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Fulminant type 1 diabetes: a novel clinical entity requiring special attention by all medical practitioners

Abstract

Fulminant type 1 diabetes is a recently discovered subtype of type 1 diabetes. It is defined as diabetes in which the process of β-cell destruction and the progression of hyperglycemia and ketoacidosis are extremely rapid. The pathogenesis of this disease remains to be clarified, but the involvement of both genetic background—especially human leukocyte antigen genes—and viruses has been suggested. Fulminant type 1 diabetes has the following clinical characteristics: duration of hyperglycemic symptoms is 4 days on average; there is a high prevalence of preceding common-cold-like and gastrointestinal symptoms; there is a near-normal level of glycated hemoglobin in spite of very high plasma glucose levels associated with ketoacidosis; the disease is sometimes related to pregnancy; and there are increased serum pancreatic enzyme levels, absent C-peptide levels, but virtually no detectable autoantibodies against constituents of pancreatic β cells. The presence of the above characteristics strongly indicates the diagnosis of fulminant type 1 diabetes. Once the diagnosis of this disease is suspected, treatment of diabetic ketoacidosis must be started immediately, as in all other cases of type 1 diabetes. Otherwise, the death of the patient is likely to occur within 24 h. All medical practitioners must remember that this extremely rapidly progressing type of diabetes does exist, and they must pay special attention not to overlook it.

Key Points

  • Fulminant type 1 diabetes is defined as diabetes in which the progression from normoglycemia to hyperglycemia accompanied with ketoacidosis is extremely rapid

  • Without appropriate therapy, the death of the patient is inevitable within several days

  • Clinical features include common-cold-like and/or abdominal symptoms preceding disease onset, disease duration of less than 1 week from the start of hyperglycemia, a near-normal glycated hemoglobin level, no residual insulin secretory capacity, a lack of anti-islet autoantibodies, and elevation of pancreatic enzyme levels; association with pregnancy is not rare

  • Human leukocyte antigen DR4–DQ4 confers susceptibility to the disease, and viruses are suspected to be involved in the pathogenesis

  • Fulminant type 1 diabetes at onset should be treated the same as other diabetic ketoacidosis with intravenous infusion of saline and regular insulin; this treatment should be followed by an intensive insulin therapy including continuous subcutaneous insulin infusion

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Figure 1: Schematic process showing the destruction of the hypothetical β-cell mass in fulminant type 1 diabetes and type 1A (autoimmune) diabetes.
Figure 2: Distribution of ages at onset of fulminant type 1 diabetes.
Figure 3: Year-to-year variation in number of patients with fulminant type 1 diabetes from 1990 to 2000.
Figure 4: Seasonal variation of fulminant type 1 diabetes.

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Acknowledgements

We are indebted to Drs N Itoh, J Miyagawa and Y Matsuzawa for discussions, also to the doctors of the Osaka IDDM study group and the Committee of the Japan Diabetes Society on the Research of Fulminant Type 1 Diabetes Mellitus for collaboration. This study was supported by the a grant-in-aid for scientific research from the Japan Society for the Promotion of Science, a grant-in-aid from the Japan Medical Association, and a grant from the Japan Diabetes Society.

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Correspondence to Toshiaki Hanafusa.

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Hanafusa, T., Imagawa, A. Fulminant type 1 diabetes: a novel clinical entity requiring special attention by all medical practitioners. Nat Rev Endocrinol 3, 36–45 (2007). https://doi.org/10.1038/ncpendmet0351

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