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.

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.

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 (B-T2DM) group (n=30), and type 2 diabetes mellitus with macrovascular disease (B-T2DM+CVD) group (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 R-T2DM+CVD.

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 (HbA_1c), 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, HbA_1c, 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 2 h blood glucose, HbA_1c, 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 OGTT 2 h glucose level and HbA_1c 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 2 h blood glucose (OR=1.205, 95%CI=1.001-1.451) and HbA_1c (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 2 h glucose (OR=1.118, 95%CI=0.867-1.441), HbA_1c (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.

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 HbA_1c. Tryptase might have no influence on the regression of type 2 diabetic macrovascular disease.