2型糖尿病患者血清TLR-4水平与骨密度及影响因素关系研究
发布时间：2019-06-22 17:32
【摘要】：目的:糖尿病(diabetes mellitus,DM)是一组以慢性血浆葡萄糖水平升高为特征的代谢性疾病,是由于胰岛素分泌和(或)作用缺陷所引起。长期碳水化合物和脂肪、蛋白质代谢紊乱可引起多系统损害,导致慢性进行性病变,影响患者生活质量。糖尿病通过多种机制影响骨代谢,2型糖尿病对骨质疏松症影响的机制尚未明确,但已有证据表明2型糖尿病可以增加骨折风险。Toll样受体(Toll like receptor,TLR)是一类天然免疫受体,最早发现此类受体的基因是与果蝇胚胎腹、背侧的发育有关,随着研究的深入,人们还发现哺乳动物体内也有类似的同源受体,并统一称为TLR家族。TLR的分布十分广泛,主要存在于多形核细胞、淋巴细胞、巨噬细胞、单核细胞、树突样细胞及自然杀伤细胞等细胞的表面。目前发现TLR家族至少已包括了13个成员,不同的TLR的配体也有所不同,目前TLR-4尤为关注。研究表明,新诊断的2型糖尿病患者体内TLR-4的表达及其配体、信号通路、功能均增加,参与炎症状态的形成。2型糖尿病患者持续血糖水平升高,作用于TLR-4,激活炎症信号通路,使细胞因子产生增加,造成2型糖尿病患者的慢性炎症状态1。脂肪酸水平在代谢性疾病如脂代谢紊乱、肥胖及糖尿病的患者中是增加的。已有证据表明,饱和脂肪酸、炎症及胰岛素抵抗之间存在联系。给健康人输注饱和脂肪酸可使ROS产生、核因子κB受体活化因子配体(receptor activator of NF-κB ligand,NF-κB)活性及血浆中细胞因子水平增加2。TLR-4可通过My D88依赖通路和My D88非依赖通路活化NF-κB,激活破骨细胞的基因表达3,参与破骨细胞的激活,从而影响骨代谢。此外,研究表明,TLR-4可能通过抑制经典Wnt信号而促进破骨细胞的活性而影响骨代谢。本研究旨在探讨2型糖尿病患者血清TLR-4水平与骨密度及其影响因素关系,为预防2型糖尿病患者骨质疏松症防治提供理论依据。方法:选取2014年1月至2014年10月河北医科大学第三医院内分泌二科2型糖尿病住院患者88例作为受试者,全部受试者接受双能X线吸收测定仪检测三个部位的骨密度,其中包括正位腰椎(腰2-4),双侧髋部(股骨颈、大转子、粗隆间)骨密度,根据WHO骨质疏松症的诊断标准(DEXA)将上述受试者分为2型糖尿病骨量正常组(38例,normal BMD group),2型糖尿病骨量减少组(29例,Osteopenia group)和2型糖尿病骨质疏松症组(21例,Osteoporosis group),分别记录患者性别、年龄、身高、体重、腹围、糖尿病病程等相关资料,计算体重指数(Body Mass Index,BMI),测定空腹血糖(Fasting plasma glucose,FBG)、糖化血红蛋白(Glycated hemoglobin,Hb Alc)、甘油三脂(triglycerides,TG)、胆固醇(cholesterol,TC)、高密度脂蛋白(High density lipoprotein cholesterol,HDL-C)、低密度脂蛋白(Low density lipoprotein,LDL-C)等生化指标,应用酶联免疫吸附法(enzyme-linked immunosorbent assay,ELISA)测定血清TLR-4水平,数据以均数±标准差(x±SD)表示,使用SPSS13.0对数据进行分析。结果:1采用单因素方差分析对骨质疏松组、骨量减少组和骨量正常组的血清TLR-4水平、年龄、糖尿病病程、BMI、Hb A1C进行比较,结果显示三组之间血清TLR-4水平存在统计学差异(F=113.190,P0.05),进一步采用LSD法进行两两比较,结果显示骨质疏松组TLR-4水平高于骨量减少、骨量正常组,骨量减少组TLR-4水平高于骨量正常组;三组之间年龄也存在统计学差异(F=12.902,P0.05),进一步采用LSD法进行两两比较,结果显示骨质疏松组不同于骨量减少组及骨量正常组,而骨量减少组与骨量正常组无统计学差异;三组之间糖尿病病程、BMI及糖化血红蛋白均无统计学差异,F值分别为(0.302,1.961,1.176),P值分别为(0.740,0.147,0.314)。采用卡方检验对骨质疏松组、骨量减少组和骨量正常组的性别进行统计分析,结果显示三组间存在统计学差异(卡方值=15.584,P0.05)。2采用直线相关对糖尿病患者的骨密度与TLR-4水平进行相关性分析,结果显示糖尿病患者TTBMD及RTTBMD与TLR-4之间存在负相关性(r=-0.251,P=0.018),(r=-0.278,P=0.009);而LTTBMD与TLR-4之间无相关性。采用直线相关对糖尿病患者的骨密度与BMI进行分析,结果显示糖尿病患者的TTBMD及RTTBMD与BMI之间存在正相关性(r=0.226,P=0.034),(r=0.317,P=0.003);而LTTBMD与BMI之间无相关性。3采用直线相关对糖尿病患者血清中TLR-4水平与年龄进行相关性分析,结果显示年龄与TLR-4之间存在正相关(r=0.395,P=0.000);对糖尿病患者血清中TLR-4水平与BMI进行相关性分析,结果显示BMI与TLR-4之间存在负相关(r=-0.229,P=0.032);对糖尿病患者血清中TLR-4水平与糖尿病病程、糖化血红蛋白、血脂水平(TC、TG、LDL-C、VLDL)进行相关性分析,结果显示TLR-4水平与糖尿病病程、糖化血红蛋白、TC、TG、LDL-C、VLDL之间无明显的相关性,r分别为0.119,0.036,-0.118,-0.097,0.005,-0.113;P值分别为0.268,0.736,0.276,0.371,0.963,0.296。4采用曲线拟合(Linear,Quadratic,Compound,Exponential)分别对2型糖尿病骨量正常组、骨量减少组、骨质疏松组TLR-4水平与病程进行分析,其中2型糖尿病骨量正常组P值分别为0.409,0.714,0.474,0.474;2型糖尿病骨量减少组P值分别为0.569,0.348,0.482,0.482;2型糖尿病骨质疏松组P值分别为0.135,0.254,0.189,0.189。采用曲线拟合(Linear,Quadratic,Compound,Exponential)分别对2型糖尿病骨量正常组、骨量减少组、骨质疏松组TLR-4水平与糖化血红蛋白进行分析,其中2型糖尿病骨量正常组P值分别为0.116,0.179,0.132,0.132;2型糖尿病骨量减少组P值分别为0.463,0.686,0.476,0.476;2型糖尿病骨质疏松组P值分别为0.906,0.942,0.577,0.577。5采用逐步回归方法对糖尿病患者血清中TLR-4水平、骨密度(TTBMD、RTTBMD、LTTBMD)及影响因素(年龄、BMI、病程、糖化血红蛋白)进行分析,其中自变量age及BMI,进入模型,P值均0.05,有统计学意义,回归方程为TLR-4=4.544+0.114age-0.251BMI。结论:1 2型糖尿病患者的骨密度受性别和年龄的影响,2型糖尿病患者骨质疏松组年龄高于骨量减少组和骨量正常组,而2型糖尿病患者骨量减少组与骨量正常组年龄无统计学差异。与BMI、糖尿病病程、糖化血红蛋白无明显关联;2 2型糖尿病骨质疏松组TLR-4水平高于骨量减少组和骨量正常组,骨量减少组TLR-4水平高于骨量正常组;3 TLR-4水平受年龄及BMI的影响,与病程、性别、糖化血红蛋白、血脂水平无明显关联。
[Abstract]:Objective: Diabetes (DM) is a group of metabolic diseases characterized by elevated levels of chronic plasma glucose, which is caused by insulin secretion and/ or functional deficiency. Long-term carbohydrate and fat, protein metabolism disorders can cause multiple system damage, resulting in chronic lesions that affect the quality of life of the patient. Diabetes has an effect on bone metabolism through a variety of mechanisms, and the mechanism of type 2 diabetes on the effect of osteoporosis is not yet clear, but there is evidence that type 2 diabetes can increase the risk of fracture. Toll-like receptor (TLR) is a kind of natural immune receptor. It is the first to find that the gene of the receptor is related to the development of the ventral and dorsal side of the Drosophila. The distribution of TLR is very extensive, mainly in the surfaces of polymorphonuclear cells, lymphocytes, macrophages, monocytes, dendritic cells and natural killer cells. At present, the TLR family has at least 13 members, and the ligands of the different TLR are also different, and the TLR-4 is particularly concerned. The results showed that the expression of TLR-4 and its ligand, signal pathway and function in the newly diagnosed type 2 diabetic patients were increased and involved in the formation of inflammatory state. Resulting in a chronic inflammatory state 1 of type 2 diabetes. The level of fatty acid is increased in patients with metabolic disorders such as lipid metabolism disorders, obesity and diabetes. There is evidence that there is a link between saturated fatty acids, inflammation and insulin resistance. The infusion of saturated fatty acids to healthy people can increase the activity of ROS, the activity of the receptor activator of NF-B and the increase of the level of the cytokines in the plasma. The TLR-4 can be used to activate NF-B by the way of My D88 and the non-dependent via of My D88. The gene expression 3, which activates osteoclasts, is involved in the activation of osteoclasts, thereby affecting bone metabolism. In addition, studies have shown that TLR-4 may affect bone metabolism by inhibiting the activity of the classical Wnt signal to promote osteoclast activity. The purpose of this study was to explore the relationship between serum TLR-4 level and bone mineral density and its influencing factors in type 2 diabetic patients and to provide a theoretical basis for preventing and treating osteoporosis in type 2 diabetes. Methods:88 patients with type 2 diabetes mellitus in the third hospital of Hebei Medical University from January 2014 to October 2014 were selected as subjects. All the subjects received double energy X-ray absorptiometry to detect the bone density of the three parts, including the right lumbar (lumbar 2-4). The bone mineral density of the two-sided hip (femoral neck, large rotor, and tuberosity) was divided into normal group (38 normal BMD group) and type 2 diabetic bone reduction group (29 cases) according to the diagnosis standard (DEXA) of the WHO osteoporosis. Osteopenia group and type 2 diabetic osteoporosis group (21 cases, Osteoarthritis group) were used to record relevant data such as sex, age, height, body weight, abdominal circumference, and course of diabetes, and calculate body mass index (BMI) and measure fasting plasma glucose (FBG). The biochemical indexes such as glycosylated hemoglobin (Hb Alc), triglyceride (TG), cholesterol (cholesterol (TC), high density lipoprotein (HDL-C), low density lipoprotein (LDL-C) and the like are applied to the enzyme-linked immunosorbent assay (ELISA). The serum TLR-4 levels were determined by ELISA, and the data was expressed in the mean square standard deviation (x-SD), and the data was analyzed using the SPSS13.0. Results:1 The serum TLR-4 levels, age, duration of diabetes, BMI and Hb A1C were compared with single-factor analysis of variance. The results showed that there was a significant difference in the serum TLR-4 level among the three groups (F = 113.190, P0.05). The results showed that the level of TLR-4 in the osteoporosis group was higher than that in the normal group of bone, and there was a statistical difference between the three groups (F = 12.902, P0.05). The results showed that the osteoporosis group was different from that of the bone reduction group and the normal group of bone mass, and there was no statistical difference between the osteopenia group and the normal bone mass group, and there was no statistical difference between the three groups, and the F value was (0.302, 1.961, 1.176), and the P value was (0.740, 0.147, 0.314), respectively. The results showed that there was a statistical difference between the three groups (the carlag value = 15.584, P0.05). The correlation between the bone mineral density and the TLR-4 level in the diabetic patients was analyzed by the linear correlation. The results showed that there was a negative correlation between TBMD and TLR-4 in diabetic patients (r =-0.251, P = 0.018), (r =-0.278, P = 0.009), and there was no correlation between TTBMD and TLR-4. The results showed that there was positive correlation between TBMD and RTTBMD and BMI in diabetic patients (r = 0.226, P = 0.034), (r = 0.317, P = 0.003). The correlation between the levels of TLR-4 and age in the serum of patients with diabetes was analyzed by linear correlation. The results showed that there was a positive correlation between age and TLR-4 (r = 0.395, P = 0.000), and the correlation between the level of TLR-4 and BMI in the serum of patients with diabetes was analyzed. The results showed that there was a negative correlation between BMI and TLR-4 (r =-0.229, P = 0.032). The level of TLR-4 in serum of patients with diabetes was associated with the course of diabetes, glycosylated hemoglobin and blood lipid level (TC, TG, LDL-C, VLDL). The results showed that the level of TLR-4 and the course of diabetes, glycosylated hemoglobin, TC, There was no significant correlation between TG, LDL-C and VLDL, r was 0.119, 0.036,-0.118,-0.097, 0.005,-0.113, P was 0.268, 0.736, 0.276, 0.371, 0.963 and 0.296.4, respectively. The P-values of type 2 diabetes were 0.409, 0.714, 0.474 and 0.474, respectively. The P-values of type 2 diabetes were 0.569, 0.348, 0.482 and 0.482, respectively. P values of type 2 diabetes were 0.135, 0.254, 0.189, and 0.189, respectively. The levels of TLR-4 and glycosylated hemoglobin of type 2 diabetes were analyzed by curve fitting (Linear, Quadratic, Compound, and Expression), respectively. The P-values of type 2 diabetes were 0.116, 0.179, 0.132 and 0.132, respectively. The P-values of type 2 diabetic bone were 0.463, 0.686, 0.476 and 0.476, respectively. The P-values of type 2 diabetic osteoporosis group were 0.906, 0.942, 0.577 and 0.577.5. The levels of TLR-4, bone mineral density (TBMD, RTTBMD, LTTBMD) and the influencing factors (age, BMI, The course of the disease and the glycosylated hemoglobin were analyzed, with the independent age and BMI, the entry model and the P value of 0.05, and the regression equation was TLR-4 = 4.544 + 0.114age-0.251 BMI. Conclusion: The bone mineral density of type 2 diabetic patients is affected by sex and age, and the age of osteoporosis group in type 2 diabetes is higher than that of bone reduction group and normal group. Compared with BMI, course of diabetes and glycosylated hemoglobin, the TLR-4 level in type 2 diabetic osteoporosis group was higher than that in bone reduction group and normal group, and the level of TLR-4 in osteopenia group was higher than that in the normal group. The level of TLR-4 was affected by age and BMI. No significant association was found between the level of glycated hemoglobin and blood lipid.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R587.1
本文编号：2504813
[Abstract]:Objective: Diabetes (DM) is a group of metabolic diseases characterized by elevated levels of chronic plasma glucose, which is caused by insulin secretion and/ or functional deficiency. Long-term carbohydrate and fat, protein metabolism disorders can cause multiple system damage, resulting in chronic lesions that affect the quality of life of the patient. Diabetes has an effect on bone metabolism through a variety of mechanisms, and the mechanism of type 2 diabetes on the effect of osteoporosis is not yet clear, but there is evidence that type 2 diabetes can increase the risk of fracture. Toll-like receptor (TLR) is a kind of natural immune receptor. It is the first to find that the gene of the receptor is related to the development of the ventral and dorsal side of the Drosophila. The distribution of TLR is very extensive, mainly in the surfaces of polymorphonuclear cells, lymphocytes, macrophages, monocytes, dendritic cells and natural killer cells. At present, the TLR family has at least 13 members, and the ligands of the different TLR are also different, and the TLR-4 is particularly concerned. The results showed that the expression of TLR-4 and its ligand, signal pathway and function in the newly diagnosed type 2 diabetic patients were increased and involved in the formation of inflammatory state. Resulting in a chronic inflammatory state 1 of type 2 diabetes. The level of fatty acid is increased in patients with metabolic disorders such as lipid metabolism disorders, obesity and diabetes. There is evidence that there is a link between saturated fatty acids, inflammation and insulin resistance. The infusion of saturated fatty acids to healthy people can increase the activity of ROS, the activity of the receptor activator of NF-B and the increase of the level of the cytokines in the plasma. The TLR-4 can be used to activate NF-B by the way of My D88 and the non-dependent via of My D88. The gene expression 3, which activates osteoclasts, is involved in the activation of osteoclasts, thereby affecting bone metabolism. In addition, studies have shown that TLR-4 may affect bone metabolism by inhibiting the activity of the classical Wnt signal to promote osteoclast activity. The purpose of this study was to explore the relationship between serum TLR-4 level and bone mineral density and its influencing factors in type 2 diabetic patients and to provide a theoretical basis for preventing and treating osteoporosis in type 2 diabetes. Methods:88 patients with type 2 diabetes mellitus in the third hospital of Hebei Medical University from January 2014 to October 2014 were selected as subjects. All the subjects received double energy X-ray absorptiometry to detect the bone density of the three parts, including the right lumbar (lumbar 2-4). The bone mineral density of the two-sided hip (femoral neck, large rotor, and tuberosity) was divided into normal group (38 normal BMD group) and type 2 diabetic bone reduction group (29 cases) according to the diagnosis standard (DEXA) of the WHO osteoporosis. Osteopenia group and type 2 diabetic osteoporosis group (21 cases, Osteoarthritis group) were used to record relevant data such as sex, age, height, body weight, abdominal circumference, and course of diabetes, and calculate body mass index (BMI) and measure fasting plasma glucose (FBG). The biochemical indexes such as glycosylated hemoglobin (Hb Alc), triglyceride (TG), cholesterol (cholesterol (TC), high density lipoprotein (HDL-C), low density lipoprotein (LDL-C) and the like are applied to the enzyme-linked immunosorbent assay (ELISA). The serum TLR-4 levels were determined by ELISA, and the data was expressed in the mean square standard deviation (x-SD), and the data was analyzed using the SPSS13.0. Results:1 The serum TLR-4 levels, age, duration of diabetes, BMI and Hb A1C were compared with single-factor analysis of variance. The results showed that there was a significant difference in the serum TLR-4 level among the three groups (F = 113.190, P0.05). The results showed that the level of TLR-4 in the osteoporosis group was higher than that in the normal group of bone, and there was a statistical difference between the three groups (F = 12.902, P0.05). The results showed that the osteoporosis group was different from that of the bone reduction group and the normal group of bone mass, and there was no statistical difference between the osteopenia group and the normal bone mass group, and there was no statistical difference between the three groups, and the F value was (0.302, 1.961, 1.176), and the P value was (0.740, 0.147, 0.314), respectively. The results showed that there was a statistical difference between the three groups (the carlag value = 15.584, P0.05). The correlation between the bone mineral density and the TLR-4 level in the diabetic patients was analyzed by the linear correlation. The results showed that there was a negative correlation between TBMD and TLR-4 in diabetic patients (r =-0.251, P = 0.018), (r =-0.278, P = 0.009), and there was no correlation between TTBMD and TLR-4. The results showed that there was positive correlation between TBMD and RTTBMD and BMI in diabetic patients (r = 0.226, P = 0.034), (r = 0.317, P = 0.003). The correlation between the levels of TLR-4 and age in the serum of patients with diabetes was analyzed by linear correlation. The results showed that there was a positive correlation between age and TLR-4 (r = 0.395, P = 0.000), and the correlation between the level of TLR-4 and BMI in the serum of patients with diabetes was analyzed. The results showed that there was a negative correlation between BMI and TLR-4 (r =-0.229, P = 0.032). The level of TLR-4 in serum of patients with diabetes was associated with the course of diabetes, glycosylated hemoglobin and blood lipid level (TC, TG, LDL-C, VLDL). The results showed that the level of TLR-4 and the course of diabetes, glycosylated hemoglobin, TC, There was no significant correlation between TG, LDL-C and VLDL, r was 0.119, 0.036,-0.118,-0.097, 0.005,-0.113, P was 0.268, 0.736, 0.276, 0.371, 0.963 and 0.296.4, respectively. The P-values of type 2 diabetes were 0.409, 0.714, 0.474 and 0.474, respectively. The P-values of type 2 diabetes were 0.569, 0.348, 0.482 and 0.482, respectively. P values of type 2 diabetes were 0.135, 0.254, 0.189, and 0.189, respectively. The levels of TLR-4 and glycosylated hemoglobin of type 2 diabetes were analyzed by curve fitting (Linear, Quadratic, Compound, and Expression), respectively. The P-values of type 2 diabetes were 0.116, 0.179, 0.132 and 0.132, respectively. The P-values of type 2 diabetic bone were 0.463, 0.686, 0.476 and 0.476, respectively. The P-values of type 2 diabetic osteoporosis group were 0.906, 0.942, 0.577 and 0.577.5. The levels of TLR-4, bone mineral density (TBMD, RTTBMD, LTTBMD) and the influencing factors (age, BMI, The course of the disease and the glycosylated hemoglobin were analyzed, with the independent age and BMI, the entry model and the P value of 0.05, and the regression equation was TLR-4 = 4.544 + 0.114age-0.251 BMI. Conclusion: The bone mineral density of type 2 diabetic patients is affected by sex and age, and the age of osteoporosis group in type 2 diabetes is higher than that of bone reduction group and normal group. Compared with BMI, course of diabetes and glycosylated hemoglobin, the TLR-4 level in type 2 diabetic osteoporosis group was higher than that in bone reduction group and normal group, and the level of TLR-4 in osteopenia group was higher than that in the normal group. The level of TLR-4 was affected by age and BMI. No significant association was found between the level of glycated hemoglobin and blood lipid.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R587.1
【参考文献】
相关期刊论文 前4条
1 Bipradas Roy;;Biomolecular basis of the role of diabetes mellitus in osteoporosis and bone fractures[J];World Journal of Diabetes;2013年04期
2 敏思聪;俞银贤;马金忠;;TLR4信号转导通路与骨关节炎[J];国际骨科学杂志;2013年04期
3 白庆霞;杨博;张艳;刘晓静;陆群;;Toll样受体4与经典Wnt信号在破骨样细胞中作用机制的初步研究[J];牙体牙髓牙周病学杂志;2013年03期
4 Kannikar Wongdee;Narattaphol Charoenphandhu;;Osteoporosis in diabetes mellitus: Possible cellular and molecular mechanisms[J];World Journal of Diabetes;2011年03期
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