Abstract

OBJECTIVES: The incidence of gestational diabetes mellitus (GDM) is increasing and is associated with adverse maternal, fetal and neonatal outcomes. Arterial stiffness (AS) is raised in pregnancies complicated by placental-mediated diseases such as pre-eclampsia. We investigated if AS is different between healthy pregnancies and women with GDM on different treatment modalities. METHODS: We conducted a prospective longitudinal cohort study to assess and compare AS in pregnancies complicated by GDM with low-risk controls. AS, measured by pulse wave velocity (PWV) and brachial (BrAIx) and aortic (AoAIx) augmentation Index, was recorded using the Arteriograph® at four gestational windows: 24+0 to 27+6; 28+0 to 31+6; 32+0 to 35+6 and ≥36+0 weeks of gestation (windows W1-W4, respectively). Women with GDM were considered both as a single group, and as subgroups defined by treatment modality. Data were analyzed using a linear mixed model on each AS variable (log-transformed) with group, gestational windows, maternal age, ethnicity, parity, body mass index, mean arterial pressure and heart rate as fixed effects and individual as a random effect. We compared the group means including relevant contrasts and adjusted the p-values using the Bonferroni correction. RESULTS: The study population comprised 155 low-risk controls and 127 with GDM, of whom 59 were treated with dietary intervention, 47 with metformin alone and 21 with metformin plus insulin. The two-way interaction term of study group and gestational age was significant for BrAIx and AoAIx (p<0.001), though there was no evidence (p=0.729) that mean AoPWV was different between the study groups. Women in the control group demonstrated significantly lower BrAIx and AoAIX at gestational windows W1-3 compared to the combined GDM group, but not at W4. Mean (95% CI) difference in log adjusted BrAIx was -0.37 (-0.52, 0.22), -0.23 (-0.35, -0.12), and -0.29 (-0.40, -0.18) at W1, W2 and W3, respectively. Mean (95% CI) difference in log adjusted AoAIx was -0.49 (-0.69, -0.3), -0.32 (-0.47, -0.18) and -0.38 (-0.52, -0.24) at W1, W2 and W3, respectively. Similarly, women in the control group also demonstrated significantly lower BrAIx and AoAIx compared with each of the GDM treatment subgroups (diet, metformin and metformin plus insulin) at W1-3. The increase in mean BrAIx and AoAIx seen between W2 and W3 in the women with GDM treated with dietary management was attenuated in the metformin and metformin with insulin groups, however the mean differences in BrAIx and AoAIx between these treatment groups were not statistically significant at any gestational window. CONCLUSIONS: Pregnancies complicated by GDM demonstrate significantly higher AS compared to low-risk pregnancies regardless of treatment modality. Our data provides a basis for further investigation into the association of metformin therapy with changes in AS and risk of placental-mediated diseases. This article is protected by copyright. All rights reserved.