Genetic Link in Diabetes, Low Birth Weight?

Low birth weight caused by genetic factors increases risk of developing type 2 diabetes later in life, according to researchers from the Tulane University School of Public Health and Tropical Medicine in New Orleans, La.

Observational studies have shown low birth weight may be associated with type 2 diabetes, but whether it is causal has been difficult to tease out, given that other factors such as socioeconomic factors and lifestyle also play a role. However, analyzing genetic associations, which are less affected by external factors, can shed light on causal relationships.

A team led by Tiange Wang, MD, PhD, a postdoc research fellow and Lu Qi, MD, PhD, HCA Regents Distinguished Chair and Professor in the Department of Epidemiology, developed a genetic risk score based on five single nucleotide polymorphisms (SNPs) related to low birth weight.

Using data from 3,627 people with type 2 diabetes and 12,974 controls of European ancestry, all participating in the Nurses’ Health Study and the Health Professionals Follow-Up Study, the team developed a genetic risk score based on five single nucleotide variations that are related to low birth weight. They found that for each point increase on the scale, which ranged from 1 to 10, the risk of developing type 2 diabetes rose by 6 percent. They then used a Mendelian randomization analysis to estimate potential causality and found evidence that low birth weight indeed seems to cause the increased risk for type 2 diabetes.

Low birth weight indicates restricted intrauterine growth, so it is possible that the risk factors for restricted growth that causes the low birthrate are also causing the rise in type 2 diabetes risk. These factors include malnutrition, anemia, infection, and placental insufficiency.

"A genetically lowered birth weight was associated with increased susceptibility to type 2 diabetes,” the authors wrote in the report published online on June 23 in Diabetologia. “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."