2型糖尿病患者血清Cys-c、NLR与骨质疏松症的相关性分析

发布时间：2018-05-05 07:58

本文选题：2型糖尿病 + 骨质疏松症　；参考：《延安大学》2017年硕士论文

【摘要】：目的:探讨血清胱抑素C(Cystatin C,Cys-c)、中性粒细胞/淋巴细胞比率(blood neutrophil lymphocyte ratio,NLR)在2型糖尿病(Type 2 Diabetes Mellitus,T2DM)患者骨密度(Bone mineral density,BMD)改变中的作用,为早期防治骨质疏松症(Osteoporosis,OP)提供一定的理论依据。方法:纳入205例T2DM患者,根据1998年世界卫生组织(World health organization,WHO)制定的OP诊断标准,按照BMD的T值将T2DM患者分为骨质疏松组(n=65)、骨量减少组(n=97)和骨量正常组(n=43),记录所有患者的一般资料,包括性别、年龄、糖尿病病程、体质指数(Body mass index,BMI)、血压、糖尿病并发症等情况,检测糖化血红蛋白(Hemoglobin Alc,HbA1c)、甘油三酯(Triglyceride,TG)、总胆固醇(Total cholesterol,TC)、高密度脂蛋白胆固醇(High density lipoprotein cholesterol,HDL-C)、低密度脂蛋白胆固醇(Low density lipoprotein cholesterol,LDL-C)、血钙(Calcium,Ca)、血磷(Phosphorus,P)、血碱性磷酸酶(Alkaline phosphatase,ALP)、血清Cys-c、尿酸(Uric acid,UA)、血尿素氮(Blood urea nitrogen,BUN)、血肌酐(Serum creatinine,Scr)等生化指标,测定空腹血糖(Fasting plasma glucose,FPG)、空腹血胰岛素(Fasting serum insulin,FINS)计算胰岛素抵抗指数(Homeostasis model assessment of insulin resistance,HOMA-IR),测定钙调节激素:25羟基维生素D【25 hydroxy vitamin D,25(OH)D】、甲状旁腺激素(Parathyroid hormone,PTH),测定血常规进行白细胞计数(White biood cell count,WBC)、中性粒细胞计数(Neutrophil count,NEU)及淋巴细胞计数(Lymphocyte count,LYM),计算NLR值,采用双能X线吸收仪(Dual-energy X-ray absorption,DEXA)测量腰椎、股骨颈、大转子、华氏三角、总髋部BMD,比较三组间各参数差异,将腰椎总BMD、髋部总BMD与各指标进行Pearson相关性分析;同时将所有研究对象以血清Cys-c上四分位数为切点分为高Cys-c组(血Cys-c≥1.11mg/L,n=51)与低Cys-c组(血Cys-c1.11mg/L,n=154),将所有研究对象以NLR上四分位数为切点分为高NLR组(NLR≥2.41,n=51)与低NLR组(NLR2.41,n=154),分别比较两组OP患病率及各部位BMD水平;将Cys-c、NLR与各指标进行Pearson相关性分析及多元逐步回归分析;采用非条件logistic回归分析T2DM发生OP的危险因素,自变量筛选方法为向前步进(条件)(步进概率:进入0.05,删除0.10);采用ROC曲线评估Cys-c、NLR预测T2DM发生OP的最佳临界点。结果:1.骨质疏松组、骨量减少组及骨量正常组相比1.1一般临床资料比较本研究选取T2DM患者205例,骨质疏松组占31.7%,骨量减少组占47.3%,骨量正常组占21.0%,骨质疏松组患者的年龄骨量减少组与骨量正常组;骨质疏松组患者BMI骨量正常组;三组间DBP、MAP比较骨质疏松组骨量减少组骨量正常组。差异有统计学意义(p0.05)。1.2一般生化指标比较三组间HbA1c、FINS比较骨质疏松组骨量减少组,骨质疏松组骨量正常组;三组间ALP、UA、FPG、HOMA-IR、PTH比较骨质疏松组骨量减少组骨量正常组;三组间25(OH)D比较骨质疏松组骨量正常组,骨量减少组骨量正常组。差异有统计学意义(p0.05)。1.3血清Cys-c、NLR等指标比较三组间血Cys-c、NLR比较骨质疏松组骨量减少组骨量正常组;三组间NEU比较骨质疏松组骨量正常组,骨量减少组骨量正常组;三组间LYM比较骨质疏松组骨量减少组,骨质疏松组骨量正常组。差异有统计学意义(p0.05)。1.4各部位骨密度比较三组间腰2-4 BMD、腰椎总BMD、股骨颈BMD、大转子BMD、华氏三角BMD、髋部总BMD比较骨质疏松组骨量减少组骨量正常组。差异有统计学意义(p0.05)。1.5 2型糖尿病患者腰椎总BMD、髋部总BMD与临床各指标相关性分析腰椎总BMD与年龄、DBP、MAP、ALP、UA、Cys-c、T4、FINS、FPG、HOMA-IR、NLR、PTH成负相关,与糖尿病病程、BMI、Scr、WBC、LYM、25(OH)D成正相关(p0.05),与其余各指标无显著相关性(p0.05);髋部总BMD与年龄、DBP、MAP、ALP、UA、Cys-c、FINS、FPG、HOMA-IR、NLR、PTH成负相关,与BMI、ALT、Scr、LYM、25(OH)D成正相关(p0.05),与其余各指标无显著相关性(p0.05)。2.高胱抑素C组与低胱抑素C组相比2.1临床特征比较高Cys-c组中骨质疏松组占56.9%,低Cys-c组中骨质疏松组占23.4%,高Cys-c组OP的发生率是低Cys-c组的2.43倍。高Cys-c组腰2 BMD、腰3 BMD、腰4 BMD、腰椎总BMD、股骨颈BMD、大转子BMD、华氏三角BMD、髋部总BMD均明显低于低Cys-c组。2.2 T2DM患者血清Cys-c与临床各指标相关性分析血清Cys-c与年龄、糖尿病病程、UA、FPG、NLR之间成正相关,与腰3 BMD、腰4 BMD、腰椎总BMD、股骨颈BMD、大转子BMD、华氏三角BMD、髋部总BMD之间成负相关(p0.05);与其余各指标无显著相关性(p0.05)。进行多元逐步回归分析,结果显示:腰椎总BMD、糖尿病病程、UA最终进入回归方程,是影响T2DM患者血清Cys-c水平的独立相关因素(p0.05)。3.高NLR组与低NLR组相比3.1临床特征比较在高NLR组中骨质疏松组占60.8%,低NLR组中骨质疏松组占22.1%,高NLR组OP的发生率是低NLR组的2.75倍。高NLR组腰2 BMD、腰3 BMD、腰4 BMD、腰椎总BMD、大转子BMD、华氏三角BMD、髋部总BMD均明显低于低NLR组。3.2 T2DM患者NLR与各指标相关性分析NLR与年龄、糖尿病病程、MAP、UA、FPG、HOMA-IR、Cys-c、NEU之间成正相关,与腰3 BMD、腰4 BMD、腰椎总BMD、股骨颈BMD、大转子BMD、华氏三角BMD、髋部总BMD、LYM之间成负相关(p0.05);NLR与其余各指标无显著相关性(p0.05)。4.2型糖尿病发生骨质疏松症的危险因素与T2DM发生OP成正相关有年龄(OR=1.055,p=0.027)、PTH(OR=1.046,p=0.011)、HbA1c(OR=1.757,p=0.007)、DBP(OR=1.121,p=0.000)、Cys-c(OR=16.498,p=0.029)、NLR(OR=3.712,p=0.000)、FPG(OR=3.569,p=0.000)。5.将T2DM合并OP(BMD≤-2.5SD)为切点,作Cys-c、NLR的ROC曲线,并求其曲线下面积。Cys-c最佳临界值为1.105mg/L时,预测T2DM发生OP的敏感度为44.6%,特异度为84.3%,曲线下面积为0.656(95%可信区间:0.576~0.737);NLR最佳临界值为1.975时,预测T2DM发生OP的敏感度为78.5%,特异度为64.3%,曲线下面积为0.736(95%可信区间:0.663~0.809);二者曲线下面积比较,差异有统计学意义(p0.05)。结论:1.T2DM患者中血清Cys-c、NLR水平增高与OP发生密切相关,Cys-c1.105mg/L、NLR1.975的T2DM患者发生OP的风险增加,Cys-c预测价值较低,NLR预测价值中等,可作为新的预测因子,提示慢性炎症反应可能参与了DO的发生发展。因此,抑制炎症通路可能是未来治疗DO的新思路。2.T2DM合并OP患者年龄、血糖、血压、ALP、UA、PTH水平升高,BMI、25(OH)D水平下降,提示上述因素也可能参与了DO的发生发展。因此,治疗OP的同时还需密切关注上述指标并积极采取措施进行干预,早期发现OP患者或延缓OP发生发展过程。
[Abstract]:Objective: To explore the role of serum cystatin C (Cystatin C, Cys-c), neutrophils / lymphocyte ratio (blood neutrophil lymphocyte ratio, NLR) in the changes of bone density in patients with type 2 diabetes mellitus (Type 2 Diabetes Mellitus) to provide a certain theoretical basis for early prevention and control of osteoporosis. Methods: according to the OP diagnostic criteria established by WHO (World Health Organization, WHO) in 205 cases, the T2DM patients were divided into osteoporosis group (n=65), osteopenia group (n=97) and bone mass normal group (n=43) according to the T value of BMD in 1998. The general data of all patients were recorded, including sex, age, course of diabetes and constitution. Body mass index (BMI), blood pressure, and diabetic complications, such as Hemoglobin Alc (HbA1c), triglyceride (Triglyceride, TG), total cholesterol (Total cholesterol, TC), high density lipoprotein cholesterol (LDL), low density lipoprotein cholesterol (LDL) Cholesterol, LDL-C), blood calcium (Calcium, Ca), blood phosphorus (Phosphorus, P), serum alkaline phosphatase (Alkaline phosphatase, ALP), serum Cys-c, uric acid (Uric acid), blood urea nitrogen, blood creatinine, and fasting blood insulin Um insulin, FINS) to calculate the insulin resistance index (Homeostasis model assessment of insulin resistance, HOMA-IR), and the determination of calcium regulating hormone: 25 hydroxyl vitamin D [25 hydroxy] The cell count (Neutrophil count, NEU) and lymphocyte count (Lymphocyte count, LYM) were used to calculate the NLR value. The lumbar vertebra, the neck of the femur, the large rotors, the Fahrenheit triangle, the total hip BMD were measured by the dual energy X-ray absorptiometer (Dual-energy X-ray absorption, DEXA). The differences in the parameters between the three groups were compared. At the same time, all the subjects were divided into high Cys-c group (blood Cys-c > 1.11mg/L, n=51) and low Cys-c group (blood Cys-c1.11mg/L, n=154), and all the subjects were divided into high NLR group (NLR > 2.41, n=51) and low Cys-c, respectively, and two groups were compared. Rate and BMD level in each part; Pearson correlation analysis and multiple stepwise regression analysis were carried out with Cys-c, NLR and each index. The risk factors of OP in T2DM were analyzed by non conditional logistic regression. The selection method of independent variables was forward step (condition) (step probability: entering 0.05, deleting 0.10); ROC curve was used to evaluate Cys-c, NLR predicts T2DM OP. Results: 1. osteoporosis group, osteopenia group and bone mass normal group compared 1.1 general clinical data compared with 205 cases of T2DM patients, osteoporosis group 31.7%, osteopenia group accounting for 47.3%, bone mass normal group 21%, osteoporosis group patients with annual age osteopenia group and bone quantity normal group, osteoporosis group patients. BMI bone mass normal group; DBP, MAP in the three groups compared with the osteoporosis group bone quantity normal group. The difference was statistically significant (P0.05).1.2 general biochemical indexes compared between three groups of HbA1c, FINS in osteoporosis group bone mass reduction group, osteoporosis group bone mass normal group; three groups ALP, UA, FPG, HOMA-IR, PTH compared with osteoporosis group bone mass reduction Group bone mass in normal group; 25 (OH) OH D compared to osteoporosis group, bone mass normal group, osteopenia group bone mass normal group. The difference was statistically significant (P0.05).1.3 serum Cys-c, NLR and other indicators compared three groups of blood Cys-c, NLR compared to osteoporosis group bone mass decrease group bone quantity normal group; three groups of NEU compared to osteoporosis group normal group, bone mass reduction The bone mass in the three groups was compared with the normal group of the three groups, and the bone mass in the osteoporotic group was compared with the normal group. The difference was statistically significant (P0.05) the bone mineral density in each part of the.1.4 was compared between the three groups and the lumbar 2-4 BMD, the total lumbar BMD, the femoral neck BMD, the large trochanter BMD, the Fahrenheit triangle BMD, the total hip total BMD in the bone mass reduction group and the bone mass normal group. The total lumbar BMD of patients with type.1.5 2 diabetes mellitus (P0.05) and total hip BMD of the hip were correlated with the clinical indexes of the total lumbar BMD and age, DBP, MAP, ALP, UA, Cys-c, T4, and there was a negative correlation with the course of diabetes. 05) the total hip BMD was negatively correlated with age, DBP, MAP, ALP, UA, Cys-c, FINS, FPG, HOMA-IR, NLR, PTH, and there was no significant correlation with BMI, DBP, and other indexes. The occurrence rate of the pine group was 23.4%, the incidence of OP in the high Cys-c group was 2.43 times that of the low Cys-c group. The waist 2 BMD, the waist 3 BMD, the waist 4 BMD, the lumbar total BMD, the femoral neck BMD, the large trochanter BMD, the Fahrenheit triangle BMD were significantly lower than those of the low Cys-c group. NLR was positively correlated with lumbar 3 BMD, lumbar 4 BMD, lumbar total BMD, femoral neck BMD, large trochanter BMD, Fahrenheit trigonometric BMD, and total hip BMD (P0.05); there was no significant correlation with the other indexes (P0.05). The independent correlation factor of serum Cys-c level (P0.05).3. high NLR group compared with the low NLR group, the 3.1 clinical features compared with the high NLR group, the osteoporosis group was 60.8%, the low NLR group was 22.1% in the osteoporosis group, and the incidence of the OP in the high NLR group was 2.75 times that of the low NLR group. The total BMD of the Department was significantly lower than that of the low NLR group.3.2 T2DM patients with the correlation analysis of NLR and each index. NLR was positively correlated with age, the course of diabetes, MAP, UA, FPG, HOMA-IR, Cys-c, and NEU, and was negatively correlated with the waist 3, lumbar 4, lumbar vertebra, the big rotor, the Fahrenheit triangle, the hip total, and the other indexes The risk factors of osteoporosis in type.4.2 diabetes mellitus (P0.05) are positively related to the occurrence of OP in T2DM (OR=1.055, p=0.027), PTH (OR=1.046, p=0.011), HbA1c (OR=1.757, p=0.007). When the ROC curve of Cys-c, NLR is made, and the optimum critical value of the area.Cys-c under the curve is 1.105mg/L, the sensitivity of T2DM to OP is 44.6%, the specificity is 84.3%, the area under the curve is 0.656 (95% confidence interval: 0.576~0.737); when the optimum critical value of NLR is 1.975, the sensitivity of T2DM OP is 78.5%, the specificity is 64.3%, the curve is 64.3%, and the curve is under the curve. The area was 0.736 (95% confidence interval: 0.663~0.809); the area under the curve of two cases was compared. The difference was statistically significant (P0.05). Conclusion: the serum Cys-c in 1.T2DM patients and the increase of NLR are closely related to OP. The risk of OP in Cys-c1.105mg/L, NLR1.975's T2DM patients is added, the Cys-c prediction value is lower, and the NLR prediction is of medium value, which can be used as new Predictive factors suggest that chronic inflammatory responses may be involved in the development of DO. Therefore, inhibition of the inflammatory pathway may be a new approach to the treatment of DO in the future..2.T2DM combined with OP patients age, blood glucose, blood pressure, ALP, UA, PTH levels, BMI, 25 (OH) D levels decline, suggesting that the above factors may also participate in DO development. Therefore, the treatment of OP is as a result. We need to pay close attention to the above indicators and take active measures to intervene in early detection of OP patients or delay the occurrence and development of OP.

【学位授予单位】：延安大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R587.1;R580

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