title: Slowly progressing form of type 1 diabetes mellitus in children: genetic analysis compared with other forms of diabetes mellitus in Japanese children.
abstract: OBJECTIVE
  Slowly progressing insulin-dependent diabetes mellitus (SPIDDM, hereafter referred to as IDDMS in this article) is a unique subtype of type 1 diabetes in Japanese children. To clarify the genetic background of IDDMS, we analyzed HLA-DRB1, -DQB1 and -DQA1 alleles, phenotypes, and genotypes and compared them with acute-onset type 1 diabetes, non-insulin-dependent diabetes mellitus (NIDDM), and control subjects.
  
  
  METHODS
  HLA-DRB1, -DQA1, and -DQB1 types were defined by DNA analysis using polymerase chain reaction (PCR), and typing for human leukocyte antigen (HLA) was performed by the sequencing-based typing (SBT) method using Match Maker and MT Navigator in combination. HLA-A24 was determined by the PCR-sequence-specific oligo-nucleotide probe (PCR-SSOP) method. The 234 patients with type 1 diabetes were divided into three groups: 32 cases of IDDMS, 137 cases of acute-onset form aged more than 5 yr (IDDMA), and 65 cases of acute-onset form less than 5 yr of age at onset (IDDME). In addition, we studied 55 children with type 2 diabetes (NIDDM) and 97 normal controls.
  
  
  RESULTS
  The patients with IDDMS were older at diagnosis and had a greater body mass index (BMI) than those with IDDM (A + E). The prevalence of islet autoantbodies was not significantly different from IDDMA. The allele frequencies of DRB1*0405, DQA1*0302, and DQB1*0401 were significantly increased; however, DRB1*0901, DQA1*03, DQB1*0303, and HLA-A24 were low and not significantly different from control subjects.
  
  
  CONCLUSIONS
  HLA phenotypes and genotypes in patients with IDDMS were different from those in NIDDM and control subjects and were closer to those of IDDMA. Together with a low prevalence of HLA-A24, the genetic features are similar to those of SPIDDM and latent autoimmune diabetes in adults (LADA) in adults. In our series, the clinical features such as lack of obesity and lack of responsiveness to oral hypoglycemic agents were most different from those of adults' onset.
authors.affiliation: Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Ohtsu
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Takubo
authors.forename: Mayumi
authors.initials: M
authors.lastname: Kazahari
authors.forename: Keiko
authors.initials: K
authors.lastname: Nomoto
authors.forename: Fumiyuki
authors.initials: F
authors.lastname: Yokota
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kikuchi
authors.forename: Akemi
authors.initials: A
authors.lastname: Koike
authors.forename: Nobuo
authors.initials: N
authors.lastname: Matsuura
mesh_terms: D017668:Age of Onset; D001120:Arginine; D044466:Asian People / Q000235:genetics; D001224:Aspartic Acid; D001323:Autoantibodies / Q000032:analysis; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000276:immunology; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D010641:Phenotype
chemical_list: D001323:Autoantibodies; D001224:Aspartic Acid; D001120:Arginine