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

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posted on 18.01.2022, 23:51 authored by Laura M. Jacobsen, Kendra Vehik, Riitta Veijola, Katharina Warncke, Jorma Toppari, Andrea K. Steck, Patricia Gesualdo, Beena Akolkar, Markus Lundgren, William A. Hagopian, Jin-Xiong She, Marian Rewers, Anette G. Ziegler, Jeffrey P. Krischer, Helena Elding Larsson, Michael J. Haller, the TEDDY Study Group
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<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.

Funding

The TEDDY Study Group is funded by U01 DK63829, U01 DK63861, U01 DK63821, U01 DK63865, U01 DK63863, U01 DK63836, U01 DK63790, UC4 DK63829, UC4 DK63861, UC4 DK63821, UC4 DK63865, UC4 DK63863, UC4 DK63836, UC4 DK95300, UC4 DK100238, UC4 DK106955, UC4 DK112243, UC4 DK117483, U01 DK124166, and Contract No. HHSN267200700014C from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Environmental Health Sciences (NIEHS), Centers for Disease Control and Prevention (CDC), and JDRF. This work supported in part by the NIH/NCATS Clinical and Translational Science Awards to the University of Florida (UL1 TR000064) and the University of Colorado (UL1 TR002535).

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