title: Family history of Type 1 diabetes affects insulin secretion in patients with 'Type 2' diabetes.
abstract: OBJECTIVE
  The aim was to evaluate the impact of family history of diabetes on the phenotype of patients diagnosed with Type 2 diabetes and the frequency of susceptibility genotypes.
  
  
  METHODS
  Patients with Type 2 diabetes with family history for both Type 1 and Type 2 diabetes (FH(MIX, n) = 196) or Type 2 diabetes only (FH(T2), n = 139) matched for age, sex, BMI and age at diagnosis, underwent an oral glucose tolerance test and a combined glucagon test and insulin tolerance test. Glutamic acid decarboxylase (GAD) antibodies and major Type 1 and Type 2 diabetes susceptibility gene variants were analysed. Patients were stratified into groups according to family history or GAD antibody positivity (GADA+, GADA-) or a combination of these (GADA+/FH(MIX), GADA+/FH(T2), GADA-/FH(MIX), GADA-/FH(T2)).
  
  
  RESULTS
  Compared with other patients, those with FH(MIX) more often had GAD antibodies (14.3 vs. 4.3%, P = 0.003), and those with both FH(MIX) and GAD antibodies had the highest frequency of insulin deficiency (stimulated serum C-peptide < 0.7 nmol/l, GADA+/FH(MIX) 46.4% vs. GADA-/FH(MIX) 9.5% (P < 0.00001), GADA-/FH(T2) 4.5% (P < 0.00001), GADA+/FH(T2) 0%). Patients with GADA+/FH(MIX) more often had HLA-DQB1 risk genotypes compared with patients with GADA-/FH(MIX) or GADA-/FH(T2D) (47 vs. 23 or 14%, P = 0.05 and P < 0.00001, respectively). In logistic regression analyses, FH(MIX), GAD antibody positivity and HLA risk genotypes were independently associated with insulin deficiency.
  
  
  CONCLUSIONS
  A family history for both type 1 and type 2 diabetes was associated with higher prevalence of GAD antibodies and HLA-DQB1 risk genotypes than a family history of type 2 diabetes only, and was associated with earlier and more severe development of insulin deficiency, which was only partially explained by GAD antibodies and HLA.
authors.affiliation: Department of Medicine, Helsinki University Central Hospital, Research Program of Molecular Medicine, University of Helsinki, Folkhalsan Research Centre, Helsinki, Finland. virve.lundgren@hus.fi
authors.forename: V M
authors.initials: VM
authors.lastname: Lundgren
authors.forename: M K
authors.initials: MK
authors.lastname: Andersen
authors.forename: B
authors.initials: B
authors.lastname: Isomaa
authors.forename: T
authors.initials: T
authors.lastname: Tuomi
mesh_terms: D000293:Adolescent; D000328:Adult; D002096:C-Peptide / Q000097:blood / Q000235:genetics; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005387:Finland / Q000453:epidemiology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005951:Glucose Tolerance Test; D005968:Glutamate Decarboxylase / Q000097:blood* / Q000276:immunology; D006680:HLA Antigens / Q000097:blood* / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D010641:Phenotype
chemical_list: D002096:C-Peptide; D006680:HLA Antigens; D007328:Insulin; D005968:Glutamate Decarboxylase