title: Etiological investigation of diabetes in young adults presenting with apparent type 2 diabetes.
abstract: OBJECTIVE
  Young adults with newly diagnosed apparent type 2 diabetes present the clinician with a wide differential diagnosis of possible etiology, including autoimmune and genetic causes as well as young-onset type 2 diabetes (YT2D). The characteristics of these groups have been described, but it is not known in which subjects investigation for etiology may be beneficial.
  
  
  METHODS
  A total of 268 unselected U.K. Caucasian subjects diagnosed at ages 18-45 years and not treated with permanent insulin for < or =6 months were studied. All subjects underwent clinical assessment and screening for GAD antibodies (GADA) and tyrosine phosphatase IA-2 antibodies (IA-2A). Screening for a common mutation in the hepatocyte nuclear factor-1 alpha (HNF-1 alpha) gene and the common mitochondrial mutation was performed in the antibody-negative subjects. Subjects without insulin resistance were selected for sequencing of the HNF-1 alpha gene.
  
  
  RESULTS
  A specific etiology was defined in 11.6% of the 268 subjects and in 24.7% of the lean subjects. Twenty-six subjects (9.7%) were positive for a beta-cell antibody, one subject had familial partial lipodystrophy and the lamin A/C mutation R482W, and two subjects had the mitochondrial mutation A3243G. Two of 15 selected subjects had HNF-1 alpha mutations, the novel missense mutation A501T, and the previously reported R583Q.
  
  
  CONCLUSIONS
  This unselected series shows that there is considerable heterogeneity in apparent YT2D. beta-Cell autoantibodies should be performed in all those presenting at ages 18-45 years. Genetic investigations can be targeted to phenotypically defined subjects. The finding of a specific etiology will allow individualization of management and give patients valuable information about their condition.
authors.affiliation: Peninsula Medical School, Department of Diabetes and Vascular Medicine, Exeter, Devon, UK. k.r.owen@exeter.ac.uk
authors.forename: Katharine R
authors.initials: KR
authors.lastname: Owen
authors.forename: Amanda
authors.initials: A
authors.lastname: Stride
authors.forename: Sian
authors.initials: S
authors.lastname: Ellard
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Hattersley
mesh_terms: D000328:Adult; D017668:Age of Onset; D000419:Albuminuria / Q000453:epidemiology; D015992:Body Mass Index; D003327:Coronary Disease / Q000453:epidemiology; D004268:DNA-Binding Proteins; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology* / Q000235:genetics; D003925:Diabetic Angiopathies / Q000453:epidemiology; D003930:Diabetic Retinopathy / Q000453:epidemiology; D005260:Female; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D006801:Humans; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics; D010375:Pedigree; D014157:Transcription Factors / Q000235:genetics; D006113:United Kingdom; D044465:White People
chemical_list: D004268:DNA-Binding Proteins; C496487:HNF1A protein, human; C496495:HNF1B protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D009687:Nuclear Proteins; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta