In Type 1 Diabetes, Glycemic Control in Adolescence Can Stave Off Neurological Damage

Nelly Mauras, MD

Improved glycemic control could reduce the risk of diabetes-related brain damage among teens and adolescents with type 1 diabetes, according to data from a proof-of-concept pilot study.

Conducted by clinicians from Nemours Children’s Health and Stanford University School of Medicine, results of the study, which assessed the effects of an automated hyped closed-loop system in patients with type 1 diabetes receiving insulin therapy, indicate improved glycemic control was linked to significantly greater improvement in several of the study’s primary outcomes indicative of neurotypical development during adolescence, including cortical surface area, regional gray volumes, and fractional anisotropy.

“These results offer hope that harm to the developing brain from Type 1 diabetes might be reversible with rigorous glucose control,” said the paper’s senior author, and co-principal investigator, pediatric endocrinologist Nelly Mauras, MD, of Nemours Children’s Health Jacksonville and professor of pediatrics at Mayo Clinic College of Medicine, in a statement. “Use of an automated hybrid closed-loop system—an insulin delivery system linked to a continuous glucose monitor—was associated with better blood glucose concentrations, which translated in our study to quantifiable differences in brain structure and cognition.”

With a multitude of studies and research projects outlining the impact of suboptimal glycemic control on neurological health among patients with diabetes, the proof-of-concept pilot study was launched with the intent of exploring whether MRI-derived indices of brain development and function and standardized IQ scores among adolescents with type 1 diabetes could be improved with optimized glycemic control through use of a hybrid closed-loop insulin delivery system. With this in mind, the trial was designed to compare use of a hybrid-closed loop system or standard diabetes care on neurological outcomes among patients aged 14-17 years with a diagnosis of type 1 diabetes before 8 years of age.

With recruitment conducted in 5 academic medical centers in the US, investigators assessed 46 participants for eligibility. Of these, 44 met the inclusion criteria and underwent randomization. Investigators pointed out that 2 of these participants failed to complete baseline assessments and were excluded from final analyses. As part of the study protocol, all patients who underwent randomization underwent cognitive assessment and multimodal brain imaging at baseline and after the conclusion of the 6-month study period.

Primary outcomes of interest for the study included white matter volume, fractional anisotropy, and multiple metrics of gray matter, including total and regional volumes as well as cortical surface area and thickness. Investigators determined the estimated power to detect the predicted treatment effect was 0.83 with two-tailed α=.05.

Upon analysis, results indicated individuals randomized to the hybrid closed-loop group showed significantly greater improvement for several primary outcomes compared to the standard care group including cortical surface area, regional gray volumes, and fractional anisotropy. However, investigators noted there were no significant differences in total gray and white matter volumes or cortical thickness. Further analysis suggested those randomized to the hybrid closed-loop group had greater Perceptual Reasoning Index IQ scores and functional brain activity, which were both included as secondary outcomes, compared to the standard care group. Investigators pointed out no adverse efforts associated with study participation were observed during the study.

“We have known for some time that better control of blood glucose levels in persons with type 1 diabetes can prevent or reduce damage to a number of biological systems. Our new research joins with other studies to highlight that better control of blood glucose levels in children with Type 1 diabetes can potentially reduce injury to the maturing brain and lead to measurable improvements in brain development and function as well,” said lead author and coprincipal investigator, Allan Reiss, MD, the Howard C. Robbins Professor of Psychiatry and Behavioral Sciences and a professor of radiology at Stanford, in the aforementioned statement.

This study, “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,” was published Nature Communications.