Jordan Shaked

Restless nights can take a toll that goes beyond next-day tiredness. Sleep influences nearly every aspect of our health, and chronic disruptions to sleep patterns have been linked to increased risks for different diseases. To further investigate this connection, a 

 explored the association between sleep-related leg movements and diabetes.

Sleep-related leg movements, or SRLMs, are the twitches, jerks, or other leg movements that can disturb sleep. These can include periodic limb movements of sleep (PLMS), in which the legs repeatedly contract during the night, and restless legs syndrome, in which uncomfortable sensations create an urge to move. Because many people notice these movements themselves or hear about them from a bed partner, SRLMs are typically patient-reported rather than measured in a sleep study.

According to the senior author of the study, 

, associate professor of medicine in Yale School of Medicine’s 

Section of Pulmonary, Critical Care and Sleep Medicine

 (Yale-PCCSM), SRLMs are fairly common and may be tied to changes in heart rate, blood pressure, and sympathetic nervous system activity.

“Theoretically, these changes could have an impact on chronic conditions linked to sympathetic activation, like hypertension or diabetes,” he explains. Prior work has also shown that PLMS measured in sleep studies can predict the development of diabetes, findings that helped shape the rationale for this study.

"This is the kind of work that can ultimately transform how we approach widespread chronic conditions such as diabetes, hypertension, and heart disease, yielding high-impact change in prevention and management."

For the study, the researchers analyzed data from more than 9,000 adults in a publicly available health database to determine how frequently sleep-related leg movements were associated with diabetes. They explored whether short sleep duration or inflammation markers in the body might help explain the link.

After adjusting for demographic and clinical factors—such as age, body mass index, sleep apnea, and hypertension—the researchers found that people who reported SRLMs were 72% more likely to have diabetes than those who did not report these movements. Short sleep duration and inflammation explained only a small portion of the relationship.

Zinchuk emphasized that the study is exploratory, a proof of concept that suggests there may be a relationship. “What we need to do next is measure these limb movements and potential mechanisms objectively to see if the link holds,” he says.

Exploratory studies like this are important because they can uncover new disease risk factors, he adds.

According to Zinchuk, this research is a new way of looking at SRLMs, which are typically considered benign. “This is the kind of work that can ultimately transform how we approach widespread chronic conditions such as diabetes, hypertension, and heart disease, yielding high-impact change in prevention and management,” he says.

The study’s first author is Qinglan “Priscilla” Ding, PhD, of Purdue University, who completed her doctorate and post-doctoral training at Yale School of Medicine (YSM) under Zinchuk’s mentorship. Other YSM authors of the study include 

. The study also included collaborators from Indiana University School of Medicine and Capital Medical University in Beijing.


Pulmonary, Critical Care and Sleep Medicine is one of 10 sections in the Yale Department of Internal Medicine. To learn more about Yale-PCCSM, visit

Articles

Chronic sleep disruptions, such as sleep-related leg movements (SRLMs), are linked to increased disease risks, including diabetes. A recent study analyzed data from over 9,000 adults, finding that individuals reporting SRLMs were 72% more likely to have diabetes. Although short sleep duration and inflammation explained only a small part of this relationship, the study suggests a potential link between SRLMs and diabetes. The research, led by Andrey Zinchuk, MD, emphasizes the need for further objective measurement of SRLMs to confirm these findings and explore new disease risk factors.

New research links sleep-related leg movements to a higher risk of diabetes.

Uncovering Hidden Risk Factors: Sleep-Related Leg Movements and Diabetes

Cholesterol plays a vital role in the body, providing structural support to cells and serving as a building block for hormone synthesis. However, when cholesterol accumulates or is improperly distributed, it can contribute to the development and progression of disease. In a new study, 

Proceedings of the National Academy of Sciences

, Yale School of Medicine (YSM) researchers showed that excess cholesterol stored in the liver can directly drive fibrosis in the context of metabolic disease.

, the study aimed to identify key molecular triggers of metabolic dysfunction–associated steatohepatitis (MASH), a progressive liver disease marked by fat accumulation, inflammation, and fibrosis. According to Shulman, George R. Cowgill Professor of Medicine (Endocrinology) and professor of cellular and molecular physiology at YSM, understanding the drivers of fibrosis is critical to improving outcomes for patients with MASH.

“Once fibrosis develops, it becomes very difficult to reverse and may ultimately progress to end-stage liver disease,” he says.

Interestingly, says Shulman, it wasn’t the total amount of cholesterol in the liver that mattered most, but rather where it was stored. Specifically, cholesterol accumulated within liver fat droplets emerged as a key driver of liver inflammation and fibrosis.

“It’s not just how much cholesterol is present, it’s about where it ends up,” says Shulman. “In this case, it was the cholesterol in the lipid droplets that triggers the damage. When it comes to lipids and liver disease, it’s all about location.”

The researchers first identified this link using preclinical models and then validated their findings in human liver tissue. They hypothesize that when cholesterol accumulates within liver fat droplets, it may protrude through the droplet coating and trigger an inflammatory response.

“We think that exposed cholesterol triggers intracellular stress pathways, particularly involving lysosomes, that in turn activate hepatic stellate cells and set off a chain reaction that leads to liver inflammation and fibrosis,” says Shulman.

This mechanistic insight offers a possible explanation for how cholesterol drives liver injury and points to new potential therapeutic targets. Shulman and his team are now investigating whether inhibiting the cholesterol synthesis pathway, possibly in combination with other agents, can improve not only liver inflammation and fibrosis but also insulin resistance and fat accumulation in the liver.

“This work gives us new insight into the pathophysiology of MASH,” he says. “We now have the tools and drugs to test this hypothesis, and within the next few years, we hope to design studies that can evaluate these potential therapies more effectively.”

The research reported in this news article was supported by the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (awards F31DK126362, T32GM007324, P30DK34989, R01DK119968, R01DK113984, P30DK045735, and R01DK133143) and Yale University. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additional support was provided by the Manpei Suzuki Diabetes Foundation, Mishima Kaiun Memorial Foundation, Kowa Life Science Foundation, Japan Foundation for Applied Enzymology, Takeda Science Foundation, Ono Medical Research Foundation, and Japan's Ministry of Education, Culture, Sports, Science, and Technology.

Endocrinology and Metabolism, one of 10 sections in the Yale Department of Internal Medicine, improves the health of individuals with endocrine and metabolic diseases by advancing scientific knowledge, applying

 new information to patient care, and training the next generation of physicians and scientists to become leaders in the field. To learn more, visit 

Cholesterol's role in metabolic dysfunction-associated steatohepatitis (MASH) is highlighted by its accumulation in liver fat droplets, which drives inflammation and fibrosis. Yale researchers, led by Dr. Gerald I. Shulman, identified that the location of cholesterol, rather than its total amount, is crucial in liver disease progression. Their study suggests that cholesterol within lipid droplets triggers intracellular stress pathways, activating hepatic stellate cells. This insight opens avenues for potential therapeutic targets, with ongoing investigations into inhibiting cholesterol synthesis to improve liver conditions and related metabolic issues.

Cholesterol in liver fat droplets has been found as a key driver of liver inflammation and fibrosis.