Abnormality of cellular immunity of Ketosis-prone diabetes

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K09010
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Saitama Medical University
• Principal Investigator: Shimada Akira 埼玉医科大学, 医学部, 教授 (60206167)
• Co-Investigator(Kenkyū-buntansha): 及川 洋一 埼玉医科大学, 医学部, 准教授 (30296561)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 糖尿病 / 細胞性免疫 / 外分泌酵素 / HLA / インスリン

Outline of Final Research Achievements

Ketosis-prone diabetes (KPD) is characterized by the sudden onset of diabetic ketoacidosis (DKA) without precipitating factors, negative anti-islet autoantibodies and preservation of β-cell function after recovery from DKA. Although this phenotype often appears with DKA just like acute-onset type 1 diabetes (AT1D), the involvement of anti-pancreas immune responses remains unknown. We sought to clarify the immunological role of pancreatic antigens in KPD. Overall, one third of KPD participants showed positive insulin-peptide-specific reactivity in peripheral blood; the positivity rate in KPD was similar to that in AT1D. Moreover, frequency of HLA DRB1*08:03 was higher in KPD as compared to controls and the HLA type was correlated with higher exocrine enzyme levels. These findings suggest the involvement of insulin-peptide-specific immunoreactivity in the pathophysiology of KPD. Moreover, there may exist anti-exocrine tissue antigen reactivity in KPD with HLA DRB1*08:03.

Free Research Field

内分泌代謝学

Academic Significance and Societal Importance of the Research Achievements

KPD(ketosis-prone diabetes)と通常のケトーシスを伴わない２型糖尿病の病態が異なり、１型糖尿病との異同が明確になることで、治療介入が変わり、患者の予後を大きく左右する可能性がある。したがって、本研究は、KPDを１型糖尿病のいわば「亜型」としてとらえようとする視点から非常に独創的であり、学術的に高く、また、適切な対応をしないと致命的になる糖尿病ケトアシドーシスを繰り返し起こすリスクの高いKPDの病態を解明することで糖尿病診療に寄与することは、社会的にも大きな意味を持つと考える。