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Time to Peak Glucose and Peak C-Peptide During the Progression to Type 1 Diabetes in the Diabetes Prevention Trial and TrialNet Cohorts

Voss, Michael G. ; Cuthbertson, David D. ; Cleves, Mario M. ; Xu, Ping ; Evans-Molina, Carmella ; Palmer, Jerry P. ; Redondo, Maria J. ; Steck, Andrea K. ; Lundgren, Markus LU and Larsson, Helena LU , et al. (2021) In Diabetes Care 44(10). p.2329-2336
Abstract

OBJECTIVE: To assess the progression of type 1 diabetes using time to peak glucose or C-peptide during oral glucose tolerance tests (OGTTs) in autoantibody-positive relatives of people with type 1 diabetes. RESEARCH DESIGN AND METHODS: We examined 2-h OGTTs of participants in the Diabetes Prevention Trial Type 1 (DPT-1) and TrialNet Pathway to Prevention (PTP) studies. We included 706 DPT-1 participants (mean ± SD age, 13.84 ± 9.53 years; BMI Z-score, 0.33 ± 1.07; 56.1% male) and 3,720 PTP participants (age, 16.01 ± 12.33 years; BMI Z-score, 0.66 ± 1.3; 49.7% male). Log-rank testing and Cox regression analyses with adjustments (age, sex, race, BMI Z-score, HOMA-insulin resistance, and peak glucose/C-peptide levels, respectively) were... (More)

OBJECTIVE: To assess the progression of type 1 diabetes using time to peak glucose or C-peptide during oral glucose tolerance tests (OGTTs) in autoantibody-positive relatives of people with type 1 diabetes. RESEARCH DESIGN AND METHODS: We examined 2-h OGTTs of participants in the Diabetes Prevention Trial Type 1 (DPT-1) and TrialNet Pathway to Prevention (PTP) studies. We included 706 DPT-1 participants (mean ± SD age, 13.84 ± 9.53 years; BMI Z-score, 0.33 ± 1.07; 56.1% male) and 3,720 PTP participants (age, 16.01 ± 12.33 years; BMI Z-score, 0.66 ± 1.3; 49.7% male). Log-rank testing and Cox regression analyses with adjustments (age, sex, race, BMI Z-score, HOMA-insulin resistance, and peak glucose/C-peptide levels, respectively) were performed. RESULTS: In each of DPT-1 and PTP, higher 5-year diabetes progression risk was seen in those with time to peak glucose >30 min and time to peak C-peptide >60 min (P < 0.001 for all groups), before and after adjustments. In models examining strength of association with diabetes development, associations were greater for time to peak C-peptide versus peak C-peptide value (DPT-1: χ2 = 25.76 vs. χ2 = 8.62; PTP: χ2 = 149.19 vs. χ2 = 79.98; all P < 0.001). Changes in the percentage of individuals with delayed glucose and/or C-peptide peaks were noted over time. CONCLUSIONS: In two independent at-risk populations, we show that those with delayed OGTT peak times for glucose or C-peptide are at higher risk of diabetes development within 5 years, independent of peak levels. Moreover, time to peak C-peptide appears more predictive than the peak level, suggesting its potential use as a specific biomarker for diabetes progression.

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organization
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type
Contribution to journal
publication status
published
subject
in
Diabetes Care
volume
44
issue
10
pages
8 pages
publisher
American Diabetes Association
external identifiers
  • scopus:85118285799
  • pmid:34362815
ISSN
1935-5548
DOI
10.2337/dc21-0226
language
English
LU publication?
yes
id
a1ab5f41-a840-4575-bd97-c4f012aa20a8
date added to LUP
2022-10-13 08:45:03
date last changed
2024-06-27 21:27:22
@article{a1ab5f41-a840-4575-bd97-c4f012aa20a8,
  abstract     = {{<p>OBJECTIVE: To assess the progression of type 1 diabetes using time to peak glucose or C-peptide during oral glucose tolerance tests (OGTTs) in autoantibody-positive relatives of people with type 1 diabetes. RESEARCH DESIGN AND METHODS: We examined 2-h OGTTs of participants in the Diabetes Prevention Trial Type 1 (DPT-1) and TrialNet Pathway to Prevention (PTP) studies. We included 706 DPT-1 participants (mean ± SD age, 13.84 ± 9.53 years; BMI Z-score, 0.33 ± 1.07; 56.1% male) and 3,720 PTP participants (age, 16.01 ± 12.33 years; BMI Z-score, 0.66 ± 1.3; 49.7% male). Log-rank testing and Cox regression analyses with adjustments (age, sex, race, BMI Z-score, HOMA-insulin resistance, and peak glucose/C-peptide levels, respectively) were performed. RESULTS: In each of DPT-1 and PTP, higher 5-year diabetes progression risk was seen in those with time to peak glucose &gt;30 min and time to peak C-peptide &gt;60 min (P &lt; 0.001 for all groups), before and after adjustments. In models examining strength of association with diabetes development, associations were greater for time to peak C-peptide versus peak C-peptide value (DPT-1: χ2 = 25.76 vs. χ2 = 8.62; PTP: χ2 = 149.19 vs. χ2 = 79.98; all P &lt; 0.001). Changes in the percentage of individuals with delayed glucose and/or C-peptide peaks were noted over time. CONCLUSIONS: In two independent at-risk populations, we show that those with delayed OGTT peak times for glucose or C-peptide are at higher risk of diabetes development within 5 years, independent of peak levels. Moreover, time to peak C-peptide appears more predictive than the peak level, suggesting its potential use as a specific biomarker for diabetes progression.</p>}},
  author       = {{Voss, Michael G. and Cuthbertson, David D. and Cleves, Mario M. and Xu, Ping and Evans-Molina, Carmella and Palmer, Jerry P. and Redondo, Maria J. and Steck, Andrea K. and Lundgren, Markus and Larsson, Helena and Moore, Wayne V. and Atkinson, Mark A. and Sosenko, Jay M. and Ismail, Heba M.}},
  issn         = {{1935-5548}},
  language     = {{eng}},
  month        = {{10}},
  number       = {{10}},
  pages        = {{2329--2336}},
  publisher    = {{American Diabetes Association}},
  series       = {{Diabetes Care}},
  title        = {{Time to Peak Glucose and Peak C-Peptide During the Progression to Type 1 Diabetes in the Diabetes Prevention Trial and TrialNet Cohorts}},
  url          = {{http://dx.doi.org/10.2337/dc21-0226}},
  doi          = {{10.2337/dc21-0226}},
  volume       = {{44}},
  year         = {{2021}},
}