本文選題：糖尿病微血管病變 + 中醫(yī)證候��； 參考：《中國中醫(yī)科學(xué)院》2017年碩士論文

【摘要】：目的:通過分析糖尿病患者一般資料、臨床癥狀、中醫(yī)證候及實驗室檢查,找到與糖尿病微血管病變相關(guān)的危險因素,在此基礎(chǔ)上,通過配對糖尿病視網(wǎng)膜病變患者的危險因素后,篩查患者獨立的易感基因,為今后2型糖尿病微血管病變的防治及糖尿病視網(wǎng)膜病變的深入研究提供依據(jù)。方法:(1)采用自行編制的調(diào)查表,收集北京、石家莊、保定等13家醫(yī)院在2016年3月至2017年1月期間內(nèi)分泌門診和住院部T2DM患者的相關(guān)信息,進(jìn)行橫斷面分析。采用Logistic回歸分析對各因素進(jìn)行單因素及多因素分析。(2)在前期找出DR危險因素的基礎(chǔ)上,將具備DR所有危險因素的DR患者與未并發(fā)DR的T2DM患者的相關(guān)信息(包括一般資料,臨床癥狀及實驗室檢查)進(jìn)行匹配,選取相關(guān)信息完全一致的DR和非DR患者為一對,納入研究,提取患者靜脈全血的DNA,采用ILLUMINA人類SNP分型檢測芯片技術(shù),對DR患者242901個SNP位點進(jìn)行篩查,找出所有納入組均存在差異的位點,通過NCBI數(shù)據(jù)庫(http://www.ncbi.nlm.nih.gov/)、UCSC 數(shù)據(jù)庫(http://genome.ucsc.edu/)、lncR NASNP(http://bioinfo.life.hust.edu.cn/)數(shù)據(jù)庫和 HGNC 數(shù)據(jù)庫(http://www.gen enames.org/)查詢差異位點所處的基因,再通過KEGG數(shù)據(jù)庫(http://www.kegg.jp/)查找基因代謝通路。結(jié)果:最終有2041例糖尿病患者進(jìn)入調(diào)查研究,其中有微血管病變的患者1318例(并發(fā)糖尿病視網(wǎng)膜病變患者734例,僅并發(fā)糖尿病視網(wǎng)膜病變患者138例;并發(fā)糖尿病腎病患者468例,僅并發(fā)糖尿病腎病患者的96例;并發(fā)糖尿病周圍神經(jīng)病變患者1044例,僅并發(fā)糖尿病周圍神經(jīng)病變患者379例),未發(fā)生微血管病變的患者723例。單因素logistic回歸分析結(jié)果顯示年齡(OR=1.016,95%CI 1.008-1.023,P=0.000),病程(OR=1.071,95%CI 1.005-1.086,P=0.000),家族史(OR=1.306,95%CI 1.085-1.573,P=0.005),高血壓病(OR=1.651,95%CI 1.376-1.983,P=0.000),高脂血癥病(OR=1.270,95%CI 1.056-1.529,P=0.011),心血管病(OR=1.978,95%CI 1。608-2.433,P=0.000),腦血管病(OR=1.269,95%CI 1.009-1.595,P=0.042),BMI(OR=1.035,95%CI 1.011-1.059,P=0.003),FBG(OR= 1.025,95%CI 1.001-1.050,P=0.045),2hPBG(OR=1.112,95%CI 1.083-1.142,P=0.000),HbA1c(OR=1.100,95%CI 1.053-1,150,P=0.000),SBP(OR=1.008,95%CI 1.002-1.013,P=0.004),DBP(OR=0.997,95%CI 0.995-1.000,P=0.024),瘀血阻滯證(OR=1.247,95%CI 1.038-1.502,P=0.018),痰瘀互阻證(OR=1.460,95%CI 1.144-1.865,P=0.002),陰虛燥熱證(OR=0.444,95%CI 0.326-0.606,P=0.000),脾腎陽虛證(O R=2.335,95%CI 1.549-3.520,P=0.000)與糖尿病微血管病變有相關(guān)性。經(jīng)多因素回歸分析后發(fā)現(xiàn)病程(OR=1.052,95%CI 1.036-1.069,P=0.000),家族史(O R=1.241,95%CI 1.016-1.517,P=0.035),高血壓病(OR=1.315,95%CI 1.052-1.643,P=0.035),心血管病(OR=1.522,95%CI 1.204-1.924,P=0.000),2h PBG(OR= 1.098,95%CI 1.065-1.132,P=0.000),HbA1c(OR=1.043,95%CI 1.002-1.084,P=0.038),瘀血阻滯證(OR=1.251,95%CI 1.025-1.528,P=0.028),痰瘀互阻證(OR=1.319,95%CI 1.016-1.712,P=0.038),陰虛燥熱證(O R=0.535,95%CI 0.383-0.749,P=0.000)和脾腎陽虛證(OR=1.660,95%CI 1.074-2.565,P=0.022)與糖尿病微血管病變有相關(guān)性。病程(OR=1.069,95%CI 1.054-1.086,P=0.000),家族史(OR=1.324,95%CI 1.085-1.615,P=0.006),2hPBG(OR=1.099,95%CI 1.069,P=1.129),陰虛燥熱證(OR=0.515,95%C 1 0.345-0.768,P=0.001)和脾腎陽虛證(OR=1.536,95%CI 1.072-2.202,P=0.019)與 DR 有相關(guān)性。年齡(OR=0.979,95%CI 0.968-0.989,P=0.000),病程(OR=1.047,95%CI 1.030-1.064,P=0.000),高血壓病(OR=1.697,95%CI 1.311-2.196,P=0.000),心血管病(OR=1.345,95%CI 1.053-1.718,P=0.018),腦血管病(OR=1.354,95%CI 1.031-1.777,P=0.029),FBG(OR=1.029,95%C 1 1.001-1.059,P,0.044),2hPBG(OR=1.051,95%CI 1.021-1.082,P=0.001),SBP(OR=1.008,95%CI 1.001-1.014,P=0.015),痰瘀互阻證(OR=1.438,95%CI 1.099-1.881,P=0.015),陰虛燥熱證(OR=0.603,95%CI 0.376-0.968,P=0.036),脾腎陽虛證(OR=2.286,95%CI 1.583-3.301,P=0.000)與 DN 有相關(guān)性。病程(OR=1.043,95%CI 1.029-1.058,P=0.000),家族史(OR=1.399,95%CI 1.158-1.691,P=0.001),高脂血癥(OR=1.328,95%CI 1.049-1.682,P=1.328),心血管病(OR=1.555,95%CI 1.253-1.929,P=0.000),BMI(OR=1.033,95%CI 1.008-1.058,P=0.009),2hPBG(OR=1.093,95%CI 1.064-1.123,P=0.000),痰瘀互阻證(OR=1.386,95%CI 1.088-1.765,P=0.008),陰虛燥熱證(OR=0.683,95%CI 0.487-0.957,P=0.027)及脾腎陽虛證(OR=1.541,95%CI 1.060-2.241,P=0.023)與DPN有相關(guān)性。由患者臨床證型可知位于前三位的是氣陰兩虛證(58.3%)瘀血阻滯證(43.4%)和痰瘀互阻證(18.5%)。由病程可知:病程≤5年,有52.1%患者出現(xiàn)微血管病變;病程6-10年,有61.8%患者出現(xiàn)微血管病變;病程11-15年,有72.9%患者出現(xiàn)微血管病變,病程16-20年,有77.6%患者出現(xiàn)微血管病變;病程20年,有80.9%患者出現(xiàn)微血管病變。由HbA1c可知,HbA1c水平越高,微血管病變發(fā)生率就越高;同樣,由B MI可知,BMI水平越高,微血管病變發(fā)生率就越高。根據(jù)前期研究得到的5個DR危險因素,在2041例T2DM患者中進(jìn)行匹配,最終納入符合條件的12對共24例T2DM患者,所有患者之間均無血緣關(guān)系。提取的DNA樣品全部符合實驗要求,將芯片掃描結(jié)果比對Hapmap數(shù)據(jù),篩選出7691個有效SNP位點,最后篩選出 rs9345283、rs738322、rs2844795、rs1727638、rs16984239、rs12505641、rs12142968、rs11243897、rs11175883這9個12對患者均存在差異的的基因位點,通過NCBI數(shù)據(jù)庫、UCSC數(shù)據(jù)庫、lncRNASNP數(shù)據(jù)庫和HGNC數(shù)據(jù)庫查詢到rs738322位點位于PLA2G6基因,rs2844795位點位于TRIM31基因,rs 1727638 位點位于 LINC01626 基因,rs12505641 位點位于 LOC105374524 基因 r s11243897 位點位于 AK8 基因;而 rs9345283 位點、rs16984239 位點、rs12142968位點及rs1 1175883位點未找到所在基因。通過KEGG數(shù)據(jù)庫查找相關(guān)基因功能:PLA2G6基因參與炎癥調(diào)節(jié)及脂質(zhì)代謝,TRIM31基因參與免疫應(yīng)答調(diào)控,AK8基因參與上皮細(xì)胞遷移中的負(fù)調(diào)控,未查找到LOC105374524基因和LINC 01626基因相應(yīng)的功能。結(jié)論:1病程,家族史,高血壓病,心血管病,2hPBG,HbA1c,瘀血阻滯證,痰瘀互阻證,陰虛燥熱證和脾腎陽虛證為糖尿病微血管病變的危險因素;病程,家族史,2hPBG,陰虛燥熱證和脾腎陽虛證是DR的危險因素;年齡,病程,高血壓病,心血管病,腦血管病,FBG,2hPBG,SBP,痰瘀互阻證,陰虛燥熱證,脾腎陽虛證是DN的危險因素;病程,家族史,高脂血癥,心血管病,BMI,2h PBG,痰瘀互阻證,陰虛燥熱證及脾腎陽虛證是DPN的危險因素。2考慮PLA2基因多態(tài)性可能通過炎癥介導(dǎo)、調(diào)節(jié)胰島分泌及胰島細(xì)胞功能、調(diào)節(jié)血管平滑肌收縮功能,參與糖尿病視網(wǎng)膜病變的發(fā)生。Trim31基因可能通過活化NLRP3炎性體作用,參與糖尿病視網(wǎng)膜病變的發(fā)生。
[Abstract]:Objective: to find out the risk factors associated with diabetic microangiopathy by analyzing the general data, clinical symptoms, TCM syndromes and laboratory tests of diabetic patients, and on the basis of the risk factors of diabetic retinopathy, screening patients' independent susceptibility genes for the future type 2 diabetic microvascular lesions. The in-depth study of prevention and treatment and diabetic retinopathy was provided. Methods: (1) a self compiled questionnaire was used to collect information about the T2DM patients in the endocrinology outpatient department and the inpatient department of Beijing, Shijiazhuang and Baoding during the period from March 2016 to January 2017. The cross section analysis was carried out. The factors were analyzed by Logistic regression analysis. Single factor and multi factor analysis. (2) on the basis of identifying the risk factors of DR in the early stage, the relevant information (including general data, clinical symptoms and laboratory tests) with all the DR patients with all the risk factors of DR (including general data, clinical symptoms and laboratory tests) was matched, and a pair of DR and non DR patients with all relevant information were selected and included in the study. The DNA of the venous whole blood of the patient, using the ILLUMINA human SNP typing detection chip technology, screening 242901 SNP loci of the DR patients to find all the different sites in the group, through the NCBI database (http://www.ncbi.nlm.nih.gov/), the UCSC database (http:// genome.ucsc.edu/), lncR NASNP. According to the library and the HGNC database (http://www.gen enames.org/), the gene was searched for the loci of the heterotopic and the KEGG database (http://www.kegg.jp/) was used to find the gene metabolic pathway. Results: 2041 cases of diabetic patients entered the investigation, including 1318 patients with microangiopathy (734 cases of diabetic retinopathy, only 734 cases of diabetic retinopathy, " There were 138 patients with diabetic retinopathy, 468 patients with diabetic nephropathy, 96 patients with diabetic nephropathy, 1044 patients with diabetic peripheral neuropathy, 379 patients with diabetic peripheral neuropathy and 723 patients without microvascular disease. Single factor Logistic regression analysis showed year Age (OR=1.016,95%CI 1.008-1.023, P=0.000), course of disease (OR=1.071,95%CI 1.005-1.086, P=0.000), family history (OR=1.306,95%CI 1.085-1.573, P=0.005), hypertension (OR=1.651,95%CI 1.376-1.983, P=0.000), hyperlipidemia, cardiovascular disease, cerebrovascular disease 9,95%CI 1.009-1.595, P=0.042), BMI (OR=1.035,95%CI 1.011-1.059, P=0.003), FBG (OR= 1.025,95%CI 1.001-1.050, P=0.045). 95%CI 1.038-1.502, P=0.018), phlegm and stasis syndrome (OR=1.460,95%CI 1.144-1.865, P=0.002), yin deficiency and heat syndrome (OR=0.444,95%CI 0.326-0.606, P=0.000), spleen kidney yang deficiency syndrome (O R=2.335,95%CI 1.549-3.520) and diabetic microvascular disease. O R=1.241,95%CI 1.016-1.517 (P=0.035), hypertension (OR=1.315,95%CI 1.052-1.643, P=0.035), cardiovascular disease (OR=1.522,95%CI 1.204-1.924, P=0.000), 2h PBG, stagnation of blood stasis syndrome, syndrome of stagnation of phlegm and blood stasis syndrome (phlegm and stasis syndrome). OR=1.319,95%CI 1.016-1.712, P=0.038), yin deficiency and heat syndrome (O R=0.535,95%CI 0.383-0.749, P=0.000) and spleen and kidney yang deficiency syndrome (OR=1.660,95%CI 1.074-2.565, P=0.022) are related to diabetic microvascular disease. =1.129), yin deficiency and heat syndrome (OR=0.515,95%C 1 0.345-0.768, P=0.001) and spleen and kidney yang deficiency syndrome (OR=1.536,95%CI 1.072-2.202, P=0.019) are related to DR. Age (OR=0.979,95%CI 0.968-0.989, P=0.000), disease course (OR=1.047,95%CI), high blood pressure disease, cardiovascular disease (1.) 053-1.718, P=0.018), cerebrovascular disease (OR=1.354,95%CI 1.031-1.777, P=0.029), FBG (OR=1.029,95%C 1 1.001-1.059, P, 0.044), 2hPBG (OR=1.051,95%CI 1.021-1.082), syndrome of stagnation of phlegm and stasis, spleen deficiency and heat syndrome OR=2.286,95%CI 1.583-3.301 (P=0.000) has a correlation with DN. The course of disease (OR=1.043,95%CI 1.029-1.058, P=0.000), family history (OR=1.399,95%CI 1.158-1.691, P=0.001), hyperlipidemia (OR=1.328,95%CI 1.049-1.682), cardiovascular disease. G (OR=1.093,95%CI 1.064-1.123, P=0.000), phlegm and blood stasis syndrome (OR=1.386,95%CI 1.088-1.765, P=0.008), yin deficiency and heat syndrome (OR=0.683,95%CI 0.487-0.957, P=0.027) and spleen and kidney yang deficiency syndrome (OR=1.541,95%CI 1.060-2.241) are related. It is known from the patient's bed syndrome that the first three places are Qi Yin two deficiency syndrome (58.3%) stagnation of blood stasis syndrome (43.4%) and the mutual obstruction syndrome of phlegm and stasis (18.5%). It is known from the course of the disease that the course of the disease is less than 5 years, there are 52.1% patients with microvascular lesions, 61.8% patients have microvascular lesions for 6-10 years, 11-15 years in the course of disease, 72.9% patients with microvascular lesions, 77.6% patients with microvascular lesions, 20 years in the course of disease, and microvascular lesions in 80.9% patients. HbA1c shows that the higher the level of HbA1c, the higher the incidence of microvascular lesions; also, the higher the level of BMI, the higher the BMI level, the higher the incidence of microvascular lesions. According to the 5 DR risk factors obtained from the previous study, 2041 cases of T2DM patients were matched, and 12 pairs of T2DM patients were included, and all the patients had no blood. The extracted DNA samples all meet the requirements of the experiment. 7691 effective SNP loci are screened by the results of the chip scanning compared with the Hapmap data. Finally, the rs9345283, rs738322, rs2844795, rs1727638, rs16984239, rs12505641, rs12142968, rs11243897, and rs11175883 are the 9 12 gene loci, which are different in the number of patients. According to the library, the UCSC database, the lncRNASNP database and the HGNC database inquire that the rs738322 loci are located in the PLA2G6 gene, the rs2844795 site is located in the TRIM31 gene, the RS 1727638 loci is located in the LINC01626 gene, and the rs12505641 loci is located in the LOC105374524 gene. 68 loci and RS1 1175883 loci did not find the gene. Through the KEGG database to find the related gene function: PLA2G6 gene involved in the regulation of inflammation and lipid metabolism, TRIM31 gene involved in the regulation of immune response, AK8 gene involved in the negative regulation of epithelial cell migration, and the function of LOC105374524 gene and LINC 01626 gene was not found. Conclusion: 1 The course, family history, hypertension, cardiovascular disease, 2hPBG, HbA1c, stagnation of blood stasis syndrome, phlegm and stasis syndrome, yin deficiency and heat syndrome and spleen kidney yang deficiency syndrome are the risk factors of diabetic microvascular disease; the course of disease, family history, 2hPBG, yin deficiency and heat syndrome and spleen kidney yang deficiency syndrome are risk factors for DR; age, course of disease, hypertension, cardiovascular disease, cerebrovascular disease, FBG, 2h PBG, SBP, mutual obstruction of phlegm and stasis syndrome, yin deficiency and heat syndrome, spleen kidney yang deficiency syndrome are the risk factors of DN; the course of disease, family history, hyperlipidemia, cardiovascular disease, BMI, 2h PBG, phlegm stasis syndrome, yin deficiency and heat syndrome and spleen kidney yang deficiency syndrome are the risk factors of DPN, which can regulate the secretion of islet and the function of islet cell, regulate the function of islet cells and regulate the function of islet cells, and regulate the function of islet cells. The contractile function of vascular smooth muscle and the involvement of.Trim31 gene in diabetic retinopathy may be involved in the pathogenesis of diabetic retinopathy by activating the role of NLRP3 inflammatory body.

【學(xué)位授予單位】：中國中醫(yī)科學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R259;R276.7

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