Metformin as the first drug of choice for glucose lowering in gestational diabetes (GDM) is still controversial, despite recent publications reporting similar outcomes in comparison to insulin, both for offspring and mothers. The use of metformin during pregnancy is increasing and several recent guidelines recommend metformin use in GDM pregnancies. Background, current metformin use and unresolved concerns are discussed in the context of the article from Gante and coworkers.
Kristin Godang, Kathrine Frey Frøslie, Tore Henriksen, Elisabeth Qvigstad and Jens Bollerslev
Neonatal body fat is an important indicator of foetal energy supply and growth with potential importance for long-term health. In this study, we wanted to explore seasonal variation of 25-hydroxy-vitamin D (25(OH)D) in maternal and umbilical cord plasma (UCP) to examine whether maternal and foetal 25(OH)D levels were associated with maternal BMI and neonatal fat mass (FM), and to explore the relationship among maternal and neonatal 25(OH)D levels, maternal glucose/insulin levels and UCP C-peptide.
An observational, prospective study of determinants of foetal growth and birth weight in healthy pregnant women. Total body composition in 202 newborns was measured by dual-energy X-ray absorptiometry. Circulating levels of biomarkers were assessed in mothers at gestational weeks 14–16 and 30–32 and UCP.
The mean 25(OH)D concentration in UCP was significantly lower than in maternal circulation (31 vs 45 nmol/l, P<0.001). Maternal and UCP 25(OH)D levels varied significantly with season. No significant association between maternal BMI (weeks 14–16) and UCP 25(OH)D concentration was found. We found a strong positive association between maternal 25(OH)D and UCP 25(OH)D (P<0.001). There was no significant linear association between maternal BMI (weeks 14–16) and maternal 25(OH)D. We found no association between maternal 25(OH)D levels and glucose/insulin levels, nor with maternal or UCP 25(OH)D on UCP C-peptide levels. Finally, neonatal total body FM was positively associated with UCP 25(OH)D, P=0.02.
We demonstrated seasonal variation in maternal and neonatal 25(OH)D levels at northern latitudes. UCP, but not maternal, 25(OH)D was a significant predictor of neonatal total FM. Maternal BMI and metabolic parameters such as glucose, insulin and UCP C-peptide levels were not associated with 25(OH)D in mothers or offspring.
Gunn-Helen Moen, Christine Sommer, Rashmi B Prasad, Line Sletner, Leif Groop, Elisabeth Qvigstad and Kåre I Birkeland
To summarize the current knowledge on epigenetic alterations in mother and offspring subjected to gestational diabetes (GDM) and indicate future topics for research.
We performed extensive searches in PubMed, EMBASE and Google scholar, using a combination of the search terms: GDM, gestational diabetes, epigenetic(s), methylation, histone modification, histone methylation, histone acetylation, microRNA and miRNA. Studies that compared women diagnosed with GDM and healthy controls were included. Two authors independently scanned the abstracts, and all included papers were read by at least two authors. The searches were completed on October 31st, 2016.
We identified 236 articles, of which 43 were considered relevant for this systematic review. Studies published showed that epigenetic alterations could be found in both mothers with GDM and their offspring. However, differences in methodology, diagnostic criteria for GDM and populations studied, together with a limited number of published studies and small sample sizes, preclude clear conclusions about the role of epigenetic modifications in transmitting risk from GDM mothers to their offspring.
The current research literature suggests that GDM may have impact on epigenetic modifications in the mother and offspring. However, larger studies that include multiple cohorts of GDM patients and their offspring are needed.
Gunn-Helen Moen, Marissa LeBlanc, Christine Sommer, Rashmi B Prasad, Tove Lekva, Kjersti R Normann, Elisabeth Qvigstad, Leif Groop, Kåre I Birkeland, David M Evans and Kathrine F Frøslie
Hyperglycaemia during pregnancy increases the risk of adverse health outcomes in mother and child, but the genetic aetiology is scarcely studied. Our aims were to (1) assess the overlapping genetic aetiology between the pregnant and non-pregnant population and (2) assess the importance of genome-wide polygenic contributions to glucose traits during pregnancy, by exploring whether genetic risk scores (GRSs) for fasting glucose (FG), 2-h glucose (2hG), type 2 diabetes (T2D) and BMI in non-pregnant individuals were associated with glucose measures in pregnant women.
We genotyped 529 Norwegian pregnant women and constructed GRS from known genome-wide significant variants and SNPs weakly associated (p > 5 × 10−8) with FG, 2hG, BMI and T2D from external genome-wide association studies (GWAS) and examined the association between these scores and glucose measures at gestational weeks 14–16 and 30–32. We also performed GWAS of FG, 2hG and shape information from the glucose curve during an oral glucose tolerance test (OGTT).
GRSFG explained similar variance during pregnancy as in the non-pregnant population (~5%). GRSBMI and GRST2D explained up to 1.3% of the variation in the glucose traits in pregnancy. If we included variants more weakly associated with these traits, GRS2hG and GRST2D explained up to 2.4% of the variation in the glucose traits in pregnancy, highlighting the importance of polygenic contributions.
Our results suggest overlap in the genetic aetiology of FG in pregnant and non-pregnant individuals. This was less apparent with 2hG, suggesting potential differences in postprandial glucose metabolism inside and outside of pregnancy.