ObjectiveTo investigate the changes of serum A20 level in patients with type 2 diabetes mellitus (T2DM) and its related factors.MethodsIt was a cross-sectional study. A total of 156 T2DM patients visited the Department of Endocrinology and Metabolism, Shanghai Tongji Hospital, Tongji University and 182 community non-diabetic subjects (age≥50 years) receiving health checkups from 2022 to 2023 were selected as the research subjects. Clinical data were collected, blood biochemistry, grip strength, simple physical fitness test and serum A20 levels were measured. Comparisons between groups were performed using independent sample t test, non-parametric test and chi-square test. The Pearson correlation analysis was used to evaluate the relationship between serum A20 level and other clinical data. Multiple linear regression analysis was used to evaluate the correlation between LnA20 and fasting blood glucose and glycosylated hemoglobin. Univariate and multivariate logistic regression analyses were conducted to explore the relationship between A20 and T2DM.ResultsThe thigh circumference, calf circumference, left hand grip strength, right hand grip strength, hemoglobin, A20 level, total cholesterol and high density lipoprotein cholesterol were all lower in the T2DM group than those in the control group (all P<0.05), while the waist circumference, waist to hip ratio, fasting blood glucose and glycosylated hemoglobin were all higher than those in the control group (all P<0.001). Pearson correlation analysis showed that in non-T2DM subjects, serum A20 levels was negatively correlated with fasting blood glucose and glycosylated hemoglobin (both P< 0.05). In the overall study population, serum A20 levels was negatively correlated with waist to hip ratio, fasting blood glucose and glycosylated hemoglobin, while positively correlated with hemoglobin (all P<0.05). Multiple linear regression analysis revealed that in T2DM patients, after adjusting for waist to hip ratio and hemoglobin, the correlations of LnA20 with fasting blood glucose and glycosylated hemoglobin were not statistically significant. In non-T2DM subjects, after adjusting for waist to hip ratio and hemoglobin, LnA20 remained independently negatively associated with fasting blood glucose and glycosylated hemoglobin (both P<0.05). In the overall study population, after adjusting for waist to hip ratio and hemoglobin, LnA20 was independently negatively associated with fasting blood glucose and glycosylated hemoglobin (both P<0.05). Multivariate logistic regression analysis showed that for each unit increase in A20, the risk of T2DM decreased by 60% (P<0.05).ConclusionSerum A20 level is decreased in patients with T2DM. Besides, serum A20 level is negatively correlated with fasting blood glucose and glycosylated hemoglobin in non-T2DM population and all subjects. A decline in serum A20 level may be a risk factor for T2DM.