Summary: Improved glucose control can reverse or reduce brain changes and support cognitive function in young people with Type 1 diabetes.
Source: Nemours
Tight blood glucose control in teenagers with Type 1 diabetes appears to lessen the condition’s harmful effects on the developing brain, according to a study published today in Nature Communications. The trial suggests that better glucose management can restore brain structure and cognitive performance toward levels seen in peers without diabetes.
This proof-of-concept pilot study—the most detailed to date examining neurodevelopmental outcomes in young people with Type 1 diabetes—was led jointly by Nemours Children’s Health in Jacksonville and Stanford University School of Medicine.
“These findings raise the possibility that brain changes associated with early-onset Type 1 diabetes are at least partly reversible with sustained, rigorous glucose control,” said senior author and co-principal investigator Nelly Mauras, MD, pediatric endocrinologist at Nemours Children’s Health Jacksonville and professor of pediatrics at Mayo Clinic College of Medicine.
The intervention tested was an automated hybrid closed-loop insulin delivery system—an insulin pump paired with a continuous glucose monitor (CGM) that adjusts insulin delivery automatically. In the study, use of this closed-loop system led to improved blood glucose metrics, which in turn were associated with measurable improvements in brain imaging and cognitive tests.
The trial was organized through the five-center Diabetes Research in Children Network (DirecNet), funded by the National Institutes of Health (NIH). DirecNet has tracked groups of children with and without diabetes for nearly eight years. Previous DirecNet findings linked higher blood glucose levels in childhood to structural and functional brain differences, and to lower-than-expected scores on cognitive assessments.
For the current study, investigators enrolled 42 adolescents aged 14 to 17 who were diagnosed with Type 1 diabetes before age eight and were using insulin therapy. Participants were randomized to either a hybrid closed-loop insulin delivery system or to standard diabetes care. Cognitive testing and multi-modal brain imaging were performed for all participants before and after the six-month study period.
Hybrid closed-loop systems combine a CGM sensor—measuring glucose every few minutes—with an insulin pump that automatically adjusts dosing based on the most recent glucose readings. When used consistently, these systems increase the percentage of time blood glucose stays within a target range and help reduce dangerous swings, particularly overnight when hypoglycemia can be hard to detect and treat.
Adolescents randomized to the hybrid closed-loop group demonstrated significantly greater improvement on several MRI-derived metrics of normal adolescent brain development compared with those receiving standard care. These brain metrics included measures such as cortical surface area, regional gray matter volumes, and white matter integrity (fractional anisotropy). In other words, imaging results from the closed-loop group moved closer to patterns seen in youth without diabetes.
The closed-loop group also showed higher cognitive performance on standardized testing—specifically improvements in perceptual reasoning IQ scores—and greater functional brain activity patterns consistent with neurotypical development. No adverse events related to participation in the study were reported.
“Prior research has established that improved glycemic control reduces risk for long-term complications in organs such as the kidneys, eyes, nerves, and blood vessels,” said lead author and co-principal investigator Allan Reiss, MD, Howard C. Robbins Professor of Psychiatry and Behavioral Sciences and professor of radiology at Stanford. “Our study adds to that evidence by showing measurable brain and cognitive benefits from better glucose control in adolescents with early-onset Type 1 diabetes.”
Type 1 diabetes is an autoimmune condition in which the body attacks insulin-producing beta cells in the pancreas. The disorder affects an estimated 244,000 children and adolescents in the United States and can lead to acute complications as well as chronic health problems over time.
These results build on prior work demonstrating that strict blood sugar management reduces rates of diabetes-related complications such as blindness, kidney failure, and amputations. Importantly, this trial points to the potential for targeted glucose management technologies to protect and possibly restore brain development during adolescence.
Funding: This research was supported by grants from the NIH Eunice Kennedy Shriver National Institute of Child Health and Human Development (Grant 5R01-HD-078463) and by a grant from the Juvenile Diabetes Research Foundation. Additional investigators from Nemours who contributed include Larry Fox, MD; Allison Cato, PhD; Keisha Bird, DNP; and Kim Englert, RN. Collaborating investigators were Bruce Buckingham, MD (Stanford University); Neil White, MD (Washington University in St. Louis); Eva Tsalikian, MD (University of Iowa); Stuart Weinzimer, MD (Yale University); and John Lum (Jaeb Center for Health Research).
About this diabetes research news
Author: Heather Jameson
Source: Nemours
Contact: Heather Jameson – Nemours
Image: The image is in the public domain
Original Research: Open access, “A Pilot randomized trial to examine effects of a hybrid closed-loop insulin delivery system on neurodevelopmental and cognitive outcomes in adolescents with type 1 diabetes” by Nelly Mauras et al. Nature Communications
Abstract
A Pilot randomized trial to examine effects of a hybrid closed-loop insulin delivery system on neurodevelopmental and cognitive outcomes in adolescents with type 1 diabetes
Type 1 diabetes (T1D) has been associated with lower scores on cognitive tests and with structural and functional brain differences in children. This pilot randomized trial (ClinicalTrials.gov Identifier NCT03428932) evaluated whether improved glycemic control delivered by a hybrid closed-loop insulin system could produce measurable improvements in MRI indices of brain development and in standardized IQ scores among adolescents with early-onset T1D.
Eligible participants were 14 to 17 years old with a diagnosis of T1D before age eight. After screening, consent, and enrollment, 44 participants were randomized; 42 completed baseline and follow-up assessments and were included in the final analyses. Study procedures, including cognitive scoring and imaging processing, were performed with the investigators blinded to treatment assignment.
Primary outcomes focused on gray matter measures (total and regional volumes, cortical surface area, and thickness), white matter volume, and fractional anisotropy. The trial was powered to detect expected treatment effects with an estimated power of 0.83 at α = 0.05.
Adolescents using the hybrid closed-loop system showed greater improvements on several primary MRI outcomes that reflect typical adolescent neurodevelopment—such as cortical surface area, select regional gray matter volumes, and fractional anisotropy—compared with the standard care group. While total gray and white matter volumes and cortical thickness did not differ significantly between groups, the closed-loop group also achieved higher perceptual reasoning IQ scores and displayed functional brain activity more consistent with neurotypical development. No study-related adverse effects were observed.
These findings support the idea that brain alterations linked to childhood-onset T1D might be preventable or even reversible with rigorous glucose control. Further long-term research is needed to confirm and extend these results.