It’s such an obvious fact that it hardly feels worth stating, but we all know that eating more calories than you burn makes you gain weight, leading to obesity. What is poorly understood, however, is why this often leads to Type 2 diabetes. In an attempt to get to the bottom of this, a team of researchers fed a group of volunteers an impressive 6,000 calories a day, and monitored how their body reacted.

There are many health conditions – from heart disease, to diabetes and obesity – that have been linked to overeating. It’s thought that resistance to the hormone insulin, which plays a role in the body’s ability to mop up excess glucose, is probably a precursor to the development of diabetes. When your body becomes resistant it still produces the hormone, but can’t remove all the excess glucose from your bloodstream, which can then go on to damage your kidneys and heart, for example. The new study, published in Science Translational Medicine has found a possible mechanism by which this resistance develops.

The small study took six healthy men and fed them up on 6,000 calories of a “typical American” diet every day for a week. This clocks in at around two and a half times what they should normally be eating. The experiment took place at a hospital where the participants were bed bound for the week, not allowed to exercise, and continuously monitored.

In addition to gaining a whopping 3.5 kilograms (7.7 pounds) on average during the week, after just two days of overeating they started to show signs of insulin resistance. There have been several hypotheses as to why high-calorie diets lead to resistance, such as too many free fatty acids or inflammation. But when tested by the researchers, neither of these ideas held true.

When analyzing the participants' urine, however, they may have found a clue. They discovered the volunteers were excreting increasing amounts of oxidised compounds, a sign of oxidative stress. An excess of these compounds can damage cell membranes, and the researchers suspect that they may be altering the shape of a particular glucose transporter protein, GLUT4, which sits in the membrane of cells and removes glucose from the blood. This change in shape may affect the protein's ability to take up glucose when instructed to do so by insulin, thus leading to insulin resistance.

They then looked at biopsies of fat tissue taken from the participants, and found similar signs of oxidative stress. According to the researchers, this suggests that a treatment that targets oxidative stress and which focuses on the GLUT4 protein could be used to treat obesity-linked insulin resistance.