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

TEDDY Study Group, 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, Marian Rewers, Aaron Barbour, Kimberly BautistaJudith Baxter, Daniel Felipe-Morales, Brigitte I Frohnert, Marisa Stahl, Patricia Gesualdo, Rachel Haley, Michelle Hoffman, Rachel Karban, Edwin Liu, Alondra Munoz, Jill Norris, Stesha Peacock, Hanan Shorrosh, Suvi Ahonen, Mari Åkerlund, Leena Hakola, Heikki Hyöty, Mikael Knip, Mirva Koreasalo, Kalle Kurppa, Salla Kuusela, Jutta Laiho, Katri Lindfors, Maria Lönnrot, Markus Mattila, Tiina Niininen, Mia Nyblom, Sami Oikarinen, Anne Riikonen, Päivi Tossavainen, Suvi M Virtanen

Research output: Contribution to journalArticleScientificpeer-review

Abstract

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.

Original languageEnglish
JournalDiabetes care
DOIs
Publication statusPublished - 2022
Externally publishedYes
Publication typeA1 Journal article-refereed

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