Insulin Resistance — Not the Whole Story

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This is not good news, but it is important. Ace blogger Janet “Jenny” Ruhl of Diabetes Update reports that “[A new study proves that] the epidemic of [Type 2] diabetes we are seeing among children and people in their teens is NOT caused by overeating and failure to exercise. It’s caused by genetic damage to the mitochondria — the parts of the cell that burn glucose.”

The study by European researchers in the March 2010 issue of Diabetes Care found specific genetic damage in the muscle cells of young people with diabetes. Their muscle cells did not respond to exercise the way most people’s muscles do; the subjects’ cells expressed much less of the chemicals needed to metabolize glucose.

The exact chemistry involved is complicated and can be reviewed by reading the study’s abstract, but one thing seems clear. Young people with diabetes have genetic damage, not necessarily bad lifestyles. The same may be true of obese young people who do not have diabetes.

Janet wrote,

Genetic damage like this occurs when children have been damaged in the womb by chemical exposures to substances ranging from pharmaceutical drugs the mother takes, to the herbicide atrazine in the water their mother drank, to pesticides in their food, to PCBs in dust, and to the plastics leaching into food from cans and containers. Once you damage a gene that occurs in every cell that burns glucose, the damage is not reversible.

Remember that Type 2 diabetes has usually been considered a disease of insulin resistance (IR). The beta cells break down because they can’t keep up with increased demands caused by IR. I wrote Janet to ask about this theory.

She wrote back, “The belief that Type 2 is almost entirely caused by insulin resistance is commonly cited in the media and many doctors, but it isn’t supported by the evidence.” She quoted an international study, which found that “most of the [gene variants associated with diabetes] influence insulin secretion rather than insulin resistance.”

“Insulin resistance is not Type 2 diabetes,” she continued. “It’s important to realize that two thirds of older adults are insulin resistant, but only about 9% develop diabetes. The rest just grow more beta cells and stay insulin resistant, with mildly abnormal blood sugars that don’t progress. You really do need some borderline and/or broken genes to take that next step.” To read more of her interesting take on diabetes, see her Web site, Blood Sugar 101.

What Does This Mean?
The reason I say this is “not good news” is that there is no treatment for genetic damage. If you have this kind of damage, exercise will probably not do you as much good as we would like. You are much more likely to need insulin.

We can add these genetic damage–related causes of insulin resistance to the genetic damage–related causes of poor insulin production — a condition usually called MODY, or maturity-onset diabetes of the young. There are at least six different types of MODY, and now we may have another dozen genetic types of insulin resistance.

I don’t totally agree with Janet. The whole theory expressed in my book, that stress (especially socioeconomic stress) and physical inactivity are the main causes of Type 2, might be less true if genetic damage is more important than IR. Janet says that poor people might have more Type 2 because they are exposed to more pollution, not because they are under more stress. I think she might be generalizing from a group of younger Type 2s, who probably do have MODY (as she herself does) or other genetic defects, to include everyone with Type 2, most of whom may not.

But in any case, insulin resistance is still important. For one thing, it predisposes you to cholesterol problems and high blood pressure, as well as diabetes. It also comes along with inflammation, causing blood vessel damage.

We still want to reduce stress, increase exercise, and do the things that tend to reduce IR. But what we should NOT do is blame Type 2 on “lifestyle.” Nor should we expect dramatic improvements in diabetes based on lifestyle change in people who have this genetic damage.

It’s hard to find out if you have such damage, however. There are roughly 20 gene variants that have been connected with Type 2, and getting tested for all of them would be very expensive. Also, since there isn’t much you can do about them, it might be better just to treat how you feel and do what keeps your numbers down. One thing is certain: For docs who say to stay off insulin because it makes you fat, and fat is the problem, this research is another slap in the face. Maybe they’ll stop talking soon.

I would like to hear what you think about this. Does knowing that you may have some of these genetic defects make you feel better or worse? Do you even believe it could be true? What, if anything, do you see yourself doing with this knowledge?

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