Yale Researchers Identify New Strategy to Protect the Brain in Type 1 Diabetes

From medicine.yale.edu

By Jordan Shaked 

Insulin is a cornerstone of treatment for patients with type 1 diabetes, essential for lowering blood glucose levels. However, if insulin doses are not appropriately matched to the body’s needs, glucose levels can fall too low, resulting in hypoglycaemia, a common and potentially dangerous complication of treatment. Hypoglycaemia can impair thinking and cause symptoms ranging from dizziness and confusion to loss of consciousness.

New research from Yale, published in Diabetes, identifies a potential new strategy for protecting the brain from the cognitive effects of hypoglycaemia in people with type 1 diabetes.

The brain relies heavily on glucose as its primary source of fuel, explains Raimund Herzog, MD, MHS, associate professor of medicine (endocrinology and metabolism) and senior author of the study. “When glucose falls below a certain threshold, the neurons in the brain stop working properly,” he says.

The goal of all of our studies is to help people achieve better glucose control without the associated hypoglycemia. We’re dedicated to finding a safe way for people to maintain that balance.

Raimund Herzog, MD, MHS

Associate Professor of Medicine (Endocrinology)

“The easiest answer would be to take less insulin, but we know that higher glucose over the long term causes complications,” Herzog adds. “The challenge is balancing good glucose control with the risk of hypoglycaemia.”

Herzog and his team investigated whether ketones, molecules the body can use as an alternative source of energy, could protect the brain from the cognitive effects of low blood sugar. Specifically, the researchers focused on a ketone called beta-hydroxybutyrate.

“When patients with type 1 diabetes hear ketones, some of their alarm bells go off,” says Herzog. Ketones are often a warning sign for patients with type 1 diabetes because they can indicate diabetic ketoacidosis, a potentially life-threatening complication of severe insulin deficiency. When the body lacks insulin, as is the case in untreated type 1 diabetes, it rapidly breaks down fat and produces ketones, which can accumulate to dangerous levels and make the blood acidic, explains Herzog.

However, Herzog and his team found benefits of ketones when they explored them in a different metabolic setting. Participants in the study continued to receive treatment with insulin, while dietary supplementation was used to modestly increase ketone levels as an additional source of fuel for the brain when glucose was low.

The study found that participants who received dietary supplementation to increase their ketone levels performed better on tests of working memory during hypoglycaemia than those who received a standard diet, suggesting that increasing ketone availability may help preserve cognitive function when blood glucose is low.

The researchers believe this effect may be related to how the brain adapts to repeated episodes of low blood sugar. Previous studies have shown that recurrent hypoglycaemia increases the brain’s ability to transport certain alternative fuels, including ketones, across the blood-brain barrier. The findings suggest that dietary supplementation could take advantage of this adaptation, providing the brain with an alternative source of fuel when glucose is scarce.

Herzog hopes these findings could eventually offer an additional layer of protection for patients who experience recurrent hypoglycaemia, particularly those without access to technologies that continuously monitor glucose levels.

“Continuous glucose sensors and modern insulin pumps have made hypoglycaemia much less frequent, but not everybody has access to that technology,” says Herzog. “Globally, many patients still rely on insulin injections and finger sticks to measure their glucose, so hypoglycaemia remains a significant risk.”

Herzog also emphasized the collaborative nature of the research, which brought together expertise in endocrinology, neuroscience, and brain imaging through longstanding partnerships with Yale’s Magnetic Resonance Research Center. He believes this multidisciplinary approach will continue to drive advances in diabetes research.

“The goal of all of our studies is to help people achieve better glucose control without the associated hypoglycaemia,” says Herzog. “We’re dedicated to finding a safe way for people to maintain that balance.”

Endocrinology and Metabolism, one of 10 sections in the Yale Department of Internal Medicine, improves the health of individuals with endocrine and metabolic diseases by advancing scientific knowledge, applying new information to patient care, and training the next generation of physicians and scientists to become leaders in the field. To learn more, visit Endocrinology and Metabolism.

https://medicine.yale.edu/news-article/protecting-brain-type-1-diabetes/