OGTT Early C-Peptide Index for Clamp-Measured Acute Beta-Cell Secretory Capacity
- 1Wayne State University
Abstract
Acute glucose-stimulated {beta}-cell secretion is a key dimension of {beta}-cell function, but the hyperglycemic clamp used to assess it is technically demanding and resource-intensive, limiting its use at scale. We aimed to develop and validate the oral glucose tolerance test (OGTT) Early C-peptide (OEC) Index for estimating clamp-derived acute C-peptide response to glucose (ACPRg). We defined OEC as the 0-60-min incremental C-peptide area under the curve (AUC) normalized to the geometric mean of incremental and total glucose AUCs, with a fasting-glucose correction of 100/G. OEC was evaluated in paired OGTT-clamp data from RISE Adult Medication (baseline n=257; internal validation) and BetaFat (baseline n=70; external validation). Predictive R{superscript 2} and Pearson r for log-ACPRg were assessed using participant-level 5-fold cross-validation in RISE and external validation without refitting in BetaFat, with the C-peptidogenic, insulinogenic, and CIR30 indices as comparators. In RISE Adult, cross-validated R{superscript 2} for OEC was 0.47, 0.61, and 0.54 at baseline, 12, and 15 months, respectively, with corresponding Pearson r of 0.69, 0.78, and 0.74; nested cross-validation showed only modest attenuation. Applied without refitting in BetaFat, OEC yielded R{superscript 2} of 0.55, 0.41, and 0.39 at baseline, 12, and 24 months, with corresponding r of 0.76, 0.70, and 0.64. OEC had higher predictive R{superscript 2} point estimates than all three comparators at every visit in both cohorts. OEC provides a simple, transparent OGTT-based estimate of acute {beta}-cell secretory capacity that retained predictive performance in BetaFat and may broaden access to physiological assessment of early {beta}-cell function.
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BibTeX
@misc{zhang2026ogtt,
title = {{OGTT Early C-Peptide Index for Clamp-Measured Acute Beta-Cell Secretory Capacity}},
author = {R. Zhang},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.05.26364738},
url = {https://www.medrxiv.org/content/10.64898/2026.10.05.26364738v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - OGTT Early C-Peptide Index for Clamp-Measured Acute Beta-Cell Secretory Capacity
AU - R. Zhang
PY - 2026
DA - 2026/10/05
PB - medRxiv
DO - 10.64898/2026.10.05.26364738
UR - https://www.medrxiv.org/content/10.64898/2026.10.05.26364738v1
AB - Acute glucose-stimulated {beta}-cell secretion is a key dimension of {beta}-cell function, but the hyperglycemic clamp used to assess it is technically demanding and resource-intensive, limiting its use at scale. We aimed to develop and validate the oral glucose tolerance test (OGTT) Early C-peptide (OEC) Index for estimating clamp-derived acute C-peptide response to glucose (ACPRg). We defined OEC as the 0-60-min incremental C-peptide area under the curve (AUC) normalized to the geometric mean of incremental and total glucose AUCs, with a fasting-glucose correction of 100/G. OEC was evaluated in paired OGTT-clamp data from RISE Adult Medication (baseline n=257; internal validation) and BetaFat (baseline n=70; external validation). Predictive R{superscript 2} and Pearson r for log-ACPRg were assessed using participant-level 5-fold cross-validation in RISE and external validation without refitting in BetaFat, with the C-peptidogenic, insulinogenic, and CIR30 indices as comparators. In RISE Adult, cross-validated R{superscript 2} for OEC was 0.47, 0.61, and 0.54 at baseline, 12, and 15 months, respectively, with corresponding Pearson r of 0.69, 0.78, and 0.74; nested cross-validation showed only modest attenuation. Applied without refitting in BetaFat, OEC yielded R{superscript 2} of 0.55, 0.41, and 0.39 at baseline, 12, and 24 months, with corresponding r of 0.76, 0.70, and 0.64. OEC had higher predictive R{superscript 2} point estimates than all three comparators at every visit in both cohorts. OEC provides a simple, transparent OGTT-based estimate of acute {beta}-cell secretory capacity that retained predictive performance in BetaFat and may broaden access to physiological assessment of early {beta}-cell function.
ER -