By closely monitoring people with disrupted sleep patterns, researchers have documented the metabolic disarray produced by working at night and sleeping during the day.

As soon as their circadian rhythms became separated from a day-night cycle, test subjects' levels of key metabolic hormones went haywire — the most compelling evidence yet that shift work isn't just an inconvenience, but an occupational hazard.

"Normally, the body clock prepares the body for certain activities at a certain time of day," said study co-author Frank Scheer, a Harvard Medical School neuroscientist. "But when it's out of synchronization, it doesn't prepare it properly."

For years, scientists have known that people who work night shifts — about 15 million people in the United States — are unusually prone to heart disease, bone fractures, cancer, diabetes and obesity.

The patterns were initially explained as a function of poor nutrition and low exercise, but night workers don't necessarily live less healthy lives than their day shift counterparts. Risks remained high even when lifestyle was removed from the equation.

That left hypotheses about links between biological clocks and metabolic hormone regulation. Studies on animals suggest a connection, but relatively little research has been conducted on people engaged in shift work.

The latest findings, published Monday in the Proceedings of the National Academy of Sciences, chart a clear path from work-sleep cycles to metabolic disregulation to disease.

"It's an excellent study," said University of Chicago endocrinologist Eve Van Cauter, who was not involved in the research. "It's groundbreaking in some ways."

To create circadian disruption, Scheer's team put test subjects on a

28-hour cycle for eight days, each day waking them four hours later than on the previous day. The researchers took hourly blood samples when test subjects were awake, and monitored their blood pressure, heart rate, body temperature and oxygen consumption around the clock.

The subjects' bodies soon produced less leptin, a hormone secreted from fatty tissue that signals a body to stop eating by triggering feelings of satiety. They experienced increases in blood glucose and insulin, which are linked to diabetes. Levels of cortisol, a hormone released during periods of stress and linked to nearly every disorder in which night work has been implicated, shot up. Test subjects' blood pressure also rose.

"The surprising finding for us is that even so brief a misalignment caused quite impressive changes," said Scheer.

Night shift workers often attempt to keep semi-normal hours on their off days, said Scheer, preventing their circadian rhythms from ever becoming settled. Van Couter added that even a small exposure to daylight while commuting could continually re-set their biological clocks.

Scientists are not yet certain how circadian rhythms regulate metabolism, said Van Cauter, but animal studies have found circadian machinery in the hypothalamus — a brain structure linking the nervous and endocrine systems — and other parts of the body, including the glucose-regulating pancreas and leptin-releasing fatty tissue.

But Scheer cautioned that the experiment only approximated shift work.

"The future question is whether changes in these mechanisms would be maintained after chronic exposure and observed in a more lifelike situation," he said. "Our study was highly controlled and mechanistic. Now it's time to do something less controlled and more realistic."

If the findings are replicated, researchers will try to find therapies capable of restoring metabolic order. The best therapy of all, said Van Cauter, would be a permanent move to night work.

"That's better than shifting between day and night work constantly," she said, "but very few people want to always be a night worker."

*Citation: "Adverse metabolic and cardiovascular consequences of circadian misalignment." By Frank A. J. L. Scheer, Michael F. Hilton,

Christos S. Mantzoros, and Steven A. Shea. Proceedings of the National

Academy of Sciences, Vol. 106, No. 9, March 2, 2009. *

Image: Flickr/nicksarebi

See Also:

Brandon Keim's Twitter stream and Del.icio.us feed; Wired Science on Facebook.