本文選題：2型糖尿病 + 非酒精性脂肪性肝病��； 參考：《河北醫(yī)科大學》2017年碩士論文

【摘要】：目的:2型糖尿病(Type 2 diabetes mellitus,T2DM)是一組常見的以血漿葡萄糖水平異常增高及脂代謝紊亂為主要表現(xiàn)的內(nèi)分泌代謝疾病。而非酒精性脂肪性肝病(Nonalcoholic fatty liver disease,NAFLD)是指排除大量飲酒史和其他有明確原因所致的肝組織脂肪沉積、變性等組織學改變?yōu)橹鞯呐R床病理特征。T2DM人群中NAFLD的發(fā)病率顯著高于健康人群,胰島素抵抗(Insulin resistance,IR)被認為是T2DM和NAFLD共同的病理生理學基礎(chǔ)。近年來多種研究發(fā)現(xiàn)T2DM和NAFLD的發(fā)病與機體自身免疫反應密切相關(guān)。本實驗通過比較初診T2DM及合并NAFLD患者外周血中白介素-22(Interleukin 22,IL-22)水平以及CD4~+T細胞亞群(Th1、Th2、Th17、Treg、Th22)比例,探討IL-22及各亞群比例變化與IR及β細胞功能損傷的關(guān)系,分析IL-22及CD4~+T細胞亞群比例與NAFLD的相關(guān)性,以及免疫炎癥機制在T2DM合并NAFLD發(fā)病中的作用,為初診T2DM合并NAFLD的診斷篩選早期敏感指標。方法:初診T2DM患者56例,根據(jù)其是否合并NAFLD分為:單純T2DM組,27例(男性13例,女性14例),平均年齡58.47+7.04Y;T2DM合并NAFLD組,29例(男性14例,女性15例),平均年齡60.04~+7.03Y;對照組為同期健康體檢者,29例(男性15例,女性14例),平均年齡54.41+4.78Y。收集患者及健康體檢者的基本資料,包括身高、體重、現(xiàn)病史、既往史及家族史。抽取患者及健康體檢者靜脈血,分離血清,分別測量如下指標:甘油三酯(TG)、膽固醇(TC)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、谷丙轉(zhuǎn)氨酶(ALT)、谷草轉(zhuǎn)氨酶(AST)、谷氨酰轉(zhuǎn)移酶(GGT)、堿性磷酸酶(ALP)、C反應蛋白(CRP)、空腹血糖(FPG)、空腹胰島素(FINS)、空腹C肽水平及糖化血紅蛋白(Hb A1c)。根據(jù)FINS、FPG值計算胰島素抵抗指數(shù)(HOMA-IR),評價IR水平;同時計算動態(tài)胰島素分泌指數(shù)(MBCI)、胰島素分泌指數(shù)(HOMA-β),評價胰島素分泌功能。酶聯(lián)免疫吸附法(ELISA)測量3組血清IL-22水平。應用流式細胞儀檢測3組患者外周血中CD4~+T細胞亞群Th1、Th2、Th17、Treg及Th22細胞的比例。應用超聲檢測肝臟,并計算肝臟內(nèi)脂肪含量(Liver fat content,LFC)。比較各組間指標的差異,分析血清IL-22水平及CD4~+T細胞亞群比例變化對HOMA-IR、MBCI、HOMA-β及LFC的影響,探討其在T2DM合并NAFLD發(fā)病中的作用。結(jié)果:1單純T2DM組的FPG、TG、TC、LDL、ALT、AST、FINS、Hb A1c、HOMA-IR均高于對照組,HDL、HOMA-β、MBCI值均低于對照組,差異有統(tǒng)計學意義(P0.05);T2DM合并NAFLD組的FPG、TG、TC、LDL、AST、ALT、GGT、ALP、FINS、Hb A1c、HOMA-IR、LFC、CRP均高于對照組,HDL、HOMA-β、MBCI均低于對照組,差異具有統(tǒng)計學意義(P0.05)。與單純T2DM組相比,T2DM合并NAFLD組TG、TC、LDL、ALT、GGT、ALP、FINS、HOMA-IR、LFC、CRP均高于單純T2DM組,差異具有統(tǒng)計學意義(P0.05)。2與對照組相比,血清IL-22水平在T2DM合并NAFLD組顯著升高,差異具有統(tǒng)計學意義(P0.05)。單純T2DM組與T2DM合并NAFLD組外周血各Th細胞亞群占總CD4~+T細胞的比例均有不同程度升高,以Th22細胞的水平改變?yōu)橹?兩組相比有統(tǒng)計學意義(P0.05);Th1細胞比例在T2DM合并NAFLD組顯著高于單純T2DM組和對照組(P0.05);Th17細胞比例在T2DM合并NAFLD組及單純T2DM組顯著高于對照組,差異具有統(tǒng)計學意義(P0.05);Treg比例在T2DM合并NAFLD組顯著低于對照組,差異具有統(tǒng)計學意義(P0.05),而單純T2DM組與T2DM合并NAFLD組比無統(tǒng)計學意義(P0.05)。3相關(guān)分析顯示不同程度升高的CD4~+T細胞的Th細胞亞群之間均存在相關(guān)關(guān)系。Th22與Th1、Th17正相關(guān)(r分別為0.567,0.702,P0.01);Th1與Th17正相關(guān)(r=0.405,P0.01);Th22細胞比例及血清IL-22水平與HOMA-IR呈正相關(guān)(r分別為0.591,0.645,P0.01),與HOMA-β呈負相關(guān)(r分別為-0.69,-0.68,P0.01)。結(jié)論:初診T2DM患者即出現(xiàn)外周血促炎性CD4~+T細胞的不同程度升高,而T2DM合并NAFLD患者出現(xiàn)血清IL-22水平明顯升高和CD4~+T細胞的異常上調(diào),表明在T2DM合并NAFLD患者中該異�？蛇M一步加重。Th22細胞比例及血清IL-22水平與HOMA-IR呈正相關(guān),與HOMA-β呈負相關(guān),可部分闡釋免疫炎癥機制在T2DM合并NAFLD發(fā)病中的作用,可能會成為診斷T2DM合并NAFLD的早期敏感指標。
[Abstract]:Objective: type 2 diabetes (Type 2 diabetes mellitus, T2DM) is a common group of endocrine and metabolic diseases characterized by abnormal high plasma glucose level and lipid metabolism disorder. Non alcoholic fatty liver disease (Nonalcoholic fatty liver disease, NAFLD) refers to the exclusion of a large number of drinking history and other specific causes of the liver group. The incidence of NAFLD in.T2DM population is significantly higher than that in healthy people. Insulin resistance (Insulin resistance, IR) is considered to be the basis of the common pathophysiology of T2DM and NAFLD. In recent years, many studies have found that the pathogenesis of T2DM and NAFLD is closely related to the immune response of the body. By comparing the levels of interleukin -22 (Interleukin 22, IL-22) in peripheral blood and the proportion of CD4~+T cell subsets (Th1, Th2, Th17, Treg, Th22) in the peripheral blood of patients with primary T2DM and NAFLD, the correlation between the proportion of IL-22 and each subgroup and the dysfunction of beta cell function was analyzed. And the role of immune inflammatory mechanism in the pathogenesis of T2DM combined with NAFLD, for the early diagnosis of T2DM combined with NAFLD diagnostic screening early sensitive indicators. Methods: first diagnosis of T2DM patients in 56 cases, according to whether the combination of NAFLD is divided into simple T2DM group, 27 cases (male 13 cases, female 14 cases), average age 58.47+7.04Y; T2DM combined NAFLD group, 29 cases (male 14 cases, female 15 cases) The average age was 60.04~+7.03Y; the control group was a healthy physical examination in the same period, 29 cases (15 men, 14 women), the average age of 54.41+4.78Y. collected the basic data of the patients and health examiners, including the height, weight, the history, the past history and family history. The venous blood of the patients with Ji Jian Kang was extracted and the serum was separated, the following indexes were measured as follows: glycerol, respectively: glycerol Three ester (TG), cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), glutamic aminotransferase (ALT), glutamic aminotransferase (AST), glutamyl transferase (GGT), alkaline phosphatase (ALP), C reactive protein (CRP), fasting glucose (FPG), fasting insulin (FINS), fasting peptide level and glycosylated hemoglobin. Resistance index (HOMA-IR), evaluation of IR level, dynamic insulin secretion index (MBCI), insulin secretion index (HOMA- beta), evaluation of insulin secretion function. Enzyme linked immunosorbent assay (ELISA) was used to measure the serum IL-22 level in 3 groups. The CD4~+T cell subgroup Th1, Th2, Th17, Treg, and Th22 cells in the peripheral blood of 3 groups were detected by flow cytometry. Liver fat content (LFC) was used to detect the liver, and the difference between the indexes of each group was compared. The effects of serum IL-22 level and the change of CD4~+T cell subgroup ratio on HOMA-IR, MBCI, HOMA- beta and LFC were analyzed. AST, FINS, Hb A1c, HOMA-IR were higher than the control group, HDL, HOMA- beta, MBCI values were all lower than the control group, and the T2DM combined NAFLD group was higher than the control group. Compared with the control group, the levels of TG, TC, LDL, ALT, GGT, ALP, FINS, HOMA-IR and LFC were higher than those of the control group, and the difference had statistical significance compared with the control group, and the difference was statistically significant. The proportion of T cells increased in varying degrees, with the level of Th22 cells changed, and the two groups were statistically significant (P0.05), and the proportion of Th1 cells in the T2DM combined NAFLD group was significantly higher than that in the pure T2DM group and the control group (P0.05), and the proportion of Th17 cells in T2DM combined NAFLD group and single pure T2DM group was significantly higher than that in the control group. The difference was statistically significant. 0.05), the proportion of Treg in the T2DM combined NAFLD group was significantly lower than that in the control group, and the difference was statistically significant (P0.05), but there was no statistical significance between the T2DM group and the T2DM group NAFLD group (P0.05).3 correlation analysis (P0.05). .702, P0.01); the positive correlation between Th1 and Th17 (r=0.405, P0.01); the proportion of Th22 cells and the level of serum IL-22 were positively correlated with HOMA-IR (R respectively 0.591,0.645, P0.01). The level of serum IL-22 and the abnormal up-regulation of CD4~+T cells showed that in the patients with NAFLD, the abnormality could further aggravate the proportion of.Th22 cells and the level of serum IL-22, which was positively correlated with HOMA-IR, and negatively correlated with HOMA- beta, which could partly explain the role of the immune inflammatory mechanism in the pathogenesis of T2DM and NAFLD, which may be a diagnostic T2. Early sensitive indicators of DM combined with NAFLD.

【學位授予單位】：河北醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R587.1;R575.5

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