Do maternal haemodynamics have a causal influence on treatment for gestational diabetes?

BACKGROUND: Arterial stiffening is believed to contribute to the worsening of insulin resistance, and factors which are associated with needing pharmacological treatment of gestational diabetes (GDM), such as maternal obesity or advanced age, are associated with impaired cardiovascular adaptation to pregnancy. In this observational study, we aimed to investigate causal relationships between maternal haemodynamics and treatment requirement amongst women with GDM. METHODS: We assessed maternal haemodynamics in women with GDM, comparing those who remained on dietary treatment with those who required pharmacological management. Maternal haemodynamics were assessed using the Arteriograph® (TensioMed Ltd, Budapest, Hungary) and the NICOM® non-invasive bio-reactance method (Cheetah Medical, Portland, Oregon, USA). A graphical causal inference technique was used for statistical analysis. RESULTS: 120 women with GDM were included in the analysis. Maternal booking BMI was identified as having a causative influence on treatment requirement, with each unit increase in BMI increasing the odds of needing metformin and/or insulin therapy by 12% [OR 1.12 (1.02 - 1.22)]. The raw values of maternal heart rate (87.6 ± 11.7 vs. 92.9 ± 11.90 bpm, p = 0.014) and PWV (7.8 ± 1.04 vs. 8.4 ± 1.61 m/s, p = 0.029) were both significantly higher amongst the women requiring pharmacological management, though these relationships did not remain significant in causal logistic regression. CONCLUSIONS: Maternal BMI at booking has a causal, rather than simply associational, relationship on the need for pharmacological treatment of GDM. No significant causal relationships were found between maternal haemodynamics and the need for pharmacological treatment.

This observational study is the first to examine relationships between maternal haemodynamics and treatment requirement for gestational diabetes (GDM). This is also the first study to demonstrate a causative, rather than simply associational, relationship between maternal body mass index (BMI) and the need for pharmacological treatment of GDM, with each unit increase in BMI increasing the odds of needing metformin and/or insulin therapy by 12%. Maternal heart rate and pulse wave velocity were significantly higher among women with GDM requiring pharmacological management, but this finding did not remain significant in logistic regression analysis, and no causative relationships between maternal hemodynamics and treatment requirement were identified. Our findings highlight the importance of pre- and peri-conception weight control, but do not support a role for measurement of maternal hemodynamics in the prediction of women who are likely to require pharmacological management of GDM.

Arterial stiffness throughout pregnancy: Arteriograph device-specific reference ranges based on a low-risk population.

OBJECTIVE: The maternal cardiovascular system undergoes significant adaptation during pregnancy. We aimed to examine the changes in arterial stiffness parameters during normal pregnancy and establish reference ranges for the general population. METHODS: We performed a prospective cross-sectional observational study at the University Hospitals of Leicester. We included low-risk healthy pregnant women with singleton and viable pregnancies with no evidence of foetal abnormality or aneuploidy. Smokers, women with pre-existing or gestational hypertensive disorders and diabetes, booking BMI at least 30, on medication that could affect cardiac function and/or those who delivered before 37 completed weeks of gestation, and/or a neonate with birthweight less than 10th centile were excluded. Brachial (BrAIx) and aortic augmentation indices (AoAIx), and pulse wave velocity (PWV) were assessed using the Arteriograph. Data were analysed using a linear mixed model. RESULTS: We analysed a total of 571 readings from 259 women across different gestational ages and present the 10th, 25th, 50th, 75th and 90th centiles for BrAIx, AoAIx and PWV from 12+0 to 42+0 weeks' gestation. All haemodynamic variables were significantly associated with maternal heart rate. BrAIx, AoAIx and PWV demonstrated significant change with gestation, with all reaching their lowest value in the second trimester. CONCLUSION: The current study presents reference ranges for BrAIx, AoAIx and PWV in low-risk singleton pregnancies. Further work is required to establish if women in whom measures of arterial stiffness lie above the 90th centile could be at increased risk of adverse pregnancy outcomes and to identify the optimum time for screening.

Effect of metformin on biomarkers of placental- mediated disease: A systematic review and meta-analysis.

Metformin reduces the incidence of placental-mediated disease (PMD) in pregnancies with and without diabetes, but the mechanism through which it exerts these effects is not yet fully understood. We performed a systematic review and meta-analysis to examine the effect of metformin on biomarkers implicated in the pathogenesis of PMD. We searched Medline, Embase and the Cochrane Library for studies of metformin and biomarkers of PMD in pregnancy. Meta-analysis was undertaken where comparable data were obtained from two or more studies. 12 studies were included in the final review. Meta-analysis of 2 studies including 323 pregnant women showed significantly reduced CRP levels following treatment with metformin compared to placebo [mean difference = -1.72, 95% CI (-2.97; -0.48); p = 0.007]. Metformin exposure was also associated with decreased levels of the inflammatory cytokines TNFα, IL-1a, IL-1b and IL-6 in serum, placenta and omental tissue taken from pregnant women. Metformin significantly decreased the release of anti-angiogenic factors sFlt-1 and sEng from ex-vivo placental and umbilical vein tissue, and increased maternal serum levels of non-phosphorylated IGFBP-1. Overall, our findings show that metformin mediates several molecular pathways implicated in the pathogenesis of pre-eclampsia and intrauterine growth retardation. Metformin therefore has exciting potential as a therapeutic, as well as preventative, agent in the treatment of PMD, which warrants further investigation.