title: Early impairment of glucose tolerance and β-cell function in obese children.
abstract: BACKGROUND
  A clinical criterion of the Wolfram syndrome is the coexistence of diabetes and optic atrophy recognized before the age of 15. Diabetes present in Wolfram syndrome is a result of the selective β cell loss and failed insulin secretion which is probably associated with non-autoimmune pathogenesis.
  
  
  OBJECTIVE
  The aim of the study was an evaluation of HLA subtypes and presence of β-cell autoantibodies in patients with molecularly confirmed Wolfram syndrome.
  
  
  METHODS
  9 patients with Wolfram syndrome aged 10-24 years were examined. We also studied 218 patients with type 1 diabetes as a reference group. A control group of 176 healthy individuals was included in the study. Besides the clinical assessment the HLA typing by PCR-SSO was performed. Islet cell antibodies (ICA), antibodies to glutamic acid decarboxylase (GADA), thyrosine phosphatase antibodies (IA2A) and insulin antibodies (IAA) were also detected.
  
  
  RESULTS
  In all nine patients the coexistence of diabetes with optic atrophy was observed and in 8/9 individuals additional symptoms were recognized. In patients with Wolfram syndrome a significantly lower age of diagnosis of diabetes (Me=5.0 years) than in type 1 diabetic children (Me=10.4; p=0.002) was observed. Studies of HLA subtypes demonstrated an increased prevalence of HLA-DQw1, DRB1⋅03 and/or 04 and DR2. A comparison of the frequency of the HLA alleles in patients with Wolfram syndrome with type 1 diabetic children showed a more frequent presence of the DRB1⋅1501 (p=0.03; OR=13.28 (2.44-72.12)) and DQB1⋅06 (p=0.016; OR=10.15 (2.49-41.35)) alleles in patients with Wolfram syndrome.
  
  
  CONCLUSIONS
  Polish patients with Wolfram syndrome have a different profile of the HLA antigens with the presence of DR2, DQw1 and DRB3/4 allele and are negative for diabetes-related autoantibodies, which may confirm non-autoimmune β-cell destruction in this syndrome.
authors: Department of Pediatric Diabetes and Obesity, Poznan University of Medical Sciences, Poland. pfichna@ump.edu.pl
authors: Piotr
authors: P
authors: Fichna
authors: Bogda
authors: B
authors: Skowrońska
authors: Katarzyna
authors: K
authors: Majewska
authors: Witold
authors: W
authors: Stankiewicz
mesh_terms: D000293:Adolescent; D001323:Autoantibodies / Q000276:immunology*; D002648:Child; D005260:Female; D005951:Glucose Tolerance Test; D006683:HLA-DQ Antigens / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D015802:HLA-DR2 Antigen / Q000276:immunology; D059811:HLA-DRB1 Chains; D059826:HLA-DRB3 Chains; D006801:Humans; D050417:Insulin-Secreting Cells / Q000276:immunology*; D008297:Male; D009765:Obesity / Q000150:complications* / Q000378:metabolism*; D014929:Wolfram Syndrome / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D015802:HLA-DR2 Antigen; D059811:HLA-DRB1 Chains; D059826:HLA-DRB3 Chains; C024211:islet cell antibody