Heterogeneity of DKA Incidence and Age-Specific Clinical Characteristics in Children Diagnosed With Type 1 Diabetes in the TEDDY Study
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<0.0001), fasting insulin (HR=0.89 (0.83-0.95), p=0.0009), and glucose-to-insulin ratio (HR=1.29 (1.16-1.43), p<0.0001) were associated with risk of progression to type 1 diabetes. Younger children had fewer autoantibodies with more symptoms at diagnosis. Of 23/379 (6.1%) children with DKA at onset, only 1/23 (4.3%) had a first-degree relative (FDR) with type 1 diabetes compared to 102/356 (28.7%) FDR children without DKA (p=0.008). Children in DKA were more likely to be non-adherent to study protocol (p=0.047), with longer duration between their last TEDDY evaluation and diagnosis (median 10.2 vs 2.0 months without DKA, p<0.001).
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.
