Large-scale study to investigate the impact of type 1 diabetes on childhood brain development

About half of adults with type 1 diabetes have significant cognitive impairment, including problems with working memory and executive function that affect everyday thinking. But less is known about how the condition affects children during a period that is considered critical for healthy brain development.

A large, new, longitudinal study led by the Keck School of Medicine of USC will combine 12 research centers across the United States to investigate this important question. Researchers will work together to recruit a large, diverse group of children newly diagnosed with diabetes, thoroughly reviewing the environmental, lifestyle, social and clinical factors that affect how 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: What factors might accelerate or decrease the risk of developing brain-related complications in children newly diagnosed with type 1 diabetes?

Kathleen Alanna Page, MD, PhD, assistant 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 for its commitment to recruiting a group of participants from a diverse range of race, ethnicity, and income. Most previous studies of type 1 diabetes have focused on white children.

“We want to translate these insights into real-world options that can help as many children with diabetes as possible,” Page said.

Ultimately, the results could help refine clinical guidelines for treating type 1 diabetes, including what glucose levels are safest for healthy brain development. The study could also help develop targeted treatments for the condition, including changes to sleep, diet and physical activity that could help specific patients.

“All of this will be critical to improving outcomes for children with diabetes and putting them on a path to better long-term health,” 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 use these devices to conduct research in new ways.

Continuous glucose monitors provide detailed, real-time glucose reporting, including information about how glucose levels fluctuate throughout the day and how much time you spend in “high” and “low” glucose states.

“Comparing this data with information about brain health can help us refine our clinical guidelines and goals 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: Are repeated episodes of low or high glucose levels harmful, and how narrow a range of glucose levels must be to keep the brain healthy? Do these factors differ between children and adults, or between people with type 1 and type 2 diabetes?

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

“We not only have more sophisticated ways to monitor and treat type 1 diabetes, but also powerful ways to study the brain like we never had before,” Page said.

Critical window

Studying the brain in childhood can yield valuable insights into long-term health. The brain develops rapidly during this period and is particularly susceptible to external insults, including changes in glucose levels, that can affect brain function.

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

Scientists from each of the 10 study sites will meet soon to create a detailed study protocol and then begin recruiting participants. Page will lead the study from the Southern California site, along with co-principal investigators Jennifer Raymond, MD, assistant professor of pediatric endocrinology at Children’s Hospital Los Angeles, and Anna H. Xiang, PhD, director of biostatistical research at Kaiser Permanente Southern California.

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