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Effect of Oral Insulin on Early Combined Glucose and C-Peptide Endpoints in Individuals at High-Risk for Type 1 Diabetes

Triolo, Taylor M. ; Jacobsen, Laura M. ; Cuthbertson, David ; Sims, Emily K. ; Ismail, Heba M. ; Redondo, Maria J. ; Lundgren, Markus LU ; Dimeglio, Linda A. ; Gottlieb, Peter A. and Atkinson, Mark A. , et al. (2024) In Pediatric Diabetes 2024.
Abstract

Background: The TrialNet Oral Insulin (OI) prevention trial showed no overall treatment effect, using the diagnosis of type 1 diabetes as an endpoint. A significant delay in onset was only found in a high-risk stratum (termed secondary stratum 1) of participants with low first-phase insulin release (FPIR).Methods: Since trials with an endpoint of type 1 diabetes take years to complete, in this post hoc analysis, we assessed whether a novel combination of glucose and C-peptide markers could identify a therapeutic benefit after 1 year of follow-up (trial participants followed for a median 2.7 years).Results: Participants were relatives with multiple islet autoantibodies and low FPIR (n = 40). Glucose rose, and C-peptide declined in the... (More)

Background: The TrialNet Oral Insulin (OI) prevention trial showed no overall treatment effect, using the diagnosis of type 1 diabetes as an endpoint. A significant delay in onset was only found in a high-risk stratum (termed secondary stratum 1) of participants with low first-phase insulin release (FPIR).Methods: Since trials with an endpoint of type 1 diabetes take years to complete, in this post hoc analysis, we assessed whether a novel combination of glucose and C-peptide markers could identify a therapeutic benefit after 1 year of follow-up (trial participants followed for a median 2.7 years).Results: Participants were relatives with multiple islet autoantibodies and low FPIR (n = 40). Glucose rose, and C-peptide declined in the placebo group, whereas glucose rose minimally, and C-peptide increased in the OI group. When glucose and C-peptide were plotted on two-dimensional grids using 30-120-min oral glucose tolerance test (OGTT) time points, changes in ratios of their central points (centroid ratio) differed between groups (p=0.037 adjusted for age, BMI, and baseline C-peptide and glucose).Conclusions: These findings support a favorable early effect of OI on combined glucose and C-peptide endpoints in high-risk individuals, indicating metabolic benefit. With further study, these measures may allow for shorter trials compared to the standard endpoint of type 1 diabetes diagnosis.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
C-peptide, oral insulin, prevention, type 1 diabetes
in
Pediatric Diabetes
volume
2024
article number
8343868
publisher
Wiley-Blackwell
external identifiers
  • scopus:85207120658
ISSN
1399-543X
DOI
10.1155/2024/8343868
language
English
LU publication?
yes
id
0e5b720a-5e96-4d35-89af-9b2eefd863d8
date added to LUP
2025-01-02 15:13:10
date last changed
2025-01-02 15:14:33
@article{0e5b720a-5e96-4d35-89af-9b2eefd863d8,
  abstract     = {{<p>Background: The TrialNet Oral Insulin (OI) prevention trial showed no overall treatment effect, using the diagnosis of type 1 diabetes as an endpoint. A significant delay in onset was only found in a high-risk stratum (termed secondary stratum 1) of participants with low first-phase insulin release (FPIR).Methods: Since trials with an endpoint of type 1 diabetes take years to complete, in this post hoc analysis, we assessed whether a novel combination of glucose and C-peptide markers could identify a therapeutic benefit after 1 year of follow-up (trial participants followed for a median 2.7 years).Results: Participants were relatives with multiple islet autoantibodies and low FPIR (n = 40). Glucose rose, and C-peptide declined in the placebo group, whereas glucose rose minimally, and C-peptide increased in the OI group. When glucose and C-peptide were plotted on two-dimensional grids using 30-120-min oral glucose tolerance test (OGTT) time points, changes in ratios of their central points (centroid ratio) differed between groups (p=0.037 adjusted for age, BMI, and baseline C-peptide and glucose).Conclusions: These findings support a favorable early effect of OI on combined glucose and C-peptide endpoints in high-risk individuals, indicating metabolic benefit. With further study, these measures may allow for shorter trials compared to the standard endpoint of type 1 diabetes diagnosis.</p>}},
  author       = {{Triolo, Taylor M. and Jacobsen, Laura M. and Cuthbertson, David and Sims, Emily K. and Ismail, Heba M. and Redondo, Maria J. and Lundgren, Markus and Dimeglio, Linda A. and Gottlieb, Peter A. and Atkinson, Mark A. and Krischer, Jeffrey P. and Schatz, Desmond A. and Sosenko, Jay M.}},
  issn         = {{1399-543X}},
  keywords     = {{C-peptide; oral insulin; prevention; type 1 diabetes}},
  language     = {{eng}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Pediatric Diabetes}},
  title        = {{Effect of Oral Insulin on Early Combined Glucose and C-Peptide Endpoints in Individuals at High-Risk for Type 1 Diabetes}},
  url          = {{http://dx.doi.org/10.1155/2024/8343868}},
  doi          = {{10.1155/2024/8343868}},
  volume       = {{2024}},
  year         = {{2024}},
}