title: Immunogenetic and clinical characterization of slowly progressive IDDM.
abstract: OBJECTIVE
  To examine the clinical and immunogenetic heterogeneity of IDDM.
  
  
  METHODS
  We divided 207 IDDM patients into groups based on the interval from clinical onset to initiation of insulin therapy: group A (< 3 mo, acute clinical-onset group, n = 134), group B (3-12 mo, intermediate group, n = 31), and group C (> or = 13 mo, slowly progressive group, n = 42). Immunogenetic and clinical markers were compared between group A and group C.
  
  
  RESULTS
  The mode age of onset was higher in group C (52 yr) than group A (10 yr). Group C had a higher prevalence of islet cell antibodies (42.9%, 18 of 42) than group A (25.4%, 34 of 134, P = 0.05). Serum C-peptide immunoreactivity assayed by radioimmunoassay in response to a 100-g oral glucose tolerance test was significantly higher in group C than in group A. Group C patients were also more likely to have a family history of NIDDM (26.1%, 11 of 42) among their first-degree relatives than group A patients (11.2%, 15 of 134, P = 0.039). The prevalences of family history of IDDM and endocrine autoimmune diseases were not different between groups C and A. The frequency of complications of endocrine autoimmune disease was not different between group A (6.7%, 9 of 134) and group C (2.3%, 1 of 42). Significant associations with two class I major histocompatibility complex antigens (HLA-A24 and -Bw54) and one class II antigen (HLA-DR4) were observed in group A. Group A patients were associated with three diabetogenic HLA-DQ haplotypes including DQA1*0301-DQB1*0401, DQA1*0301-DQB1*0302, and DQA1*0301-DQB1*0303. In contrast, group C lacked the association with class I antigens, although HLA-DR4 and HLA-DQA1*0301-DQB1*0401 were more common in this group than in control subjects.
  
  
  CONCLUSIONS
  These results indicate that the clinical subtype with slowly progressive course (slowly progressive IDDM) has distinct findings including late-age onset, high prevalence of islet cell antibodies, preserved beta-cell function, and high family history of NIDDM. An additive effect of class I and class II major histocompatibility complex antigens is suggested as an explanation for the acute clinical manifestations and more severe beta-cell destruction in group A patients.
authors.affiliation: Department of Endocrinology and Metabolism, Toranomon Hospital, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kobayashi
authors.forename: K
authors.initials: K
authors.lastname: Tamemoto
authors.forename: K
authors.initials: K
authors.lastname: Nakanishi
authors.forename: N
authors.initials: N
authors.lastname: Kato
authors.forename: M
authors.initials: M
authors.lastname: Okubo
authors.forename: H
authors.initials: H
authors.lastname: Kajio
authors.forename: T
authors.initials: T
authors.lastname: Sugimoto
authors.forename: T
authors.initials: T
authors.lastname: Murase
authors.forename: K
authors.initials: K
authors.lastname: Kosaka
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood; D001483:Base Sequence; D002096:C-Peptide / Q000097:blood / Q000652:urine; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology / Q000503:physiopathology*; D005260:Female; D005787:Gene Frequency; D006442:Glycated Hemoglobin / Q000032:analysis; D015234:HLA-A Antigens / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics; D006683:HLA-DQ Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006650:Histocompatibility Testing; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012016:Reference Values
chemical_list: D001323:Autoantibodies; D002096:C-Peptide; D006442:Glycated Hemoglobin; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D009838:Oligodeoxyribonucleotides; C024211:islet cell antibody