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Jacobsen, L.M.* ; Vehik, K.* ; Veijola, R.* ; Warncke, K. ; Toppari, J.* ; Steck, A.K.* ; Gesualdo, P.* ; Akolkar, B.* ; Lundgren, M.* ; Hagopian, W.A.* ; She, J.X.* ; Rewers, M.* ; Ziegler, A.G.* ; Krischer, J.P.* ; Larsson, H.E.* ; Haller, M.J.* ; TEDDY Study Group (Gezginci, C. ; Heublein, A. ; Hummel, S. ; Knopff, A. ; Koch, C. ; Koletzko, S. ; Roth, R. ; Schmidt, J. ; Scholz, M. ; Stock, J. ; Wendel, L. ; Winkler, C.)

Heterogeneity of DKA incidence and age-specific clinical characteristics in children diagnosed with type 1 diabetes in the TEDDY Study.

Diabetes Care 45, 624-633 (2022)

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OBJECTIVE: The Environmental Determinants of Diabetes in the Young (TEDDY) study is uniquely capable of investigating age-specific differences associated with type 1 diabetes. Because 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, HLAs, family history of diabetes, presence of DKA, symptomatology at onset, and adherence to TEDDY protocol. Time-varying analysis compared those with oral glucose tolerance test data with TEDDY children who did not progress to diabetes. RESULTS: Increasing fasting glucose (hazard ratio [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 (6.1%) of 379 children with DKA at onset, only 1 (4.3%) of 23 had a first-degree relative (FDR) with type 1 diabetes compared with 102 (28.7%) of 356 FDR children without DKA (P = 0.008). Children with DKA were more likely to be nonadherent 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.

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