It has long been understood that pregnant women with diabetes are more likely to have children with obesity than women who do not have diabetes during pregnancy. But scientists have not fully understood the cause or why babies born to mothers with diabetes are also more likely to develop obesity and associated metabolic disorders later in life.
It has long been understood that pregnant women with diabetes are more likely to have children with obesity than women who do not have diabetes during pregnancy. But scientists have not fully understood the cause or why babies born to mothers with diabetes are also more likely to develop obesity and associated metabolic disorders later in life.
To help find answers, Keck School of Medicine of USC researcher Shan Luo, PhD, has been awarded $3.1 million in funding from the National Institutes of Health and the National Institute of Diabetes and Digestive and Kidney Diseases to study the early brain development of babies born to women with diabetes during pregnancy, including type 1, type 2 and gestational diabetes. Luo’s research will focus on the development of these babies’ brains in the first 1000 days of life to compare how their development differs from babies born to mothers without diabetes during pregnancy.
“The first few years after birth is a period of intense brain development,” said Luo, who is an assistant professor of medicine, psychology, and pediatrics at the Keck School of Medicine. “We know how the brain develops in babies whose mothers do not have diabetes, but little or no research has been done on how the brains of babies who develop in a diabetic environment are different.”
New technology, new insights
To date, most research related to the brain of offspring born to mothers with diabetes has been done with older children. Until recently, explained Luo, it was difficult to study the brain during very early childhood, but new imaging technology has made it possible for researchers to finally understand how the brain develops in this critical time frame.
For her research, Luo is using neuroimaging data collected by a large, multinational neuroimaging consortium called Enhancing Neuroimaging Genetics through Meta-Analysis, or ENIGMA, which is led by Paul Thompson, PhD, professor of ophthalmology, neurology, psychiatry and the behavioral sciences, radiology, psychiatry, and engineering at the Keck School of Medicine. Specific to this project, ENIGMA-ORIGINs working group participants have neuroimaging data collected from more than 3,500 babies in four different countries, beginning shortly after birth and at multiple times during the first several years of life.
The ENIGMA data is not only large and diverse, it is also more comprehensive than other imaging studies on brain development because researchers employed several types of neuroimaging technology, rather than relying on single modality, such as a traditional MRI.
Using the ENIGMA data, Luo will evaluate the development in structure and function of several key parts of the brain that are involved in obesity development. Luo said they expect to find differences in the development of the mesolimbic system, which is the reward and motivation circuitry in the brain; the prefrontal cortex, which is involved in executive function and decision making; and the metabolic system, which regulates the metabolism and energy balance.
Luo also plans to compare the neuroimaging abnormalities found in these babies’ brains with gene expression maps to identify genetics that may be involved in the structural and functional changes in the brain. This piece of the project will connect the findings with the underlying biology and potentially provide new targets for drug development.
Obesity increasingly believed to be rooted in biology
A growing body of research has shown obesity to be a brain disorder, which is why Luo said it is important to understand how the brain’s earliest stages of development are affected by exposure to a diabetic environment in the womb.
According to World Health Organization estimates, around 40 million children under the age of 5 were overweight or obese in 2020. Almost 90% of the children who were obese by 3 years of age continued to be classified as overweight or obese in adolescence.
Being obese also raises the risk of developing diabetes and cardiovascular disease. Luo added that some babies at the age of three exhibit inflammation markers that are associated with cardiovascular disease later in life.
“With obesity rates as high as they are – 20% among young people and over 40% of adults – it is critical that we identify the major risk factors that contribute to obesity and understanding the etiology of obesity during the early, plastic phase of development is critical to reverse this epidemic,” said Luo. “Only then will we be able to develop prevention strategies that can be taken early to mitigate the obesity risk.”
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