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A case of local delayed-type allergy to zinc-containing insulin as a cause of diabetic ketoacidosis in a patient with type 1 diabetes mellitus undergoing continuous subcutaneous insulin infusion

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Abstract

We herein report a case involving a woman with type 1 diabetes and a history of metal allergy who developed a local delayed-type (type IV) allergy to zinc-containing insulin. She had been treated by continuous subcutaneous insulin infusion, but her glycemic control was poor, and she developed diabetic ketoacidosis. Her plasma insulin concentration was unexpectedly low during use of insulin lispro, but it was recovered by changing from the zinc-containing insulin lispro to the zinc-free insulin glulisine. Intradermal tests showed no reactions to various insulins except for zinc chloride. A skin biopsy at the injection site of insulin lispro showed invasion of lymphocytes, neutrophils, and eosinophils, but a skin biopsy at the injection site of insulin glulisine showed invasion of only lymphocytes. A drug lymphocyte stimulation test against polaprezinc, an antiulcer drug containing zinc, was positive. Therefore, we diagnosed the patient with local delayed allergy to zinc-containing insulin. Insulin allergy should be considered as a possible cause of poor glycemic control and diabetic ketoacidosis in patients with type 1 diabetes.

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Correspondence to Ken-ichi Nemoto.

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Conflict of interest

H. Maegawa has received honoraria for manuscripts from Takeda Pharmaceutical Co., Ltd.; Merck Sharp & Dohme Corp.; Sanofi K.K.; Nippon Boehringer Ingelheim Co., Ltd.; Asteralls Pharma Inc.; Taisho Toyama Pharmaceutical Co., Ltd.; Kowa Pharmaceutical Co., Ltd.; Daiichi Sankyo Inc., Ono Pharmaceutical Co., Ltd.; and Mitsubishi Tanabe Pharma Co., Ltd. K. Nemoto, S. Ugi, S. Ogaku, N. Nakaizumi, K. Fuse, O. Sekine, K. Morino, and H. Maegawa received scholarship grants from Takeda Pharmaceutical Co., Ltd.; Merck Sharp & Dohme Corp.; Teijin Pharma Ltd.; Sanofi K.K.; Nippon Boehringer Ingelheim Co., Ltd.; and Kyowa Hakko Kirin Co., Ltd. T. Kato and T. Tanaka declare that they have no conflict of interest.

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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. Informed consent or a substitute for it was obtained from all patients for being included in the study.

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Nemoto, Ki., Ugi, S., Ogaku, S. et al. A case of local delayed-type allergy to zinc-containing insulin as a cause of diabetic ketoacidosis in a patient with type 1 diabetes mellitus undergoing continuous subcutaneous insulin infusion. Diabetol Int 7, 447–450 (2016). https://doi.org/10.1007/s13340-016-0264-0

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  • DOI: https://doi.org/10.1007/s13340-016-0264-0

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