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Those findings could lead to new weight loss drugs that manipulate the timing of hormone fluctuations.
“There is a cyclic clock protein that acts as the brakes on sugar production in the liver. This protein is low at the end of the night, when we have been ‘fasting’, and allows the liver to produce sugar in preparation for activity as we awake,” said Steve Kay, a professor of biology and neurology at the University of Southern California. His lab is testing a drug that increases this clock protein to see if it can reverse obesity by preventing this rise in blood sugar.
Perhaps most pressing is the need to more fully understand the impact that erratic body clocks have on disease risks. In a 2009 study, Scheer and his colleagues recruited 10 healthy volunteers to live in a lab at the Brigham for 11 days on a 28-hour daily cycle with no natural light or other time cues from the outside world. “Their internal circadian system was never able to adjust to this regular 28-hour sleep-wake cycle during the study,” Scheer said.
Besides sleep disruptions and moderately increased blood pressure, those with continuously out-of-sync clocks experienced a sharp rise in blood sugar and the hormone insulin, which is a risk factor for diabetes. Three of the participants had blood sugar levels that put them into full-blown insulin resistance or pre-diabetes within the first three days of study, a condition that reversed after the end of the study.
Those findings don’t bode well for those who confuse their body clocks with frequent travel across time zones or night-shift work. And it raises concerns about possible health risks faced by a significant percentage of the population who have naturally disrupted circadian rhythms.
About 10 percent of the population have strong morning or evening preferences in their circadian rhythms, making them night owls or larks. About a third of these folks are at the extreme end, having a sleep disorder that makes their bodies yearn for sleep early in the evening or several hours past midnight. These genetic tendencies can make their sleep habits seem downright wacky in our culture that expects most office workers to arrive at around 9 a.m. — not at 4 a.m. or noon.
“I suspect that they’re sick in a deeper biological way; they probably have abnormal rhythms throughout their body, not just in their sleep-wake cycle,” Dr. Robert Thomas, codirector of the sleep center at Beth Israel Deaconess Medical Center, who has treated more than 1,000 patients over the past decade with the conditions. “But there’s very little research data on these patients; they aren’t the ones studied in circadian labs.”
Often misdiagnosed as having insomnia, people with a condition called delayed sleep phase syndrome feel chronically jet-lagged, as if they are set on Hawaii time while living in Boston. Those with advance sleep phase syndrome feel as if they’re on European time, or on an earlier schedule.
Treatment for a delayed sleep phase often involves nudging the clock ahead hour by hour over days or weeks. Patients use a light box that mimics outdoor light at a scheduled time in the morning, starting around when they would naturally wake up, and getting progressively earlier every few days. They also take melatonin supplements a few hours before their scheduled bedtime to send their brain a message that night has arrived. Treatment for advance sleep phase is similar, but with light therapy given later in the morning and melatonin later at night.