本文選題：1型糖尿病 + 高遷移率族蛋白B1�。� 參考：《鄭州大學》2017年碩士論文

【摘要】：目的本文通過神經心理學量表測驗1型糖尿病(T1DM)患者的認知功能改變,利用氫質子磁共振波譜分析(1H-MRS)、靜息態(tài)功能磁共振(rs-fMRI)掃描量化分析T1DM患者的海馬代謝物、腦功能連接改變,并通過酶聯(lián)免疫吸附法(ELISA)檢測血清中高遷移率族蛋白B1(HMGB1)等炎癥因子,結合糖化血紅蛋白(HbA1C)、血糖波動參數(shù)等,以期發(fā)現(xiàn)T1DM患者是否出現(xiàn)認知功能改變及其大腦結構基礎、早期生物學指標及危險因素。方法1.本研究分為兩組,T1DM組:30例1型糖尿病患者,來自鄭州大學人民醫(yī)院內分泌代謝科的住院患者,正常對照組:36例健康對照者,來自鄭州大學人民醫(yī)院體檢中心的健康體檢者。2.收集受試者臨床資料,并采用ELISA測定受試者血清中HMGB1、白介素1β(IL-1β)、白介素6(IL-6)、腫瘤壞死因子α(TNF-α)的濃度,應用72h動態(tài)血糖監(jiān)測儀監(jiān)測,評估T1DM患者的血糖波動。3.采用神經心理學量表測驗受試者認知功能:數(shù)字符號替換測驗(DSST)、數(shù)字廣度測驗(DST)、連線測驗(TMT)、Rey聽覺詞語學習測驗(RAVLT)、Rey-Osterrieth復雜圖形測驗(ROCF),評估受試者信息處理速度、注意力、執(zhí)行功能、記憶、視空間能力。4.受試者行頭顱核磁共振掃描,通過1H-MRS測定海馬N-乙酰天冬氨酸(NAA)、膽堿復合物(Cho)、肌酸(Cr)的濃度;采用rs-fMRI掃描,后行全腦范圍的Granger因果分析,以測定腦區(qū)間的功能連接。5.SPSS 19.0統(tǒng)計軟件進行數(shù)據(jù)分析。結果1.兩組間臨床資料、炎癥因子的比較T1DM組與正常對照組相比,年齡、性別、受教育程度、吸煙史、BMI差異無統(tǒng)計學意義(P0.05),LDL-C低于正常對照組(P0.05),HMGB1、IL-1β、TNF-α、IL-6均高于正常對照組(P0.05)。2.T1DM組患者的病程、HbA1C、血糖波動參數(shù)T1DM組患者病程9.2±6.0年,HbA1C:9.44±2.41%,平均血糖(MBG):9.43±2.44mmol/l,平均血糖波動幅度(MAGE):6.20±2.24mmol/l,日間血糖平均絕對差(MODD):3.87±1.58mmol/l,血糖標準差(SDBG):2.39±0.85mmol/l,低血糖指數(shù)(LBGI):2.50±2.44,血糖低于3.9mmol/l百分比(glu70):3.37±3.88%。3.兩組間認知功能、海馬代謝物、腦功能連接的比較T1DM組與正常對照組相比,DSST、RAVLT(1-5)測驗總和、ROCF臨摹低于正常對照組(P0.05);左側海馬NAA/Cr低于對照組(P0.05),右側海馬NAA/Cr、雙側海馬Cho/Cr差異無統(tǒng)計學意義(P0.05);以左測海馬(HIP.L)為種子點,GC外向流中,T1DM組自HIP.L到右側角回、頂上回及韋尼克區(qū)的部分腦區(qū)的連接較正常對照組增強(P0.05),GC內向流中,T1DM組自額上回、額中回、中央前回、中央后回、輔助運動區(qū)、楔葉、左側枕上回到HIP.L的連接較正常對照組減弱(P0.05)。4.T1DM組Pearson、Spearman相關性分析及多元回歸分析認知功能與其他指標的相關性分析示:受教育程度、HbA1C、MAGE、SDBG、HMGB1、TNF-α、右側海馬Cho/Cr與DSST相關(P0.05),MODD、SDBG與DST相關(P0.05),受教育程度、MAGE、HMGB1、TNF-α與TMT-B相關(P0.05),受教育程度、MAGE、SDBG、HMGB1、IL-1β、IL-6、左側海馬NAA/Cr與RAVLT(1-5)測驗總和相關(P0.05),HMGB1、IL-1β、IL-6與RAVLT延遲回憶相關(P0.05),年齡、LBGI與ROCF臨摹相關(P0.05)。HbA1C、血糖波動參數(shù)與HMGB1的相關性分析示:HbA1C與HMGB1無相關關系(P0.05),MAGE與HMGB1相關(P0.05)。HMGB1與其他炎癥因子的相關性分析示:HMGB1與IL-1β、TNF-α、IL-6相關(P0.05)。HbA1C、血糖波動參數(shù)、HMGB1與海馬代謝物的相關性分析示:MODD、glu70與左測海馬NAA/Cr相關(P0.05),glu70與左測海馬Cho/Cr相關(P0.05),HbA1C、HMGB1與海馬組織中代謝物質無明顯相關性(P0.05)。多元回歸分析:以認知功能測驗為因變量,其他指標為自變量,行多元回歸分析示:DSST的危險因素是受教育程度、HbA1C、SDBG、HMGB1;DST的危險因素是HbA1C、MODD;TMT-B的危險因素是受教育程度、HMGB1;RAVLT(1-5)測驗總和的危險因素是MAGE、SDBG、左側海馬NAA/Cr;RAVLT延遲回憶的危險因素是MODD、HMGB1;ROCF臨摹的危險因素是年齡、HMGB1、左側海馬NAA/Cr。結論1.1型糖尿病患者信息處理速度、記憶、視空間能力下降。2.1型糖尿病患者左側海馬與多個腦區(qū)功能連接異常,NAA下降是短時記憶的危險因素,提示腦功能影像改變可能是1型糖尿病相關認知功能下降的結構基礎。3.HbA1C、血糖波動是1型糖尿病患者認知功能下降的危險因素,可能通過促進HMGB1等炎癥因子分泌,參與1型糖尿病相關并發(fā)認知功能下降的發(fā)生機制。
[Abstract]:The purpose of this paper through the neuropsychological tests of type 1 diabetes mellitus (T1DM) changes in cognitive function and proton magnetic resonance spectroscopy (1H-MRS), using resting state functional magnetic resonance imaging (rs-fMRI) scanning quantitative analysis of hippocampal metabolite T1DM patients, brain functional connectivity changes, and by enzyme-linked immunosorbent assay (ELISA) high mobility group protein B1 in serum (HMGB1) and other inflammatory factors, combined with glycosylated hemoglobin (HbA1C), blood glucose fluctuation parameters, in order to find out whether T1DM patients with cognitive function and brain structure, early biological markers and risk factors. Methods 1. patients were divided into two groups, group T1DM: 30 cases patients with type 1 diabetes inpatients from Zhengzhou University people's hospital endocrine metabolism section, normal control group: 36 healthy subjects and healthy subjects.2. were collected from medical examination center of people's Hospital of Zhengzhou University The clinical data, and the ELISA was tested by serum HMGB1, interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF- alpha) concentration, the application of 72h dynamic blood glucose monitoring, blood glucose fluctuation.3. assessment in patients with T1DM cognitive function using neuropsychological testing participants: the digit Symbol Substitution Test (DSST), digital span test (DST), trail making test (TMT), Rey auditory verbal learning test (RAVLT), Rey-Osterrieth Complex Figure Test (ROCF), the evaluation of subjects with information processing speed, attention, executive function, memory, visual spatial ability.4. subjects MRI, determined by 1H-MRS N- in the hippocampus of N-acetylaspartate (NAA), choline (Cho), creatine (Cr) concentration; by rs-fMRI scan, Granger causality analysis was to determine the scope of the whole brain, brain functional connectivity interval.5.SPSS 19 statistical software for data The results of analysis. 1. clinical data between the two groups, inflammatory factor T1DM group compared with normal control group, age, gender, education level, smoking history, there was no significant difference of BMI (P0.05), LDL-C lower than the normal control group (P0.05), HMGB1, IL-1 beta, TNF- alpha, IL-6 were higher than that of normal control group HbA1C (P0.05).2.T1DM group, the course of disease, blood glucose fluctuation parameters in T1DM group were 9.2 + 6 years duration, HbA1C:9.44 + 2.41%, the average blood glucose (MBG): 9.43 + 2.44mmol/l, average blood glucose fluctuation (MAGE): 6.20 + 2.24mmol/l, daytime blood glucose average absolute difference (MODD): 3.87 + 1.58mmol/l. Standard deviation of blood glucose (SDBG): 2.39 + 0.85mmol/l, low glycemic index (LBGI): 2.50 + 2.44, the percentage of blood glucose less than 3.9mmol/l (glu70): 3.37 + 3.88%.3. between the two groups of cognitive function and hippocampal metabolites, brain functional connectivity than than in the T1DM group compared with the normal control group, DSST, RAVLT (1-5) test total the ROCF copy is below 甯稿鐓х粍(P0.05);宸︿晶嫻烽┈NAA/Cr浣庝簬瀵圭収緇，

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