Diabetes and Children’s Brain Development

A recent longitudinal study examines diabetes type 1 and brain cognitive differences in children. 

Type 1 diabetes is one of the most prevalent and chronic endocrine diseases, afflicting an estimated 1.2 million American children and adults. Although technological improvements have enhanced diabetes control, children with this disease continue to endure poor glycemic control. Whether instability in type 1 diabetes has adverse effects on the neurons’ development has attracted endocrinologists and neuroscientists. Children with early-onset type 1 diabetes, generally described as onset before ages 4–7 years, have been the topic of particular concern, with more significant cognitive impairment and decreased academic achievement recognized in these children relative to those with a later onset. Behavioral studies concentrated on identifying mental changes experienced by individuals with type 1 diabetes have reported moderate impairments in executive functioning, including working memory. Recognizing these alterations’ mechanisms is essential given the high cognitive load required for optimal adherence to a complex therapy regimen, and findings indicating increased executive function may correlate with more reliable disease management.

A recently published longitudinal study examined diabetes type one and brain cognitive differences in children. The institutional review boards approved this study at each of the five participating DirecNet research centers and by the National Institutes of Health (NIH)-designated Data Safety Monitoring Board, including Nemours Children’s Health System Jacksonville, Stanford University, University of Iowa, Washington University in St. Louis, and Yale University. Parents or authorized supervisors granted written informed consent, and participants presented assent according to local guidelines.

Investigators selected one hundred forty-four children with type one diabetes and insulin treatment between 4 and 9 years of age. Inclusions for the investigation were stability to insulin therapy, not prematurity, without other chronic illnesses, seizures, psychiatric, or any development delay diagnosis. Researchers also recruited 72 healthy, age-matched control individuals without diabetes and with comparable inclusion and exclusion criteria. Children participating in the investigation had clinical and glycemic assessments, structural brain magnetic resonance imaging, and neurocognitive testing at baseline. At the same time, they obtained continuous monitoring of glucose quarterly in the diabetes group. During the eight-year study period, up to four magnetic resonance imaging exams measuring the volumes of white and gray matter in various brain regions were performed for all participants. In the type 1 diabetes group, the research team assessed total cumulative hyperglycemic exposure since diagnosis. Also, they had a complete physical examination and pubertal assessment. Some of the children were recruited whenever possible. They examined a third time for an average of 2.9 years from the last evaluation and two years later for up to four separate assessments. Researchers analyzed free-surfer-derived brain volumes and cognitive metrics evaluated longitudinally between groups using mixed-effects models at 6, 8, 10, and 12 years.

Researchers noted that total brain, white and gray matter measures, and full-scale and verbal intelligence quotients (I.Q.s) were lower in children with diabetes at 6, 8, 10, and 12 years at the end of the investigation. They perceived differences in full-scale IQs of -4.15, -3.81, 23.46, -3.11, respectively, for a P of < 0.05. Also, children demonstrated total brain volume discrepancies of -15,410, -21,159. -25,548, and -,28,577 mm3 x 103 for a P of < 0.05. Inconsistencies at baseline endured or extended over time, and the brain measurements and cognitive scores were negatively associated with a life-long hemoglobin A1c index and higher sensor glucose in diabetes. Researchers observed notable variations in full-scale intelligence quotient and verbal intelligence quotient and lesser total, gray, and white matter volumes in the diabetes group using a mixed-effects model longitudinal interpretation. These differences persisted and, in the case of structural brain measures, increased over time.

Future research should examine whether better diabetes control could reverse the observed brain changes. Such studies could also follow people with type 1 diabetes into early adulthood to see whether brain and cognitive problems affect long-term education and vocational outcomes. 

Practice Pearls: 

• Children with diabetes have the risk of developing learning and behavioral problems correlated with the disease. 
• The brain is a target of diabetes complexities in young children.
• Future studies should assess type 1 diabetes into early adulthood to examine long-term education and vocational outcomes. 

Foland-Ross, Lara C., et al. “Brain Function Differences in Children With Type 1 Diabetes: A Functional MRI Study of Working Memory.” Diabetes 69.8 (2020):

Mauras, N., Buckingham, B., White, N. H., Tsalikian, E., Weinzimer, S. A., Jo, B., . . . Reiss, A. L. (2021). Impact of type 1 diabetes in the developing brain in children: A longitudinal study. Diabetes Care, 44(2), Dc202125. doi:10.2337/dc20-2125

Marianis Barreto Quintana, PharmD. Candidate, LECOM School of Pharmacy