Ketosis-prone type 2 diabetes with autoantibody negative and beta cell function positive group (KPD) is recognized as atypical diabetes characterized by the onset of disease at a relatively young age, obesity, sudden onset of ketosis and a transient decrease in insulin secretion. Previously we have reported that insulin peptide reactive T cells are detected in KPD patients (2017, ADA meeting). In this study, we examined the correlation between insulin peptide reactive T cells and clinical background such as C-peptide, HbA1c, and HLA types especially focusing on class I region to assess the significance of insulin peptide reactive T cells detected in KPD subjects. Peripheral blood was obtained from enrolled subjects with informed consent, and stimulated with insulin peptides (insulin B9-23, B10-24, B11-25, B12-26) for 24 hours, then interferon (IFN)-gamma spots were counted. Maximum spots more than 2.5 were considered as positive based on the data from control subjects. Seven out of 21 (33.3%) KPD participants (21 males, 0 females, mean age 40.3 years) showed positive result, and this frequency was similar to that in acute-onset type 1 diabetes (17 out of 50; 34.0%) (22 males, 28 females, mean age 44.5 years); these results were consistent with our previous observation. Only 1 out of 35 (2.9%) showed positive result in controls (26 males, 9 females, mean age 61.8 years). In KPD participants, serum C-peptide level was significantly lower in the ELISpot positive group than in the negative group (1.40±0.55 ng/mL vs. 2.35±0.76 ng/mL; p <0.05). Moreover, there was a significant positive correlation between the spot number and HbA1c at onset in the positive group (rs= 0.6232, (p <0.05 by Spearman correlation test). Furthermore, HLA A*02:01 or A*24:02 positive rate was significantly higher in the ELISpot positive group (n=7) than the negative group (n=14) (86% vs. 36%; p <0.05). These findings suggest that insulin peptide reactive IFN-gamma-producing T cells may reflect disease activity of KPD.
A. Satomura: None. S. Suzuki: None. A. Haisa: None. Y. Oikawa: None. A. Shimada: Advisory Panel; Self; Astellas Pharma Inc. Speaker’s Bureau; Self; Eli Lilly Japan K.K., Novo Nordisk Inc., Sanofi-Aventis.