METHODS: A double blind randomized trial. 103 women scheduled to receive two doses of 12-mg intramuscular dexamethasone 12-hour apart were separately randomized to take prophylactic metformin or placebo after stratification according to their gestational diabetes (GDM) status. First oral dose of allocated study drug was taken at enrolment and continued 500 mg twice daily for 72 hours if not delivered. Six-point blood sugar profiles were obtained each day (pre- and two-hour post breakfast, lunch and dinner) for up to three consecutive days. A hyperglycemic episode is defined as capillary glucose fasting/pre-meal ≥ 5.3 mmol/L or two-hour post prandial/meal ≥ 6.7 mmol/L. Primary outcome was hyperglycemic episodes on Day-1 (first six blood sugar profile points) following antenatal corticosteroids.
RESULTS: Number of hyperglycemic episodes on the first day were not significantly different (mean ± standard deviation) 3.9 ± 1.4 (metformin) vs. 4.1 ± 1.6 (placebo) p = 0.64. Hyperglycemic episodes markedly reduced on second day in both arms to 0.9 ± 1.0 (metformin) vs. 1.2 ± 1.0 (placebo) p = 0.15 and further reduced to 0.6 ± 1.0 (metformin) vs. 0.7 ± 1.0 (placebo) p = 0.67 on third day. Hypoglycemic episodes during the 3-day study period were few and all other secondary outcomes were not significantly different.
CONCLUSIONS: In euglycemic and diet controllable gestational diabetes mellitus women, antenatal corticosteroids cause sustained maternal hyperglycemia only on Day-1. The magnitude of Day-1 hyperglycemia is generally low. Prophylactic metformin does not reduce antenatal corticosteroids' hyperglycemic effect.
TRIAL REGISTRATION: The trial is registered in the ISRCTN registry on May 4 2017 with trial identifier https://doi.org/10.1186/ISRCTN10156101 .
Methods: 53 women with GDM (30 managed with diet only (GDM-diet) and 23 treated with insulin (GDM-insulin)) and 43 pregnant women with normal glucose tolerance (NGDM) were studied, with GIP and GLP-1 levels measured at 24-28 weeks (E1), prior (E2) and after (E3) delivery, and postpuerperium (E4).
Results: Basal GIP was shown to be low in GDM groups compared to NGDM in E1, and in E4 for GDM-diet. GLP-1 was low in GDM groups during pregnancy and afterwards. At E1, serum GIP and GLP-1 were inversely associated with GDM and participants with lower levels of GIP (<0.23 ng/mL) and GLP-1 (<0.38 ng/mL) had a 6 (95% CI 2.5-14.5)- and 7.6 (95% CI 3.0-19.1)-fold higher risk of developing GDM compared with the higher level, respectively. In the postpuerperium, when there is a drop in β-cell function, participants with previous GDM (pGDM) presented lower GLP-1 (in both GDM subgroups) and lower GIP in GDM-diet subgroup compared to controls.
Conclusion: There is an independent, inverse association between fasting incretins and higher risk of GDM. Furthermore, lowered levels of these peptides may play an important role in the abnormality of glucose regulation following pregnancy.
METHODS: Chorionic arteries and veins were isolated from human placenta from normal, gestational diabetes mellitus and type 1 diabetes mellitus pregnancies. Isometric tension recording measured responses to adenosine and the thromboxane A2 analogue U46619 (thromboxane A2 mediates fetoplacental vasoconstriction to adenosine). Adenosine and thromboxane prostanoid receptor protein expression was determined by immunoblotting.
RESULTS: Adenosine elicited contractions in chorionic arteries and veins which were impaired in both gestational diabetes mellitus and type 1 diabetes mellitus. Contractions to potassium chloride were unchanged. Adenosine A2A and A2B receptor protein levels were not different in gestational diabetes mellitus and normal pregnancies. Contractions to U46619 were unaltered in gestational diabetes mellitus arteries and increased in type 1 diabetes mellitus arteries. Overnight storage of vessels restored contractility to adenosine in gestational diabetes mellitus arteries and normalized contraction to U46619 in type 1 diabetes mellitus arteries.
CONCLUSION: These data are consistent with the concept of aberrant adenosine signalling in diabetes; they show for the first time that this involves impaired adenosine contractility of the fetoplacental vasculature.