The effects of metformin on maternal haemodynamics in gestational diabetes mellitus: A pilot study

Background: Gestational diabetes mellitus (GDM) is a major clinical challenge and is likely to remain so as the incidence of GDM continues to increase. Aim: To assess longitudinal changes in maternal haemodynamics amongst women diagnosed with GDM requiring either metformin or dietary intervention in comparison to low-risk healthy controls. Methodology: Fifty-six pregnant women attending their first appointment at the GDM clinic and 60 low-risk healthy pregnant controls attending their routine antenatal clinics were recruited and assigned to three groups: GDM Metformin (GDM-M), GDM Diet (GDM-D) and Control. Non-invasive assessment of maternal haemodynamics, using recognised measures of arterial stiffness and central blood pressure (Arteriograph (R)), were undertaken under controlled conditions within four gestational windows: antenatal; AN1 (26-28 weeks), AN2 (32-34 weeks) and AN3 (37-40 weeks), and postnatal (PN) (6-8 weeks after delivery). Data were analysed using a linear mixed model incorporating gestational age and other relevant predictors, including age, blood pressure (BP), baseline bodyweight and pulse as fixed effects, and patient as a random effect. Results: Fitted linear mixed models showed evidence of a two-way interaction effect between groups (GDM-D, GDM-M and Control) and stages of gestation (AN1, AN2, AN3 and PN) for maternal haemodynamic parameters: brachial artery augmentation index (AIx) (p = 0.004), aortic AIx (p = 0.008), and central systolic BP (p = 0.001). However, differences in respect of aortic pulse wave velocity (p = 0.001) and heart rate (p < 0.001) were only significant for gestational stage. At AN2, we did not observe any evidence that the mean brachial Aix in the GDM-M was different from the control group (p = 0.158). Conclusion: AIx and central systolic BP measures of arterial stiffness are adversely affected by GDM in comparison to controls during pregnancy. The possible beneficial effects of metformin therapy seen at 32 to 34 weeks of gestation require further exploration. (C) 2018 Elsevier B.V. All rights reserved.