Heterogeneity of DKA Incidence and Age-Specific Clinical Characteristics in Children Diagnosed With Type 1 Diabetes in the TEDDY Study

Objective: The Environmental Determinants of Diabetes in the Young (TEDDY) study is uniquely capable of investigating age-specific differences associated with type 1 diabetes. As age is a primary driver of heterogeneity in type 1 diabetes, we sought to characterize by age, metabolic derangements prior to diagnosis and clinical features associated with diabetic ketoacidosis (DKA). Research Design and Methods: The 379 TEDDY children who developed type 1 diabetes were grouped by age at onset (0-4, 5-9, and 10-14 years; n=142, 151 and 86, respectively) with comparisons of autoantibody profiles, HLA, family history of diabetes, presence of DKA, symptomatology at onset, and adherence to TEDDY protocol. Time-varying analysis of those with OGTT data was compared to TEDDY children who did not progress to diabetes. Results: Increasing fasting glucose (HR=1.09 (95% CI 1.04-1.14), p=0.0003), stimulated glucose (HR=1.50 (1.42-1.59), p Conclusions: DKA at onset in TEDDY is uncommon, especially for FDRs. For those without familial risk, metabolic monitoring continues to provide a primary benefit of reduced DKA but requires regular follow-up. Clinical and laboratory features vary by age at onset adding to the heterogeneity of type 1 diabetes.