Irregular sleep patterns linked to metabolic disorders

Obesity, diabetes, high cholesterol more prevalent among irregular sleepers

June 5, 2019

Science Daily/NIH/National Heart, Lung and Blood Institute

A new study has found that not sticking to a regular bedtime and wakeup schedule -- and getting different amounts of sleep each night -- can put a person at higher risk for obesity, high cholesterol, hypertension, high blood sugar and other metabolic disorders. In fact, for every hour of variability in time to bed and time asleep, a person may have up to a 27% greater chance of experiencing a metabolic abnormality.

The results of the study, which was funded by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, appear today in the journal Diabetes Care.

"Many previous studies have shown the link between insufficient sleep and higher risk of obesity, diabetes, and other metabolic disorders," said study author Tianyi Huang, Sc.D., epidemiologist of the Channing Division of Network Medicine at Brigham and Women's Hospital, Boston. "But we didn't know much about the impact of irregular sleep, high day-to-day variability in sleep duration and timing. Our research shows that, even after considering the amount of sleep a person gets and other lifestyle factors, every one-hour night-to-night difference in the time to bed or the duration of a night's sleep multiplies the adverse metabolic effect."

For the current study, researchers followed 2,003 men and women, ages 45 to 84, participating in the NHLBI-funded Multi-Ethnic Study of Atherosclerosis (MESA). The participants were studied for a median of six years to find out the associations between sleep regularity and metabolic abnormalities. To ensure objective measurement of sleep duration and quality, participants wore actigraph wrist watches to closely track sleep schedules for seven consecutive days. They also kept a sleep diary and responded to standard questionnaires about sleep habits and other lifestyle and health factors. Participants completed the actigraphy tracking between 2010 and 2013 and were followed until 2016 and 2017.

"Objective metrics and a big and diverse sample size are strengths of this study," said Michael Twery, Ph.D., director of the NHLBI's National Center on Sleep Disorders Research. "As is the study's ability to look not only at current factors, but to conduct a prospective analysis that allowed us to assess whether patterns of irregular sleep could be linked to future metabolic abnormalities."

The researchers' hypothesis that there were, in fact, such associations, proved correct. Individuals with greater variations in their bedtimes and in the hours they slept had a higher prevalence of metabolic problems, and these associations persisted after adjusting for average sleep duration. This was also the case when they looked at the participants who developed metabolic disorders during the 6.3 years of follow up.

The prospective results showed that the variations in sleep duration and bedtimes preceded the development of metabolic dysfunction. According to the authors, this provides some evidence supporting a causal link between irregular sleep and metabolic dysfunction.

Participants whose sleep duration varied more than one hour were more likely to be African-Americans, work non-day shift schedules, smoke, and have shorter sleep duration. They also had higher depressive symptoms, total caloric intake, and index of sleep apnea.

Increasing sleep duration or bedtime variability was strongly associated with multiple metabolic and simultaneous problems such as lower HDL cholesterol and higher waist circumference, blood pressure, total triglycerides, and fasting glucose.

"Our results suggest that maintaining a regular sleep schedule has beneficial metabolic effects," said study coauthor Susan Redline, M.D., senior physician in the Division of Sleep and Circadian Disorders at Brigham and Women's Hospital. "This message may enrich current prevention strategies for metabolic disease that primarily focus on promoting sufficient sleep and other healthy lifestyles."

https://www.sciencedaily.com/releases/2019/06/190605133514.htm

Importance of studying sleep and eating in tandem

October 13, 2017

Science Daily/Scripps Research Institute

A new study from scientists on the Florida campus of The Scripps Research Institute (TSRI) offers important insights into possible links between sleep and hunger -- and the benefits of studying the two in tandem. A related paper from the same lab is providing researchers an accessible tool for pursuing further investigations involving multiple fruit fly behaviors.

While many humans enjoy a daily caffeine fix, scientists have found that caffeine repels Drosophila melanogaster -- a species of fruit fly often used as a model for studying human conditions and genetics. Scientists believe that plants produce the caffeine molecule as a defense mechanism to prevent organisms such as fruit flies from eating them. Regardless of the cause of the fly's aversion, caffeine does seem to negatively impact their sleep, much like it does in humans.

Caffeine is known to stave off sleep in humans through pharmacological effects on the adenosine receptor. Nonetheless, many studies in mammals have shown genetic differences in responses to caffeine. Interestingly, caffeine apparently can prevent sleep in fruit flies despite the fact that it doesn't act through their adenosine receptor.

Erin Keebaugh, Ph.D., a postdoctoral researcher in Associate Professor William Ja's Laboratory at TSRI, suspected that the systems responsible for caffeine's impact on fly (and maybe human) sleep patterns are more complex than a single caffeine and receptor interaction.

In her study, published in the journal Sleep on October 3, 2017, her team gave groups of flies varying levels of dietary caffeine. They then measured how much the flies slept in the following 24 hours while on those diets. They also studied whether varying levels of caffeine impacted the insects' feeding behavior by measuring how much they ate over the same 24-hour period.

Interestingly, the team found that sleep loss couldn't be explained by caffeine intake alone. Instead, they believe that the sleep loss was mediated by changes in the animal's feeding behavior. "There could still be a pharmacological effect, but there's definitely dietary inputs to that," said Keebaugh.

The study reinforced the idea that the processes of sleep and eating need to be studied together, explained the scientists, especially as a growing number of researchers investigate the relationship between sleep and metabolic disorders. Further studies into this relationship could lead to the development of therapies that treat disorders such as obesity and diabetes.

A Closer Look at Fly Behavior

To that end, another member of the Ja Laboratory, Graduate Student Keith Murphy, has developed a new open-source, customizable technique for jointly studying multiple fly behaviors. Many studies designed to understand the interactions between multiple fly behaviors require researchers to measure each behavior separately; for example, one study measures how much the flies eat while a second study measures how much they sleep, and then the data are combined and compared. With Murphy's device, the Activity Recording CAFE (ARC), researchers could measure both behaviors simultaneously, giving the researchers a cleaner, simpler strategy to investigate previously convoluted questions.

Using the ARC protocol, as described in a paper recently published in Nature Protocols, anyone with access to a 3D printer can print the chamber and set it up in two hours or less to collect fly data. The chamber is hooked up to a computer that continuously tracks both the amount of food that a fly consumes and its position in the chamber, which can tell a researcher whether or not it's sleeping.

Though the protocol is specifically designed for studying sleep and feeding behaviors, Murphy emphasized that the ARC could be customized to study a variety of behaviors in flies. Researchers could program the machine vision program on the computer to apply optogenetic controls tied to certain behaviors, deliver vibrations or cause the fly's food to move to assess memory, motivation and other behaviors.

"We're hoping that this paper creates a community around the tool and people come up with new uses," said Murphy. "If others get on board, this thing could change what a small lab can do."

https://www.sciencedaily.com/releases/2017/10/171013132234.htm

Disrupted Circadian Rhythm May Cause Triglycerides to Rise

August 4, 2010

Science Daily/Cell Press

When the circadian rhythm gets thrown off, it could come with an unexpected side effect: high triglycerides. The discovery, based on studies in mice with a "broken clock," helps to explain the normal rise and fall in triglycerides, which happens at about the same time each day, according to researchers who report their findings in the August issue of Cell Metabolism, a Cell Press publication.

"We show that the normal up and down [of triglycerides] is lost in clock mutants," said M. Mahmood Hussain of SUNY Downstate Medical Center. "They have high triglycerides all the time." An elevated triglyceride level is a risk factor for atherosclerosis and heart disease.

Several biological, physiological, and behavioral activities show a characteristic recurrence with 24-hour intervals attuned to sunrise and sunset, the researchers explained. That circadian rhythm is driven by the interaction of so-called clock genes.

In normal mice, plasma triglycerides double or triple over the course of the day, reaching their lowest point at night when the nocturnal animals eat and are most active, the new report shows. In clock mutants, triglyceride levels don't change; rather, they stay high all the time.

The researchers delved further into the mechanism linking the animal's internal clocks to triglycerides. They found that a core component of the circadian circuitry -- a protein known as CLOCK -- controls levels of another protein (called microsomal triglyceride transfer protein, or MTP) that helps to ferry triglycerides through the bloodstream. That control takes place via yet another transcription factor.

"Metabolic syndrome and obesity are major metabolic disorders characterized by high plasma lipid concentrations," the researchers conclude. "Plasma lipids are tightly controlled by mechanisms regulating their production and clearance. Here, we show that light-entrained mechanisms involving clock genes also play a role in regulating plasma triglyceride."

If the findings in mice can be extrapolated to humans, it suggests that the effects of drugs designed to lower triglyceride levels by acting on MTP might depend on when they are taken each day, the researchers said.

"The dose needed may vary depending on the time of day," Hussain said. "Now we can start to think about [the role of] drug timing in controlling disease states."

The findings also suggest that activities that disrupt the circadian rhythm -- staying up until 2:00 a.m. or traveling overseas -- might come with real consequences for lipid metabolism, he added.

http://www.sciencedaily.com/releases/2010/08/100803132736.htm