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The Deterrence of Rapid Metabolic Decline Within 3 Months After Teplizumab Treatment in Individuals at High Risk for Type 1 Diabetes

End points that provide an early identification of treatment effects are needed to implement type 1 diabetes prevention trials more efficiently. To this end, we assessed whether metabolic end points can be used to detect a teplizumab effect on rapid β-cell decline within 3 months after treatment in...

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Autores principales: Sims, Emily K., Cuthbertson, David, Herold, Kevan C., Sosenko, Jay M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8660991/
https://www.ncbi.nlm.nih.gov/pubmed/34551936
http://dx.doi.org/10.2337/db21-0519
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author Sims, Emily K.
Cuthbertson, David
Herold, Kevan C.
Sosenko, Jay M.
author_facet Sims, Emily K.
Cuthbertson, David
Herold, Kevan C.
Sosenko, Jay M.
author_sort Sims, Emily K.
collection PubMed
description End points that provide an early identification of treatment effects are needed to implement type 1 diabetes prevention trials more efficiently. To this end, we assessed whether metabolic end points can be used to detect a teplizumab effect on rapid β-cell decline within 3 months after treatment in high-risk individuals in the TrialNet teplizumab trial. Glucose and C-peptide response curves (GCRCs) were constructed by plotting mean glucose and C-peptide values from 2-h oral glucose tolerance tests on a two-dimensional grid. Groups were compared visually for changes in GCRC shape and movement. GCRC changes reflected marked metabolic deterioration in the placebo group within 3 months of randomization. By 6 months, GCRCs resembled typical GCRCs at diagnosis. In contrast, GCRC changes in the teplizumab group suggested metabolic improvement. Quantitative comparisons, including two novel metabolic end points that indicate GCRC changes, the within-quadrant end point and the ordinal directional end point, were consistent with visual impressions of an appreciable treatment effect at the 3- and 6-month time points. In conclusion, an analytic approach combining visual evidence with novel end points demonstrated that teplizumab delays rapid metabolic decline and improves the metabolic state within 3 months after treatment; this effect extends for at least 6 months.
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spelling pubmed-86609912022-12-01 The Deterrence of Rapid Metabolic Decline Within 3 Months After Teplizumab Treatment in Individuals at High Risk for Type 1 Diabetes Sims, Emily K. Cuthbertson, David Herold, Kevan C. Sosenko, Jay M. Diabetes Pharmacology and Therapeutics End points that provide an early identification of treatment effects are needed to implement type 1 diabetes prevention trials more efficiently. To this end, we assessed whether metabolic end points can be used to detect a teplizumab effect on rapid β-cell decline within 3 months after treatment in high-risk individuals in the TrialNet teplizumab trial. Glucose and C-peptide response curves (GCRCs) were constructed by plotting mean glucose and C-peptide values from 2-h oral glucose tolerance tests on a two-dimensional grid. Groups were compared visually for changes in GCRC shape and movement. GCRC changes reflected marked metabolic deterioration in the placebo group within 3 months of randomization. By 6 months, GCRCs resembled typical GCRCs at diagnosis. In contrast, GCRC changes in the teplizumab group suggested metabolic improvement. Quantitative comparisons, including two novel metabolic end points that indicate GCRC changes, the within-quadrant end point and the ordinal directional end point, were consistent with visual impressions of an appreciable treatment effect at the 3- and 6-month time points. In conclusion, an analytic approach combining visual evidence with novel end points demonstrated that teplizumab delays rapid metabolic decline and improves the metabolic state within 3 months after treatment; this effect extends for at least 6 months. American Diabetes Association 2021-12 2021-09-22 /pmc/articles/PMC8660991/ /pubmed/34551936 http://dx.doi.org/10.2337/db21-0519 Text en © 2021 by the American Diabetes Association https://www.diabetesjournals.org/content/licenseReaders may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www.diabetesjournals.org/content/license.
spellingShingle Pharmacology and Therapeutics
Sims, Emily K.
Cuthbertson, David
Herold, Kevan C.
Sosenko, Jay M.
The Deterrence of Rapid Metabolic Decline Within 3 Months After Teplizumab Treatment in Individuals at High Risk for Type 1 Diabetes
title The Deterrence of Rapid Metabolic Decline Within 3 Months After Teplizumab Treatment in Individuals at High Risk for Type 1 Diabetes
title_full The Deterrence of Rapid Metabolic Decline Within 3 Months After Teplizumab Treatment in Individuals at High Risk for Type 1 Diabetes
title_fullStr The Deterrence of Rapid Metabolic Decline Within 3 Months After Teplizumab Treatment in Individuals at High Risk for Type 1 Diabetes
title_full_unstemmed The Deterrence of Rapid Metabolic Decline Within 3 Months After Teplizumab Treatment in Individuals at High Risk for Type 1 Diabetes
title_short The Deterrence of Rapid Metabolic Decline Within 3 Months After Teplizumab Treatment in Individuals at High Risk for Type 1 Diabetes
title_sort deterrence of rapid metabolic decline within 3 months after teplizumab treatment in individuals at high risk for type 1 diabetes
topic Pharmacology and Therapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8660991/
https://www.ncbi.nlm.nih.gov/pubmed/34551936
http://dx.doi.org/10.2337/db21-0519
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