THE MELBOURNE-PREDIABETES-STUDY - PREDICTION OF TYPE-1 DIABETES-MELLITUS USING ANTIBODY AND METABOLIC TESTING

Objectives: To determine the utility of various autoantibodies in pred icting progression to clinical diabetes in first-degree relatives of p atients with type 1 diabetes mellitus. Participants: 3315 first-degree relatives of patients with type 1 diabetes (1161 parents, 1206 siblin gs and 948 offspring) recruited through diabetes clinics, private endo crinologists, Diabetes Australia and the Juvenile Diabetes Foundation. Main outcome measures: Prevalence of islet cell antibodies (ICA) leve ls greater than or equal to 20 JDFu, insulin autoantibodies (IAA) leve ls >100 nU/mL, and antibodies to glutamic acid decarboxylase (GADAb) a nd tyrosine phosphatase IA2 (IA2Ab); change in beta cell function over time; and development of clinical diabetes. Results: 2.6% of relative s had elevated ICA levels, 1.3% had elevated IAA levels and 0.3% had b oth. High ICA levels were significantly more frequent in siblings than in offspring or parents, and were more frequent in relatives younger than 20 years. GADAb were detected in 68% and IA2Ab in 57% of relative s with elevated ICA and/or IAA levels. Diabetes developed in 33 relati ves (25 siblings, 2 offspring and 6 parents). Before diagnosis of clin ical diabetes, high ICA levels were detected in 18 (58%), high IAA lev els in 7 (23%), both in 5 (15%), and either in 19 (61%); GADAb were de tected in 26 (84%), IA2Ab in 13 (42%), both in 11 (35%), and either in 28 (90%). First phase insulin release (FPIR) less than 50 mU/L was ve ry strongly associated with progression to diabetes. In relatives with FPIR initially greater than 50 mU/L who eventually developed diabetes , there was a gradual and continuous reduction in FPIR over time befor e diagnosis. Conclusions: Type 1 diabetes can be diagnosed in the prec linical stage. The recently described antibodies to glutamic acid deca rboxylase and tyrosine phosphatase IA2 appear superior to ICA as scree ning tools for the preclinical diagnosis of type 1 diabetes.