Abstract: Background Diabetic macrovascular complications represent prevalent and severe consequences of diabetes mellitus，characterized by high morbidity and significant clinical impact. To date，the pathogenesis of the disease remains undefined. Inflammation and oxidative stress have long been the key research focuses in the pathogenesis. Multiple inflammatory mediators have been confirmed to contribute to the occurrence and development of diabetes-associated macrovascular disease. However，whether tryptase，an important inflammatory mediator，is involved in its pathogenesis has rarely been reported. Objective Serum tryptase levels were analyzed in patients with type 2 diabetes mellitus complicated by macrovascular disease. A non-interventional follow-up study was conducted in patients newly diagnosed with diabetes through oral glucose tolerance test（OGTT）. A repeated survey was conducted after 10 years. This survey identified two groups of patients：those with type 2 diabetes complicated by macrovascular disease and those with type 2 diabetes alone. We aimed to explore baseline serum tryptase levels across these outcome groups，and to investigate factors influencing diabetic macrovascular disease progression. Methods A cluster random sampling method was employed to select residents from three communities in Luzhou for physical examinations，questionnaire surveys，and laboratory tests between April and November 2011. Three groups were established：Healthy individuals were randomly selected as the normal control group（NG，n=30），newly diagnosed type 2 diabetes patients as the type 2 diabetes mellitus group（B-T2DM，n=30），and type 2 diabetes patients with macrovascular disease as the type 2 diabetes mellitus with macrovascular disease group（B-T2DM+CVD，n=30）. During the baseline survey，newly diagnosed diabetes mellitus patients were enrolled in a 10-year non-interventional follow-up. An investigation was conducted between April and December 2021. It aimed to randomly select the type 2 diabetes mellitus group（R-T2DM）and type 2 diabetes mellitus with macrovascular disease group（R-T2DM+CVD）. Results Comparison of clinical and biochemical parameters among populations with different baseline statuses was performed. There were statistically significant differences in fasting plasma glucose （FPG），OGTT 2 h，glycated hemoglobin A1c（HbA1c），triglycerides（TG），high-density lipoprotein cholesterol（HDL-C），body mass index（BMI），and tryptase levels among different groups（P<0.05）. The B-T2DM+CVD group had higher levels of FPG，OGTT 2h blood glucose，HbA1c，tryptase than the NG group and B-T2DM group，and higher levels of TG and BMI than NG group（P<0.05）. Correlation between tryptase and baseline indicators：tryptase levels demonstrated positive correlations with FPG，OGTT 2h blood glucose，HbA1c，TC，LDL-C，BMI，and waist-to-hip ratio（WHR）（r=0.226，0.296，0.185，0.272，0.213，0.245，0.278），and negative correlations with HDL-C（r=-0.209）（P<0.05）. The influence of tryptase on B-T2DM+CVD：Univariate Logistic regression analysis showed that tryptase was a risk factor for B-T2DM+CVD（OR=1.832，95%CI=1.015~3.308），while multivariate logistic regression analysis showed that tryptase was not an influencing factor for type 2 diabetes mellitus complicated by macrovascular disease（P>0.05）. After 10 years of follow-up，26 of 331 diabetes patients developed type 2 diabetes mellitus complicated by macrovascular disease. At baseline，both the OGTT2h glucose level and HbA1c were higher in the R-T2DM+CVD group than in the R-T2DM group（P<0.05）；no statistically significant difference was observed in baseline tryptase levels between the two groups（P>0.05）. Univariate Logistic regression analysis showed that OGTT 2h blood glucose（OR=1.205，95%CI=1.001-1.451）and HbA1c（OR=1.699，95%CI=1.009-2.863）were influencing factors for regression of type 2 diabetes mellitus complicated by macrovascular disease（P<0.05），while the multivariate logistic regression analysis showed that OGTT 2h blood glucose（OR=1.118，95%CI=0.867-1.441），HbA1c（OR=1.331， 95%CI=0.664-2.795）and tryptase（OR=1.003，95%CI=0.513-1.961）were not influencing factors for regression of type 2 diabetic macrovascular disease. Conclusions Serum tryptase levels in patients with type 2 diabetic macrovascular disease were higher than those in the type 2 diabetes group and the normal group. Tryptase was a risk factor for type 2 diabetic macrovascular disease，but this effect disappeared after adjusting for FPG，OGTT 2h and HbA1c. Tryptase might have no influence on the regression of type 2 diabetic macrovascular disease.

Key words: Diabetes mellitus, type 2；Coronary vessels；Cholesterol, HDL；Cholesterol, LDL；Tryptases

摘要： 背景 糖尿病大血管并发症是糖尿病的常见并发症，其患病率高，危害大。但目前发病机制尚不明确，炎症反应、氧化应激一直是其发病机制中的研究热点，现已明确多种炎症介质参与糖尿病合并大血管病变的发生、发展，而类胰蛋白酶作为一种重要的炎症介质，是否与2型糖尿病合并大血管的发病相关目前尚鲜有报道。目的 分析2型糖尿病合并大血管病变者血清类胰蛋白酶水平，并对经口服葡萄糖耐量试验（OGTT）确诊为新诊断糖尿病者进行非干预性随访，10年后再次进行重复调查，筛选出2型糖尿病合并大血管变、2型糖尿病人群，探讨不同转归人群基线时血清类胰蛋白酶水平及糖尿病大血管并发症转归的影响因素。方法 采用整群随机抽样法，选取2011年4—11月泸州市区内茜草、大山坪、龙马潭3个社区居民4 000名为研究对象，行查体、问卷收集、生化检查。从中随机选取健康人群作为正常对照组（NG组，n=30）、新诊断2型糖尿病者作为2型糖尿病组（B-T2DM 组，n=30）、2型糖尿病合并大血管病变者作为2型糖尿病合并大血管病变组（B-T2DM+CVD 组，n=30）。对基线调查时新诊断糖尿病者331例进行10年非干预性随访，于 2021 年 4—11 月再次重复调查，随机筛选出2型糖尿病组（R-T2DM 组，n=30）和 2型糖尿病合并大血管病变组（R-T2DM+CVD 组，n=26）。结果 基线调查时，不同组别空腹血糖（FPG）、OGTT 2 h血糖、糖化血红蛋白（HbA1c）、三酰甘油（TG）、高密度脂蛋白胆固醇（HDL-C）、BMI、类胰蛋白酶水平比较，差异有统计学意义（P<0.05），其中 B-T2DM 组 FPG、OGTT 2 h 血糖、HbA1c、TG、BMI、类胰蛋白酶水平均高于 NG 组；B-T2DM+CVD 组 FPG、OGTT 2 h 血糖、HbA1c、类胰蛋白酶水平高于 B-T2DM 组和 NG 组，TG 和 BMI 高于 NG 组（P<0.05）。类胰蛋白酶与 FPG、OGTT 2 h 血糖、HbA1c、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、BMI、腰臀比（WHR）呈 正 相 关（r 值 分 别 为 0.226、0.296、0.185、0.272、0.213、0.245、0.278）， 与 HDL-C 呈 负 相 关（r 值 为 -0.209）（P<0.05）。单因素 Logistic 回归分析结果显示，类胰蛋白酶是 2 型糖尿病合并大血管病变的危险因素（OR=1.832，95%CI=1.015~3.308），但多因素 Logistic 回归分析显示类胰蛋白酶并非 2 型糖尿病合并大血管病变的影响因素（P>0.05）。随访 10 年后，331 例糖尿病患者中 26 例转归为 2 型糖尿病合并大血管病变患者。R-T2DM+CVD 组基线时 OGTT 2h 血糖、HBA1C 均高于 R-T2DM 组（P<0.05），两组基线时类胰蛋白酶比较，差异无统计学意义（P>0.05）。单因素 Logistic回归分析，结果筛选出 OGTT 2h 血糖（OR=1.205，95%CI=1.001~1.451）、HBA1C（OR=1.699，95%CI=1.009~2.863）是转归为 2 型糖尿病合并大血管病变的影响因素（P<0.05），多因素 Logistic 回归分析显示 OGTT 2h 血糖（OR=1.118，95%CI=0.867~1.441）、HbA1c（OR=1.331，95%CI=0.664~2.795）、 类 胰 蛋 白 酶（OR=1.003，95%CI=0.513~1.961） 不是转归为 2 型糖尿病合并大血管病变的危险因素（P>0.05）。结论 2型糖尿病合并大血管病变者血清类胰蛋白酶高于2 型糖尿病组及正常组；血清类胰蛋白酶水平与 FPG、OGTT2h血糖、HbA1c、TC、LDL-C、BMI、WHR 呈正相关，与 HDL-C 呈负相关；类胰蛋白酶为 2 型糖尿病合并大血管病变的危险因素，但在调整 FPG、OGTT 2h 血糖、HbA1c 后这种作用消失；类胰蛋白酶可能对 2 型糖尿病合并大血管病变的转归无影响。

关键词: 糖尿病, 2 型；冠状血管；胆固醇, HDL；胆固醇, LDL；类胰蛋白酶类