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Fulminant Type 1 Diabetes

A nationwide survey in Japan

¹ Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Suita, Japan
² First Department of Internal Medicine, Osaka Medical College, Takatsuki, Japan
³ Diabetes Center, Tokyo Women’s Medical University School of Medicine, Tokyo, Japan
⁴ Diabetes Center, Kasori Hospital, Chiba, Japan
⁵ Unit of Metabolism/Diabetes and Clinical Nutrition, Nagasaki University School of Medicine, Nagasaki, Japan
⁶ Third Department of Internal Medicine, University of Yamanashi School of Medicine, Nakakoma, Japan
⁷ Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
⁸ Ehime Prefectural Central Hospital, Internal Medicine, Matsuyama, Japan
⁹ Department of Virology, Kurume University School of Medicine, Kurume, Japan
¹⁰ Department of Internal Medicine, Saitama Social Insurance Hospital, Urawa, Japan
¹¹ Department of Laboratory Medicine, Ehime University School of Medicine, Ehime, Japan

Address correspondence and reprint requests to Toshiaki Hanafusa, MD, PhD, FACP, Professor and Chairman, First Department of Internal Medicine, Osaka Medical College, 2–7 Daigaku-machi, Takatsuki, 569-8686, Japan. E-mail: hanafusa{at}poh.osaka-med.ac.jp

OBJECTIVE— To describe the clinical and immunologic characteristics of fulminant type 1 diabetes, a novel subtype of type 1 diabetes, we conducted a nationwide survey.

RESEARCH DESIGN AND METHODS—History and laboratory data, including islet-related autoantibodies, were examined in 222 patients with fulminant and nonfulminant type 1 diabetes in our hospitals in addition to another 118 patients with fulminant type 1 diabetes located outside our hospitals in Japan.

RESULTS—In our hospitals, of the 222 patients studied, 43 (19.4%) were diagnosed with fulminant type 1 diabetes, 137 (61.7%) were classified as having autoimmune type 1 diabetes, and 42 were type 1 diabetic subjects who were not fulminant and did not have anti-islet antibodies. An additional 118 fulminant patients outside our hospitals were enrolled, making a total of 161 fulminant type 1 diabetic subjects (83 male and 78 female subjects; 14 children/adolescents and 147 adults) identified from all over Japan. (In 2000, the average incidence was three cases per month.) Flu-like symptoms and pregnancy were more frequently observed in the fulminant than in the autoimmune group (P < 0.001). In the fulminant patients, 4.8% were positive for anti-GAD antibodies and none were positive for anti–islet antigen 2 antibodies.

CONCLUSIONS—Fulminant type 1 diabetes is a distinct subtype and accounts for 20% of the ketosis-onset type 1 diabetes cases in Japan. Flu-like symptoms are characteristic of disease onset. Metabolic derangement is more severe in this subtype than in autoimmune type 1 diabetes.

Abbreviations: ADA, American Diabetes Association • ALT, alanine aminotransferase • AST, aspartate aminotransferase • GADAb, GAD antibody • IAA, insulin autoantibody • IA-2, islet antigen 2 • IA-2Ab, IA-2 antibody • ICA, islet cell antibody • WHO, World Health Organization

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