Andrea K Steck1, Xiang Liu2, Jeffrey P Krischer2, Michael J Haller3, Riitta Veijola4, Markus Lundgren5, Simi Ahmed6, Beena Akolkar7, Jorma Toppari8,9, William A Hagopian10, Marian J Rewers1, Helena Elding Larsson5. 1. Barbara Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, Colorado. 2. Health Informatics Institute, University of South Florida, Tampa, Florida. 3. Department of Pediatrics, University of Florida, Gainesville, Florida. 4. Department of Pediatrics, PEDEGO Research Unit, MRC Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland. 5. Department of Clinical Sciences, Lund University CRC, Skåne University Hospital, Malmö, Sweden. 6. Immunology of T1D, JDRF International, New York, New York. 7. Division of Diabetes, Endocrinology and Metabolism, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, Maryland. 8. Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, Turku, Finland. 9. Pacific Diabetes Research Institute, Seattle, Washington. 10. Department of Pediatrics, Turku University Hospital, Turku, Finland.
Abstract
CONTEXT: Understanding factors involved in the rate of C-peptide decline is needed to tailor therapies for type 1 diabetes (T1D). OBJECTIVE: Evaluate factors associated with rate of C-peptide decline after a T1D diagnosis in young children. DESIGN: Observational study. SETTING: Academic centers. PARTICIPANTS: A total of 57 participants from the Environmental Determinants of Diabetes in the Young (TEDDY) study who were enrolled at 3 months of age and followed until T1D, and 56 age-matched children diagnosed with T1D in the community. INTERVENTION: A mixed meal tolerance test was used to measure the area under the curve (AUC) C-peptide at 1, 3, 6, 12, and 24 months postdiagnosis. OUTCOME: Factors associated with rate of C-peptide decline during the first 2 years postdiagnosis were evaluated using mixed effects models, adjusting for age at diagnosis and baseline C-peptide. RESULTS: Adjusted slopes of AUC C-peptide decline did not differ between TEDDY subjects and community controls (P = 0.21), although the former had higher C-peptide baseline levels. In univariate analyses combining both groups (n = 113), younger age, higher weight and body mass index z-scores, female sex, an increased number increased number of islet autoantibodies, and IA-2A or ZnT8A positivity at baseline were associated with a higher rate of C-peptide loss. Younger age, female sex, and higher weight z-score remained significant in multivariate analysis (all P < 0.02). At 3 months after diagnosis, higher HbA1c became an additional independent factor associated with a higher rate of C-peptide decline (P < 0.01). CONCLUSION: Younger age at diagnosis, female sex, higher weight z-score, and HbA1c were associated with a higher rate of C-peptide decline after T1D diagnosis in young children.
CONTEXT: Understanding factors involved in the rate of C-peptide decline is needed to tailor therapies for type 1 diabetes (T1D). OBJECTIVE: Evaluate factors associated with rate of C-peptide decline after a T1D diagnosis in young children. DESIGN: Observational study. SETTING: Academic centers. PARTICIPANTS: A total of 57 participants from the Environmental Determinants of Diabetes in the Young (TEDDY) study who were enrolled at 3 months of age and followed until T1D, and 56 age-matched children diagnosed with T1D in the community. INTERVENTION: A mixed meal tolerance test was used to measure the area under the curve (AUC) C-peptide at 1, 3, 6, 12, and 24 months postdiagnosis. OUTCOME: Factors associated with rate of C-peptide decline during the first 2 years postdiagnosis were evaluated using mixed effects models, adjusting for age at diagnosis and baseline C-peptide. RESULTS: Adjusted slopes of AUC C-peptide decline did not differ between TEDDY subjects and community controls (P = 0.21), although the former had higher C-peptide baseline levels. In univariate analyses combining both groups (n = 113), younger age, higher weight and body mass index z-scores, female sex, an increased number increased number of islet autoantibodies, and IA-2A or ZnT8A positivity at baseline were associated with a higher rate of C-peptide loss. Younger age, female sex, and higher weight z-score remained significant in multivariate analysis (all P < 0.02). At 3 months after diagnosis, higher HbA1c became an additional independent factor associated with a higher rate of C-peptide decline (P < 0.01). CONCLUSION: Younger age at diagnosis, female sex, higher weight z-score, and HbA1c were associated with a higher rate of C-peptide decline after T1D diagnosis in young children.
Authors: Jay M Sosenko; Susan Geyer; Jay S Skyler; Lisa E Rafkin; Heba M Ismail; Ingrid M Libman; Yuk-Fun Liu; Linda A DiMeglio; Carmella Evans-Molina; Jerry P Palmer Journal: Pediatr Diabetes Date: 2017-11-24 Impact factor: 4.866
Authors: Kevan C Herold; Brian N Bundy; S Alice Long; Jeffrey A Bluestone; Linda A DiMeglio; Matthew J Dufort; Stephen E Gitelman; Peter A Gottlieb; Jeffrey P Krischer; Peter S Linsley; Jennifer B Marks; Wayne Moore; Antoinette Moran; Henry Rodriguez; William E Russell; Desmond Schatz; Jay S Skyler; Eva Tsalikian; Diane K Wherrett; Anette-Gabriele Ziegler; Carla J Greenbaum Journal: N Engl J Med Date: 2019-06-09 Impact factor: 91.245
Authors: M Wallensteen; G Dahlquist; B Persson; M Landin-Olsson; A Lernmark; G Sundkvist; B Thalme Journal: Diabetologia Date: 1988-09 Impact factor: 10.122
Authors: D Dabelea; E J Mayer-Davis; J S Andrews; L M Dolan; C Pihoker; R F Hamman; C Greenbaum; S Marcovina; W Fujimoto; B Linder; G Imperatore; R D'Agostino Journal: Diabetologia Date: 2012-09-20 Impact factor: 10.122
Authors: Carla J Greenbaum; Andrea M Anderson; Lawrence M Dolan; Elizabeth J Mayer-Davis; Dana Dabelea; Giuseppina Imperatore; Santica Marcovina; Catherine Pihoker Journal: Diabetes Care Date: 2009-07-08 Impact factor: 17.152