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Dynamic OGTT-derived C-peptide trajectories for metabolic heterogeneity and adverse pregnancy outcomes in gestational diabetes mellitus: a nested case‒control study.


ABSTRACT:

Background

Existing diagnostic criteria for gestational diabetes mellitus (GDM) rely solely on glucose thresholds, which are insufficient to capture metabolic heterogeneity. We aimed to evaluate the role of C-peptide measured during the oral glucose tolerance test (OGTT) in assisting the development of stratified treatment strategies and predicting the risk of adverse pregnancy outcomes.

Methods

This nested case-control study conducted within the Xi'an Longitudinal Mother-Child Cohort included 1014 pregnant women with GDM and 1014 without GDM (non-GDM) who delivered singleton live-born infants between January 1, 2017, and December 31, 2018. C-peptide levels were measured at three intervals during the OGTT. Latent class trajectory modeling was used to identify distinct C-peptide trajectories, and logistic regression was used to assess their associations with adverse fetal and maternal outcomes.

Results

Two principal C-peptide trajectories were identified in GDM despite similar glucose profiles. GDM Class 1 (771, 76.04%) presented a delayed 120-min C-peptide peak and poorer beta-cell secretion, whereas GDM Class 2 (243, 23.96%) presented a sharp 60-min peak followed by a decline and significantly increased insulin resistance, with greater risks of delivering large for gestational age (LGA) (adjusted odds ratio (aOR), 1.52; 95% confidence interval (CI), 1.07-2.15) and macrosomia (aOR, 1.83; 95% CI, 1.13-2.97). Surprisingly, 21.7% (220) of the non-GDM group had a high C-peptide response associated with elevated preeclampsia risk (aOR, 2.91; 95% CI, 1.25-6.74).

Conclusions

Dynamic OGTT-derived C-peptide trajectories revealed clinically significant metabolic subgroups of GDM that were obscured by glucose-only diagnostics, with the predominantly insulin-resistant Class being at higher risk of fetal overgrowth.

SUBMITTER: Wang X 

PROVIDER: S-EPMC12366374 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature

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Dynamic OGTT-derived C-peptide trajectories for metabolic heterogeneity and adverse pregnancy outcomes in gestational diabetes mellitus: a nested case‒control study.

Wang Xinyue X   He Zhangya Z   Ji Jing J   Zhang Simin S   Li Jinglin J   Zhang Jiahui J   Yu Wenlu W   Yang Hexiang H   Han Zhen Z   Mi Yang Y   Luo Xiaoqin X  

BMC medicine 20250820 1


<h4>Background</h4>Existing diagnostic criteria for gestational diabetes mellitus (GDM) rely solely on glucose thresholds, which are insufficient to capture metabolic heterogeneity. We aimed to evaluate the role of C-peptide measured during the oral glucose tolerance test (OGTT) in assisting the development of stratified treatment strategies and predicting the risk of adverse pregnancy outcomes.<h4>Methods</h4>This nested case-control study conducted within the Xi'an Longitudinal Mother-Child Co  ...[more]

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