10 July 2018

Disrupted circadian rhythm increases risk of type 2 diabetes

A reversal of the day and night rhythm, due to shift work for example, leads to a disturbance in blood sugar levels. Scientists from Maastricht University have demonstrated this for the first time in humans. Their research shows that a disruption of the biological clock results in a lower insulin sensitivity, an important indicator for the development of type 2 diabetes.

The findings of the Maastricht research team, led by Professor Patrick Schrauwen, are being published today in the renowned scientific journal Proceedings of the National Academy of Sciences (PNAS).

24-hour economy

The study by Professor Schrauwen and his team fits within one of the most pressing questions from the Dutch National Research Agenda: ‘What are the effects of the advancing 24-hour economy on people’s health?’. This not only concerns the traditional night shifts of nurses or police officers, for example. Nowadays, people are online everywhere, at every hour, so they are activated throughout the day. People also travel between different time zones much more often than before.

A known unhealthy side effect is that people do not sleep as well. Disruptions to eating patterns, obesity and the risk of developing cancer have also already been linked to increasing disturbances in the natural sleep-wake cycle. From the research published today by the Maastricht scientists, it has now become clear that a disrupted circadian rhythm also makes a substantial contribution to reducing insulin sensitivity. Reduced insulin sensitivity is an important indicator for the development of type 2 diabetes.

Respiration chambers

For their research, the scientists closed 14 test subjects in Maastricht University’s five special respiration chambers for three consecutive days. In these climate chambers, the subjects could not have contact with the outside world, there was no time indication, and only artificial light and Netflix were available. They were served food and drinks through an airlock.

After the first ‘normal’ night, the researchers triggered a reversal of the day and night rhythm in the middle of the afternoon by letting the subjects sleep for a few hours after lunch. In the evening, they were awakened again for breakfast and a new, full day followed. Then in the early morning they had dinner. This reversed day/night schedule was then repeated again, after which various measurements were taken.

“With this unique set-up, we were able to measure the subjects in the evening, but after they had slept a normal 6 to 7 hours”, explains Professor Schrauwen. “Using a glucose clamp [the gold standard for measuring insulin resistance] and stable isotopes, we were able to very accurately measure the insulin sensitivity of the liver and muscle. By taking muscle biopsies from the subjects, we then studied exactly which processes were affected in the muscle.”

Biological clock

The measurements of the Maastricht scientists not only show that the insulin sensitivity in the muscles of the 14 subjects after their stay in the respiration chambers had become significantly lower, but also that something remarkable happened to the subjects during the sudden reversal of their day and night rhythm.

“The biological clock is not only located in our brain, but in all cells of our body”, says researcher Jakob Wefers. “In our study, we discovered that this biological clock did not adapt to the new timetable; in the muscle we found that the molecular biological clock was clearly still running according to the old time. This probably explains why the insulin sensitivity of the muscle also decreased. And that could possibly be another explanation for the increased risk of type 2 diabetes in people who do shift work.”

Further research should be done to show whether a disruption of the circadian rhythm actually leads to type 2 diabetes.