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Gestational Pre-Diabetes Modifies Leptin Gene in Utero

One of the most exciting and biologically highly plausible reasons for the childhood obesity epidemic may well be that current generations are far more susceptible to obesity because of “epigenetic programming”.

Simply put, the notion is that exposure to an adverse fetal environment, as in the case of maternal obesity, diabetes or hypertension during pregnancy, can lead to a lifelong change in the genetic program of the offspring, making them genetically more prone to obesity.

Thus, although the children are born with the same genetic code as their parents, whether or not certain genes are “more” or “less” active, is determined by the fetal (and possibly early post-natal) environment.

While these “epigenetic” changes are well documented in animal studies, exactly which genes are affected in the context of intergenerational transmission of obesity is not clear.

A study by Luigi Bouchard and colleagues from Université de Montréal, Canada, just published online in Diabetes Care, suggests that one of the modified genes may well be leptin, a key regulator of energy balance.

The researchers examined placental tissues as well as maternal and cord blood samples from 48 women, 23 of who had gestational impaired glucose tolerance (= gestational pre-diabetes).

Not only was there a positive association between the DNA methylation levels of the offspring’s leptin gene (measured in the placenta) and the glucose response to an oral glucose test, but there was also a negative relationship to placental leptin gene expression.

DNA methylation is a form of “epigenetic” modification that determines the extent to which a given gene is expressed in vivo. Thus although the genetic code or DNA sequence for that gene may be identical between two individuals, variations in DNA methylation will determine how “active” this gene is in a given individual.

The authors conclude that impaired glucose tolerance during pregnancy is associated with epigentic modification of the leptin gene with potential functional impacts that could in part account for the detrimental health effects associated with fetal programming such as long-term increased risk of developing obesity and type 2 diabetes.

As I have noted before, obesity may well start in the womb, which is why recent recommendations have focussed on improving maternal health, including the prevention of excess weight gain during pregnancy, as a key strategy to reduce childhood obesity.

Edmonton, Alberta

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Bouchard L, Thibault S, Guay SP, Santure M, Monpetit A, St-Pierre J, Perron P, & Brisson D (2010). Leptin Gene Epigenetic Adaptation to Impaired Glucose Metabolism during Pregnancy. Diabetes care PMID: 20724651


  1. As well as improving maternal health, doctors should tell new mothers that the gestational diabetes has affected the child, making him/her prone to obesity.

    The mother can then take proper steps, with the help of doctors and nutritionists, to deal with the situation and prevent the child from becoming obese.

    It would be negligent (not to mention cruel) for a doctor not to make sure a mother understands the danger her child faces, and to provide help.

    Also the child’s chart should note this problem so that the child can be carefully monitored for proper weight gain. It is very easy for extra weight in an otherwise healthy child to be brushed off as insignificant, however in this case extra weight should be a red flag of developing obesity.

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  2. I agree with anonymous and Dr. Sharma. There is not only a genetic link now proven, but the environmental link is further solidified of the mother does not have proper weight management and nutrition counceling pre and post partum. If the mother is overeating, likely so will the child. I have worked with obese kids and shrinking abdominal fat stores is the most difficult of all our patients. They are genetically “stubborn” and now I understand the possible reason. How should I modify expectations for weight loss/management based on this research? If at all.

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  3. Anon,

    While the evidence is starting to pile up in terms of support for epigenetic programming, I think it might be a little too early to suggest that this does indeed make them prone to obesity to the point where physicians should give out warnings to parents.

    Studies at the level of gene expression must be compared to actual obesity rates of children with these manifestations for the results to be more conclusive.

    Would you agree Dr. Sharma?

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  4. If the science isn’t certain, then the warning to the mothers should say that the studies aren’t conclusive.

    Tell the mother “Evidence is starting to pile up, but we’re not sure yet. Just to be on the safe side, monitor your child so you can nip any developing obesity in the bud. Keeping your child at a healthy weight is a good thing to do whatever the outcome of these studies turns out to be.”

    The goal of a physician should be to protect the health of patients, not to provide a group of obese children to be a basis of a study of gene expression.

    You wouldn’t be telling the mother to do something unusual on the basis of an inconclusive study – not a good idea –
    but you would be making her aware that there is a possibility that for her child it may be especially important to work at keeping a healthy weight.

    Preventing obesity is important because it is serious and extremely difficult to cure.
    If a study pointed out that gene expression caused some minor and temporary problem that the child would naturally out-grow, then there would be no reason to concern parents until results are conclusive.

    Imagine 10 years from now. If I had an overweight child who had the condition mentioned here, I would be very disappointed that I had not been warned about a possible danger to health. It is of course up to the mother to feed any child to keep a healthy weight, but knowing a child may have a particular succeptibility for gaining weight can help a mother be vigilant and not fall into the “don’t worry, s/he’ll grow out of it” trap.
    If 10 years from now it turned out that the studies disproved this theory, I’d have lost nothing but a bit of extra time spent on careful menu planning, and I’d be more likely to have a healthy, not overweight, child.

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  5. I do agree, but shouldn’t doctors tell ALL parents to monitor for the beginnings of obesity? After all, gene expression isn’t the only potential cause.

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  6. Well, having had a mother who tried to micromanage my eating habits (even though my health and weight has always been in great shape, esp. compared to her), I don’t think that parental involvement is really the answer. Having said that, I do think that it’s helpful to those with predilections to obesity and diabetes to know that. At 21, when I first started gaining excess weight, I could see what the long-term effects would be For Me because my mother and various family members were already struggling with them. It was the impetus to start (and have maintained for 20 years) an exercise program, to monitor cholesterol/ blood pressure/ blood sugar every year and use rigorous standards (more than just “not diabetic yet”) as a goal and then a maintenance. Given the cultural climate towards alcohol, junk food, etc., being able to say (to myself and to friends) that their habits may be okay for them, but my habits need to aspire to a different standard, has been very powerful.

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  7. I guess my girls don’t follow the rules. I had GD only with my middle daughter who is the only one in our entire household considered of normal BMI. None of us have diabetes.

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  8. I learned alot from this article. I just want to know how can I motivate my 10 year old son to lose weight?

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