A recent study has revealed an intriguing genetic overlap between type 2 diabetes and structural changes in subcortical brain regions.
This discovery sheds light on the molecular mechanisms that may link metabolic disease and cognitive decline.
The research team was able to identify a complex network of genetic factors shared between the disease and brain structure, with the analysis revealing 129 common genetic locations that affect both aspects.
One of the most prominent of these sites is the famous APOE gene associated with Alzheimer's disease, which has been shown to have a strong association with both diabetes risk and the size of the nucleus accumbens in the brain.
The TCF7L2 gene, which is responsible for risk of type 2 diabetes, was also associated with amygdala volume, and the Hp 1-1 gene with hippocampal volume. Furthermore, polygenic risk scores for glycated hemoglobin (HbA1c) were associated with gray matter volume, and genetic risk for several hippocampal morphological features was also associated with type 2 diabetes.
Another notable finding of the study is that specific genes, such as TUFM and JAZF1, play a combined role in diabetes risk and the size of specific brain regions, opening the door to developing more accurate diagnostic and therapeutic approaches.
The study, which analyzed genetic data from thousands of individuals, found that these shared genes are concentrated in regions responsible for energy metabolism and nervous system development. The researchers also noted that these genes are most active during the fetal stage, suggesting that the effects of diabetes on the brain may begin very early in development.
An important finding in the study is that some diabetes-related genes specifically affect the size of the hippocampus—the brain region responsible for forming memories—which may explain why diabetics have a twice-increased risk of dementia compared to those without the condition.
To understand the underlying mechanisms, the research team analyzed gene expression in various tissues and discovered that genes shared by diabetes and brain structure are concentrated in the pancreas, liver, and heart, and are involved in essential biological processes such as energy metabolism and nervous system development. A chronological analysis also showed that these genes are most active during the fetal stage, suggesting that the genetic basis for the diabetes-brain relationship may begin to form very early, even before birth.
"These findings open the door to developing new diagnostic tools that can predict the risk of cognitive decline in diabetic patients based on genetic makeup," noted Professor Liang Zhou, a geneticist at Peking University and lead author of the study.
He added, "A deeper understanding of these mechanisms could lead to the development of preventive therapies that target these shared genetic pathways."
