Among children with early-onset type 1 diabetes (T1D), detectible changes in brain volume and cognitive scores persist over time and are associated with metrics of hyperglycemia, according to research published in Diabetes Care.
Researchers conducted a longitudinal, observational study (Clinicaltrials.gov Identifier: NCT02351466) to examine whether previously identified brain and cognitive differences in children with T1D persist, worsen, or improve through puberty, as well as if – and how – these differences are associated with hyperglycemia.
Investigators recruited a cohort of 144 children with T1D and 72 age-matched control participants (mean age, 7±1.8 years; girls, 47%) for the initial assessment.
Participants underwent unsedated brain magnetic resonance imaging, neurocognitive testing, and glycemic assessments up to 4 times over a period of 6.4±0.4 years (range, 5.3-7.8). All but 2 control group participants returned for the first follow-up at 18 months; 74% returned for the third assessment (T1D group, n=107; control group, n=50), and the researchers recruited 57 new participants as replacement. From that group, 95% of those participants returned for a fourth assessment 2 years later.
Evaluations of full-scale IQ, performance IQ, and verbal IQ demonstrated significantly lower scores in the group with T1D compared with the control group; however, widening or narrowing of these between-group differences between ages 6 and 12 years was not significant for any of the 3 neurocognitive measures. Estimates of between-group changes during those years was 1.04, 2.02, and -0.21 for each measure, respectively, and mean blood glucose was comparable at timepoints before the cognitive studies.
Total, gray, and white matter volumes were not significantly different at baseline; over time, group differences in brain structures were apparent, and volume was lower in children with T1D. These differences became more pronounced as children got older, and investigators noted a significant widening of between-group differences from ages 6 to 12 years across all structural measures (total brain volume, -13,167 mm3 × 103; gray matter, -7519 mm3 × 103; white matter, -5833 mm3 × 103). Mean blood glucose was comparable before the magnetic resonance imaging studies.
Investigators found several significant positive correlations between total, grey, and white matter volumes and cognitive measures (full-scale IQ, performance IQ, and verbal IQ) throughout the entire course of the longitudinal study. Correlations remained stable over the mean 6.4 years of follow-up.
Consistent hyperglycemia was also present (>180 mg/dL) roughly 50% of the time at all 4 timepoints, indicative of persistent chronic exposure to hyperglycemia. Lifelong hyperglycemia index (glycated hemoglobin area under the curve >6%) was also consistently high throughout the study.
Study limitations included the need to replace 26% of the participants at the time of the third observation and a lack of subanalysis of the results on the basis of diabetic ketoacidosis or severe hypoglycemia episodes throughout the course of the study.
“We report here the longest longitudinal study of brain structure and cognition using modern diabetes technology,” the researchers concluded. “These data support the lowering of glycemic targets in children [while the] acceptance of higher-than-normal blood sugars as adequate metabolic control in very young children needs to be revisited.”
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Mauras N, Buckingham B, White NH, et al; Diabetes Research in Children Network (DirecNet). Impact of type 1 diabetes in the developing brain in children: A longitudinal study. Diabetes Care. 2021;44(4):983-992. doi:10.2337/figshare.13549097.