Andrea K Steck1, Helena Elding Larsson2, Xiang Liu3, Riitta Veijola4, Jorma Toppari5,6, William A Hagopian7, Michael J Haller8, Simi Ahmed9, Beena Akolkar10, Åke Lernmark2, Marian J Rewers1, Jeffrey P Krischer3. 1. Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, Colorado. 2. Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden. 3. Health Informatics Institute, University of South Florida, Tampa, Florida. 4. Department of Pediatrics, PEDEGO Research Unit, MRC Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland. 5. Turku Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland. 6. Department of Pediatrics, Turku University Hospital, Turku, Finland. 7. Pacific Northwest Diabetes Research Institute, University of Washington, Seattle, WA. 8. Department of Pediatrics, University of Florida, Gainesville, Florida. 9. Immunology of T1D, JDRF International, New York, New York. 10. Division of Diabetes, Endocrinology & Metabolism, National Institute of Diabetes, Digestive, & Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
Abstract
OBJECTIVE: To explore whether children diagnosed with type 1 diabetes during islet autoantibody surveillance through The Environmental Determinants of Diabetes in the Young (TEDDY) study retain greater islet function than children diagnosed through the community. METHODS: TEDDY children identified at birth with high-risk human leukocyte antigen and followed every 3 months until diabetes diagnosis were compared to age-matched children diagnosed with diabetes in the community. Both participated in long-term follow up after diagnosis. Hemoglobin A1c (HbA1c) and mixed meal tolerance test were performed within 1 month of diabetes onset, then at 3, 6, and 12 months, and biannually thereafter. RESULTS: Comparison of 43 TEDDY and 43 paired control children showed that TEDDY children often had no symptoms (58%) at diagnosis and none had diabetic ketoacidosis (DKA) compared with 98% with diabetes symptoms and 14% DKA in the controls (P < 0.001 and P = 0.03, respectively). At diagnosis, mean HbA1c was lower in TEDDY (6.8%, 51 mmol/mol) than control (10.5%, 91 mmol/mol) children (P < 0.0001). TEDDY children had significantly higher area under the curve and peak C-peptide values than the community controls throughout the first year postdiagnosis. Total insulin dose and insulin dose-adjusted A1c were lower throughout the first year postdiagnosis for TEDDY compared with control children. CONCLUSIONS: Higher C-peptide levels in TEDDY vs community-diagnosed children persist for at least 12 months following diabetes onset and appear to represent a shift in the disease process of about 6 months. Symptom-free diagnosis, reduction of DKA, and the potential for immune intervention with increased baseline C-peptide may portend additional long-term benefits of early diagnosis.
OBJECTIVE: To explore whether children diagnosed with type 1 diabetes during islet autoantibody surveillance through The Environmental Determinants of Diabetes in the Young (TEDDY) study retain greater islet function than children diagnosed through the community. METHODS: TEDDY children identified at birth with high-risk human leukocyte antigen and followed every 3 months until diabetes diagnosis were compared to age-matched children diagnosed with diabetes in the community. Both participated in long-term follow up after diagnosis. Hemoglobin A1c (HbA1c) and mixed meal tolerance test were performed within 1 month of diabetes onset, then at 3, 6, and 12 months, and biannually thereafter. RESULTS: Comparison of 43 TEDDY and 43 paired control children showed that TEDDY children often had no symptoms (58%) at diagnosis and none had diabetic ketoacidosis (DKA) compared with 98% with diabetes symptoms and 14% DKA in the controls (P < 0.001 and P = 0.03, respectively). At diagnosis, mean HbA1c was lower in TEDDY (6.8%, 51 mmol/mol) than control (10.5%, 91 mmol/mol) children (P < 0.0001). TEDDY children had significantly higher area under the curve and peak C-peptide values than the community controls throughout the first year postdiagnosis. Total insulin dose and insulin dose-adjusted A1c were lower throughout the first year postdiagnosis for TEDDY compared with control children. CONCLUSIONS: Higher C-peptide levels in TEDDY vs community-diagnosed children persist for at least 12 months following diabetes onset and appear to represent a shift in the disease process of about 6 months. Symptom-free diagnosis, reduction of DKA, and the potential for immune intervention with increased baseline C-peptide may portend additional long-term benefits of early diagnosis.
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