本文選題：2型糖尿病 + 骨質疏松癥��； 參考：《延安大學》2017年碩士論文

【摘要】：目的:探討血清胱抑素C(Cystatin C,Cys-c)、中性粒細胞/淋巴細胞比率(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)改變中的作用,為早期防治骨質疏松癥(Osteoporosis,OP)提供一定的理論依據(jù)。方法:納入205例T2DM患者,根據(jù)1998年世界衛(wèi)生組織(World health organization,WHO)制定的OP診斷標準,按照BMD的T值將T2DM患者分為骨質疏松組(n=65)、骨量減少組(n=97)和骨量正常組(n=43),記錄所有患者的一般資料,包括性別、年齡、糖尿病病程、體質指數(shù)(Body mass index,BMI)、血壓、糖尿病并發(fā)癥等情況,檢測糖化血紅蛋白(Hemoglobin Alc,HbA1c)、甘油三酯(Triglyceride,TG)、總膽固醇(Total cholesterol,TC)、高密度脂蛋白膽固醇(High density lipoprotein cholesterol,HDL-C)、低密度脂蛋白膽固醇(Low density lipoprotein cholesterol,LDL-C)、血鈣(Calcium,Ca)、血磷(Phosphorus,P)、血堿性磷酸酶(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)等生化指標,測定空腹血糖(Fasting plasma glucose,FPG)、空腹血胰島素(Fasting serum insulin,FINS)計算胰島素抵抗指數(shù)(Homeostasis model assessment of insulin resistance,HOMA-IR),測定鈣調節(jié)激素:25羥基維生素D【25 hydroxy vitamin D,25(OH)D】、甲狀旁腺激素(Parathyroid hormone,PTH),測定血常規(guī)進行白細胞計數(shù)(White biood cell count,WBC)、中性粒細胞計數(shù)(Neutrophil count,NEU)及淋巴細胞計數(shù)(Lymphocyte count,LYM),計算NLR值,采用雙能X線吸收儀(Dual-energy X-ray absorption,DEXA)測量腰椎、股骨頸、大轉子、華氏三角、總髖部BMD,比較三組間各參數(shù)差異,將腰椎總BMD、髖部總BMD與各指標進行Pearson相關性分析;同時將所有研究對象以血清Cys-c上四分位數(shù)為切點分為高Cys-c組(血Cys-c≥1.11mg/L,n=51)與低Cys-c組(血Cys-c1.11mg/L,n=154),將所有研究對象以NLR上四分位數(shù)為切點分為高NLR組(NLR≥2.41,n=51)與低NLR組(NLR2.41,n=154),分別比較兩組OP患病率及各部位BMD水平;將Cys-c、NLR與各指標進行Pearson相關性分析及多元逐步回歸分析;采用非條件logistic回歸分析T2DM發(fā)生OP的危險因素,自變量篩選方法為向前步進(條件)(步進概率:進入0.05,刪除0.10);采用ROC曲線評估Cys-c、NLR預測T2DM發(fā)生OP的最佳臨界點。結果:1.骨質疏松組、骨量減少組及骨量正常組相比1.1一般臨床資料比較本研究選取T2DM患者205例,骨質疏松組占31.7%,骨量減少組占47.3%,骨量正常組占21.0%,骨質疏松組患者的年齡骨量減少組與骨量正常組;骨質疏松組患者BMI骨量正常組;三組間DBP、MAP比較骨質疏松組骨量減少組骨量正常組。差異有統(tǒng)計學意義(p0.05)。1.2一般生化指標比較三組間HbA1c、FINS比較骨質疏松組骨量減少組,骨質疏松組骨量正常組;三組間ALP、UA、FPG、HOMA-IR、PTH比較骨質疏松組骨量減少組骨量正常組;三組間25(OH)D比較骨質疏松組骨量正常組,骨量減少組骨量正常組。差異有統(tǒng)計學意義(p0.05)。1.3血清Cys-c、NLR等指標比較三組間血Cys-c、NLR比較骨質疏松組骨量減少組骨量正常組;三組間NEU比較骨質疏松組骨量正常組,骨量減少組骨量正常組;三組間LYM比較骨質疏松組骨量減少組,骨質疏松組骨量正常組。差異有統(tǒng)計學意義(p0.05)。1.4各部位骨密度比較三組間腰2-4 BMD、腰椎總BMD、股骨頸BMD、大轉子BMD、華氏三角BMD、髖部總BMD比較骨質疏松組骨量減少組骨量正常組。差異有統(tǒng)計學意義(p0.05)。1.5 2型糖尿病患者腰椎總BMD、髖部總BMD與臨床各指標相關性分析腰椎總BMD與年齡、DBP、MAP、ALP、UA、Cys-c、T4、FINS、FPG、HOMA-IR、NLR、PTH成負相關,與糖尿病病程、BMI、Scr、WBC、LYM、25(OH)D成正相關(p0.05),與其余各指標無顯著相關性(p0.05);髖部總BMD與年齡、DBP、MAP、ALP、UA、Cys-c、FINS、FPG、HOMA-IR、NLR、PTH成負相關,與BMI、ALT、Scr、LYM、25(OH)D成正相關(p0.05),與其余各指標無顯著相關性(p0.05)。2.高胱抑素C組與低胱抑素C組相比2.1臨床特征比較高Cys-c組中骨質疏松組占56.9%,低Cys-c組中骨質疏松組占23.4%,高Cys-c組OP的發(fā)生率是低Cys-c組的2.43倍。高Cys-c組腰2 BMD、腰3 BMD、腰4 BMD、腰椎總BMD、股骨頸BMD、大轉子BMD、華氏三角BMD、髖部總BMD均明顯低于低Cys-c組。2.2 T2DM患者血清Cys-c與臨床各指標相關性分析血清Cys-c與年齡、糖尿病病程、UA、FPG、NLR之間成正相關,與腰3 BMD、腰4 BMD、腰椎總BMD、股骨頸BMD、大轉子BMD、華氏三角BMD、髖部總BMD之間成負相關(p0.05);與其余各指標無顯著相關性(p0.05)。進行多元逐步回歸分析,結果顯示:腰椎總BMD、糖尿病病程、UA最終進入回歸方程,是影響T2DM患者血清Cys-c水平的獨立相關因素(p0.05)。3.高NLR組與低NLR組相比3.1臨床特征比較在高NLR組中骨質疏松組占60.8%,低NLR組中骨質疏松組占22.1%,高NLR組OP的發(fā)生率是低NLR組的2.75倍。高NLR組腰2 BMD、腰3 BMD、腰4 BMD、腰椎總BMD、大轉子BMD、華氏三角BMD、髖部總BMD均明顯低于低NLR組。3.2 T2DM患者NLR與各指標相關性分析NLR與年齡、糖尿病病程、MAP、UA、FPG、HOMA-IR、Cys-c、NEU之間成正相關,與腰3 BMD、腰4 BMD、腰椎總BMD、股骨頸BMD、大轉子BMD、華氏三角BMD、髖部總BMD、LYM之間成負相關(p0.05);NLR與其余各指標無顯著相關性(p0.05)。4.2型糖尿病發(fā)生骨質疏松癥的危險因素與T2DM發(fā)生OP成正相關有年齡(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.將T2DM合并OP(BMD≤-2.5SD)為切點,作Cys-c、NLR的ROC曲線,并求其曲線下面積。Cys-c最佳臨界值為1.105mg/L時,預測T2DM發(fā)生OP的敏感度為44.6%,特異度為84.3%,曲線下面積為0.656(95%可信區(qū)間:0.576~0.737);NLR最佳臨界值為1.975時,預測T2DM發(fā)生OP的敏感度為78.5%,特異度為64.3%,曲線下面積為0.736(95%可信區(qū)間:0.663~0.809);二者曲線下面積比較,差異有統(tǒng)計學意義(p0.05)。結論:1.T2DM患者中血清Cys-c、NLR水平增高與OP發(fā)生密切相關,Cys-c1.105mg/L、NLR1.975的T2DM患者發(fā)生OP的風險增加,Cys-c預測價值較低,NLR預測價值中等,可作為新的預測因子,提示慢性炎癥反應可能參與了DO的發(fā)生發(fā)展。因此,抑制炎癥通路可能是未來治療DO的新思路。2.T2DM合并OP患者年齡、血糖、血壓、ALP、UA、PTH水平升高,BMI、25(OH)D水平下降,提示上述因素也可能參與了DO的發(fā)生發(fā)展。因此,治療OP的同時還需密切關注上述指標并積極采取措施進行干預,早期發(fā)現(xiàn)OP患者或延緩OP發(fā)生發(fā)展過程。
[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.

【學位授予單位】：延安大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R587.1;R580

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