Front Endocrinol (Lausanne). 2026 Jan 28;17:1763137. doi: 10.3389/fendo.2026.1763137. eCollection 2026.
ABSTRACT
INTRODUCTION: 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.
METHODS: 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.
RESULTS: 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).
DISCUSSION: 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.
CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT04315545, identifier NCT04315545.
PMID:41685244 | PMC:PMC12890645 | DOI:10.3389/fendo.2026.1763137
