The study found that higher blood glucose (HbA1c) levels were associated with lower autonomic nervous system activity (measured by heart rate variability, HRV) and lower functional connectivity in brain networks related to autonomic control (S-CAN). These associations were more pronounced in older adults (for HbA1c and connectivity) and in women (for HRV and connectivity).
Glycemic control refers to the body’s ability to maintain blood glucose levels within a healthy range. It plays a crucial role in the proper functioning of the cardiovascular system, psychological health, and the brain.
One way to measure glycemic control over the long term (over approximately three months) is through a test called glycated hemoglobin (HbA1c).
Research in people diagnosed with diabetes has shown that glycemic control and brain function are closely linked to heart rate variability (HRV), which is an indicator of autonomic nervous system (ANS) function.
The ANS controls automatic bodily functions such as heartbeat and breathing. Studies suggest that the ANS, as measured by HRV, may play an important role in the relationship between glycemic control and brain function.
While impaired glycemic control is often associated with diabetes, it is important to note that even individuals without a diagnosis of diabetes can have significant variations in this ability. For example, some people are classified as prediabetic, with HbA1c levels between 5.7% and 6.4%.
These levels indicate elevated blood glucose levels, but not yet high enough to be considered diabetes. This condition is more common in older adults. However, it is unclear whether the findings on the impact of diabetes on brain health can be generalized to healthy individuals.
HRV is a measure of the variation in the time interval between consecutive heartbeats and is a valuable indicator of ANS activity. This measure can be broken down into several metrics. For example:
RMSSD (root mean square of the squared differences between heartbeat intervals): Mainly reflects the activity of the parasympathetic nervous system.
HF-HRV (high-frequency heart rate variability): A reliable marker of parasympathetic activity.
Studies in people with diabetes or prediabetes show an inverse correlation between blood glucose levels and HRV. This is due to the development of cardiac autonomic neuropathy, a condition in which high glucose levels progressively damage the nerves of the parasympathetic system, particularly the vagus nerve, and eventually affect the sympathetic system.
In healthy individuals, the relationship between glycemic control and HRV is less clear. Some studies show that higher blood glucose levels are associated with lower HRV, similar to what is seen in people with diabetes, but other studies have not found this association.
These discrepancies may be explained by factors such as age and sex, which have not yet been fully explored in studies of healthy populations.
Aging is associated with higher blood glucose levels, regardless of sex, and also with a reduction in parasympathetic ANS activity until age 70, as indicated by metrics such as RMSSD.
In addition, women have better long-term glycemic control (lower HbA1c) compared to men, until they reach menopause. In contrast, women generally have lower HRV throughout life compared to men. HRV also appears to be linked to menopausal status, suggesting that age and sex interact to influence ANS function.
HRV not only reflects ANS activity, but is also associated with the activity of brain regions. Neuroimaging studies show that fluctuations in HRV are correlated with the functional connectivity (FC) of ANS-related brain networks, such as the central-autonomic network (S-CAN) and the salience network (SN).
These networks involve important areas such as the insula, amygdala, and anterior cingulate cortex, which help regulate emotional, sensory, and autonomic responses.
To explore these relationships, a recent study of 146 healthy adults investigated the connections between glycemic control (measured by HbA1c), HRV, and functional connectivity in ANS-related brain networks.
Heart rate variability and longevity. Source: Timeline Longevity
The researchers formulated several hypotheses, including whether higher HbA1c would be associated with reduced parasympathetic activity (measured by RMSSD and HF-HRV). Or, higher HbA1c would be associated with reduced functional connectivity in the S-CAN and SN networks.
Furthermore, parasympathetic activity (HRV) and functional connectivity would be correlated with each other. Finally, the relationships between HbA1c, HRV, and functional connectivity would vary by age and sex.
The results showed that HbA1c was inversely related to functional connectivity in the S-CAN network, but not in the SN. Furthermore, HbA1c was inversely related to HRV.
Important differences emerged, the relationship between HbA1c and functional connectivity was stronger in older adults, with age being an important factor. Also, the associations between HRV and functional connectivity were more evident in women.
This study advances our understanding of the interactions between glycemic control, ANS, and brain function, extending findings from populations with diabetes to healthy individuals. It also highlights the role of factors such as age and sex in these relationships, underscoring the importance of taking these variables into account in future research.
READ MORE:
The associations among glycemic control, heart variability, and autonomic brain function in healthy individuals: Age- and sex-related differences
Jeffrey X. Yu, Ahmad Hussein, Linda Mah, and J. Jean Chen
Neurobiology of Aging. Volume 142, October 2024, Pages 41-51
Abstract:
The purpose of this study was to clarify the relationships between glycemia and function of the autonomic nervous system (ANS), assessed via resting-state functional connectivity (FC) and heart-rate variability (HRV). Data for this study were extracted from the Leipzig Study for Mind-Body-Emotion Interactions, including 146 healthy adults (114 young, 32 older). Variables of interest were glycated hemoglobin (HbA1c), resting-state FC in the salience aspect of the central-autonomic (S-CAN) and salience network (SN) and HRV (RMSSD and high-frequency HRV (HF-HRV)). HbA1c was inversely correlated with FC in the S-CAN but not SN. HbA1c was inversely correlated with HRV. Both RMSSD and log(HF-HRV) were correlated with FC in the S-CAN and SN. Age- (not sex-related) differences were observed in the Hb1Ac-FC associations (stronger in older adults) while sex- (not age-related) differences were observed in the HRV-FC (stronger in females). These findings extend the diabetes literature to healthy adults in relating glycemia and brain function. The age- and sex-related differences in these relationships highlight the need to account for the potential effects of age and sex in future investigations.
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