It should not surprise anyone to hear that overeating can lead to obesity and the development of type-2 diabetes. However, it is surprising how quickly a pre-diabetic state can be triggered in individuals who indulge in overeating. This phenomena is prompting experts in the field of diabetes research to examine potential new treatment pathways for patients who are at-risk of type-2 diabetes, or patients who already have type 2 diabetes.

A recent study conducted by investigators from Temple University in Philadelphia examined this pattern, and the results were revealing. Six men—all between 30 and 50 years of age—were asked to abandon exercise and transition from a normal diet for sedentary males (around 2,200 calories per day) to a diet of 6,000 calories per day for a period of one week. Within that one-week period, all of the men gained an average of eight pounds. In addition, all of the men entered a metabolic phase known as “insulin resistance,” the pre-diabetic state which often occurs before the onset of diabetes.

Current medical research points to a causal relationship between fatty acids, inflammation, cellular stress, and the development of insulin resistance and ultimately type 2 diabetes. This study from Temple is different because it points to oxidative stress on cells—the direct result of overeating—as a previously overlooked catalyst. Despite the life-giving benefits of oxygen, the overproduction of oxygen byproducts can be toxic at the cellular level, which is why dieticians have long promoted the health benefits of antioxidants in food.

In this study, a post-hoc analysis of the men’s urine and fatty tissue indicated a distinct increase in proteins associated with oxidative stress. The researchers also noted alterations to the GLUT4 transporter protein that may have affected its ability to take-up glucose in response to insulin, causing insulin resistance.

Dr. David Marrero, PhD, is an expert in the field of diabetes research and treatment. In addition to his duties as a Professor of Medicine at Indiana University Medical School, Dr. Marrero is also the Director of the Diabetes Translational Research Center in Indianapolis, Indiana, and the President of Health Care & Education for the American Diabetes Åssociation. While he believes that the results of this study from Temple University are definitely interesting, further studies on larger, more diverse populations will be needed before any definitive conclusions can be drawn.

“Clearly, obesity is the number one risk factor for type 2 diabetes, and a huge problem for millions of Americans.” said Dr. Marrero. “And no one doubts the link between overeating and type-2 diabetes. That’s why most treatment pathways for type 2 diabetes will start with diet and exercise. However, genetic factors must always be considered. For example, some ethnic groups—like African Americans—are more predisposed to develop the disease. Unfortunately, genetics are not uniform—there’s still a great deal to learn about the biological and physiological factors that contribute to type 2 diabetes in individuals. At the very least, what this study tells us is that the GLUT4 receptor and its potential association with oxidative stress and the development of type 2 diabetes may merit further scientific scrutiny in larger, more inclusive trials.”

Overeating is a serious problem in the United States, where more than 34.9% (78.6 million) of adults and 17% (12.7 million) of children and adolescents are obese. As Dr. Marrero points out, diet and exercise are always the first, best choices to combat obesity and type 2 diabetes, but medicinal therapy must be an option for some patients. Studies like this may lead to future treatments that target GLUT4 to control insulin resistance in patients at-risk of type 2 diabetes.

David Marrero, PhD, J.O. Ritchey Endowed Professor of Medicine and Director, Diabetes Translational Research Center at Indiana University School of Medicine, reviewed this article.


"Very high-calorie diets show how overeating may lead to diabetes." September 9, 2015.

David Marrero, PhD, J.O. Ritchey Endowed Professor of Medicine and Director, Diabetes Translational Research Center, at Indiana University School of Medicine. Interview with source, October 18, 2015.

Adult Obesity Facts. Centers for Disease Control and Prevention. Page last updated: September 21, 2015.

Childhood Obesity Facts. Centers for Disease Control and Prevention. Page last updated: June 19, 2015.