News Release

Maternal B12 deficiency may increase child's risk of type 2 diabetes

Peer-Reviewed Publication

University of Warwick

Dr. Ponnusamy Saravanan, University of Warwick

image: Dr. Ponnusamy Saravanan. view more 

Credit: Warwick Medical School, University of Warwick

B12 deficiency during pregnancy may predispose children to metabolic problems such as type-2 diabetes, according to research presented today at the Society for Endocrinology's annual Conference in Brighton. These findings could lead to a review of current vitamin B12 requirements for pregnant women, whether through an improved diet or supplements.

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. Previous studies show that mothers with low B12 levels had a higher BMI and were more likely to give birth to babies with low birth weight as well as high cholesterol levels. These children also had higher insulin resistance in childhood - a risk factor for type-2 diabetes.

In this study, a team of researchers at the University of Warwick's Warwick Medical School hypothesised that the changes associated with B12 deficiency may be the result of abnormal levels of leptin - the hormone that tells us we are full after eating. Leptin is produced by our body's fat cells and its levels rise in response to eating food. Whilst lean diets are associated with normal levels of leptin, obesity causes levels to rise and remain consistently higher than normal. This can eventually lead to leptin resistance, continued overeating, and an increased risk of insulin resistance, which leads to type-2 diabetes. Scientists and doctors therefore see leptin as providing an effective 'marker' for body fat.

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 whilst the foetus grows.

"The nutritional environment provided by the mother can permanently program the baby's health," said Dr Ponusammy Saravanan, senior author of the study. "We know that children born to under or over nourished 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."

The next steps in the study will be to determine the details of how and why the leptin increase is seen in babies born to mothers with low B12. "The leptin can increase for two reasons," said Dr Adaikala Antonysunil, who also worked on the study.

"Either low B12 drives fat accumulation in the foetus, and this leads to increased leptin, or the low B12 actually causes chemical changes in the placental genes that produce leptin, making more of the hormone. As B12 is involved in methylation reactions in the body which can affect whether genes are turned on and off, we suspect it may be the latter."


The research was presented as a conference abstract showing only preliminary results, and has not been peer reviewed.

Abstract P188

Low maternal B12 associates with higher leptin in maternal adipose tissue, placental tissue and cord blood

Antonysunil Adaikalakoteswari1, Manu Vatish2, Ilona Goljan3 & Ponnusamy Saravanan1,3

1University of Warwick, Warwick, UK; 2University of Oxford, Oxford, UK; 3George Eliot Hospital, Nuneaton, UK

Background: Evidences show that maternal vitaminB12 deficiency at periods of development influence metabolic status and degree of metabolic syndrome of the offspring into adulthood. VitaminB12 is required for the synthesis of methionine, which is the precursor of S-adenosyl-methionine, a key methyl donor for DNA methylation. So vitaminB12 deficiency might cause methylation changes, which are thought to alter gene expression of regulatory factors and could result in adverse metabolic phenotypes. Our recent study showed that low maternal vitaminB12 was associated with adverse cord blood lipid profile and higher BMI which provided the clue to explore the link between the adiposity marker, leptin, and vitaminB12. We hypothesize that maternal B12 might program leptin levels in-utero. Therefore we investigated whether maternal B12 levels associate with leptin in maternal adipose tissue, placental tissue and cord blood.

Methods: Paired maternal venous and cord blood samples(n=91), adipose tissue(n=42) and placental tissue(n=83) were collected at delivery. Serum vitaminB12 was determined by electro-chemiluminescent immunoassay. Leptin levels were measured by ELISA. To assess the underlying mechanism, human pre-adipocyte cell line (Chub-S7) was differentiated in various B12 concentrations (1) Control: (B12-500nM); (2) LowB12 (0.15nM) (3) Control + methylation inhibitor (AZ): (B12-500nM + 5-Aza-dC-200nM).

Results: B12 deficiency (<150pmol/L) was common (mothers-40%; neonates-29%). In regression analysis, adjusted for likely confounders, maternal B12 independently associated with neonatal leptin (?=-0.662; p=0.002; R2=12.7%). Leptin gene expression was higher in adipose tissue and placental tissue from mothers with low B12. Leptin gene was higher in adipocytes (Chubs-S7) cultured with low B12 (0.15nM) and treated with normal B12 (500nM) in the presence of methylation inhibitor (5-Aza-dC).

Conclusion: Our study highlights that low maternal B12 associates with higher leptin in cord blood, maternal adipose tissue and placental tissue, suggesting leptin gene could represent a mechanism of adverse programming either in the placental tissue or maternal adipose tissue.?

Notes for editors

1. For further information about the study please contact:

Dr Ponnusamy Saravanan
Gibbet Hill
Warwick Medical School
University of Warwick
Tel: +44 (0)7717 843260

2. The study "Low maternal B12 associates with higher leptin in maternal adipose tissue, placental tissue and cord blood" will be presented by Dr Adaikala Antonysunil at 13.15 Monday & Tuesday 7-8 November 2016, at the Society for Endocrinology BES 2016 Conference in Brighton, UK.

3. For press enquiries, please contact the Society for Endocrinology press office:

Omar Jamshed
Communications Executive
Tel: +44 (0)1454 642 206 (office)
Tel: +44 (0) 7876824027 (mobile)

4. The Society for Endocrinology's annual conference is held at the Brighton Conference Centre from 7-9 November 2016. The conference features some of the world's leading basic and clinical endocrinologists who present their work. Journalists wishing to attend should contact the Society for Endocrinology press office using the details above. The scientific programme is available on the conference webpage.

5. The Society for Endocrinology is a UK-based membership organisation representing a global community of scientists, clinicians and nurses who work with hormones. Together we aim to improve public health by advancing endocrine education and research, and engaging wider audiences with the science of hormones.

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