In ketosis prone type 2 diabetes with A-beta+ phenotype (= autoantibodies absent, beta cell function present; KPD), we found insulin peptide reactive T cell response, and reported in ADA meeting 2017. This time, we examined not only T cell response but also HLA genotype because characteristics of HLA in KPD is unknown. This study was approved by institutional review board. 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 IFN-gamma spots were counted (duplicate). Forty three point three percent (13 out of 30) of KPD (28 male, 2 female, mean age 41.1 years, mean duration 2.6 years) was found to be positive for the spots; we confirmed the previous data even we increased the patient numbers. This was similar level in acute onset type 1 diabetes (=T1D, 45.3% (24 out of 53), 19 male, 34 female, mean age 45.7 years, mean duration 5.7 years), but only 1 out of 35 (0.03%) was positive in controls (26 male, 9 female, mean age 61.8 years). On the other hand, the frequency of susceptible HLA in Japanese type 1 diabetes (DRB1*04:or DRB1*09:01) examined was 39.1% in KPD, 89.4% in T1D, and 45.7% in controls (KPD vs. T1D, p<0.001). Moreover, frequency of protective HLA in type 1 diabetes (DRB1*15:01 or DRB1*15:02) was 21.7% in KPD, 2.1% in T1D, and 20.0% in controls (KPD vs. T1D, p<0.05). Therefore, although insulin peptide T cell response was detected in KPD as same degree in T1D, characteristics of HLA genotype in KPD was different from T1D. These results suggest that even though autoreactivity exists in KPD, “less susceptible” and “protective” HLA genotype of type 1 diabetes in KPD may contribute to the suppression of the disease progression, and may explain the different clinical course after onset of ketoacidosis between KPD and T1D.


A. Shimada: Speaker's Bureau; Self; Eli Lilly and Company, Sanofi-Aventis, Novo Nordisk A/S. Y. Oikawa: None. A. Satomura: None. A. Haisa: None.

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