A new study published in Neurobiology of Aging suggests that even in people without diabetes, higher blood sugar levels may be associated with reduced brain function in networks involved in autonomic regulation. Conducted by researchers at Baycrest Health Sciences and the University of Toronto, the study found that elevated levels of glycated hemoglobin — a measure of long-term blood sugar — were linked to both lower heart rate variability and weaker communication between brain regions that regulate the body’s automatic responses. These associations were stronger in older adults and, for some measures, differed between men and women.

The study aimed to clarify whether relationships observed in people with diabetes — such as those between blood sugar, heart health, and brain function — also appear in healthy adults. Previous research has shown that individuals with diabetes often experience changes in the way their brains function, particularly in areas involved in regulating the autonomic nervous system, which controls heart rate, blood pressure, and other vital functions.

However, it has remained uncertain whether these patterns extend to people who do not have diabetes but still exhibit variability in their blood sugar levels. The researchers also wanted to examine how these relationships might differ by age and sex, factors that influence both metabolic and brain function.

To investigate these questions, the researchers used data from the LEMON dataset — an open-access database focused on mind-body-emotion interactions. From the initial pool of 227 healthy adults, the researchers excluded those with missing or poor-quality data, resulting in a final sample of 146 participants. This group included 114 younger adults (average age 25) and 32 older adults (average age 68), with both sexes represented.

Participants underwent several procedures. Blood was drawn to measure glycated hemoglobin (HbA1c), which reflects average blood glucose levels over the past three months. Functional magnetic resonance imaging (fMRI) was used to assess brain activity while participants rested, and electrocardiogram (ECG) data were collected simultaneously to assess heart rate variability. Heart rate variability refers to the natural variation in time between heartbeats and is considered a marker of autonomic nervous system activity. The researchers focused on two specific indicators of heart rate variability: RMSSD and high-frequency HRV, both of which reflect parasympathetic nervous system function.

For the brain data, researchers examined resting-state functional connectivity — a measure of how well different parts of the brain work together during rest. They focused on two networks. The first was a subset of the central autonomic network (referred to as S-CAN), which includes the insula and amygdala and is important for regulating the body’s internal state. The second was the salience network, which includes overlapping regions but is more involved in processing emotionally significant information.

The findings revealed several key patterns. Across the whole sample, higher HbA1c levels were associated with lower heart rate variability, suggesting reduced parasympathetic activity. This relationship was stronger in older adults but did not differ by sex. Similarly, higher HbA1c levels were associated with weaker connectivity in the S-CAN, but not in the salience network. Once again, this association was more pronounced in older adults, particularly in the right hemisphere of the brain. These results suggest that even in the absence of diabetes, higher blood sugar levels may relate to less efficient brain functioning in areas tied to autonomic regulation — especially as people age.

The study also found that lower heart rate variability was associated with weaker connectivity within the S-CAN. Interestingly, these associations were stronger in women than in men, and were more prominent in the left hemisphere. This pattern suggests that while age may intensify the link between blood sugar and brain function, sex may influence how autonomic nervous system activity relates to brain connectivity. Notably, women in the study did not have significantly different blood sugar or heart rate variability levels compared to men, but the relationship between heart variability and brain function was stronger.

The researchers interpret these findings as evidence that healthy people with slightly elevated blood sugar — including those in the prediabetic range — may already be experiencing changes in how their brain networks function. They emphasize that these effects appear to be subtle but detectable, and they highlight the importance of considering age and sex when studying these relationships.

While the study provides new insights, it also has limitations. The sample included fewer older adults than younger ones, and people in middle age were not represented, making it difficult to draw conclusions across the full adult lifespan. The dataset also lacked information on race, ethnicity, and medication use, which could influence both metabolic and neurological health. Additionally, the imaging methods did not include coverage of the brainstem, a region that plays a key role in autonomic regulation and is part of the full central autonomic network.

The researchers also note that posture differences during data collection — with participants lying down for MRI scans and sitting for heart recordings — may have introduced variability, though this would likely affect all participants in the same way. Finally, because the study was cross-sectional, it cannot establish whether high blood sugar causes changes in brain function or vice versa.

Despite these limitations, the study broadens our understanding of how metabolic health is related to brain activity, even in individuals without a diabetes diagnosis. It suggests that subtle variations in blood sugar may be linked to brain function in networks responsible for regulating bodily systems — and that these links vary with age and sex. Future research could explore whether improving blood sugar control in healthy individuals leads to measurable changes in brain function and whether these effects differ across demographic groups.

The study, “The associations among glycemic control, heart variability, and autonomic brain function in healthy individuals: Age- and sex-related differences,” was authored by Jeffrey X. Yu, Ahmad Hussein, Linda Mah, and J. Jean Chen.