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 2022-01-18, 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<u>Objective:</u> 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).
<p><u>Research Design and
Methods:</u>
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.</p>
<p><u>Results:</u> 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).
</p>
<p><u>Conclusions:</u> 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.</p>
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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