Diabetes Forecast

Reducing Deep Fat May Curb Insulin Resistance

Photograph by Robert Houser

Tracey McLaughlin, MD

Tracey McLaughlin, MD
Endocrinologist, Stanford University School of Medicine
Insulin Resistance
ADA Research Funding
Clinical Translational Award

Evolutionarily speaking, storing fat makes a lot of sense. Food hasn't always been as plentiful or easy to put on the table as it is for most people today. In times when famine could easily follow feast, it made lots of sense to pack away extra calories for the future.

The best place to store those extra calories is in our subcutaneous fat cells—literally, under the skin. Sometimes they end up elsewhere, though. Fat gets deposited deep inside the body, in organs such as the liver, and marbled through our muscle tissue.

Stanford University researcher Tracey McLaughlin thinks the different destinations may account for a medical mystery: Why do some overweight or obese people have type 2 diabetes and other diseases while others, equally overweight, are entirely healthy? "I believe it's not just total fat mass but the character of the fat," McLaughlin says.

One key indicator that all fat isn't the same is insulin resistance, a major cause of type 2 diabetes. Insulin-resistant people need more of the hormone to signal their bodies to begin absorbing glucose. The pancreas, working extra hard to produce enough insulin, eventually tires out and insulin production dwindles. With less and less insulin, blood glucose levels rise to a point at which diabetes is diagnosed.

Yet it turns out that measures of overweight and obesity such as a high body mass index (BMI) are not necessarily good indicators of insulin resistance. "We've been studying overweight to moderately obese individuals, and not all of them are equally insulin resistant," McLaughlin says. "Maybe it has to do with the fact that one person has different fat than another, or has to do with where they put their fat."

Help support diabetes science: Join the Summit Circle, ADA's society of individuals who make a planned gift. Please call 1-888-700-7029 or go to diabetes.org/giving.

To solve this puzzle, McLaughlin has set up an experiment with the help of a grant from the American Diabetes Association. Unlike researchers who put patients on diets to see what happens, she's interested in how the body reacts to weight gain. McLaughlin is recruiting two dozen people with BMIs between 25 and 35 (these scores, rough estimates of total body fat, are in the overweight-to-obese range). She's asking them to eat an extra 1,000 calories a day for a month. Half of the people in the study are already insulin resistant; the others respond well to insulin despite being overweight or obese.

Participants in the study get relatively healthy foods, such as trail mix, juice, and pre-packaged breakfast bars, to top off their regular diets. "They're things that are low in saturated fat and higher in better kinds of fat," McLaughlin says. "It's a relatively healthy calorie excess, not like going out to McDonald's."

The goal is rapid, measurable weight gain. So far, people in the study have gained 5 to 10 pounds over the course of the four weeks. "Overfeeding is essentially a stress test for fat," McLaughlin says. People are tested at the beginning to see where their body fat is distributed: An MRI looks for liver fat; a CT scan shows fat that's under the skin, as opposed to deep inside the body; and a fat biopsy takes a look at the fat cells and their genetic makeup. When the four weeks are over, participants are tested again to see where the new fat ended up. For ethical reasons, they're then enrolled in a weight-loss program.

Early results from McLaughlin's "stress test" show how close the relationship between fat and insulin resistance is: Insulin resistance increased 46 percent on average, just with a 5- or 6-pound weight gain.

As she works through the data, McLaughlin hopes to see clear connections between insulin resistance and different types of body fat. "The role of fat is to store excess nutrients, and individuals able to meet excess calorie demands and store it in the right places—subcutaneous fat deposits—will be relatively protected," she predicts. "People who have trouble will experience stress in fat cells, which can provide a link to whole-body insulin resistance." Fat deposits in muscle or organ tissue, for example, may make it harder for the body to take up glucose, or cause inflammation that interferes with insulin's signals.

Armed with a better understanding of how—and why—the body directs fat to places it shouldn't be, doctors could then devise ways to nudge fat in the right direction. Safely under the skin, those stored calories would be less likely to tip the body toward insulin resistance, or worse. "There might be a pharmaceutical intervention that would help treat insulin resistance, and maybe type 2 diabetes," McLaughlin says.



Take the Type 2
Diabetes Risk Test