Genetic risk for type 1 diabetes extends to brain cells, study finds

Type 1 diabetes is an autoimmune condition in which the body attacks its own insulin-producing cells in the pancreas. Some individuals with type 1 diabetes experience cognitive differences, sometimes described as “brain fog,” as well as memory lapses, which have often been attributed to fluctuations in blood sugar levels.

Now, a study published in Nature Communications suggests that there may be a much closer link between these symptoms and the drivers of type 1 diabetes. Researchers found that the genetic variation associated with type 1 diabetes risk is active not only in immune and pancreatic cells, but also in certain brain cells.

“There are shared biological pathways between type 1 diabetes and brain function,” says senior author David A. Alagpulinsa, Ph.D., assistant professor of comparative medicine at Yale School of Medicine. “The function in the brain cells may help regulate immune thresholds.”

The pancreas and brain share genetic signals

Scientists have observed that people with type 1 diabetes experience cognitive difficulties more often than the general population, including reduced working memory, slower cognitive processing, and challenges with planning and decision making. Research has shown that children with the condition often fall behind their peers academically.

Both type 1 diabetes and cognitive traits have strong genetic bases. Alagpulinsa was interested in whether their genetic underpinnings overlapped.

“Traditionally, researchers have studied the genetic basis of type 1 diabetes by focusing on immune cells and the pancreatic beta cells that those immune cells attack,” Alagpulinsa says. “We took a different approach. We asked whether the genetic signals that affect type 1 diabetes are also active in brain cells.”

Using large population datasets including the UK Biobank, the researchers compared approximately 20,000 individuals with type 1 diabetes with 500,000 people without the condition and identified genetic variants associated with type 1 diabetes risk. They then mapped these variants across brain cell types to determine where these genetic signals were active, or “switched on.”

Their findings pointed to microglia—the brain’s resident immune cells—as a key site of activity. This genetic pattern was consistent across developmental stages, from fetal life to adulthood.

“The most important finding in our work is the fact that the genetic risk for type 1 diabetes is also active in brain cells,” Alagpulinsa says. “This is one of the first studies tying microglia to type 1 diabetes genetic risk.”

The researchers used a statistical approach called Mendelian randomization, which uses genetic variants from large population studies to test whether one trait is likely to influence another. The team used genetic variants associated with cognitive traits, such as intelligence (reasoning and problem-solving ability), executive function (skills involved in planning, attention, and cognitive control), and educational attainment (years of schooling).

The researchers found evidence that genetic liability to certain cognitive traits was associated with different levels of type 1 diabetes risk.

“Correlation is not causation,” Alagpulinsa says. “These findings do not mean that type 1 diabetes causes cognitive differences, but rather that both may reflect shared underlying biological pathways.”

A systemic view of type 1 diabetes

These findings support a broader, systemic view of type 1 diabetes rather than one confined to the pancreas or immune cells, says Alagpulinsa.

“Neuroimmune interactions play a very important role in type 1 diabetes,” he says.

The cognitive differences observed in some patients may not be solely explained by blood sugar fluctuations, but instead part of the disease’s underlying biology, the researchers say. While the study maps genetic connections, it also highlights the roles of environment and behavior.

“Genetic variants are like seeds,” Alagpulinsa says. “But you need soil for them to grow. The soil is the environment, your lifestyle.” While individuals may inherit genetic risk, factors like education, health habits, and environment can still meaningfully shape outcomes, he says.

“Our hope is to see researchers become interested in understanding how neuroimmune communication influences type 1 diabetes,” he says.