Now a paper by Argyro Syngelaki and colleagues from the UK, published in the New England Journal of Medicine, suggests that the anti-diabetes drug metformin may limit weight gain in pregnant non-diabetic women with obesity and also reduce the incidence of pre-eclampsia.
The researchers randomised 450 pregnant women with a BMI greater than 35 and no diabetes to either metformin (3 g/day) or placebo from weeks 12-18 weeks of gestation till delivery in a double-blind fashion.
Among the 400 women who completed the study, those on metformin gained about 2 Kg less weight than the placebo group.
There was also an almost 75% decrease in the risk of developing preeclampsia.
Despite these effects, metformin did not significantly reduce the incidence of large-for-gestational-age babies or other adverse neonatal outcomes.
While these findings may be somewhat disappointing with regard to outcomes in the offspring, the reduction in pre-eclampsia is impressive and, if confirmed, could well be an interesting use of this compound in high-risk pregnancies.
Today, attendees at the 4th Canadian Obesity Summit will face the tough task of choosing between a variety of workshops dealing with topics ranging from harnessing public-private partnership to promote healthy food in retail stores to patient centredness and ensuring the physical and mental well-being of individuals living with obesity (for a full list of workshops – click here)
A workshop that I particularly look forward to is one on the determinants of the intergenerational transmission of obesity.
As the organisers of this workshop tell us,
“Studies in both animals and humans, including epidemiologic, clinical, and experimental data, have provided strong evidence implicating the intrauterine environment in downstream obesity. In recent years, significant advancements have been made regarding underlying molecular pathways and population level interventions and their effects on fetal programming of obesity.”
Thus, this workshop will provide an update on the topic and focus on the interplay between obesity, gestational weight gain (GWG), lifestyle behaviours, and early life factors (parenting) that exacerbate fetal/child growth and perpetuate the intergenerational obesity cycle.
Epigenetic and clinical evidence will be presented that demonstrates how perturbations during pregnancy affect fetal/infant phenotype and how early postpartum health (of mom and baby) predicts chronic disease risk later in life. The latest evidence from pregnancy and postpartum‐related intervention trials will be presented to identify avenues for clinical management and future research.
For more information on this workshop – click here.
Regular readers are well aware of the considerable evidence now supporting the notion that inter-generational transmission of obesity risk through epigenetic modification may well be a key factor in the recent global rise in obesity rates (over the past 100 years or so).
Now a brief review article by Susan Ozanne from the University of Cambridge, UK, published in the New England Journal of Medicine, describes how researchers have now identified a clear and conserved epigenetic signature that is associated with obesity across species (from the fruit fly all the way to humans).
The article discusses how the transmission of susceptibility to obesity can occur as a consequence of “developmental programming,” whereby environmental factors (e.g. a high-fat diet) encountered at the point of conception and during fetal and neonatal life can permanently influences the structure, function, and metabolism of key organs in the offsprin, thus leading to an increased risk of diseases such as obesity later in life.
There is now evidence that such intergenerational transmission of disease can occur through environmental manipulation of both the maternal and paternal lines – thus, this is not something that is just a matter of maternal environment.
Thus, as Ozanne points out,
“Epigenetic mechanisms that influence gene expression have been proposed to mediate the effects of both maternal and paternal dietary manipulation on disease susceptibility in the offspring (these mechanisms include alterations in DNA methylation, histone modifications, and the expression of microRNAs).”
Work in the fruit fly has linked the effect of paternal sugar-feeding on the chromatin structure at a specific region of the X chromosome and transcriptome analysis of embryos generated from fathers fed a high-sugar diet, revealed dysregulation of transcripts encoding two proteins (one of them is called Su(var)) known to change chromatin structure and gene regulation.
Subsequent analyses of microarray data sets from humans and mice likewise revealed a depletion of the Su(var) proteins in three data sets from humans and in two data sets from mice.
“This finding is consistent with the possibility that the depletion of the Su(var) pathway may be brought about by an environmental insult to the genome that is associated with obesity.”
Not only do these studies provide important insights into just how generational transmission of obesity may work but it may also lead to the development of early tests to determine the susceptibility of individuals to the future development of conditions like obesity or diabetes based on epigenetic signatures.
All of this may be far more relevant for clinical practice than most readers may think – indeed, a focus on maternal (and now paternal?) health as a target to reduce the risk of childhood (and adult) obesity is already underway.
This issue will certainly be a “hot topic” at the Canadian Obesity Summit in Toronto later this month.
Pregnancy in women after undergoing bariatric surgery are by no means uncommon. There is even some evidence from case series to suggest that babies born to mothers, who have undergone surgery may be less likely to become obese or experience the cardiometabolic complications of obesity.
This risk needs to be balanced against potential risks the known adverse effects of gastric bypass surgery on the metabolism of iron, vitamin B12, and folate,
Now a paper by Karl Johansson and colleagues, published in the New England Journal of Medicine, suggests that this may well be the case.
The researchers identified 627,693 singleton pregnancies in the Swedish Medical Birth Register from 2006 through 2011, of which 670 occurred in women who had previously undergone bariatric surgery and for whom presurgery weight was documented.
They found that pregnancies after bariatric surgery, as compared with matched control pregnancies, were associated with lower risks of gestational diabetes (1.9% vs. 6.8%; odds ratio, 0.25) and a lower incidence of large-for-gestational-age infants (8.6% vs. 22.4%; odds ratio, 0.33).
These potentially beneficial outcomes for the infant were counterbalanced by a two-fold increase in the likelihood of having a small-for-gestational-age infants (15.6% vs. 7.6%; odds ratio, 2.20) and a somewhat shorter gestation (mean difference -4.5 days)
Also, the risk of stillbirth or neonatal death was 1.7% versus 0.7% (odds ratio, 2.39).
No differences were found in the frequency of congenital malformations.
Bariatric surgery was associated with reduced risks of gestational diabetes and excessive fetal growth, shorter gestation, an increased risk of small-for-gestational-age infants, and possibly increased mortality.
Thus, the authors conclude that,
“…a history of bariatric surgery was associated with reduced risks of gestational diabetes and large-for-gestational-age infants.”
Nevertheless, they do recommend increased surveillance during pregnancy and the neonatal period, as bariatric surgery may also be associated with small-for-gestational-age infants, a shorter length of gestation, and potentially an increased risk of stillbirth or neonatal death.
For all my Canadian readers (and any international readers planning to attend), here just a quick reminder that the deadline for early bird discount registration for the upcoming 4th Canadian Obesity Summit in Toronto, April 28 – May 2, ends March 3rd.
To anyone who has been at a previous Canadian Summit, attending is certainly a “no-brainer” – for anyone, who hasn’t been, check out these workshops that are only part of the 5-day scientific program – there are also countless plenary sessions and poster presentations – check out the full program here.
To register – click here.