Children with early-onset type 1 diabetes and poor glycaemic control have slower growth of areas in the brain associated with mild cognitive deficits compared to children without diabetes, according to the study presented at the American Diabetes Association annual meeting.

The study, entitled Type 1 Diabetes and the Developing Brain—A Longitudinal Study of Brain Growth by the Diabetes Research in Children Network, found that children with early-onset type 1 diabetes have mild but significant differences in total brain and regional gray and white matter growth compared to children without diabetes.

Over time, type 1 diabetes can cause complications in multiple organ systems, including the retina, cardiovascular, kidneys and peripheral nervous system. Research also suggests the glycaemic fluctuations of hypoglycemia and hyperglycaemia associated with type 1 diabetes can negatively affect brain development. Despite improved glycaemic control due to emerging technologies and newer insulins, growing evidence demonstrates that individuals with type 1 diabetes are at risk for cognitive dysfunction.

As part of a multi-site study of the Diabetes Research in Children Network (DirecNet), researchers aimed to determine the extent to which glycaemic exposure adversely impacts the developing brain in children with early-onset type 1 diabetes. The study enrolled 138 children with type 1 diabetes with a median age of seven years. The participants had a disease duration on average of 2.4 years at the beginning of the study. Researchers conducted structural magnetic resonance imaging (MRI) studies on the participants’ brains and compared the results to those of a control group consisting of 66 age-matched children (average age of seven years) who did not have diabetes.

The MRIs were performed at three-time points (baseline, 18 months and approximately 2.9 years after the second visit), and white matter (WM) and gray matter (GM) volumes in various brain regions-of-interest were determined. Total cumulative hyperglycemic exposure was determined (lifetime HbA1c) from the time of diagnosis in the type 1 diabetes group.

Researchers found that the group with type 1 diabetes had slower growth of total cortical and subcortical GM and WM than the control group at all time points. A set of metabolically active brain regions that form the “default mode network,” which is associated with other brain disorders, showed less growth in the type 1 diabetes group compared to the control group. These regions of slower growth were associated with higher lifetime HbA1c values.

“With an ever-increasing number of people living to old age, diabetes-related cognitive dysfunction could have challenging future public health implications,” said  Nelly Mauras, MD, co-principal investigator, chief of the division of endocrinology, diabetes & metabolism at the Nemours Children’s Health System in Jacksonville, Florida, and professor of pediatrics at the Mayo College of Medicine.

“Although there have been advances in new insulin and technologies that can significantly improve care, children with diabetes are still exposed to significant hyperglycaemia and hypoglycaemia, which will continue to confer risk to the brain. The young children with type 1 diabetes in our study had significant differences in brain structure and growth compared to the control group, and poor glycaemic control may increase risk for changes in brain structure over time. However, the variability in outcomes remains unexplained.

"Therefore, understanding these early effects is a necessary step towards understanding effects later in adulthood and in developing strategies for reducing risk of brain-associated complications in type 1 diabetes. Whether scrupulous maintenance of near-normoglycaemia with advanced diabetes technologies will have a positive impact on these findings is being actively investigated.”