title: Insulin administration may trigger type 1 diabetes in Japanese type 2 diabetes patients with type 1 diabetes high-risk HLA class II and the insulin gene VNTR genotype.
abstract: BACKGROUND
  Insulin administration causes various types of immune responses to insulin. We previously reported three cases of type 1 diabetes mellitus (T1DM) triggered by insulin administration in Japanese type 2 diabetes mellitus patients.
  
  
  OBJECTIVE
  The objective of this study was to collect information and characterize insulin-triggered T1DM immunologically and genetically.
  
  
  METHODS
  Data for six patients (four men and two women) with insulin-triggered T1DM aged 59.5 ± 12.8 years were collected. Serum or urinary C-peptides, islet-related autoantibodies, insulin antibody, human leukocyte antigen, or the insulin gene variable number of tandem repeat genotype were analyzed. Th1- or Th2-associated responses were evaluated using an Enzyme-Linked ImmunoSpot assay.
  
  
  RESULTS
  None of the subjects had received insulin therapy or had an autoantibody to the 65-kDa isoform of glutamic acid decarboxylase before insulin administration. After insulin administration blood glucose control deteriorated acutely without any apparent cause, whereas C-peptide levels rapidly decreased to insulin-deficient levels. The mean duration of insulin administration to the development of T1DM was 7.7 ± 6.1 months. Islet-related autoantibodies became positive, whereas insulin allergy or a high titer of insulin antibody was observed in several cases. All had T1DM high-risk human leukocyte antigen class II (IDDM1) and the insulin gene variable number of tandem repeats genotype (IDDM2). GAD-reactive and insulin peptide-reactive Th1 cells, but not Th2 cells, were identified in two of four cases.
  
  
  CONCLUSIONS
  The findings suggest that insulin administration may have triggered TIDM in patients with type 2 diabetes mellitus. IDDM1 and IDDM 2 as well as autoreactive T cells may contribute to the development of T1DM. Developing insulin-triggered T1DM if a patient's blood glucose control acutely deteriorates after insulin administration should be carefully considered.
authors: Department of Diabetes and Molecular Genetics (W.N., R.K., H.On., H.Os., H.M.), Ehime University Graduate School of Medicine, To-on, Ehime 791-0295, Japan; Department of Internal Medicine (M.N.), Kokogawa W City Hospital, Hyogo 675-8611, Japan; Department of Metabolic Medicine (A.I.), Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan; Department of Internal Medicine (I) (T.H.), Osaka Medical College, Osaka 569-8686, Japan; University of Tsukuba (J.O.), Ibaraki, Japan; 6) Division of Diabetes (K.T.), Department of Internal Medicine, Kurashiki Central Hospital, Kurashiki 710-8602, Japan; Department of Diabetes (T.S.), Kochi Takasu Hospital, Kochi 781-5103, Japan; Sumitomo Hospital (Y.Y.), Osaka 530-0005, Japan; Diabetes Research Center (D.C.), National Center for Global Health and Medicine, Tokyo 162-8655, Japan; Department of Metabolism/Diabetes and Clinical Nutrition (E.K.), Nagasaki University Hospital, Nagasaki 852-8501, Japan; and Shiraishi Hospital Diabetes Center (H.M.), Imabari, Ehime 794-0041, Japan.
authors: Wataru
authors: W
authors: Nishida
authors: Masao
authors: M
authors: Nagata
authors: Akihisa
authors: A
authors: Imagawa
authors: Toshiaki
authors: T
authors: Hanafusa
authors: Jun
authors: J
authors: Ohashi
authors: Kenji
authors: K
authors: Takahashi
authors: Tadashi
authors: T
authors: Suehiro
authors: Yuya
authors: Y
authors: Yamada
authors: Daisuke
authors: D
authors: Chujo
authors: Eiji
authors: E
authors: Kawasaki
authors: Ryoichi
authors: R
authors: Kawamura
authors: Hiroshi
authors: H
authors: Onuma
authors: Haruhiko
authors: H
authors: Osawa
authors: Hideichi
authors: H
authors: Makino
mesh_terms: D000368:Aged; D000906:Antibodies / Q000276:immunology; D044466:Asian People / Q000208:ethnology / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000208:ethnology / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics; D005838:Genotype; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000276:immunology; D007328:Insulin / Q000009:adverse effects* / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000235:genetics; D012307:Risk Factors
chemical_list: D000906:Antibodies; D000949:Histocompatibility Antigens Class II; D007004:Hypoglycemic Agents; D007328:Insulin