Hyperglycemia Tied To Long-Term Brain Changes In Children With Type 1 Diabetes

In children with early-onset type 1 diabetes, changes in brain volumes and cognitive scores persist over time and are associated with hyperglycemia, researchers say.

"Brain volumes and cognitive scores negatively correlated with metrics of life-long exposure to high blood glucose in the children with diabetes, suggesting that poor glycemic control may increase risk for changes in brain structure, possibly followed by changes in function over time," Dr. Nelly Mauras of the Nemours Children's Health System in Jacksonville and Dr. Allan Reiss of Stanford University School of Medicine told Reuters Health in a joint email.

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"This is a potentially important finding," they said. "From a practical standpoint, these data support the lowering of glycemic targets in children and challenge the acceptance of higher-than-normal blood sugars as adequate metabolic control in very young children."

"Although the changes observed in IQ were modest, they were significant, yet we do not know if they will impact school performance or vocational learning over time at an individual level," they noted. "This requires further study."

The longitudinal, observational study published in Diabetes Care involved 144 children with type 1 diabetes and 72 age-matched non-diabetic controls. The mean age at baseline was seven; 46% were female and 81%, White. The average disease duration was 2.4 years, and participants were followed for a mean of 6.4 years.

Participants underwent structural magnetic resonance imaging up and cognitive testing up to four times during follow-up; HbA1c and continuous glucose monitoring were done quarterly. Brain volumes and age-appropriate cognitive metrics were compared between groups at six, eight, 10, and 12 years. Results were correlated with glycemia.

Total brain, gray, and white matter volumes and full-scale and verbal intelligence quotients (IQs) were lower in the diabetes group at each assessment, with estimated group differences in full-scale IQ of -4.15, -3.81, -3.46, -3.11, respectively, and total brain volume differences of -15,410, -21,159, -25,548, and -28,577 mm(3) x 10(3).

Further analyses showed that differences at baseline persisted or increased over time, and brain volumes and cognitive scores negatively correlated with a lifelong HbA1c index and higher sensor glucose in diabetes.

Drs. Mauras and Reiss said, "More recently, we have been using closed-loop artificial pancreas technologies in a group of adolescents with T1D...to see if the observed changes are reversible with more scrupulous control of blood glucose. The results of these studies are being analyzed."

"The overall take home message," they said, "is that T1D can impact the developing brain of children and that the driving factor is hyperglycemia, a factor that we can influence and better control."

Dr. Daniel DeSalvo, Type 1 Diabetes Clinic Lead and Director of Strategic Collaboration for Texas Children's Hospital's Diabetes and Endocrine Care Center, commented by email that the findings "should serve as a call to action for clinicians in supporting patients to achieve ideal glycemic control."

"In the modern era of diabetes management," he said, "we have cutting-edge therapies including automated insulin delivery systems to optimize glycemic control and reduce exposure to hyperglycemia, which should have a positive impact on the developing brain in youth with diabetes."

"While these data are concerning, it should serve as inspiration to overcome therapeutic inertia in pediatric diabetes," he told Reuters Health.

"My inspiration as a pediatric endocrinologist comes from the remarkable patients and families in my clinic who I have the privilege of shepherding on their diabetes journey," said Dr. DeSalvo, who was not involved in the study. "We must be careful to present this information about the concern for hyperglycemia exposure adversely affecting the developing brain in a supportive and compassionate manner, whereby families can feel empowered."

—Marilynn Larkin

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