title: Insulin administration may trigger pancreatic beta-cell destruction in patients with type 2 diabetes.
abstract: Insulin administration causes various types of immune response to insulin. However, there have been no reports that insulin administration triggers pancreatic beta-cell destruction in diabetic patients. We evaluated three patients who had suffered from type 2 diabetes or impaired glucose tolerance for 5-30 years. After an episode of diabetic mononeuropathy or poor glycemic control, they started human insulin therapy. All the patients' serum or urinary C-peptide levels were preserved before insulin therapy, whereas within a few months they rapidly declined to below detection limits. A high titer of insulin antibody was detected at or after the development of insulin deficiency. Shortly after the initiation of insulin therapy, two of the patients developed an insulin allergy. Autoantibodies to GAD65 or IA-2 were negative throughout the clinical course in two cases, but transiently positive in one case. In a histological examination of pancreas tissue obtained by a pancreatic biopsy in one case, mononuclear cell infiltration into the islets was observed. They all had a type 1 diabetes high-risk HLA class II haplotype in Japanese, and class I alleles of the insulin gene VNTR. The above findings suggest that insulin administration may have triggered pancreatic beta-cell destruction in these patients.
authors.affiliation: Department of Molecular and Genetic Medicine, Ehime University Graduate School of Medicine, Toon-shi, Ehime 791-0295, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Nakamura
authors.forename: Wataru
authors.initials: W
authors.lastname: Nishida
authors.forename: Yuya
authors.initials: Y
authors.lastname: Yamada
authors.forename: Daisuke
authors.initials: D
authors.lastname: Chujo
authors.forename: Yuji
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Akihisa
authors.initials: A
authors.lastname: Imagawa
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Hanafusa
authors.forename: Eiji
authors.initials: E
authors.lastname: Kawasaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Onuma
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Osawa
authors.forename: Hideichi
authors.initials: H
authors.lastname: Makino
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002096:C-Peptide / Q000097:blood / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000473:pathology*; D004342:Drug Hypersensitivity; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects; D007328:Insulin / Q000009:adverse effects*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008875:Middle Aged
chemical_list: D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin