Ketosis-prone type 2 diabetes, especially islet-associated autoantibody negative and beta-cell function reserved (A-beta+; KPD) group, is recognized as atypical diabetes. Because we detected insulin peptide reactive T cells in these KPD subjects, we realized that KPD possesses characteristics of type 1 diabetes (ADA meeting, 2017). Therefore, in this study, we examined HLA types. After institutional review board permission was obtained, written informed consent and blood samples were obtained from the enrolled Japanese subjects (KPD: 22 males and 0 female, mean onset age 36.4 years of age; acute onset type 1 diabetes (AT1D): 21 males and 22 females, mean onset age 36.3 years of age; slowly progressive type 1 diabetes (SP): 10 males and 10 females, mean onset age 49.0 years of age). Then the HLA allele frequency was compared to normal controls (http://hla.or.jp/med/frequency_search/ja/allele/search/R/). The frequencies of HLA DRB1*04:05 and DRB1*09:01, which are known susceptible alleles in Japanese type 1 diabetes, were not higher in KPD (13.6%, 27.3%, respectively) subjects as compared to controls (13.5%, 14.3%, respectively), whereas were significantly higher in AT1D (41.9%, 53.5%, respectively; both p<0.001) and SP subjects (45.0%, 40.0%, respectively; both p<0.002). However, interestingly, the frequency of HLA DRB1*08:03 was significantly higher in KPD (34.8%, p<0.001) subjects as compared to controls (8.3%), whereas it was not the case both in AT1D (4.7%) and SP (10.0%) subjects. Moreover, the frequency of HLA DRB1*04:01 which is known susceptible alleles in Caucasian type 1 diabetes was significantly higher in KPD (18.2%, p<0.001) subjects as compared to controls (0.9%), whereas it was not the case both in AT1D (2.3%) and SP (5.0%) subjects.
In conclusion, although KPD subjects possess similar insulin peptide T cell responses to type 1 diabetes, different genetic background seems to exist probably leading to different clinical phenotype.
A. Shimada: Advisory Panel; Self; Astellas Pharma Inc. Speaker’s Bureau; Self; Eli Lilly Japan K.K., Novo Nordisk Inc., Sanofi-Aventis. A. Satomura: None. S. Suzuki: None. A. Haisa: None. Y. Oikawa: None.
Saitama Medical University