title: Tyrosine phosphatase-related islet antigen 2(256-760) autoantibodies, the only marker of islet autoimmunity that increases by increasing the degree of BMI in obese subjects with type 2 diabetes.
abstract: OBJECTIVE
  Since patients with type 2 diabetes and positive for type 1 diabetes-specific antibodies have wide variations in BMI, this study evaluated whether the frequency and pattern of islet autoantibody positivity is related to BMI.
  
  
  METHODS
  Clinical and biochemical characteristics and islet autoantibodies including GAD and protein tyrosine phosphatases islet antigen-2 (IA-2)IC and IA-2(256-760) were evaluated in 1,850 patients with type 2 diabetes from the Non-Insulin Requiring Autoimmune Diabetes study cohort. BMI was evaluated in all patients, who were then subdivided in three groups according to BMI (<25, ≥25 to <30, and ≥30 kg/m(2)).
  
  
  RESULTS
  Out of 1,850, 120 (6.5%) patients were positive for at least one of the following antibodies: GAD (4.1%), IA-2(256-760) (3.3%), or IA-2IC (1.1%). GAD and IA-2IC antibodies showed decreasing frequencies with increasing BMI (P < 0.0001 and 0.0006, respectively, for trend); in contrast, the frequency of IA-2(256-760) antibodies increased with increasing BMI (P = 0.005 for trend). Patients with type 2 diabetes positive for IA-2(256-760) alone showed a phenotype resembling classical obese type 2 diabetes, with higher BMI, waist circumference, and uric acid (P < 0.005 for all), lower thyroid peroxidase antibodies, and lower progression to insulin requirement than GAD antibody-positive patients (P = 0.04 and P = 0.0005, respectively).
  
  
  CONCLUSIONS
  The IA-2(256-760) antibody appears to represent an antibody marker that mainly identifies a clinical phenotype very similar to obese type 2 diabetes, suggesting a possible different pathogenetic mechanism.
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy raffaella.buzzetti@uniroma1.it.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Buzzetti
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Spoletini
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Zampetti
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Campagna
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Lidia
authors.initials: L
authors.lastname: Marandola
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Panimolle
authors.affiliation: Diabetes Unit, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Dotta
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Tiberti
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D015551:Autoimmunity / Q000276:immunology; D015415:Biomarkers / Q000097:blood*; D015992:Body Mass Index; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000276:immunology*; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D007328:Insulin / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000150:complications* / Q000276:immunology; D010641:Phenotype; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8 / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D007328:Insulin; C056626:thyroid microsomal antibodies; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D005968:Glutamate Decarboxylase