It’s hard to miss the first clue that explains insulin resistance. Roughly 80 percent of people with type 2 diabetes are overweight or obese.
“Excess body weight is by far the strongest risk factor for diabetes,” says Harvard’s JoAnn Manson, who heads the Division of Preventive Medicine at Brigham and Women’s Hospital in Boston. And the “visceral” fat deep in your belly may boost the risk the most.
“If we could get people to a healthy weight, it could eliminate roughly half of all cases of diabetes,” says Manson. “That’s the big picture.”
Obesity doesn’t explain why we all—no matter how fat or thin—have a greater risk of diabetes as we get older. And genes, smoking, exercise, and diet also play a role. But for most people, the trouble starts when they eat too many calories, day after day.
“Any excess calories you eat are eventually turned into fat that needs to be stored,” explains Kimber Stanhope, a molecular biologist at the University of California, Davis.
At first, the fat fits into your fat cells.
“Let’s say your body is doing a good job of being able to store the fat,” says Stanhope. “But once your fat cells get too large, they’re less likely to continue to take up and retain more fat.”
Some obese people may never become insulin resistant (or diabetic) because their bodies keep making new fat cells.
“Maybe they’re just better at storing the fat because their fat cells can get bigger or they can make more fat cells,” notes Samuel. Others run out of storage room sooner. “They start to run into problems when the fat starts to spill over,” he explains.
When there’s no more room at the inn, the body stashes the fat wherever it can.
“It’s called ectopic lipid,” says Stanhope. “Fat is stored in tissues that aren’t supposed to be storing it—like the liver, muscle, and pancreas.”
Some scientists believe that misplaced fat is the key to insulin resistance. When insulin arrives at a cell, it signals a “glucose transporter” to ferry blood sugar (glucose) into the cell. Ectopic fat may block the signal, suggest studies at Yale and elsewhere.
“We think the initial insult is ectopic lipid in muscle or the liver or both,” says Samuel.
Excess fat can also lead to low levels of chronic inflammation, which makes matters worse.
“When cells get overfat, some scientists call them ‘angry fat’ because they release inflammatory proteins,” explains Sheri Colberg, professor of human movement sciences at Old Do¬minion University in Norfolk, Virginia.
In fact, some researchers contend that it’s the inflammatory proteins that keep insulin from working well.
Sources: Lancet 375: 2267, 2010. J. Clin. Invest. 116: 1793, 2006.