【摘要】：研究背景:糖尿病是心腦血管病的重要危險(xiǎn)因素,是我國(guó)重要的疾病負(fù)擔(dān)和公共衛(wèi)生問(wèn)題。關(guān)于其發(fā)病機(jī)制并未完全闡明。Corin蛋白是新近發(fā)現(xiàn)的可能與心血管病發(fā)病有關(guān)的一種絲氨酸蛋白酶。目前尚無(wú)關(guān)于Corin蛋白與血糖關(guān)系的研究報(bào)道。研究目的:了解血清Corin蛋白在一般人群的分布情況;探討Corin蛋白與高血糖的關(guān)系,為人群糖尿病危險(xiǎn)因素的探討以及臨床治療提供流行病學(xué)依據(jù)。研究對(duì)象與方法:通過(guò)多階段整群隨機(jī)抽樣的方法,隨機(jī)抽取蘇州姑蘇區(qū)4個(gè)農(nóng)村社區(qū)和4個(gè)城市社區(qū)作為調(diào)查現(xiàn)場(chǎng)。按照納入排除標(biāo)準(zhǔn)最后共有2498名研究對(duì)象符合要求。由培訓(xùn)合格的調(diào)查員采用統(tǒng)一設(shè)計(jì)的調(diào)查表,收集調(diào)查對(duì)象的人口統(tǒng)計(jì)學(xué)信息、生活方式危險(xiǎn)因素、疾病史等資料,測(cè)量并記錄身高、體重以及血壓等數(shù)據(jù)。采集空腹靜脈血,檢測(cè)空腹血糖、血脂等指標(biāo)。在實(shí)驗(yàn)室用ELISA試劑盒檢測(cè)Corin蛋白和NT-proANP。用非條件logistic回歸模型分析Corin與高血糖的關(guān)系。在分析時(shí)調(diào)整了年齡、收縮壓、吸煙、飲酒、總膽固醇和高密度脂蛋白,以控制這些因素對(duì)Corin與高血糖關(guān)系的影響。為了排除高血壓、超重/肥胖、中心性肥胖或者血脂異常對(duì)高血糖結(jié)果的潛在影響,又進(jìn)行了敏感性分析。研究結(jié)果:1、在2498名研究對(duì)象中,共有772例高血糖者,患病率為30.90%。男性共962名,其中340名是高血糖者,患病率為35.34%,女性共1536名,其中432名是高血糖者,患病率為28.13%。2、研究對(duì)象中血清Corin的平均水平為1689.2 pg/mL,男性中血清Corin的水平為2174.5 pg/m L,女性中為1515.1 pg/m L,男性Corin水平顯著高于女性(P0.001)。3、按照男女中不同的Corin四分位將研究對(duì)象分成四組,低分位到高分位組的超重/肥胖人數(shù)(患病率)分別為297(47.52%)、313(50.16%)、348(55.86%)和453(72.36%)。在年齡、性別調(diào)整分析中,Corin水平在第3、4分位組的超重/肥胖的危險(xiǎn)性分別是第1分位組的1.39倍和3.02倍(所有p0.05);在多因素調(diào)整分析中,與最低分位組相比,corin水平在第4分位組的研究對(duì)象有更高的患超重/肥胖的危險(xiǎn)性(or=2.26,p0.001)。超重/肥胖的or值隨著corin水平的升高而升高,趨勢(shì)性檢驗(yàn)具有統(tǒng)計(jì)學(xué)意義(p0.001)。從corin水平1至4分位組,中心性肥胖人數(shù)(患病率)分別為292(46.72%)、304(48.72%)、328(52.65%)和399(63.74%)。以最低分位組為參考,中心性肥胖的第3、4分位組的or值分別為1.29(p=0.033)和2.34(p0.05),多因素調(diào)整分析后,第4分位組的中心性肥胖or值是第1分位組的1.74倍(p0.001)。中心性肥胖or值也隨著corin的升高而升高(趨勢(shì)性p值=0.001)。4、根據(jù)不同性別按照corin4分位將研究對(duì)象分成4組,在男性中,從低到高分位(1、2、3和4分位)組的高血糖人數(shù)(患病率)分別為70(29.17%)、66(27.39%)、94(38.84%)和110(46.03%)。單因素logistic分析結(jié)果顯示,與1分位者相比,2、3和4分位者患高血糖的or值(95%ci)分別為0.92(0.62-1.36)、1.54(1.06-2.26)和2.07(1.42-3.02),趨勢(shì)檢驗(yàn)具有統(tǒng)計(jì)學(xué)意義。多因素logistic回歸分析結(jié)果顯示,與1分位者相比,2、3和4分位者患高血糖的or值(95%ci)分別為0.98(0.68-1.47)、1.45(0.97 2.16)和1.96(1.29-2.96),趨勢(shì)檢驗(yàn)具有統(tǒng)計(jì)學(xué)意義,并且4分位者的or值仍具有統(tǒng)計(jì)學(xué)意義(or=1.96,p=0.002)。在女性中,1、2、3和4分位組的高血糖人數(shù)(患病率)分別為87(22.60%)、95(24.87%)、118(30.65%)和132(34.38%)。單因素分析結(jié)果顯示,以第1分位者為參照,2、3和4分位者患高血糖的or值(95%ci)分別為1.13(0.81-1.58)、1.51(1.10-2.09)和1.79(1.31-2.47)。多因素調(diào)整后,以第1分位者為參照,2、3和4分位組高血糖的or值(95%ci)分別為1.08(0.76-1.54)、1.28(0.91-1.81)和1.36(0.97-1.91),趨勢(shì)性檢驗(yàn)有統(tǒng)計(jì)學(xué)意義(p=0.050)。以corin中位數(shù)作為界值,將研究對(duì)象分為高corin組和低corin組,計(jì)算高血糖的or值,結(jié)果顯示,無(wú)論調(diào)整前后,高corin組的高血糖or值均具有統(tǒng)計(jì)學(xué)意義。5、排除高血壓、超重/肥胖、中心性肥胖和血脂異常后,分析corin與高血糖的關(guān)系。男性中,單因素分析結(jié)果顯示,高corin組高血糖的or為2.3(95%ci1.14-4.63);多因素調(diào)整后,or值為2.47(95%ci1.11-5.50)。女性中,單因素分析結(jié)果顯示,高corin組高血糖的or為1.48;多因素調(diào)整后,or值為1.45。6、男性中高血糖組和正常血糖組的nt-proanp濃度分別為1.09(0.75-1.52)mmol/L和1.14(0.73-1.64)mmol/L,差異沒(méi)有統(tǒng)計(jì)學(xué)意義;女性中高血糖組和非高血糖組NT-proANP分別為1.32(0.88-1.85)和1.34(0.89-1.87)mmol/L,差別沒(méi)有統(tǒng)計(jì)學(xué)意義。結(jié)論本研究首次在大樣本的一般人群中報(bào)道了血清Corin與高血糖的關(guān)系,發(fā)現(xiàn)高血糖對(duì)象中血清Corin水平較高,并且隨著Corin水平的升高,高血糖患病率有升高趨勢(shì)。本研究提示,血清Corin可能在糖代謝中發(fā)揮作用,可能是高血糖新的危險(xiǎn)因素。本研究發(fā)現(xiàn)為進(jìn)一步的糖尿病病因和發(fā)病機(jī)制以及治療靶點(diǎn)研究提供了新思路。
[Abstract]:Background: Diabetes is an important risk factor of cardiovascular and cerebrovascular diseases. It is an important disease burden and public health problem in our country. The mechanism for its pathogenesis is not fully set out. The Corin protein is a newly discovered serine protease that may be associated with the onset of cardiovascular disease. There are no studies on the relationship between the Corin protein and the blood glucose. Objective: To study the distribution of the serum Corin protein in the general population, to study the relationship between the Corin protein and the hyperglycemia, to provide an epidemiological basis for the study of the risk factors of diabetes in the population and the clinical treatment. Methods:4 rural communities and 4 urban communities in Suzhou's Suzhou region were randomly selected as the site of investigation by means of multi-stage cluster random sampling. According to the inclusion exclusion criteria, the last total of 2498 study subjects met the requirements. Data such as height, body weight and blood pressure were measured and recorded by trained qualified investigators using a uniform design questionnaire to collect data on demographic information, lifestyle risk factors, and disease history of the subject. Fasting venous blood was collected, and the indexes such as fasting blood glucose and blood fat were detected. The Corin protein and NT-proANP were tested in a laboratory using an ELISA kit. The relationship between Corin and hyperglycemia was analyzed by non-conditional logistic regression model. Age, systolic blood pressure, smoking, alcohol, total cholesterol and high density lipoprotein were adjusted at the time of the analysis to control the effect of these factors on the relationship between Corin and hyperglycemia. In order to exclude the potential effects of hypertension, overweight/ obesity, central obesity, or dyslipidemia on the results of hyperglycemia, a sensitivity analysis was performed. Results:1. In the 2498 subjects, there were 772 hyperglycaemia, with a prevalence of 30.90%. The prevalence of serum Corin in male was 1689.2 pg/ mL, the level of serum Corin in male was 2174.5 pg/ m L, and the female was 1515.1 pg/ m L. The male Corin level was significantly higher than that of the female (P0.001).3. The subjects were divided into four groups according to the different Corin quartiles of the male and female, and the number of overweight/ obese (prevalence) in the lower and high groups was 297 (47.52%),313 (50.16%),348 (55.86%) and 453 (72.36%), respectively. In the age and sex adjustment analysis, the risk of overweight/ obesity in the group 3 and 4 was 1.39-fold and 3.02-fold (all p0.05) in the first sub-group; in the multi-factor adjustment analysis, the risk of overweight/ obesity in the Corin level was 1.39-fold and 3.02-fold, respectively (all p0.05); in the multi-factor adjustment analysis, The corin level had a higher risk of overweight/ obesity in the 4-group study (or = 2.26, p0.001). The or value of overweight/ obesity increased with the increase of corin level, and the trend test was of statistical significance (p0.001). From the corin level of 1 to 4, the number of central obesity (prevalence) was 292 (46.72%),304 (48.72%),328 (52.65%) and 399 (63.74%), respectively. The OR values of the third and fourth sub-groups in the central obesity group were 1.29 (p = 0.033) and 2.34 (p0.05), respectively. After the multi-factor adjustment analysis, the central obesity or value of the fourth group was 1.74 times (p0.001) of the first sub-group. The central obesity or value also increased with the increase of corin (trend p = 0.001).4. The subjects were divided into 4 groups according to the corin4 division according to the different sex, and the number of hyperglycemia (prevalence) in the group from low to high (1,2,3, and 4) groups was 70 (29.17%),66 (27.39%),94 (38.84%) and 110 (46.03%), respectively. The univariate logistic analysis showed that the OR value (95% CI) of the 2,3 and 4 patients with hyperglycemia was 0.92 (0.62-1.36), 1.54 (1.06-2.26) and 2.07 (1.42-3.02), respectively, and the trend test was of statistical significance. The multivariate logistic regression analysis showed that the OR value (95% CI) of the 2,3, and 4 patients with hyperglycemia was 0.98 (0.68-1.47), 1.45 (0.97. 2.16) and 1.96 (1.29-2.96), respectively, with a statistical significance for the trend test, and the OR value of the 4-debitters was still of statistical significance (or = 1.96, p = 0.002). In women, the number of hyperglycemia (prevalence) in the 1,2,3 and 4 group was 87 (22.60%),95 (24.87%),118 (30.65%), and 132 (34.38%), respectively. The results of single factor analysis showed that the OR value (95% CI) of the 2,3 and 4 patients with hyperglycemia was 1.13 (0.81-1.58), 1.51 (1.10-2.09) and 1.79 (1.31-2.47), respectively. After multi-factor adjustment, the value (95% CI) of hyperglycemia in the 2,3 and 4 group was 1.08 (0.76-1.54), 1.28 (0.91-1.81) and 1.36 (0.97-1.91), respectively, with statistical significance (p = 0.050). Using the corin median as the limiting value, the subjects were divided into high corin group and low corin group, and the or value of hyperglycemia was calculated. The results showed that the hyperglycemia or the value of the high corin group was of statistical significance.5. The hypertension, overweight/ obesity, central obesity and dyslipidemia were excluded. The relationship between corin and hyperglycemia was analyzed. In the male, the single-factor analysis showed that the high corin group had a high or 2.3 (95% ci1.14-4.63), or 2.47 (95% ci1.11-5.50) after multi-factor adjustment. In the female, the single factor analysis showed that the value of the high corin group was 1.48; after the multi-factor adjustment, the cor value was 1.45.6, and the nt-protanp concentrations of the hyperglycemic and normal blood glucose groups in the male group were 1.09 (0.75-1.52) mmol/ L and 1.14 (0.73-1.64) mmol/ L, respectively, and the difference was not statistically significant; The NT-proANP in the group was 1.32 (0.88-1.85) and 1.34 (0.89-1.87) mmol/ L, respectively. Conclusion The relationship between serum Corin and hyperglycemia was reported in the general population of large samples for the first time in this study, and the serum Corin level in the hyperglycemic subjects was found to be high, and the prevalence of hyperglycemia increased with the increase of the level of Corin. The study suggests that serum Corin may play a role in sugar metabolism and may be a new risk factor for hyperglycemia. This study has found a new way to study the causes and pathogenesis of diabetes and to study the target of treatment.
【學(xué)位授予單位】：蘇州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R587.2

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