血清可溶性Corin与高血糖关系的横断面研究

发布时间：2019-06-27 12:29

【摘要】：研究背景:糖尿病是心脑血管病的重要危险因素,是我国重要的疾病负担和公共卫生问题。关于其发病机制并未完全阐明。Corin蛋白是新近发现的可能与心血管病发病有关的一种丝氨酸蛋白酶。目前尚无关于Corin蛋白与血糖关系的研究报道。研究目的:了解血清Corin蛋白在一般人群的分布情况;探讨Corin蛋白与高血糖的关系,为人群糖尿病危险因素的探讨以及临床治疗提供流行病学依据。研究对象与方法:通过多阶段整群随机抽样的方法,随机抽取苏州姑苏区4个农村社区和4个城市社区作为调查现场。按照纳入排除标准最后共有2498名研究对象符合要求。由培训合格的调查员采用统一设计的调查表,收集调查对象的人口统计学信息、生活方式危险因素、疾病史等资料,测量并记录身高、体重以及血压等数据。采集空腹静脉血,检测空腹血糖、血脂等指标。在实验室用ELISA试剂盒检测Corin蛋白和NT-proANP。用非条件logistic回归模型分析Corin与高血糖的关系。在分析时调整了年龄、收缩压、吸烟、饮酒、总胆固醇和高密度脂蛋白,以控制这些因素对Corin与高血糖关系的影响。为了排除高血压、超重/肥胖、中心性肥胖或者血脂异常对高血糖结果的潜在影响,又进行了敏感性分析。研究结果:1、在2498名研究对象中,共有772例高血糖者,患病率为30.90%。男性共962名,其中340名是高血糖者,患病率为35.34%,女性共1536名,其中432名是高血糖者,患病率为28.13%。2、研究对象中血清Corin的平均水平为1689.2 pg/mL,男性中血清Corin的水平为2174.5 pg/m L,女性中为1515.1 pg/m L,男性Corin水平显著高于女性(P0.001)。3、按照男女中不同的Corin四分位将研究对象分成四组,低分位到高分位组的超重/肥胖人数(患病率)分别为297(47.52%)、313(50.16%)、348(55.86%)和453(72.36%)。在年龄、性别调整分析中,Corin水平在第3、4分位组的超重/肥胖的危险性分别是第1分位组的1.39倍和3.02倍(所有p0.05);在多因素调整分析中,与最低分位组相比,corin水平在第4分位组的研究对象有更高的患超重/肥胖的危险性(or=2.26,p0.001)。超重/肥胖的or值随着corin水平的升高而升高,趋势性检验具有统计学意义(p0.001)。从corin水平1至4分位组,中心性肥胖人数(患病率)分别为292(46.72%)、304(48.72%)、328(52.65%)和399(63.74%)。以最低分位组为参考,中心性肥胖的第3、4分位组的or值分别为1.29(p=0.033)和2.34(p0.05),多因素调整分析后,第4分位组的中心性肥胖or值是第1分位组的1.74倍(p0.001)。中心性肥胖or值也随着corin的升高而升高(趋势性p值=0.001)。4、根据不同性别按照corin4分位将研究对象分成4组,在男性中,从低到高分位(1、2、3和4分位)组的高血糖人数(患病率)分别为70(29.17%)、66(27.39%)、94(38.84%)和110(46.03%)。单因素logistic分析结果显示,与1分位者相比,2、3和4分位者患高血糖的or值(95%ci)分别为0.92(0.62-1.36)、1.54(1.06-2.26)和2.07(1.42-3.02),趋势检验具有统计学意义。多因素logistic回归分析结果显示,与1分位者相比,2、3和4分位者患高血糖的or值(95%ci)分别为0.98(0.68-1.47)、1.45(0.97 2.16)和1.96(1.29-2.96),趋势检验具有统计学意义,并且4分位者的or值仍具有统计学意义(or=1.96,p=0.002)。在女性中,1、2、3和4分位组的高血糖人数(患病率)分别为87(22.60%)、95(24.87%)、118(30.65%)和132(34.38%)。单因素分析结果显示,以第1分位者为参照,2、3和4分位者患高血糖的or值(95%ci)分别为1.13(0.81-1.58)、1.51(1.10-2.09)和1.79(1.31-2.47)。多因素调整后,以第1分位者为参照,2、3和4分位组高血糖的or值(95%ci)分别为1.08(0.76-1.54)、1.28(0.91-1.81)和1.36(0.97-1.91),趋势性检验有统计学意义(p=0.050)。以corin中位数作为界值,将研究对象分为高corin组和低corin组,计算高血糖的or值,结果显示,无论调整前后,高corin组的高血糖or值均具有统计学意义。5、排除高血压、超重/肥胖、中心性肥胖和血脂异常后,分析corin与高血糖的关系。男性中,单因素分析结果显示,高corin组高血糖的or为2.3(95%ci1.14-4.63);多因素调整后,or值为2.47(95%ci1.11-5.50)。女性中,单因素分析结果显示,高corin组高血糖的or为1.48;多因素调整后,or值为1.45。6、男性中高血糖组和正常血糖组的nt-proanp浓度分别为1.09(0.75-1.52)mmol/L和1.14(0.73-1.64)mmol/L,差异没有统计学意义;女性中高血糖组和非高血糖组NT-proANP分别为1.32(0.88-1.85)和1.34(0.89-1.87)mmol/L,差别没有统计学意义。结论本研究首次在大样本的一般人群中报道了血清Corin与高血糖的关系,发现高血糖对象中血清Corin水平较高,并且随着Corin水平的升高,高血糖患病率有升高趋势。本研究提示,血清Corin可能在糖代谢中发挥作用,可能是高血糖新的危险因素。本研究发现为进一步的糖尿病病因和发病机制以及治疗靶点研究提供了新思路。
[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.
【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R587.2

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