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Genetically caused low birthweight linked to diabetes risk

Each genetic risk score point increases diabetes risk by 6%

Adrian O'Dowd

Friday, 24 June 2016

People with low birthweight due to genetic factors appear to be more likely to develop type 2 diabetes, according to a study* published today in Diabetologia, the journal of the European Association for the Study of Diabetes.

It is already known that low birthweight is associated with high risk of type 2 diabetes, but it is less clear whether this relation is causal and factors due to socioeconomic status and lifestyle are difficult to fully eliminate in observational studies.

Therefore, researchers led by Dr Tiange Wang and Dr Lu Qi of Tulane University School of Public Health and Tropical Medicine, New Orleans, USA, set out to focus on the role of genetic factors.

Their new study included 3,627 people with type 2 diabetes and 12,974 controls of European ancestry from the Nurses' Health Study (a large study of nurses in the USA) and the Health Professionals Follow-up Study (a large study of male health professionals in the USA).

The researchers created a genetic risk score based on five low birthweight-related genetic variations known as single nucleotide polymorphisms.

Their analysis showed that for each 1 point increase in the genetic risk score, (with the score ranging from 1-10), the risk of developing type 2 diabetes increased by 6%.

They also found evidence that the low birthweight was actually causing the excess risk in type 2 diabetes and said the type of analysis they had carried out was a new approach for establishing causal relationships in this kind of study.

The authors said: “Evidence from both population and experimental studies has suggested that restricted early life development has long-term structural and functional influence on individuals’ predisposition to an increased risk of metabolic diseases such as type 2 diabetes.

“However, to our knowledge, this study is the first to investigate the potential causal relation between low birthweight and risk of type 2 diabetes.”

Since low birthweight represents restricted foetal growth, it could not be ruled out, they added, that it was the risk factors for this restricted growth that were causing the low birthweight and in turn causing the diabetes to develop.

They concluded: “A genetically lowered birth weight was associated with increased susceptibility to type 2 diabetes. Our findings support a potential causal relation between birth weight and risk of type 2 diabetes, providing novel evidence to support the role of intrauterine exposures in the pathogenesis of type 2 diabetes.”


* Wang T, et al. Low birthweight and risk of type 2 diabetes: a Mendelian randomisation study. Diabetologia pp 1-8, first online: 23 June 2016. DOI: 10.​1007/​s00125-016-4019-z

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