# Early pregnancy meal tolerance test responses and their association with later insulin sensitivity in overweight and obese women: an exploratory analysis

**Authors:** Puspito Arum, Anoush Kdekian, Helen L. Lutgers, Sanne J. Gordijn, Maaike K. Veenstra, Maaike Sietzema, Janine K. Kruit, Eline M. van der Beek

PMC · DOI: 10.3389/fendo.2026.1763137 · Frontiers in Endocrinology · 2026-01-28

## TL;DR

This study explores how early pregnancy blood tests can predict gestational diabetes risk in overweight and obese women.

## Contribution

The study identifies early metabolic markers that correlate with later insulin resistance and gestational diabetes risk.

## Key findings

- Fasting insulin and C-peptide in early pregnancy strongly correlate with later insulin resistance.
- Post-challenge glucose and insulin responses during early pregnancy correlate with later glucose tolerance test results.
- Early metabolic markers may help identify women at risk for gestational diabetes before standard diagnostic testing.

## Abstract

Insulin resistance increases the risk for gestational diabetes mellitus (GDM) and hyperglycemia-associated pregnancy complications. GDM is generally diagnosed at 24–28 weeks of gestation, leaving limited time to address adverse consequences. To explore metabolic markers that predict changes in insulin sensitivity and glycemic responses earlier in pregnancy, we performed a meal tolerance test (MTT) during the early and late second trimester in an at-risk population.

We included 30 pregnant women with overweight or obesity in the Pregnancy Outcomes and Maternal Insulin Sensitivity (PROMIS) study. Glucose, insulin, and C-peptide levels were measured in fasted and post-challenge blood samples between week 12-16 (MTT1, n=26), week 24-25 (MTT2, n=21), and by an oral glucose tolerance test in week 26-27 (OGTT, n=19) of gestation. Pearson’s correlation test, Spearman’s correlation test, and linear regression were applied to evaluate the association between parameters at early and late time points.

Fasting insulin and C-peptide at MTT1 were associated with insulin resistance measured by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) later in pregnancy (r=0.752, p<0.001; and r=0.825, p<0.001, respectively). Post-challenge increase in glucose, insulin, and C-peptide following MTT1 correlated with HOMA-IR in the late second trimester (r=0.626, p=0.009; r=0.739, p=0.002, and r=0.579, p=0.024, respectively). HOMA-IR and Matsuda index at MTT1 correlated with late second trimester HOMA-IR (r=0.781, p<0.001; and r=-0.826, p<0.001 respectively). Sixty, 90, and 120 minutes- post-challenge glucose during MTT2 correlated with 2 h-glucose during the OGTT (r=0.633, p=0.009; r=0.782, p<0.001, and r=0.639, p=0.008).

In the early second trimester, fasting insulin and C-peptide might be suitable to stratify women early for GDM risk. The correlation between the MTT and OGTT results supports further exploration of the MTT as a patient-friendly alternative for diagnostic purposes.

https://clinicaltrials.gov/study/NCT04315545, identifier NCT04315545.

## Linked entities

- **Proteins:** PIN (insulin precursor)
- **Diseases:** gestational diabetes mellitus (MONDO:0005406), hyperglycemia (MONDO:0002909)

## Full-text entities

- **Genes:** INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}
- **Diseases:** hyperglycemia (MESH:D006943), obese (MESH:D009765), overweight (MESH:D050177), GDM (MESH:D016640), Insulin Resistance (MESH:D007333)
- **Chemicals:** Glucose (MESH:D005947), MTT1 (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

45 references — full list in the complete paper: https://tomesphere.com/paper/PMC12890645/full.md

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Source: https://tomesphere.com/paper/PMC12890645