Type 2 diabetes in children is associated with premature vascular problems affecting the kidneys, eyes, heart and peripheral blood vessels. But what about diabetes’ effect on a teenager’s developing brain? Does the disease change the brain’s vasculature, structure or function? And if so, can interventions help prevent, delay or treat these changes?  

A new, three-year clinical study at Cincinnati Children’s is exploring these and other questions related to youth-onset Type 2 diabetes’ impact on the brain. The $2.5 million study, funded by the National Institutes of Health (NIH), will enroll 154 teens—one-third Type 2 diabetics, one-third non-diabetic adolescents with obesity, and one-third without obesity. Using advanced magnetic resonance imaging (MRI) methods, the study will comprehensively determine how the structure and function of blood vessels in the brain are impaired by Type 2 diabetes and how that might lead to brain tissue loss and cognitive problems in teens.  

The study builds on exciting data from a pilot study funded by Cincinnati Children’s and the University of Cincinnati. The study, which began in 2016, compared adolescents with youth-onset Type 2 diabetes to their peers with obesity and healthy youth. Researchers used MRI to document differences in brain structure and conducted cognitive testing to evaluate neurocognitive function.  

One set of findings, published in June 2022 in Pediatric Diabetes, showed the first evidence of cerebrovascular impairment in youth with Type 2 diabetes, manifested as reduced gray matter cerebral blood flow. The study also showed preliminary evidence that cerebral blood flow correlates with reduction in gray matter volume and working memory measures.  

“Researchers have not traditionally considered structural brain abnormalities and neurocognitive impairment related to youth-onset Type 2 diabetes,” says pediatric endocrinologist Amy Shah, MD, MS, who was the principal investigator (PI) of the pilot study and is co-PI on the new NIH study. “This work is important, because if changes in the brain are occurring earlier than previously recognized, we must understand why and design interventions. We want kids with Type 2 diabetes to have the best long-term health outcomes possible, and that extends to their brain development and cognitive ability.” 

The NIH-funded study will separate the effects of Type 2 diabetes from obesity and identify noninvasive imaging biomarkers of brain health and treatable risk factors. All study participants will undergo a brain MRI study, blood draw and cognitive testing. A subset of patients from all three groups will return after three years for a follow-up assessment.  

“We anticipate the study will provide information on whether a window exists to halt the progression or even reverse the progression of disease,” says Shah, who is director of the Adolescent Type 2 Diabetes Program at Cincinnati Children’s. “Ideally, this study will position us to test interventions for youth with Type 2 and obesity as an immediate next step.” 

The NIH-funded study is co-led by Mark DiFrancesco, PhD, a neuroimaging researcher at Cincinnati Children’s. To learn more, contact Amy.Shah@cchmc.org.