHyperuricemia高尿酸血症IFsInflammatory factors炎症因子IGFRInsulin-likegrowthfactor receptor胰岛素样生长因子受体InsInsulin,胰岛素IRInsulin resist
5、ance胰岛素抵抗IRaInsulinreceptor胰岛素受体IRSInsulin Resistance Syndrome胰岛素抵抗综合征ISIInsulin sensitivity index胰岛素敏感指数LCILacunar cerebral infarction腔隙性脑梗死LPLLipoproteinlipase脂蛋白脂肪酶MDMetabolic diseases代谢疾病MetsMetabolicSyndrome代谢综合征NAAN-acetyl-aspartic acidN-乙酰门冬氨酸OGTTOralglucosetolerancetest口服葡萄糖耐量试验OSOxidative s
6、tress氧化应激PAI-1Plasminogen activator inhibitor 1血浆纤溶酶原激活物抑制因子1缩略词表英文缩写英文全称中文全称PHPrimary hypertension原发性高血压rs-fMRIResting-state functional magnetic resonance imaging静息态功能磁共振成像SMSkeletal muscle骨骼肌SNSSympathetic nervous system交感神经系统T2MD Type 2 diabetes mellitus,2型糖尿病TGTriglyceride, 甘油三酯TRLTriglyceride-r
7、ichlipoprotein甘油三酯脂蛋白TPATissue plasminogen activator组织型纤溶酶原激活物TIATransient ischemic attack短暂性脑缺血发作UAUric acid尿酸VBMVoxel-based morphometry基于体素形态学分析VDVascular dementia血管性痴呆VLDLVery low density lipoprotein极低密度脂蛋白VMSCVascular smooth muscle cell血管平滑肌细胞VCIVascular cognitive impairment血管性认知障碍PSCIPost-strok
8、e cognitive impairment卒中后认知障碍中文摘要研究一、基于稳态模型探索胰岛素抵抗与非糖尿病急性缺血性卒中患者不良功能预后的关系研究背景及目的 胰岛素抵抗(IR)是一系列代谢综合征病理生理发展过程中的核心环节，可以导致促血栓形成和促炎状态，但是否能够预示缺血性卒中患者将具有较差的功能预后这一点观点始终存有争议。基于以往的研究成果，我们假设HOMA-IR模型反映的IR与非糖尿病急性缺血性卒中患者发生不良预后的高风险相关。本研究通过对173名非糖尿病急性缺血性卒中患者开展前瞻性队列研究，评价胰岛素抵抗与不良预后风险之间的关系。并围绕非糖尿病急性缺血性脑卒中后认知功能障碍情况展开研
9、究，分析影响非糖尿病急性缺血性脑卒中后认知功能障碍的影响因素，为防治卒中后认知功能障碍不良预后提供依据。研究方法 选择2016年2月至12月，我院神经内科或急诊科就诊并收治住院的被确诊为缺血性卒中非糖尿病患者173名为研究对象，收集患者临床资料，于入院后及出院前进行系统的神经系统功能量表评价。采用胰岛素敏感性稳态模型评估法(HOMA)分析胰岛素敏感性(HOMA指数=(空腹胰岛素空腹血糖)/22.5)。将HOMA-IR上四分位数(Q4)确定为胰岛素抵抗。使用改良Rankin量表(MRS)评估出院时的功能损害。由经过专业培训的神经内科医生于入院后或病情稳定后第3天对入组患者进行北京版蒙特利尔认知量
10、表(MoCA)检测，将患者分为PSCI组和非PSCI组，对MoCA 各维度评分与标准分进行了比较，单因素Logistic回归分析发生PSCI的危险因素。研究结果 HOMA-IR中位数(四分位距)为2.14(1.17-2.83)，Q4至少为2.83。HOMA-IR与美国国立卫生研究院中风量表呈显著正相关(r=0.408；P0.001)。在多变量分析中，IR组患者出现功能不良预后的风险较高(OR=3.23；CI=1.75-5.08；P=0.001)。在多变量模型中，将第三和第四个四分位数区间与HOMA-IR的第一个四分位数区间进行比较，结果发现HOMA-IR水平与不良预后相关，不良预后的校正风险分
11、别增加207%(OR=3.05(95% CI 1.70-4.89，P=0.006)和429%(95% CI 3.05-9.80，P0.05），具有可比性。研究组患者BMI、SBP、DBP、TC、TG、LDL-C、FBG、HbA1C水平均显著高于对照组，HDL-C水平显著低于对照组（P0.05），排除精神异常对认知功能的影响。神经心理学认知功能评估结果显示，研究组患者与对照组患者之间，各项认知功能检查结果有不同，有显著性差异（P0.05）。1H-MRS结果显示，研究组与对照组右侧额叶皮质的NAA、MI、NAA/MI差异有统计学意义（P0.05）。与对照组相比，研究组NAA、NAA/MI降低，MI
12、升高；研究组与对照组左侧额叶皮质代谢产物MI、NAA/MI差异有统计学意义（P0.05），研究组显著高于对照组，NAA/MI显著低于对照组。研究组与对照组右侧额叶白质Cho值差异有统计学意（P0.05），研究组的Cho值高于对照组。相关性分析发现，研究组病人右侧额叶皮质NAA水平，与呈明显HOMA-IR负相关关系（r=-0.595，P0.05）。研究结论 基于1H-MRS的研究发现在伴有IR的T2DM出现轻度认知障碍检测相关脑区代谢物的变化，可作为研究T2DM病人认知功能障碍特征的重要方法。伴有IR的T2DM轻度认知障碍病人额叶内侧皮质NAA值降低，白质区Cho值升高和内侧皮质区MI值升高，可
13、以作为认知障碍出现的早期预警标志物。 HOMA-IR可以作为标志物代表伴有IR的T2DM病人整体危险因素控制水平对脑内代谢物的影响。关键词：胰岛素抵抗；2型糖尿病；1H-MRS；轻度认知障碍；脑神经代谢物Homeostasis model assessment of insulin resistance in relation to the poor functional outcomes in nondiabetic patients with ischemic strokeBackground and PurposeWhether insulin resistance (IR) can p
14、redict poor functional prognosis in patients with ischemic stroke remains controversial. In this study, a prospective cohort study was conducted among 173 non-diabetic patients with acute ischemic stroke to evaluate the relationship between insulin resistance and adverse prognostic risk. This study
15、focused on the cognitive impairment of non-diabetic patients with acute ischemic stroke, and analyzed the influencing factors of cognitive impairment of non-diabetic patients with acute ischemic stroke, so as to provide evidence for the prevention and treatment of poor prognosis of post-stroke cogni
16、tive impairment.MethodsInsulin sensitivity (HOMA index = fasting insulin * fasting blood glucose) / 22.5) was analyzed by homeostasis model assessment of insulin sensitivity (HOMA). Quantile (Q4) of HOMA-IR was identified as insulin resistance. Modified Rankin Scale (MRS) was used to assess function
17、al impairment at discharge. At 14:00 on the 3rd day after admission, specially trained neurophysicians tested the patients with the Beijing version of Montreal Cognitive Scale (MoCA). According to the MoCA score, the patients were divided into the non-cognitive impairment group (MoCA 26) and the cog
18、nitive impairment group (MoCA 26). According to MoCA score, patients were divided into PSCI group and non- PSCI group. The scores of each dimension of MoCA were compared with the standard scores. The risk factors of PSCI were analyzed by single factor Logistic regression.ResultsThe median HOMA-IR (q
19、uartile distance) was 2.14 (1.17-2.83), and Q4 was at least 2.83. HOMA-IR was positively correlated with the National Institutes of Health Stroke Scale (r = 0.408; P 0.001). In multivariate analysis, the risk of poor prognosis in IR group was higher (OR = 3.23; CI = 1.75-5.08; P = 0.001). In the mul
20、tivariate model, the third and fourth quartile intervals were compared with the first quartile interval of HOMA-IR. The results showed that HOMA-IR level was associated with poor prognosis, and the adjusted risk of poor prognosis increased by 207% (OR=3.05 (95% CI 1.70-4.89, P=0.006) and 429% (95% C
21、I 3.05-9.80, P 0.05), which are comparable. BMI, SBP, DBP, TC, TG, LDL-C, FBG, and HbA1C levels were significantly higher and HDL-C levels were significantly lower in the study group than in the control group (P 0.05), excluding the effect of mental disorders on cognitive function. The results of ne
22、uro psychological cognitive function assessment showed that there were significant differences in the results of various cognitive function tests between the study group patients and the control group patients ( P 0.05). 1H-MRS results showed that NAA, MI, and NAA/MI in the right frontal cortex of t
23、he study group versus the control group ,the difference was statistically significant (P 0.05). NAA and NAA/MI were decreased in the study group compared with the control group. MI was increased; there were significant differences in the metabolites MI and NAA/MI in the left frontal cortex between t
24、he study group and the control group ( P 0.05), was significantly higher and NAA/MI was significantly lower in the study group than in the control group. There was a significant difference in Cho values in the right frontal white matter between the study and control groups (P 0.05), and the Cho valu
25、es of the study group were higher than those of the control group. Correlation analysis revealed that the NAA level in the right frontal cortex of patients in the study group, showed a significant HOMA- IR negative relationship (r = 0.595, Fig. P 0.05). Conclusion Based on the study of 1H-MRS found
26、that mild cognitive impairment in T2DM with IR detected changes in metabolites in related brain regions, which can be used as an important method to study the characteristics of cognitive dysfunction in T2DM patients. T2DM patients with mild cognitive impairment accompanied by IR have decreased NAA
27、values in the medial frontal cortex and white matter regions elevated Cho values and elevated MI values in medial cortical areas can be used as early warning markers for the appearance of cognitive impairment. HOMA-IR can be used as a parameter to represent the effect of overall risk factor control
28、level on metabolites in the brain of T2DM patients with IR. Key Words: Insulin resistance; type 2 diabetes mellitus; 1H-MRS; mild cognitive impairment; cranial neuro metabolites. 1.文献综述1.1 胰岛素抵抗 1.1.1 概述美国糖尿病协会（American Diabetes Association, ADA）将胰岛素抵抗（Insulin resistance, IR）定义为：机体对胰岛素（Insulin, Ins）
29、任何生理功能反应受损的现象。IR主要表现为机体糖代谢（Carbohydrate metabolism, CM）对胰岛素的敏感性显著降低，血糖（Blood glucose，BG）升高，机体代偿性地分泌大量的胰岛素以维持机体糖代谢的正常水平，由此机制引起继发性高胰岛素血症（Hyperinsulinemia, HIS），从而导致机体微观结构、功能出现一系列病理生理变化，包括血管内皮细胞功能、基因表达、凝血机制、糖代谢、脂肪代谢、蛋白质代谢等方面异常，并最终导致多种代谢疾病（Metabolic diseases, MD）的发生和发展1。IR之所以重要，主要是由于它被认为是胰岛素抵抗综合征（Insulin Resistance Syndrome, IRS），即高血压、高甘油三酯（Triglyceride, TG）、腹型肥胖（Abdominal obesity, AB）、高空腹血糖（Fasting blood glucose, FBG）、低高密度脂蛋白胆固醇（High-densitylipoproteincholesterol, HDL-C）在内的重要病理