Researchers have known that a lack of quality sleep can increase a person’s risk of diabetes, but it’s not been known why. The results of a study in humans by a team of sleep scientists at the University of California, Berkeley, may point to a possible answer. The researchers uncovered a mechanism in humans that could explain how and why deep-sleep brain waves at night are able to regulate the body’s sensitivity to insulin, which in turn improves blood sugar control the next day.

“Beyond revealing a new mechanism, our results also show that these deep-sleep brain waves could be used as a sensitive marker of someone’s next-day blood sugar levels, more so than traditional sleep metrics,” said Vyoma D. Shah, PhD, a researcher at the Center for Human Sleep Science. “Adding to the therapeutic relevance of this new discovery, the findings also suggest a novel, non-invasive tool—deep-sleep brain waves—for mapping and predicting someone’s blood sugar control.”

Added Matthew Walker, PhD, a UC Berkeley professor of neuroscience and psychology, “These synchronized brain waves act like a finger that flicks the first domino to start an associated chain reaction from the brain, down to the heart, and then out to alter the body’s regulation of blood sugar… In particular, the combination of two brain waves, called sleep spindles and slow waves, predict an increase in the body’s sensitivity to the hormone called insulin, which consequentially and beneficially lowers blood glucose levels.”

Walker is senior author, and Shah co-author of the team’s published paper in Cell Reports Medicine, titled “Coordinated hum13an sleeping brainwaves map peripheral body glucose homeostasis,” in which the investigators conclude that their collective findings, “… describe a sleeping-brain-body framework of optimal human glucose homeostasis, offering a potential prognostic sleep signature of glycemic control.”

World Health Organization estimates cited by the authors indicate that diabetes affects more than 420 million people worldwide, and the condition represents is a major cause of death. Experimental studies in humans and animals suggest that one major factor impairing blood glucose equilibrium is too little sleep. “Both acute and chronic partial sleep restriction, including that of non-rapid eye movement (NREM) slow-wave sleep, impair glucose tolerance and insulin sensitivity,” the authors wrote. “Conversely, sleep extension improves glucose metabolism.” What isn’t know, is why. “Currently, the mechanism(s) through which sleep optimally governs next-day glucose homeostasis in humans remains unknown,” the authors continued.

Scientist have for years studied how the coupling of non-rapid eye movement sleep spindles and deep, slow brain waves corresponded to that of learning and memory. UC Berkeley researchers previously found that deep-sleep brain waves improved the ability of the hippocampus—the part of the brain associated with learning—to retain information.

Their newly reported study suggests a novel and previously unrecognized role for these combined brain waves in humans in the critical bodily function of blood sugar management. The work builds on a 2021 rodent study, which offered up a potential candidate pathway.  “Specifically, hippocampal sharpwave ripples—which are temporally coupled with NREM slow oscillations (SOs) and sleep spindles—were associated with the moment-to-moment, top-down regulation of peripheral blood glucose through activation of the hypothalamus (which itself provides autonomic control of peripheral circulating hormones, including insulin,” they wrote in the newly released Cell Reports Metabolism paper.

The combination of two brain waves, called sleep spindles and slow waves, predict an increase in the body’s sensitivity to the hormone called insulin, which consequentially and beneficially lowers blood glucose levels.
The combination of two brain waves, called sleep spindles and slow waves, predict an increase in the body’s sensitivity to the hormone called insulin, which consequentially and beneficially lowers blood glucose levels.[Matthew Walker]

For this research the UC Berkeley researchers first examined sleep data in a group of more than 600 individuals, for which overnight polysomnography data and next-morning glucose and insulin measurements were available. The results from their analyses and evaluations showed that a specific coupled set of deep-sleep brain waves predicted next-day glucose control, even after controlling for other factors such as age, gender and the duration and quality of sleep.

“This particular coupling of deep-sleep brain waves was more predictive of glucose than an individual’s sleep duration or sleep efficiency,” said Raphael Vallat, PhD, a UC Berkeley postdoctoral fellow and co-author of the study. “That indicates there is something uniquely special about the electrophysiological quality and coordinated ballet of these brain oscillations during deep sleep.”

The team then set out to explore the descending pathway that might explain the connection between these deep-sleep brain waves sending a signal down into the body, ultimately predicting the regulation of blood glucose. Their findings point to an unfolding set of steps that could help explain how and why these deep-sleep brain waves are related to superior blood sugar control. First, they found that stronger and more frequent coupling of the deep-sleep brain waves predicted a switch in the body’s nervous system state into the more quiescent, calming branch, the parasympathetic nervous system. They measured that change in the body and the shift to this low-stress state using heart rate variability as a proxy.

Then, turning their attention to the final step of blood sugar balance, the researchers further discovered that this deep sleep switch to the calming branch of the nervous system further predicted an increased sensitivity of the body to the glucose-regulating hormone insulin, which instructs cells to absorb glucose from the bloodstream, preventing a deleterious blood sugar spike. This has particular relevance for preventing hyperglycemia and potentially also the development of type 2 diabetes.

“Taken together, these findings support a NREM sleep-oscillation brain-body framework of glucose homeostasis in humans, one that describes a mapped association between prior SO-spindle coupling and next-day glucose homeostasis,” the team concluded. “In the electrical static of sleep at night, there is a series of connected associations, such that deep-sleep brain waves telegraph a recalibration and calming of your nervous system the following day,” said Walker. “This rather marvellous associated soothing effect on your nervous system is then associated with a reboot of your body’s sensitivity to insulin, resulting in a more effective control of blood sugar the next day.”

The researchers subsequently replicated the same effects by examining a separate group of 1,900 participants. “Once we replicated the findings in a different cohort, I think we actually started to feel more confident in the results ourselves,” Walker further noted. “But I’ll wait for others to replicate it before I truly start believing, such is my British skepticism.” As the authors further noted, “Importantly, this association between SO-spindle coupling and peripheral glucose homeostasis was also validated in an independent, larger replication dataset, suggesting that the effects are less likely to be driven by single cohort-specific idiosyncrasies (though additional cohort replications are required).

The scientists said the research is particularly exciting given the potential clinical significance years down the line. Diabetes treatments already on the market can sometimes be difficult for patients to adhere to. The same is true of the recommended lifestyle changes, including different eating habits and regular exercise. Sleep, however, is a largely painless experience for most people, and is a modifiable lifestyle factor that could feasibly be used as part of a therapeutic and painless adjunct treatment for those with high blood sugar or type 2 diabetes.

The effect sizes observed in their study were, the authors “as anticipated, in the small-to-moderate range,” and similar to those observed I rodents. This was to be expected, given that an individual’s blood glucose is determined by multiple factors, including genetics, diet and gut microbiome. “Sleep—an indirect lifestyle factor—is therefore anticipated to account for a somewhat modest, yet still clinically meaningful, proportion of between-person viariability in glucose levels,” they wrote.

So, while sleep is not going to be the single magic bullet, the prospect of new technologies that can safely alter brain waves during deep sleep that this new research has uncovered may help people better manage their blood sugar. That, the research team said, is reason for hope. Noting limitations of their study, the team stated, “In conclusion, our findings suggest a sleeping-brain—glycemic-body framework of insulin-associated glucose homeostasis in humans, and further re-emphasize the  importance of sleep in the clinical management of hyperglycemia and diabetes,” the authors concluded.

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