Report of the Committee of the Japan Diabetes Society on Research on Fulminant Type 1 Diabetes Mellitus: Analysis of HLA Serotype and Diabetic Microangiopathy

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  • Hanafusa Toshiaki
    First Department of Internal Medicine, Osaka Medical College (Secretariat)
  • Imagawa Akihisa
    First Department of Internal Medicine, Osaka Medical College (Secretariat)
  • Iwahashi Hiromi
    Department of Metabolic Medicine, Graduate School of Medicine, Osaka University
  • Uchigata Yasuko
    Diabetes Center, Tokyo Women's Medical University School of Medicine
  • Kanatsuka Azuma
    Diabetes Center, Chiba Central Medical Center
  • Kawasaki Eiji
    Department of Metabolism/Diabetes and Clinical Nutrition, Nagasaki University Hospital of Medicine and Dentistry
  • Kobayashi Tetsuro
    Third Department of Internal Medicine, University of Yamanashi School of Medicine
  • Shimada Akira
    Department of Internal Medicine, Keio University School of Medicine
  • Shimizu Ikki
    Ehime Prefectural Central Hospital, Internal Medicine
  • Maruyama Taro
    Department of Internal Medicine, Saitama Social Insurance Hospital
  • Makino Hideichi
    Department of Molecular and Genetic Medicine, Ehime University Graduate School of Medicine
  • Murase Yuko
    First Department of Internal Medicine, Osaka Medical College (Secretariat)
  • Ikegami Hiroshi
    Department of Endocrinology, Metabolism and Diabetes, Kinki University School of Medicine

Bibliographic Information

Other Title
  • 劇症1型糖尿病調査研究委員会報告
  • 劇症1型糖尿病調査研究委員会報告--HLAおよび細小血管合併症について
  • ゲキショウ 1ガタ トウニョウビョウ チョウサ ケンキュウ イインカイ ホウコク HLA オヨビ サイショウ ケッカン ガッペイショウ ニ ツイテ
  • —HLAおよび細小血管合併症について—

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Objective: We clarified HLA distribution and diabetic microangiopathy in fulminant type 1 diabetes, a novel subtype of diabetes mellitus.<br>Methods: We identified patients with fulminant type 1 diabetes in Japan by using criteria established in 2004. In Study 1, HLA analysis, we studied the serotype of HLA A, DR, and DQ in 115 patients with fulminant type 1 diabetes, 98 patients with autoimmune (type 1A) diabetes, and 190 healthy controls. In Study 2 on diabetic microangiopathy, we studied clinical parameters including blood glucose, HbA1c, and serum C peptide levels, the frequency of severe hypoglycemia, optic fundus, urinary albumin excretion, and Achilles tendon reflex in 41 patients with fulminant type 1 diabetes and 76 patients with autoimmune (type 1A) diabetes as controls.<br>Results: Study 1 showed that HLA DR4, DQ4, and DR4-DQ4 haplotype were significantly more frequent in patients with fulminant type 1 diabetes than in healthy control subjects. The homozygosity of HLA DR4-DQ4 indicated a very high odds ratio of 13.3. HLA DR1, DR2, DR5, DR8, DQ1, haplotypes of DR2-DQ1 and DR8-DQ1 were significantly less frequent in patients with fulminant type 1 diabetes. Study 2 showed that the 5-year cumulative incidence of microangiopathy was 24.4% in fulminant type 1 diabetes and 2.6% in type 1A diabetes. In longitudinal studies, the cumulative incidence of each form of microangiopathy was significantly higher in fulminant type 1 diabetes than in type 1A diabetes; retinopathy was 9.8% vs 0%, nephropathy 12.2% vs 2.6%, and neuropathy 12.2% vs 1.3%. Mean HbA1c levels were similar in fulminant and type 1A diabetes groups during follow-up, but mean M and the frequency of severe hypoglycemic episodes were significantly higher and mean postprandial C-peptide level significantly lower in the fulminant type 1 diabetes group.<br>Conclusions: Our results suggest that (1) class II HLA contributes to the development of fulminant type 1 diabetes, and (2) patients with fulminant type 1 diabetes belong to a subgroup at high risk for diabetic microangiopathy.

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