More than one-third of Americans are obese. This translates to a massive 80 million people who are at risk for heart disease, diabetes, high blood pressure, and a myriad of other health conditions. Diabetes, in particular, has long been associated with obesity. We know insulin resistance is a key component of metabolic issues, but the exact way in which obesity promotes insulin resistance is not fully understood by researchers.

Insulin keeps concentrations of glucose in the blood low by decreasing the amount the liver produces and increasing its absorption into tissue like muscle and fat. When one’s body is unable to remove glucose from the bloodstream (called insulin resistance), high blood sugar can occur, which can lead to diabetes. We know obesity causes cells to be less responsive to insulin, but we don’t know how.

One new study attempted to find the missing link by having a group of six healthy, middle-aged male volunteers subject themselves to overnutrition for one week. And by overnutrition, I mean a whopping 6,000 calories every day, with no physical activity. The diet consisted of about 50 percent carbohydrates, 35 percent fats, and 15 percent protein.

The results were predictable in some ways (the men gained weight) but also held some important insight for determining the origins of obesity-related insulin resistance. The men gained an average of 8 pounds, and nearly all of it was from fat. By the second day of the study, they all also had a rapid and continuous rise in blood insulin and insulin resistance levels. The rise was enough to cause “severe systemic and adipose tissue insulin resistance in every one of six study subjects,” researchers wrote.

“By definition, they all developed diabetes,” Francis Stephens, a lecturer at the University of Nottingham in the UK told New Scientist.

Scientists know that inflammation, stress on cells, fatty acids in the blood, and a process called “oxidative stress,” where molecules containing oxygen can damage a cell’s components, are all components of insulin resistance. Which of these triggers diabetes in obese patients, though, is still a mystery. The new study provides some evidence that may actually suggest an answer.

"This work is extremely important to understand," Adam Salmon, an associate professor at the department of molecular medicine at the UT Health Science Center who was not involved in the study, told Tech Insider. "The most interesting part of this study is that they found within a few days the patients developed insulin resistance, but that this correlated only with an increase in oxidative stress and not in changes in other potential mechanisms thought to cause insulin resistance in this situation."

Basically, when researchers analyzed the men’s body fluids, they found that the initial cause of insulin resistance in fat tissues was due to oxidative stress.

Salmon says the methodology and results from the study are strong, but it’s important to remember that researchers looked at a very small sample group. In order to extrapolate the findings, Salmon says, it will be important to recreate results with a wider demographic.

The information could be useful for developing new treatments and therapies for delaying the onset of type 2 diabetes.

Source: Boden G, Homko C, Barrero C, et al. Excessive caloric intake acutely causes oxidative stress, GLUT4 carbonylation, and insulin resistance in healthy men. Science Translational Medicine. 2015.