Children with Type 1 diabetes at risk for brain dysfunction, NIH study finds

February 11, 2021

New evidence shows Type 1 diabetes affects children's brains. (AP Photo/Bikas Das)

Brain volume and IQ are lower in children with Type 1 diabetes compared to children without, a new study published by the American Diabetes Association reports.

The longitudinal, observational study published Wednesday in Diabetes Care offers new insights into growing evidence that Type 1 diabetes, or T1D, can affect various organs by investigating the extent to which glycemic exposure may have adverse effects on the developing brain in young children with early-onset T1D, providing the opportunity to assess the effects of the chronic condition over time.

The study compared brain scans of children between 6 and 12 years old who have Type 1 diabetes with those of age-matched, non-diabetic children, finding that the former are at risk for cognitive or brain dysfunction. 

Lead researchers Nelly Mauras, a clinical research scientist at Nemours Children’s Health System, and Allan Reiss, a professor at the Stanford University School of Medicine, explained how their team embarked on the study “to determine the extent to which glycemic exposure adversely impacts the developing brain in young children with early-onset T1D, and whether these differences improve, are stable or increase over time." 

“With the growing epidemic of diabetes and the ever-increasing number of people living to older age, diabetes-related cognitive dysfunction could have challenging future public health implications,” they said via email. 

The Diabetes Research in Children Network, or DirecNet, a multicenter consortium of the National Institutes of Health, formed the research team. It performed structural brain magnetic resonance imaging studies and cognitive assessments at four points in time over nearly eight years in 144 children with Type 1 diabetes and in 72 non-diabetic children as controls. Continuous glucose monitoring with advanced technologies was done on a quarterly basis, as well. 

The brain volume differences that the research team detected at baseline persisted or increased over time. Brain volumes and cognitive scores are negatively correlated with total cumulative exposure to high blood glucose, or hyperglycemia, the study concluded. 

Group differences from age 6 to 12 years old were present throughout the study across all three major structural brain measures — total, gray and white matter volumes — indicating that early effects of diabetes are detectable and significant, according to the study. Between-group divergence increased over time. Compared with non-diabetics, total brain volume, gray- and white-matter volumes, overall IQ and verbal IQ were lower in the diabetic group at 6, 8, 10 and 12 years.

The most significant influence on brain and cognitive development in the U.S. diabetic population was hyperglycemia. 

“Although cognitive differences between groups remained mild, these data suggest that continued exposure to chronic hyperglycemia may be detrimental to the developing brain,” Mauras and Reiss noted.

The implications of the findings range from treatment to emerging diabetes management technologies. The data, for example, call for lowering glycemic targets in children and revisiting the acceptance of higher-than-normal blood sugars as adequate metabolic control in very young children.

Poor glycemic control may increase the risk for changes in brain structure that can be followed by changes in brain function over time. 

“Understanding these early effects is a necessary step towards understanding effects in later adulthood and helping develop strategies for reducing the risk of brain-associated complications in T1D,”  Mauras and Reiss said. “This is a potentially important finding that suggests cumulative effects on the developing central nervous system.”

The findings also raised new questions for the authors. 

“Although the differences in IQ were mild, they were significant and persistent over time,” Mauras and Reiss said. “Hence it is important to more fully investigate if these changes affect long-term educational and vocational outcomes." 

A second follow-up study will relate to technology. 

Advanced technologies like continuous glucose monitoring systems are growing in popularity. Mauras and Reiss noted that technologies such as artificial pancreas closed-loop systems have the capacity to greatly improve glycemic control. 

“Whether the observed changes are reversible with scrupulous control of glucose using these technologies in these young children is our next line of study,” they said.

The study, “Impact of Type 1 Diabetes in the Developing Brain in Children: A Longitudinal Study,” was published Feb. 10 in Diabetes Care. The study authors are Nelly Mauras, Bruce Buckingham, Neil H. White, Eva Tsalikian, Stuart A. Weinzimer, Booil Jo, Allison Cato, Larry A. Fox, Tandy Aye, Ana Maria Arbelaez, Tamara Hershey, Michael Tansey, William Tamborlane, Lara C. Foland-Ross, Hanyang Shen, Kimberly Englert, Paul Mazaika, Matthew Marzelli and Allan L. Reiss, the Diabetes Research in Children Network. 

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