本文選題：口服葡萄糖耐量試驗 + 靜脈葡萄糖耐量試驗��； 參考：《蘇州大學》2016年博士論文

【摘要】：第一部分口服及靜脈葡萄糖耐量試驗對健康成人血清骨轉(zhuǎn)換生化標志物的影響目的:對比口服及靜脈葡萄糖耐量試驗對健康成人血清骨轉(zhuǎn)換生化標志物的影響。方法:選取24例健康成人為研究對象,分別行75g口服葡萄糖耐量試驗(OGTT)及靜脈葡萄糖耐量試驗(IVGTT,0.3g/Kg),測定60分鐘內(nèi)各時間點骨形成標志物血清1型原膠原N-端前肽(P1NP)及骨吸收標志物血清1型膠原交聯(lián)C-末端肽(β-CTX)水平,并做相關統(tǒng)計學分析。結(jié)果:OGTT及IVGTT過程中(0-60分),血清P1NP與基線水平相比均無顯著變化,而血清β-CTX均隨著時間的延長而逐步降低,在60分鐘時分別降至基線水平的66.0%和80.4%。OGTT各時間點(15分、30分、60分)的血清β-CTX降低率均顯著大于IVGTT(分別為13.1%vs.8.2%,21.8%vs.14.6%,34.0%vs.19.6%,均P0.05)。結(jié)論:OGTT對骨吸收抑制程度顯著大于IVGTT,這可能與腸促胰素有關。第二部分初診2型糖尿病患者餐后骨轉(zhuǎn)換生化標志物的動態(tài)變化目的:探討初診2型糖尿病(T2DM)患者餐后血清骨轉(zhuǎn)換生化標志物的動態(tài)變化。方法:選取46例男性初診T2DM患者(T2DM組)及40例年齡相匹配的體檢健康男性(對照組)作為研究對象,所有受試者采取空腹靜脈血后進食100g饅頭,分別測定空腹及餐后30、60、120及180分鐘血清胰高血糖素樣肽-1(GLP-1)、1型原膠原N-端前肽(P1NP)及1型膠原交聯(lián)C-末端肽(β-CTX)等指標,并做相關統(tǒng)計學分析。結(jié)果:空腹狀態(tài)下,T2DM組的血清P1NP及β-CTX水平均顯著低于對照組,而兩組間血清GLP-1水平無顯著差異。饅頭餐后T2DM組血清GLP-1曲線下面積顯著低于對照組。兩組餐后各時間點的血清P1NP水平均無顯著變化,而血清β-CTX水平均隨著時間延長顯著降低,且均在120分鐘降至最低,隨后升高。餐后120分鐘,T2DM組的血清β-CTX降低率顯著低于對照組(34.6%vs.45.2%,P0.05),相關分析表明β-CTX降低率與GLP-1曲線下面積呈顯著正相關。結(jié)論:初診T2DM患者的進食抑制骨吸收能力減弱,這可能與進食后GLP-1分泌減少有關。第三部分GLP-1受體激動劑對肥胖2型糖尿病患者血清骨轉(zhuǎn)換生化標志物及骨密度的影響目的:探討胰高血糖素樣肽-1(GLP-1)受體激動劑對肥胖2型糖尿病(T2DM)患者血清骨轉(zhuǎn)換生化標志物及骨密度的影響。方法:選取28例初診的肥胖T2DM患者為研究對象,給予GLP-1受體激動劑(艾塞那肽)治療24周,對比治療前后T2DM患者的糖化血紅蛋白(Hb A1c)、體重、空腹血清1型原膠原N-端前肽(P1NP)、空腹血清1型膠原交聯(lián)C-末端肽(β-CTX)及骨密度的變化。結(jié)果:艾塞那肽治療24周后,T2DM患者的Hb A1c顯著降低(-1.9±0.2%),體重也顯著下降(-6.2±0.9 Kg)。血清P1NP及β-CTX分別較治療前升高了11.0%和6.9%,但差異均未達到統(tǒng)計學意義(P0.05);而β-CTX/P1NP比值較治療前降低了5.6%,差異具有統(tǒng)計學意義(P0.05)。骨密度和治療前相比差異無統(tǒng)計學意義。結(jié)論:24周的艾塞那肽治療能夠有效控制肥胖T2DM患者的血糖,并減輕體重,而對骨轉(zhuǎn)換生化標志物及骨密度無顯著影響。第四部分GLP-1R基因多態(tài)性與男性峰值骨密度及身體成分表型的核心家系相關分析目的:探討胰高血糖素樣肽-1受體(GLP-1R)基因多態(tài)性與中國年輕男性人群峰值骨密度及身體成分表型之間的相關性。方法:收集427個上海市男性核心家系(包括父母親及至少一個20~40歲健康兒子),選擇GLP-1R基因的6個標簽SNP(rs2295006、rs3765468、rs3765467、rs6923761、rs1042044、rs1126476)進行基因分型。雙能X線吸收儀(DXA)檢測腰椎、左側(cè)股骨頸、全髖部位骨密度和全身脂肪含量(FM)、瘦組織含量(LM)。采用協(xié)方差和數(shù)量性狀傳遞不平衡檢測法(QTDT)分析GLP-1R基因SNP及單倍型與峰值骨密度、FM及LM的關系。結(jié)果:QTDT分析顯示,在家系內(nèi)相關中,rs1042044位點多態(tài)性與LM顯著相關,rs3765467位點多態(tài)性與FM顯著相關(P0.05)。未發(fā)現(xiàn)GLP-1R基因SNP和單倍型與腰椎、股骨頸、全髖部位峰值骨密度有相關性(P0.05)。FM和LM與上述各部位峰值骨密度成顯著正相關,多元回歸分析表明LM對骨密度變異的貢獻率為13.5%~17.3%,FM對骨密度貢獻率為4.8~5.8%。結(jié)論:GLP-1R基因多態(tài)性與中國年輕男性人群身體成分變異相關,而和峰值骨密度無顯著相關性。
[Abstract]:Part 1 Effect of oral and intravenous glucose tolerance test on serum bone conversion biochemical markers in healthy adults Objective: To compare the effect of oral and intravenous glucose tolerance test on serum bone conversion biochemical markers in healthy adults. Methods: 24 healthy adults were selected as subjects, and 75g oral glucose tolerance test (OGTT) was performed respectively. And IVGTT (0.3g/Kg), the levels of serum 1 collagen N- end propeptide (P1NP) and bone resorption marker serum 1 collagen crosslinked C- terminal peptide (beta -CTX) were measured at every time point in 60 minutes. The results were as follows: the serum P1NP and baseline levels were compared in the OGTT and IVGTT process. There was no significant change, but serum beta -CTX decreased gradually with time. The reduction rate of serum beta -CTX at 66% and 80.4%.OGTT points at 60 minutes respectively (15, 30, 60) were significantly greater than IVGTT (13.1%vs.8.2%, 21.8% vs.14.6%, 34.0%vs.19.6%, P0.05). Conclusion: OGTT has a bone absorption inhibition process. Degree significantly greater than IVGTT, which may be associated with intestinal trypsin. Second the dynamic changes in postprandial biochemical markers of postprandial bone conversion in patients with type 2 diabetes: dynamic changes in the biochemical markers of postprandial bone conversion in newly diagnosed type 2 diabetes (T2DM). Methods: 46 male patients with primary T2DM (group T2DM) and 40 age groups were selected. The healthy male (control group) was used as the study object. All subjects took 100g steamed bun after fasting venous blood. The serum glucagon like peptide -1 (GLP-1), type 1 procollagen N- end propeptide (P1NP) and type 1 collagen crosslinked C- terminal peptide (beta -CTX) were measured in the fasting and postprandial 30,60120 and 180 minutes respectively, and the related statistical credits were made. Results: the serum levels of P1NP and beta -CTX in group T2DM were significantly lower than those in the control group, but there was no significant difference in serum GLP-1 level between the two groups. The area of serum GLP-1 curve under the T2DM group after steamed bread meal was significantly lower than that of the control group. There was no significant change in the serum P1NP level of the two groups at each time point, but the serum beta -CTX level was all along with the time. The prolongation decreased significantly, and all decreased to the lowest in 120 minutes and then increased. The decrease rate of serum beta -CTX in group T2DM was significantly lower than that of the control group (34.6%vs.45.2%, P0.05) after 120 minutes of meal. The correlation analysis showed that the reduction rate of beta -CTX was significantly positively correlated with the area under the GLP-1 curve. Conclusion: the reduction of the ability to inhibit the absorption of bone in the initial diagnosis of T2DM patients is likely to be weakened. The effect of third partial GLP-1 receptor agonists on serum bone conversion biochemical markers and bone mineral density in obese type 2 diabetic patients. Objective: To explore the effect of glucagon like peptide -1 (GLP-1) receptor agonist on serum bone conversion biochemical markers and bone mineral density in obese patients with type 2 diabetes (T2DM). 28 newly diagnosed T2DM patients were treated with GLP-1 receptor agonist (erenin) for 24 weeks. The glycated hemoglobin (Hb A1c) of T2DM patients before and after treatment, body weight, N- end peptide (P1NP) of type 1 procollagen N- in fasting serum, and changes in the crosslinked C- terminal peptide (beta -CTX) and bone mineral density of type 1 colloid in the fasting serum. After 24 weeks of peptide therapy, the Hb A1c of T2DM patients decreased significantly (-1.9 + 0.2%) and the body weight decreased significantly (-6.2 0.9 Kg). The serum P1NP and beta -CTX increased by 11% and 6.9%, respectively, but the difference was not statistically significant (P0.05), but the ratio of beta -CTX/P1NP was 5.6% lower than that before treatment. The difference was statistically significant (P0.05). Conclusion: 24 weeks of alenenin therapy can effectively control the blood sugar of obese T2DM patients and reduce body weight, but has no significant influence on bone conversion biochemical markers and bone density. The fourth part of the polymorphism of the gene is related to the core family analysis of the peak bone mineral density and the body composition phenotype of male GLP-1R. To investigate the correlation between the polymorphism of glucagon like peptide -1 receptor (GLP-1R) gene and the bone mineral density and body composition phenotypes of young men in China. Methods: 427 male core families in Shanghai (including parents and at least one healthy son of 20~40 years old) were collected, and 6 label SNP (rs2295006, rs3765468, rs37) of the GLP-1R gene were selected. 65467, rs6923761, rs1042044, rs1126476) genotyping. Dual energy X-ray absorptiometer (DXA) was used to detect lumbar vertebrae, left femur neck, total hip bone density and total body fat content (FM) and thin tissue content (LM). Covariance and quantitative trait transfer imbalance assay (QTDT) were used to analyze GLP-1R gene SNP and haplotype and peak bone density, FM and LM. Results: QTDT analysis showed that the polymorphism of rs1042044 locus was significantly associated with LM, and the polymorphism of the rs3765467 locus was significantly correlated with FM (P0.05). There was no correlation between the GLP-1R gene SNP and the haplotype and the lumbar spine, the neck of the femur, and the peak bone density of the total hip (P0.05).FM and LM were significantly positive with the peak bone density of the above sites. Correlation, multivariate regression analysis showed that the contribution rate of LM to bone mineral density variation was 13.5%~17.3%, and the contribution rate of FM to bone mineral density was 4.8~5.8%. conclusion: GLP-1R gene polymorphism was related to the body composition variation in young Chinese men, but no significant correlation with peak bone mineral density.
【學位授予單位】：蘇州大學
【學位級別】：博士
【學位授予年份】：2016
【分類號】：R580

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