title: Adult-onset atypical (type 1) diabetes: additional insights and differences with type 1A diabetes in a European Mediterranean population.
abstract: OBJECTIVE
  In 1997, the American Diabetes Association proposed two subcategories for type 1 diabetes: type 1A or immunomediated diabetes and type 1B or idiopathic diabetes characterized by negative beta-cell autoimmunity markers, lack of association with HLA, and fluctuating insulinopenia. The aim of this study was to examine clinical characteristics, beta-cell function, HLA typing, and mutations in maturity-onset diabetes of the young (MODY) genes in patients with atypical type 1 diabetes (type 1 diabetes diagnosed at onset, without pancreatic autoantibodies and fluctuating insulinopenia).
  
  
  METHODS
  Eight patients with atypical type 1 diabetes (all men, 30.7 +/- 7.6 years) and 16 newly diagnosed age- and sex-matched patients with type 1A diabetes were studied retrospectively. Islet cell, GAD, tyrosine phosphatase and insulin antibodies, and basal and stimulated plasma C-peptide were measured at onset and after 1 year. HLA-DRB1-DQA1-DQB1 typing and screening for mutations in the HNF-1alpha and HNF-4alpha genes were performed from genomic DNA.
  
  
  RESULTS
  Atypical patients displayed significantly higher BMI and better beta-cell function at onset and after 12 months. Three patients carried protective or neutral type 1 diabetes haplotypes, five patients displayed heterozygosity for susceptible and protective haplotypes, and seven patients showed Asp(beta57). We found a nondescribed variant Pro436Ser in exon 10 of the HNF-4alpha gene in one atypical patient without susceptible haplotypes.
  
  
  CONCLUSIONS
  In our population, there are atypical forms of young adult-onset ketosis-prone diabetes initially diagnosed as type 1 diabetes, differing from type 1 diabetes in the absence of beta-cell autoimmunity, persistent beta-cell function capacity, fluctuating insulin requirements and ketosis-prone episodes, as well as clinical features of type 2 diabetes. Only one subgroup could be strictly classified as having type 1B diabetes. Additional information is still needed to improve our understanding of the mechanisms that finally lead to the disease.
authors.affiliation: Endocrinology and Diabetes Unit, IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Hospital Clínic i Universitari, Barcelona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Aguilera
authors.forename: Roser
authors.initials: R
authors.lastname: Casamitjana
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Ercilla
authors.forename: Josep
authors.initials: J
authors.lastname: Oriola
authors.forename: Ramon
authors.initials: R
authors.lastname: Gomis
authors.forename: Ignacio
authors.initials: I
authors.lastname: Conget
mesh_terms: D000328:Adult; D017668:Age of Onset; D001323:Autoantibodies / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000145:classification* / Q000453:epidemiology* / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D008297:Male; D019083:Mediterranean Region / Q000453:epidemiology; D012189:Retrospective Studies; D013997:Time Factors
chemical_list: D001323:Autoantibodies; D001786:Blood Glucose; D002096:C-Peptide; D006442:Glycated Hemoglobin