Kerry Buchanan1,2, Ahmed M Mehdi1, Ian Hughes3, Andrew Cotterill2, Kim-Anh Le Cao1,4, Ranjeny Thomas1, Mark Harris1,2. 1. The University of Queensland, Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia. 2. Queensland Children's Hospital, Department of Paediatric Endocrinology, Queensland Children's Hospital, South Brisbane, Queensland, Australia. 3. The University of Queensland, Mater Research Institute, Translational Research Institute, Brisbane, Australia. 4. The University of Melbourne, Melbourne Integrative Genomics and School of Mathematics and Statistics, The University of Melbourne, Melbourne, Victoria, Australia.
Abstract
BACKGROUND: Stimulated C-peptide measurement after a mixed meal tolerance test (MMTT) is the accepted gold standard for assessing residual beta-cell function in type 1 diabetes (T1D); however, this approach is impractical outside of clinical trials. OBJECTIVE: To develop an improved estimate of residual beta-cell function in children with T1D using commonly measured clinical variables. SUBJECTS/ METHODS: A clinical model to predict 90-minute MMTT stimulated C-peptide in children with recent-onset T1D was developed from the combined AbATE, START, and TIDAL placebo subjects (n = 46) 6 months post-recruitment using multiple linear regression. This model was then validated in a clinical cohort (Hvidoere study group, n = 262). RESULTS: A model of estimated C-peptide at 6 months post-diagnosis, which included age, gender, body mass index (BMI), hemoglobin A1c (HbA1c), and insulin dose predicted 90-minute stimulated C-peptide measurements (adjusted R2 = 0.63, P < 0.0001). The predictive value of insulin dose and HbA1c alone (IDAA1c) for 90-minute stimulated C-peptide was significantly lower (R2 = 0.37, P < 0.0001). The slopes of linear regression lines of the estimated and stimulated 90-minute C-peptide levels obtained at 6 and 12 months post diagnosis in the Hvidoere clinical cohort were R2 = 0.36, P < 0.0001 at 6 months and R2 = 0.37, P < 0.0001 at 12 months. CONCLUSIONS: A clinical model including age, gender, BMI, HbA1c, and insulin dose predicts stimulated C-peptide levels in children with recent-onset T1D. Estimated C-peptide is an improved surrogate to monitor residual beta-cell function outside clinical trial settings.
BACKGROUND: Stimulated C-peptide measurement after a mixed meal tolerance test (MMTT) is the accepted gold standard for assessing residual beta-cell function in type 1 diabetes (T1D); however, this approach is impractical outside of clinical trials. OBJECTIVE: To develop an improved estimate of residual beta-cell function in children with T1D using commonly measured clinical variables. SUBJECTS/ METHODS: A clinical model to predict 90-minute MMTT stimulated C-peptide in children with recent-onset T1D was developed from the combined AbATE, START, and TIDAL placebo subjects (n = 46) 6 months post-recruitment using multiple linear regression. This model was then validated in a clinical cohort (Hvidoere study group, n = 262). RESULTS: A model of estimated C-peptide at 6 months post-diagnosis, which included age, gender, body mass index (BMI), hemoglobin A1c (HbA1c), and insulin dose predicted 90-minute stimulated C-peptide measurements (adjusted R2 = 0.63, P < 0.0001). The predictive value of insulin dose and HbA1c alone (IDAA1c) for 90-minute stimulated C-peptide was significantly lower (R2 = 0.37, P < 0.0001). The slopes of linear regression lines of the estimated and stimulated 90-minute C-peptide levels obtained at 6 and 12 months post diagnosis in the Hvidoere clinical cohort were R2 = 0.36, P < 0.0001 at 6 months and R2 = 0.37, P < 0.0001 at 12 months. CONCLUSIONS: A clinical model including age, gender, BMI, HbA1c, and insulin dose predicts stimulated C-peptide levels in children with recent-onset T1D. Estimated C-peptide is an improved surrogate to monitor residual beta-cell function outside clinical trial settings.
Authors: Jaquellyne Gurgel Penaforte-Saboia; Carlos Eduardo Barra Couri; Virginia Oliveira Fernandes; Ana Paula Dias Rangel Montenegro; Lívia Aline De Araújo Batista; Lenita Zajdenverg; Carlos Antonio Negrato; Kelen Cristina Ribeiro Malmegrim; Daniela Aparecida Moraes; Juliana Bernardes Elias Dias; Maria Carolina Oliveira; Akhtar Hussain; Marilia Brito Gomes; Renan Magalhães Montenegro Journal: Front Endocrinol (Lausanne) Date: 2019-11-19 Impact factor: 5.555
Authors: Yassmin Musthaffa; Emma E Hamilton-Williams; Hendrik J Nel; Anne-Sophie Bergot; Ahmed M Mehdi; Mark Harris; Ranjeny Thomas Journal: Clin Transl Immunology Date: 2021-07-26