2型糖尿病患者血清TLR-4水平與骨密度及影響因素關(guān)系研究
發(fā)布時間：2019-06-22 17:32
【摘要】：目的:糖尿病(diabetes mellitus,DM)是一組以慢性血漿葡萄糖水平升高為特征的代謝性疾病,是由于胰島素分泌和(或)作用缺陷所引起。長期碳水化合物和脂肪、蛋白質(zhì)代謝紊亂可引起多系統(tǒng)損害,導(dǎo)致慢性進行性病變,影響患者生活質(zhì)量。糖尿病通過多種機制影響骨代謝,2型糖尿病對骨質(zhì)疏松癥影響的機制尚未明確,但已有證據(jù)表明2型糖尿病可以增加骨折風(fēng)險。Toll樣受體(Toll like receptor,TLR)是一類天然免疫受體,最早發(fā)現(xiàn)此類受體的基因是與果蠅胚胎腹、背側(cè)的發(fā)育有關(guān),隨著研究的深入,人們還發(fā)現(xiàn)哺乳動物體內(nèi)也有類似的同源受體,并統(tǒng)一稱為TLR家族。TLR的分布十分廣泛,主要存在于多形核細胞、淋巴細胞、巨噬細胞、單核細胞、樹突樣細胞及自然殺傷細胞等細胞的表面。目前發(fā)現(xiàn)TLR家族至少已包括了13個成員,不同的TLR的配體也有所不同,目前TLR-4尤為關(guān)注。研究表明,新診斷的2型糖尿病患者體內(nèi)TLR-4的表達及其配體、信號通路、功能均增加,參與炎癥狀態(tài)的形成。2型糖尿病患者持續(xù)血糖水平升高,作用于TLR-4,激活炎癥信號通路,使細胞因子產(chǎn)生增加,造成2型糖尿病患者的慢性炎癥狀態(tài)1。脂肪酸水平在代謝性疾病如脂代謝紊亂、肥胖及糖尿病的患者中是增加的。已有證據(jù)表明,飽和脂肪酸、炎癥及胰島素抵抗之間存在聯(lián)系。給健康人輸注飽和脂肪酸可使ROS產(chǎn)生、核因子κB受體活化因子配體(receptor activator of NF-κB ligand,NF-κB)活性及血漿中細胞因子水平增加2。TLR-4可通過My D88依賴通路和My D88非依賴通路活化NF-κB,激活破骨細胞的基因表達3,參與破骨細胞的激活,從而影響骨代謝。此外,研究表明,TLR-4可能通過抑制經(jīng)典Wnt信號而促進破骨細胞的活性而影響骨代謝。本研究旨在探討2型糖尿病患者血清TLR-4水平與骨密度及其影響因素關(guān)系,為預(yù)防2型糖尿病患者骨質(zhì)疏松癥防治提供理論依據(jù)。方法:選取2014年1月至2014年10月河北醫(yī)科大學(xué)第三醫(yī)院內(nèi)分泌二科2型糖尿病住院患者88例作為受試者,全部受試者接受雙能X線吸收測定儀檢測三個部位的骨密度,其中包括正位腰椎(腰2-4),雙側(cè)髖部(股骨頸、大轉(zhuǎn)子、粗隆間)骨密度,根據(jù)WHO骨質(zhì)疏松癥的診斷標準(DEXA)將上述受試者分為2型糖尿病骨量正常組(38例,normal BMD group),2型糖尿病骨量減少組(29例,Osteopenia group)和2型糖尿病骨質(zhì)疏松癥組(21例,Osteoporosis group),分別記錄患者性別、年齡、身高、體重、腹圍、糖尿病病程等相關(guān)資料,計算體重指數(shù)(Body Mass Index,BMI),測定空腹血糖(Fasting plasma glucose,FBG)、糖化血紅蛋白(Glycated hemoglobin,Hb Alc)、甘油三脂(triglycerides,TG)、膽固醇(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)等生化指標,應(yīng)用酶聯(lián)免疫吸附法(enzyme-linked immunosorbent assay,ELISA)測定血清TLR-4水平,數(shù)據(jù)以均數(shù)±標準差(x±SD)表示,使用SPSS13.0對數(shù)據(jù)進行分析。結(jié)果:1采用單因素方差分析對骨質(zhì)疏松組、骨量減少組和骨量正常組的血清TLR-4水平、年齡、糖尿病病程、BMI、Hb A1C進行比較,結(jié)果顯示三組之間血清TLR-4水平存在統(tǒng)計學(xué)差異(F=113.190,P0.05),進一步采用LSD法進行兩兩比較,結(jié)果顯示骨質(zhì)疏松組TLR-4水平高于骨量減少、骨量正常組,骨量減少組TLR-4水平高于骨量正常組;三組之間年齡也存在統(tǒng)計學(xué)差異(F=12.902,P0.05),進一步采用LSD法進行兩兩比較,結(jié)果顯示骨質(zhì)疏松組不同于骨量減少組及骨量正常組,而骨量減少組與骨量正常組無統(tǒng)計學(xué)差異;三組之間糖尿病病程、BMI及糖化血紅蛋白均無統(tǒng)計學(xué)差異,F值分別為(0.302,1.961,1.176),P值分別為(0.740,0.147,0.314)。采用卡方檢驗對骨質(zhì)疏松組、骨量減少組和骨量正常組的性別進行統(tǒng)計分析,結(jié)果顯示三組間存在統(tǒng)計學(xué)差異(卡方值=15.584,P0.05)。2采用直線相關(guān)對糖尿病患者的骨密度與TLR-4水平進行相關(guān)性分析,結(jié)果顯示糖尿病患者TTBMD及RTTBMD與TLR-4之間存在負相關(guān)性(r=-0.251,P=0.018),(r=-0.278,P=0.009);而LTTBMD與TLR-4之間無相關(guān)性。采用直線相關(guān)對糖尿病患者的骨密度與BMI進行分析,結(jié)果顯示糖尿病患者的TTBMD及RTTBMD與BMI之間存在正相關(guān)性(r=0.226,P=0.034),(r=0.317,P=0.003);而LTTBMD與BMI之間無相關(guān)性。3采用直線相關(guān)對糖尿病患者血清中TLR-4水平與年齡進行相關(guān)性分析,結(jié)果顯示年齡與TLR-4之間存在正相關(guān)(r=0.395,P=0.000);對糖尿病患者血清中TLR-4水平與BMI進行相關(guān)性分析,結(jié)果顯示BMI與TLR-4之間存在負相關(guān)(r=-0.229,P=0.032);對糖尿病患者血清中TLR-4水平與糖尿病病程、糖化血紅蛋白、血脂水平(TC、TG、LDL-C、VLDL)進行相關(guān)性分析,結(jié)果顯示TLR-4水平與糖尿病病程、糖化血紅蛋白、TC、TG、LDL-C、VLDL之間無明顯的相關(guān)性,r分別為0.119,0.036,-0.118,-0.097,0.005,-0.113;P值分別為0.268,0.736,0.276,0.371,0.963,0.296。4采用曲線擬合(Linear,Quadratic,Compound,Exponential)分別對2型糖尿病骨量正常組、骨量減少組、骨質(zhì)疏松組TLR-4水平與病程進行分析,其中2型糖尿病骨量正常組P值分別為0.409,0.714,0.474,0.474;2型糖尿病骨量減少組P值分別為0.569,0.348,0.482,0.482;2型糖尿病骨質(zhì)疏松組P值分別為0.135,0.254,0.189,0.189。采用曲線擬合(Linear,Quadratic,Compound,Exponential)分別對2型糖尿病骨量正常組、骨量減少組、骨質(zhì)疏松組TLR-4水平與糖化血紅蛋白進行分析,其中2型糖尿病骨量正常組P值分別為0.116,0.179,0.132,0.132;2型糖尿病骨量減少組P值分別為0.463,0.686,0.476,0.476;2型糖尿病骨質(zhì)疏松組P值分別為0.906,0.942,0.577,0.577。5采用逐步回歸方法對糖尿病患者血清中TLR-4水平、骨密度(TTBMD、RTTBMD、LTTBMD)及影響因素(年齡、BMI、病程、糖化血紅蛋白)進行分析,其中自變量age及BMI,進入模型,P值均0.05,有統(tǒng)計學(xué)意義,回歸方程為TLR-4=4.544+0.114age-0.251BMI。結(jié)論:1 2型糖尿病患者的骨密度受性別和年齡的影響,2型糖尿病患者骨質(zhì)疏松組年齡高于骨量減少組和骨量正常組,而2型糖尿病患者骨量減少組與骨量正常組年齡無統(tǒng)計學(xué)差異。與BMI、糖尿病病程、糖化血紅蛋白無明顯關(guān)聯(lián);2 2型糖尿病骨質(zhì)疏松組TLR-4水平高于骨量減少組和骨量正常組,骨量減少組TLR-4水平高于骨量正常組;3 TLR-4水平受年齡及BMI的影響,與病程、性別、糖化血紅蛋白、血脂水平無明顯關(guān)聯(lián)。
[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.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R587.1
本文編號：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.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R587.1
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相關(guān)期刊論文 前4條
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