EDIC Brain Studies Validate Importance of Glucose Management in Type 1 Diabetes

Modern technology can set patients on a different course and avoid brain changes

Innovations in Pediatrics | Fall 2023

The largest longitudinal study to date of type 1 diabetes and brain health has relatively good news for those with the condition. New results from the landmark Epidemiology of Diabetes Interventions and Complications (EDIC) study, published in JAMA Network Open, show that living with type 1 diabetes caused only modest changes in the brain and that these changes likely occurred in patients decades ago – early in patients’ experience with the disease and before the advent of better therapies for maintaining glucose management at target. This suggests that people diagnosed with type 1 diabetes today, especially children, may be able to avoid brain changes entirely with proper management.

Rose Gubitosi-Klug, MD, PhD

Using MRI metrics, the EDIC researchers concluded that having type 1 diabetes accelerated patients’ brain aging by six years.

“People thought that it might be 10 or 20 years, so to see six years is good news,” says study co-author Rose Gubitosi-Klug, MD, PhD, Division Chief of Pediatric Endocrinology at UH Rainbow Babies & Children’s Hospital and William T. Dahms Chair in Pediatric Endocrinology. Dr. Gubitosi-Klug has served as principal investigator in UH Rainbow’s role as the national clinical coordinating center for EDIC for the past 16 years. “Our methods of managing and optimizing the regulation of glucose have come so far that we may be able to rewrite even this modest change we're seeing now and chart a different course.”

Study methods: For the study, the researchers compared EDIC participants with type 1 diabetes to demographically similar adults without diabetes or serious current illnesses, including no prior history of stroke, matching patients and controls by race, ethnicity, age and educational attainment. Each study participant completed a cognitive assessment and an MRI of the brain. In addition, the EDIC research team developed indices for distinguishing Alzheimer’s disease-related changes from other forms of brain aging.

“One of the areas that's very commonly discussed in lay press is Alzheimer's disease as a cause of changes in the brain and poor cognition over time,” Dr. Gubitosi-Klug says. “The question became whether diabetes is accelerating the aging of the body and the brain. Is it like Alzheimer’s? Or is this something different?”

Not Alzheimer’s: Results show diabetes-related brain aging was indeed its own phenomenon. Areas marked as susceptible to Alzheimer’s-related change were similar between EDIC patients and healthy controls, while those marked more generically as brain aging were impacted more significantly in EDIC patients than their healthy counterparts, even though the difference was relatively modest.

“This suggests that, at least within this cohort of participants with an average age of 60 years (age range of 44 – 74 years) and a type 1 diabetes duration of 37 years, there is no greater atrophy in regions typically affected in Alzheimer’s,” Dr. Gubitosi-Klug says.

Potential mechanisms: Results of the current study show no link between diabetes risk factors, such as complications, and brain aging, failing to identify a direct mechanism for the effects of type 1 diabetes on brain health measures. However, previous work from the EDIC research team is pointing to some likely answers. A 32-year analysis of EDIC participants published in Lancet Diabetes and Endocrinology found that exposure to higher HbA1c levels, more episodes of severe hypoglycemia, and elevated systolic blood pressure were associated with greater decrements in psychomotor and mental efficiency. Combined, these three risk factors manifested effects equivalent to an additional 9.4 years of brain aging.

For Dr. Gubitosi-Klug, these results, although sobering, highlight the importance of the new path that people with type 1 diabetes can now take.

“The main risk factors we found for a change in cognition after all these years were a history of too many lows, very severe lows, or a history of too many highs,” she says. “Everything we do now in pediatrics, with automated insulin delivery systems where you have autonomous communication between a pump and a sensor, is trying to keep you right in range. We’re on a new trajectory, we're rewriting everything. Kids may never have to worry about changes to the brain and as they age, they'll age just like everybody else. We’re optimizing. Again, if we can find that target for an individual and get to that target, they’re going to live a happy and healthy and long life.”

For more information about UH Rainbow’s leadership in the landmark EDIC study, please email Peds.Innovations@UHhospitals.org.

Contributing Expert:
Rose Gubitosi-Klug, MD, PhD
Division Chief, Pediatric Endocrinology, Diabetes and Metabolism
UH Rainbow Babies & Children’s Hospital
Division Chief, Pediatric Endocrinology
UH Cleveland Medical Center
William T. Dahms Chair in Pediatric Endocrinology
Professor of Medicine
Case Western Reserve University School of Medicine