初诊2型糖尿病合并非酒精性脂肪性肝病患者血清IL-22及T细胞亚群的变化

发布时间：2018-04-21 07:03

本文选题：2型糖尿病 + 非酒精性脂肪性肝病　；参考：《河北医科大学》2017年硕士论文

【摘要】：目的:2型糖尿病(Type 2 diabetes mellitus,T2DM)是一组常见的以血浆葡萄糖水平异常增高及脂代谢紊乱为主要表现的内分泌代谢疾病。而非酒精性脂肪性肝病(Nonalcoholic fatty liver disease,NAFLD)是指排除大量饮酒史和其他有明确原因所致的肝组织脂肪沉积、变性等组织学改变为主的临床病理特征。T2DM人群中NAFLD的发病率显著高于健康人群,胰岛素抵抗(Insulin resistance,IR)被认为是T2DM和NAFLD共同的病理生理学基础。近年来多种研究发现T2DM和NAFLD的发病与机体自身免疫反应密切相关。本实验通过比较初诊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细胞亚群(Th1、Th2、Th17、Treg、Th22)比例,探讨IL-22及各亚群比例变化与IR及β细胞功能损伤的关系,分析IL-22及CD4~+T细胞亚群比例与NAFLD的相关性,以及免疫炎症机制在T2DM合并NAFLD发病中的作用,为初诊T2DM合并NAFLD的诊断筛选早期敏感指标。方法:初诊T2DM患者56例,根据其是否合并NAFLD分为:单纯T2DM组,27例(男性13例,女性14例),平均年龄58.47+7.04Y;T2DM合并NAFLD组,29例(男性14例,女性15例),平均年龄60.04~+7.03Y;对照组为同期健康体检者,29例(男性15例,女性14例),平均年龄54.41+4.78Y。收集患者及健康体检者的基本资料,包括身高、体重、现病史、既往史及家族史。抽取患者及健康体检者静脉血,分离血清,分别测量如下指标:甘油三酯(TG)、胆固醇(TC)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、谷氨酰转移酶(GGT)、碱性磷酸酶(ALP)、C反应蛋白(CRP)、空腹血糖(FPG)、空腹胰岛素(FINS)、空腹C肽水平及糖化血红蛋白(Hb A1c)。根据FINS、FPG值计算胰岛素抵抗指数(HOMA-IR),评价IR水平;同时计算动态胰岛素分泌指数(MBCI)、胰岛素分泌指数(HOMA-β),评价胰岛素分泌功能。酶联免疫吸附法(ELISA)测量3组血清IL-22水平。应用流式细胞仪检测3组患者外周血中CD4~+T细胞亚群Th1、Th2、Th17、Treg及Th22细胞的比例。应用超声检测肝脏,并计算肝脏内脂肪含量(Liver fat content,LFC)。比较各组间指标的差异,分析血清IL-22水平及CD4~+T细胞亚群比例变化对HOMA-IR、MBCI、HOMA-β及LFC的影响,探讨其在T2DM合并NAFLD发病中的作用。结果:1单纯T2DM组的FPG、TG、TC、LDL、ALT、AST、FINS、Hb A1c、HOMA-IR均高于对照组,HDL、HOMA-β、MBCI值均低于对照组,差异有统计学意义(P0.05);T2DM合并NAFLD组的FPG、TG、TC、LDL、AST、ALT、GGT、ALP、FINS、Hb A1c、HOMA-IR、LFC、CRP均高于对照组,HDL、HOMA-β、MBCI均低于对照组,差异具有统计学意义(P0.05)。与单纯T2DM组相比,T2DM合并NAFLD组TG、TC、LDL、ALT、GGT、ALP、FINS、HOMA-IR、LFC、CRP均高于单纯T2DM组,差异具有统计学意义(P0.05)。2与对照组相比,血清IL-22水平在T2DM合并NAFLD组显著升高,差异具有统计学意义(P0.05)。单纯T2DM组与T2DM合并NAFLD组外周血各Th细胞亚群占总CD4~+T细胞的比例均有不同程度升高,以Th22细胞的水平改变为著,两组相比有统计学意义(P0.05);Th1细胞比例在T2DM合并NAFLD组显著高于单纯T2DM组和对照组(P0.05);Th17细胞比例在T2DM合并NAFLD组及单纯T2DM组显著高于对照组,差异具有统计学意义(P0.05);Treg比例在T2DM合并NAFLD组显著低于对照组,差异具有统计学意义(P0.05),而单纯T2DM组与T2DM合并NAFLD组比无统计学意义(P0.05)。3相关分析显示不同程度升高的CD4~+T细胞的Th细胞亚群之间均存在相关关系。Th22与Th1、Th17正相关(r分别为0.567,0.702,P0.01);Th1与Th17正相关(r=0.405,P0.01);Th22细胞比例及血清IL-22水平与HOMA-IR呈正相关(r分别为0.591,0.645,P0.01),与HOMA-β呈负相关(r分别为-0.69,-0.68,P0.01)。结论:初诊T2DM患者即出现外周血促炎性CD4~+T细胞的不同程度升高,而T2DM合并NAFLD患者出现血清IL-22水平明显升高和CD4~+T细胞的异常上调,表明在T2DM合并NAFLD患者中该异常可进一步加重。Th22细胞比例及血清IL-22水平与HOMA-IR呈正相关,与HOMA-β呈负相关,可部分阐释免疫炎症机制在T2DM合并NAFLD发病中的作用,可能会成为诊断T2DM合并NAFLD的早期敏感指标。
[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.

【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R587.1;R575.5

【参考文献】