Low Vitamin B12 and Leptin: Link to Metabolic Risk in Next Generation?

Becky McCall

November 17, 2016

Vitamin B12 deficiency during pregnancy may predispose children to metabolic problems such as type 2 diabetes in the future, suggests new research presented at the recent UK Society for Endocrinology Annual Conference in Brighton.

Specifically, the researchers found that babies born to mothers with B12 deficiency had higher-than-normal leptin levels. This suggests that maternal B12 deficiency can adversely program the leptin gene, changing the levels at which the hormone is produced while the fetus grows.

Leptin is the hormone that signals satiety after eating, and high levels have previously been found in obese people. This can eventually result in leptin resistance, continued overeating, and an increased risk of insulin resistance, which can in turn lead to type 2 diabetes.

"This is the first time that maternal B12 has been linked to leptin, a metabolic risk factor, which is either derived from the placenta or the fetus's own fat cells," senior author Ponusammy Saravanan, PhD, FRCP, associate clinical professor at the University of Warwick, United Kingdom, told Medscape Medical News.

The work highlights the importance of mothers obtaining the right nutrients both before and during pregnancy, he stressed.

"The nutritional environment provided by the mother can permanently program the baby's health," said Dr Saravanan. "We know that children born to under- or overnourished mothers are at an increased risk of health problems such as type 2 diabetes, and we also see that maternal B12 deficiency may affect fat metabolism and contribute to this risk. This is why we decided to investigate leptin, the fat-cell hormone."

B12 Deficiency and High BMI

Vitamin B12 is naturally found in animal products, including fish, meat, poultry, eggs, and milk, meaning deficiency is more likely in those following a vegan diet.

The link between B12 and potential metabolic disease risk is not fully established, but prior studies strongly suggest an association exists.

Previous work by Dr Saravanan and others has shown that maternal B12 deficiency at 28 weeks of pregnancy was linked to insulin resistance in the offspring and that mothers with low B12 levels had a higher body mass index (BMI) and were more likely to have low-birth-weight babies and/or high cholesterol levels.

The incidence of gestational diabetes has also been found to double in mothers with low B12 levels.

The current study led by Dr Saravanan used data from the United Kingdom, where around 12% of women of child-bearing age have been found to be B12 deficient; furthermore, during pregnancy around 20% to 30% of women there are thought to suffer from B12 deficiency.

The researchers hypothesized that maternal B12 levels "set" leptin levels in utero, and therefore they investigated the association between maternal B12 levels and leptin in maternal adipose tissue, placental tissue, and umbilical-cord blood.

The study comprised a cohort of 91 mother/baby pairs — all deliveries were by cesarean section.

Adipocytes and fasting maternal venous and cord-blood samples were taken from mother and baby in each case, as well as adipose tissue from 42 mothers and placental tissue from 83 newborns at delivery.

B12 deficiency was common and was found in 39.6% of mothers and 29% of newborns. BMI varied, but those mothers with a B12 level < 191 ng/L had a mean BMI of 30.8 kg/m2, compared with 28.4 in those with B12 > 191 ng/L (P < .05).

The women with B12 levels below 191 ng/L also had significantly higher triglyceride and LDL-cholesterol levels compared with those women who were not deficient in B12.

B12 Deficiency and Higher Leptin Levels

Leptin levels were higher in the babies born to mothers with low B12 levels, but the researchers did not see a link between maternal leptin levels and cord-blood leptin levels.

"Initially, this was surprising, but then we realized that leptin cannot pass through the placental barrier," remarked Dr Saravanan.

"It is thought that maternal B12 deficiency can adversely program the leptin gene, changing the levels at which the hormone is produced while the fetus grows," Dr Saravanan added.

After adjustments for confounders, maternal B12 was independently associated with neonatal leptin (P = .002). In addition, leptin-gene expression was higher in adipose tissue and placental tissue from mothers with low B12 levels.

The long-term outcomes of raised leptin levels in these babies is unknown.

"We know that in patients with type 2 diabetes, the leptin levels are high and this contributes to leptin resistance. Another question is, 'What do these high leptin levels before birth do to appetites in early childhood?' We know that obesity in early years carries a high risk of obesity in adulthood," Dr Saravanan concluded.

Dr Saravanan has declared no relevant financial relationships.

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UK Society for Endocrinology Annual Conference. November 8, 2016; Brighton, United Kingdom. Abstract P188

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