title: Slowly progressive insulin-dependent (type 1) diabetes positive for anti-GAD antibody ELISA test may be strongly associated with a future insulin-dependent state.
abstract: Slowly progressive insulin-dependent (type 1) diabetes mellitus (SPIDDM), believed to be caused by β-cell destruction through islet-cell autoimmunity, gradually progresses to an insulin-dependent state over time. Although the presence of anti-glutamic acid decarboxylase antibody (GADA) is required for the diagnosis of SPIDDM, a recent change in the GADA assay kit from radioimmunoassay (RIA) to enzyme-linked immunosorbent assay (ELISA) yields mismatched GADA test results between the two kits, leading to confusion in understanding the pathological conditions of SPIDDM in Japan. Thus, this study aimed to clarify the difference in the clinical characteristics of GADA-ELISA-positive and GADA-ELISA-negative patients originally diagnosed as SPIDDM by GADA-RIA test. As a result, 42 of 63 original GADA-RIA-positive SPIDDM patients (66.7%) were found to be GADA-ELISA-positive, whereas the remaining 21 patients (33.3%) were found to be GADA-ELISA-negative. In patients with shorter disease duration, GADA-ELISA-positive patients showed significantly lower serum C-peptide levels than GADA-ELISA-negative patients. Meanwhile, in patients with longer disease duration, serum C-peptide levels were comparably decreased in GADA-ELISA-positive and GADA-ELISA-negative patients. A significant inverse correlation between serum C-peptide level and disease duration was observed in GADA-ELISA-negative patients, but not in GADA-ELISA-positive patients, suggesting that insulin secretory capacity may be gradually impaired over time also in GADA-ELISA-negative SPIDDM patients. In conclusion, physicians should be aware that GADA-ELISA-positive SPIDDM may be strongly associated with a future insulin-dependent state. Meanwhile, physicians should be careful in treating GADA-ELISA-negative SPIDDM patients diagnosed as type 2 DM, and cautiously follow the clinical course, in accordance with SPIDDM.
authors.affiliation: Department of Internal Medicine, Tokyo Saiseikai Central Hospital, Tokyo 108-0073, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Oikawa
authors.forename: Hajime
authors.initials: H
authors.lastname: Tanaka
authors.forename: Junko
authors.initials: J
authors.lastname: Uchida
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Atsumi
authors.forename: Masaya
authors.initials: M
authors.lastname: Osawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Katsuki
authors.forename: Toshihide
authors.initials: T
authors.lastname: Kawai
authors.forename: Akira
authors.initials: A
authors.lastname: Shimada
mesh_terms: D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D015551:Autoimmunity; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006801:Humans; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D001323:Autoantibodies; D007328:Insulin; D005968:Glutamate Decarboxylase