title: Types of pediatric diabetes mellitus defined by anti-islet autoimmunity and random C-peptide at diagnosis.
abstract: OBJECTIVE
  To test the hypothesis that anti-islet autoantibody expression and random serum C-peptide obtained at diagnosis define phenotypes of pediatric diabetes with distinct clinical features.
  
  
  METHODS
  We analyzed 607 children aged <19 yr consecutively diagnosed with diabetes after exclusion of 13% of cases with secondary diabetes (e.g., cystic fibrosis related, steroid induced) and 7.3% of cases lacking measurement of C-peptide and/or autoantibodies.
  
  
  METHODS
  Autoantibody positivity (A+) was defined as ≥ 1 positive out of GAD65, insulin, and ICA512 antibodies. Preserved beta-cell function (β+) was defined as random serum C-peptide at diagnosis ≥ 0.6 ng/mL. Body mass index (BMI) was measured at median 1.2 months after diagnosis. Characteristics at diagnosis and 2 yr (range 18-30 months) after diagnosis were compared among groups.
  
  
  RESULTS
  Autoantibody expression and C-peptide at diagnosis defined the following groups: A+β- (52.1% of the children), A+β+ (32.8%), A-β+ (12.5%), and A-β- (2.6%). These four groups differed in gender, race/ethnicity, and clinical characteristics at diagnosis [i.e., age, pubertal development, obesity/overweight, diabetic ketoacidosis, glycemia, and hemoglobin A1c (HbA1c)] and at 2 yr (i.e., clinical diagnosis, treatment, and HbA1c) (all p < 0.0001). Among all β+ children, C-peptide >2 ng/mL was associated with lower HbA1c at onset (p = 0.0001) and, in the A+β+ subgroup, with higher frequency of achieving HbA1c < 7% at 2 yr (p = 0.03). All three patients (0.7% of total) with monogenic diabetes (maturity onset diabetes of the young, MODY) were A-β+ with C-peptide between 0.6 and 2 ng/mL.
  
  
  CONCLUSIONS
  Anti-islet autoantibodies status and serum random C-peptide at diagnosis define four distinct phenotypes of pediatric diabetes with prognostic value.
authors: Department of Pediatrics, Section of Diabetes and Endocrinology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA. redondo@bcm.edu
authors: Maria J
authors: MJ
authors: Redondo
authors: Luisa M
authors: LM
authors: Rodriguez
authors: Mirna
authors: M
authors: Escalante
authors: E O'Brian
authors: EO
authors: Smith
authors: Ashok
authors: A
authors: Balasubramanyam
authors: Morey W
authors: MW
authors: Haymond
mesh_terms: D000293:Adolescent; D001323:Autoantibodies / Q000097:blood*; D002096:C-Peptide / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000145:classification* / Q000276:immunology; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D010641:Phenotype; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8 / Q000276:immunology
chemical_list: D001323:Autoantibodies; D002096:C-Peptide; D005968:Glutamate Decarboxylase; D006442:Glycated Hemoglobin; D007328:Insulin; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; C401141:glutamate decarboxylase 2
keywords: C-peptide; Classification; autoantibodies; children; diabetes