USC launches large-scale nationwide study of type 1 diabetes and brain development

About half of adults with type 1 diabetes face significant cognitive impairment, including problems with working memory and executive function that affect day-to-day thinking. But less is known about how the condition affects children during a window of time known to be critical for healthy brain development.

A new large-scale longitudinal study, led by the Keck School of Medicine of USC, will unite 12 research centers across the United States to explore that important question. Researchers will collaborate to recruit a large, diverse group of children newly diagnosed with diabetes, taking a sweeping look at the environmental, lifestyle, social, and clinical factors that affect the way the brain develops. The five-year study is supported by a grant of more than $2.7 million from the National Institutes of Health.

“What we really want to know is: In children newly diagnosed with type 1 diabetes, what are factors that may either accelerate or mitigate the risk of developing brain-related complications?” said Kathleen Alanna Page, MD, an associate professor of medicine at the Keck School of Medicine and one of the project’s principal investigators.

With a target sample size of more than 1,000 children, the study is one of the first large-scale efforts to look at the neurocognitive effects of type 1 diabetes in this age group. The study is also unusual in its commitment to recruiting a racially, ethnically and income-diverse group of participants. Most past research on type 1 diabetes has looked primarily at white children.

“We want to translate these insights into real-world opportunities that can help the greatest number of children with diabetes,” Page said.

Ultimately, the findings could help refine clinical guidelines for managing type 1 diabetes, including what glucose levels are safest in terms of healthy brain development. The study could also aid in the creation of targeted treatments for the condition, including changes to sleep, diet, and physical activity that can help specific patients.

“All of that is going to be critically important in improving outcomes in children with diabetes and putting them on the trajectory for better health in the long term,” Page said.

Technological breakthroughs

 Advanced tools, including insulin pumps and continuous glucose monitors, have revolutionized the way type 1 diabetes is monitored and treated. Page and her team will now leverage these devices to conduct research in a new way.

Continuous glucose monitors provide detailed reports on glucose levels in real time, including information about how glucose fluctuates throughout the day and the amount of time spent in “high-glucose” and “low-glucose” states.

“Comparing that data to information about brain health can help us refine our clinical guidelines and targets for how tight we want those glucose levels to be, and really help with the clinical management of type 1 diabetes,” Page said.

For example: Is it harmful to have multiple episodes of low glucose or high glucose, and how tight does the range of glucose levels need to be to keep the brain healthy? Do these factors differ between children and adults, or in type 1 versus type 2 diabetes?

The researchers will also use functional magnetic resonance imaging (fMRI) to look noninvasively at the structure, function and development of patients’ brains.

“We not only have more sophisticated ways of monitoring and treating type 1 diabetes, but we also have powerful ways to study the brain that we’ve never had before,” Page said.

A critical window

Studying the brain during childhood can offer valuable insights about long-term health. The brain develops rapidly during this timeframe and is particularly vulnerable to external harms, including changes in glucose that may influence how the brain functions.

To track and measure brain development, the researchers will collect data on academic performance, memory and attention, and neurobehavioral outcomes such as anxiety and behavioral health.

Researchers from each of the 10 study sites will soon convene to create a detailed study protocol, then begin recruiting participants. Page will lead the study from the Southern California hub, alongside co-principal investigators Jennifer Raymond, MD, an associate professor of pediatric endocrinology at Children’s Hospital Los Angeles, and Anny H. Xiang, PhD, director of the division of biostatistics research at Kaiser Permanente Southern California.

“This is somewhere that the Keck School can really shine, because we have all of the resources and the team to approach this question, as well as a diverse population that we serve,” Page said.

About this research

 In addition to USC, the consortiums’ other study sites are the University of Minnesota; Washington University in St. Louis; the University of North Carolina at Chapel Hill; Indiana University-Purdue University Indianapolis; the University of Florida; New York University School of Medicine; the University of California, Davis; Vanderbilt University Medical Center; Joslin Diabetes Center; Nemours Children’s Clinic; and the University of Colorado Denver.

This work is supported by the National Institutes of Health [1U01DK140786].