ABSTRACT
The GAD65 and IA-2 antibodies (Abs) are biomarkers of the development of type 1 diabetes mellitus (T1DM) in both children and adults. The upper reference limit for the autoantibodies made by the manufacture was established on an adult Chinese population. Here, we established upper reference limits for Northern European adults and children in accordance with the Clinical and Laboratory Standards Institute (CLSI) guidelines. Serum samples from healthy Danish children (0-18 years) and adults (18-70 years) were analysed for GAD65Ab and IA-2Ab using MAGLUMI 800 Chemiluminescence Immunoassay (CLIA). The Kruskal-Wallis test was used for evaluating differences between gender and age groups. No gender or age differences were found for neither GAD65Ab nor IA-2Ab, and a combined upper reference limit for both children and adults could be established. An upper reference limit of 5.1 IU/mL was defined for GAD65Ab and 11.5 U/mL for IA-2Ab. Our results showed a substantial discrepancy with the reference limits established by the manufacturer.
Subject(s)
Autoantibodies/blood , Glutamate Decarboxylase/antagonists & inhibitors , Immunoassay/standards , Receptor-Like Protein Tyrosine Phosphatases, Class 8/antagonists & inhibitors , Adolescent , Adult , Aged , Biomarkers/blood , Child , Child, Preschool , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/diagnosis , Diabetes Mellitus, Type 1/ethnology , Diabetes Mellitus, Type 1/immunology , Europe , Female , Gene Expression , Glutamate Decarboxylase/genetics , Glutamate Decarboxylase/immunology , Healthy Volunteers , Humans , Infant , Infant, Newborn , Luminescence , Male , Middle Aged , Receptor-Like Protein Tyrosine Phosphatases, Class 8/genetics , Receptor-Like Protein Tyrosine Phosphatases, Class 8/immunology , Reference Values , White PeopleABSTRACT
OBJECTIVE: To determine whether measuring diabetes-associated autoantibodies (DAA) in pediatric new onset diabetes (NODM) can be restricted to patients with equivocal diabetes type. RESEARCH DESIGN AND METHODS: Retrospective analysis of all patients with NODM admitted to Boston Children's Hospital from 1 October 2007 to 1 July 2013 who had measurement of DAA [glutamic acid decarboxylase, insulin, insulinoma-associated antigen 2 (IA-2)]. Data collection included initial diagnosis of diabetes type before DAA results and at follow-up. We used logistic regression to predict type 1 diabetes (T1D) and developed a clinical score to classify diabetes type. RESULTS: Of 1089 patients (45.4% female, 76.7% White, age 10.6 ± 4.5 yr), initial diagnosis was 1021 (93.8%) T1D, 42 (3.9%) type 2 diabetes (T2D), and 26 (2.4%) other. Of 993 patients with clinical T1D, 78 (7.9%) were DAA-, and of 42 patients with clinical T2D, 12 (28.6%) were DAA+. Type of diabetes was reclassified at follow-up in less than 6% of patients. Data from a subset of 736 patients were used to develop a scoring system to predict T1D. Using weight z-score, age, and race, the scoring system had 91.7% sensitivity, 82% specificity, and a positive predictive value of 98.6%, and suggested DAA measurement was unnecessary in 85.3% of patients. Findings were similar in a validation cohort of 234 patients. CONCLUSIONS: Application of a simple scoring system may reduce to â¼15% the number of DAA measurements needed to classify diabetes type, resulting in substantial cost savings. Clinical judgment should guide the decision to measure DAA.