The 6,000-Calorie Question

Two Temple reasearchers lead a study unearthing just how quickly overeating can result in signs of Type 2 diabetes.

Story by: 
Angelo Fichera, SMC '13
Just a few days of overeating leads to signs of Type 2 diabetes, a groundbreaking study finds.
Logic, if not experience, might suggest that excessive eating doesn’t bode well for your body. But what are the implications of just a few days of overconsumption; a brief period of decreased inhibition and increased food intake; a holiday-weekend binge? 
Two Temple researchers endeavored to find out, enlisting the help of six willing, healthy (and presumably hungry) adult men. And in a world of scientific technicalities and complexities, the participants’ simple task—to eat 6,000 calories per day for one week and refrain from physical activity—yielded groundbreaking results.
“We decided to pursue the burning question: What leads to diabetes?” Salim Merali, a School of Pharmacy professor and director of the Proteomics Research Facility, tells me. “By Day 3, these subjects were insulin-resistant—which was shocking to us. We didn’t expect to see that level of response.”
When I tell people I gave them 6,000 calories, they say, ‘Wow, that is so not natural.’ [In reality,] it’s very achievable to a lot of people.
-- Salim Merali, professor, School of Pharmacy, Moulder Center for Drug Discovery
The findings by Merali and the late Guenther Boden, professor of medicine at the Lewis Katz School of Medicine, were published in September in the journal Science Translational Medicine. They indicated that insulin resistance—a precursor to Type 2 diabetes—could be observed in healthy individuals after only a few days of intense overeating, a previously unestablished connection that drew international attention.
Though Merali and Boden’s findings promise to inform further research, they may also hold more immediate social implications. One recent study estimated half of adults in the U.S. have prediabetes or diabetes, and as Merali pointed out, “people are fascinated with diets and eating.” The ramifications unearthed by their work underscore just how rapidly a poor diet can wreak havoc.
The news headlines that followed the study’s release in the fall, from New York to Australia, noted the mesmerizing, if not macabre, detail: 6,000 calories.
The participants ranged in age from 46 to 55 years old and were lean, with no family history of diabetes. Generally, an average, moderately active 50-year-old man needs some 2,400 calories daily, according to the federal Center for Nutrition Policy and Promotion, and a moderately active 50- year-old woman, about 2,000 calories.
“When I tell people I gave them 6,000 calories, they say, ‘Wow, that is so not natural,’” Merali says. In reality, “it’s very achievable to a lot of people.”
In fact, the researchers served readily available cafeteria food to the patients: Pizza, bacon and muffins were a few of their picks, Merali says. The participants’ meals consisted of what’s been deemed a common American diet: 50 percent carbs, 35 percent fat, 15 percent protein. Patients generally ate a 1,500-calorie meal plus a snack of about 500 calories three times a day.
Common sense told me—a self-identifying foodie with little grasp of my daily caloric intake—that these numbers were rather large. Still, I had trouble picturing the amount, despite my best attempts to imagine the calories in neat stacks of pizza pies or mounds of rocky road ice cream.
What does such a disastrous diet look like, I wondered. How does it taste?
It turns out that it’s pretty familiar. And might be wrapped in a tortilla.
After I spoke with Merali, I decided to stop into a popular Mexican-inspired chain restaurant in pursuit of what I believed would have to be an outrageous meal that would set me on the path to the researchers’ outrageous diet. Make no mistake: Though I set out to overeat in the name of unscientific science, I did not go all Supersize Me.
I didn’t have to.
All I needed was a fairly basic lunch order: a steak burrito with the works—rice, black beans, corn, salsa, cheese, sour cream, lettuce, guacamole—and a side of the delicious, and apparently dangerous, chips and guacamole.
For $14.43, I got 2,150 calories. Read: For $14.43, I got nearly the suggested daily intake for an adult male.
Two more similar meals and I’d no doubt be on my way to caloric calamity; with habitual eating in that fashion, a possible diabetes diagnosis. And I didn’t even need a soda.
To Merali, who has also worked with HIV and cancer research, the study represents the beginning of continued exploration. Originally from Tanzania, Merali grew up in a village dreaming to one day “make a difference,” he says.
“Research was the way I could see myself helping a lot of people at one time,” Merali says. And obesity was a condition that “needed immediate attention.”
Merali credits Boden, a longtime clinical endocrinologist, with helping to introduce him to obesity and diabetes research. The two had collaborated on such work following Merali's arrival at Temple in 2005.
What peopole had done previoulsy is look at patients who were obese or who had diabetes and said, what are the molecular events that occur in those conditions?" Merali says. " For us, it was way too late in the process. We wanted to understand, what is actually the initial mechanism that triggers insulin resistance?"
Tp that end, the experts identified a marker known as oxidative stress that they believe preceded the insulin resistance. Meralie explains that overconsumption of food "damages the body through production of oxygen byproducts, attacking protein that allows glucose to be taken up." In essence, that impaired glucose transport fuction leads to high blood sugar which results in insluin resistance and sets the stage for Type 2 diabetes.
The idnetification of the presence of oxidative stress could be key in helping to ascertain conditions that may point to eventual diabetes.
“Obesity is becoming an epidemic worldwide,” Merali says. “How can we stop it from occurring? Can we use specific drugs that will allow for insulin resistance to stop? Can we find biomarkers—signature molecules—that will allow us to diagnose this insulin resistance, so we can tell people, ‘You have a good chance of becoming diabetic’?”
In terms of treatment, antioxidants could be one answer.
“If oxidants are the ones that are causing the damage to the proteins, especially involved in insulin resistance, then removing these oxidants by using antioxidants would be an approach for therapeutic purposes,” says Merali, who is also part of Temple’s Moulder Center for Drug Discovery Research.
Merali plans to build upon the research using the 6,000-calorie diet by introducing new elements: What happens when the patients return to normal eating? When exercise is thrown into the mix?
But for now, Merali recommends an old adage: Watch what you eat.
“We overeat because of food abundance,” he says, noting that consumers need to better track their food intake. “To me, it’s a matter of education.”
With a dinner out—some appetizers, soda and dessert to bookend the entree—people can “easily” approach the caloric intakes associated with his study’s enormous diet, he says.
And sometimes it fits into a single brown bag.