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Wednesday 9 September 2015
Volunteers ate 6000 calories a day to probe cause of diabetes
Eating two and a half times more than you should will leave you overweight and prone to type 2 diabetes, although no one is entirely sure why. Now a team that fed volunteers a whopping 6000 calories a day have found some clues.
Obesity is only one problem caused by eating too much. An overly large food intake can also increase a person’s risk of diabetes, heart disease and some cancers, but no one is sure why this should be the case.
Resistance to the hormone insulin seems to play a role. When a healthy person eats a meal, their blood glucose levels rise, and the body responds by making insulin. This hormone prompts the body to store un-needed glucose, but people who develop insulin resistance are not able to absorb excess glucose in the same way. This means that, after eating, their blood glucose levels remain high, and over time, this can damage the kidneys, nervous system and heart, for example.
Guenther Boden and Salim Merali at Temple University, Philadelphia, and their team set out to investigate how overeating might lead to insulin resistance.
They fed six healthy male volunteers 6000 calories’ worth of food every day for a week – around two and a half times what they should have been eating. “It was a regular, American diet, composed of pizzas, hamburgers and that sort of thing,” says Merali. Each volunteer stayed at a hospital for the duration of the experiment, where they were bed-bound, carefully monitored and prevented from doing any sort of exercise.
“They took to the diet, and liked it,” says Boden. While 6000 calories sounds like a lot, it’s not more than some athletes consume while training, he says. Unsurprisingly, his inactive volunteers started to put on weight. By the end of the week, each volunteer was around 3.5 kilograms heavier than when they started.
On their mega-diet, the volunteers all developed insulin resistance within two days. “By definition, they all developed diabetes,” says Francis Stephens at the University of Nottingham in the UK.
To find out why, Boden, Merali and their colleagues tested several theories. Some have suggested, for instance, that molecules called free fatty acids – which seem to be elevated in the blood of people with insulin resistance – might be the trigger for resistance to the hormone. But levels were normal in the team’s volunteers. The participants didn’t have higher levels of compounds that are known to cause inflammation, either, throwing out another theory.
Instead, daily urine tests suggested another culprit. Boden and Merali’s team noticed that, over the week, the volunteers were urinating increasing amounts of oxidised lipid compounds, which are caused by reactive oxygen species attacking cell membranes, and are a hallmark of oxidative stress within the body. When the group looked closer, they could see the signs of this stress in biopsies of the volunteers’ fat tissue. This seems to be the beginning of the process that leads to insulin resistance, says Boden.
They suggest that the oxidative stress caused by overeating hampers blood sugar regulation because it changes the structure of a protein that is normally responsible for taking glucose out of the bloodstream. Insulin sends the same message, but the glucose is not removed from the blood, says Boden. “This is a brand new way to get from over-nutrition to insulin resistance.”
“It’s a pretty cool finding,” says Francis Stephens at the University of Nottingham, UK. Oxidative stress and a damaged glucose-transporting protein may be the most important factor in insulin resistance, he says, although other mechanisms are probably still involved. Overeating can also cause fat to build up in muscles and the liver – we still don’t know the mechanisms behind this, he says.
Both the altered glucose-transporting protein and oxidative stress could be targets for future treatments, says Boden. “It is conceptually possible that adding antioxidants to a big meal could limit its effects on health,” he says.
Boden expects the volunteers to return to a healthy weight without any lasting effects, but Stephens reckons this could take a while. “Gaining 3.5 kg of fat in a week is pretty severe,” he says. “It will probably take them several months to get rid of it.”