The Damage Report

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In the past 5 years, new research has revealed just how IRS triggers these major health conditions, and how to reverse its damaging effects

CANCER When University of Toronto researchers checked insulin levels of 99 women with newly diagnosed early-stage breast cancer and an equal number of cancer-free women, they discovered that those with the highest insulin levels were nearly three times more likely to have breast cancer. "We've also found that among women in the study with breast cancer, those with the highest insulin levels had a three times higher risk of cancer recurrence and death," says breast cancer researcher Pamela Goodwin, MD, of Toronto's Mount Sinai Hospital. Growing evidence also ties high insulin to prostate and colon cancers.

"Insulin is a growth factor, and breast tumor cells have more insulin receptors than normal cells do," Goodwin says. High insulin levels stimulate the receptors; cancer cells then grow more quickly. "But not all breast cancer seems to be insulin-sensitive. We suspect some women have extra insulin receptors, while others don't," she notes.

Goodwin's team plans to test whether metformin, a diabetes drug that lowers insulin resistance, could protect some survivors against a cancer recurrence.

BEST PLAN NOW Exercise regularly. "You have to carve out the time to exercise regularly to help prevent high insulin levels," Goodwin says. "Make it a priority, as important as getting your hair done or attending a meeting."

INFERTILITY A whopping 5 to 10% of all women in their childbearing years have PCOS; numbers are rising with America's twin epidemics of overweight and inactivity. Researchers had long wondered why women with PCOS shared a constellation of seemingly unrelated health problems: from stubborn obesity to more breast and uterine (endometrial) cancers, heart disease, and a seven- to ten-times-higher risk for type 2 diabetes.

As it turns out, 8 out of every 10 women with PCOS may have IRS and higher-than-normal insulin levels. "Insulin isn't the only factor, but it is very important," says infertility specialist Sandra Carson, MD, a reproductive endocrinologist at Baylor College of Medicine.

High insulin levels may act on the ovaries to increase male hormones, she says. "The result is, you stop ovulating, you are more likely to gain weight and develop acne, and you can even have abnormal facial and body hair."

Now, Carson and other researchers are looking at whether women with PCOS can become pregnant if they take the ovulation-stimulating drug clomiphene citrate, the diabetes drug metformin, or a combination of the two. (This is the study in which Jeannine Scott participated.) Since the study is not yet complete, no one knows which drug therapy works best, or even which drugs the women who became pregnant, like Scott, took. (The drugs were discontinued once a woman had a positive pregnancy test.)

BEST PLAN NOW If your periods are more than 6 weeks apart (or absent altogether), you have stubborn weight that you can't shed, acne, and abnormal facial or body hair, you may have PCOS--and should see an endocrinologist or fertility specialist (if you're trying to conceive). Weight loss can help cut insulin levels (half of women with PCOS are overweight), but you may need drug treatment as well.

HEART DISEASE High insulin levels may erode the heart protection that premenopausal women get from healthy levels of "good-guy" HDL cholesterol. High insulin also endangers your arteries and heart by boosting blood fats called triglycerides; lowering HDLs; sending extra fat into your bloodstream after a meal and keeping it there longer; making "bad" LDL cholesterol particles smaller, denser, and better able to invade artery walls; and raising levels of fibrinogen, which makes blood clot.

Molecular biologists are studying tiny, intracellular chemical interactions responsible for insulin resistance, hoping to find new targets for drugs to reverse it. What they know so far: Fat stored inside muscle and liver cells causes IRS.

BEST PLAN NOW "We've shown in human studies that anything you can do to lower the fat in muscle and liver cells, such as exercise or weight loss, fixes insulin resistance," says researcher Gerald I. Shulman, MD, PhD, professor of medicine and physiology at Yale University School of Medicine.

TYPE 2 DIABETES Scientists have long known that faulty insulin metabolism leads to type 2 diabetes. It happens after decades of IRS, when insulin-making cells in your pancreas finally burn out, says Yehuda Handelsman, MD, medical director of the Metabolic Institute of America in Tarzana, CA. The result: Insulin levels plummet, and blood sugar rises to dangerous levels that may require drugs to control.

BEST PLAN NOW Don't wait until your blood sugar nudges into the prediabetes danger zone (over 100 mg/dl on a fasting blood test) or is high enough to indicate full-blown type 2 diabetes (a reading of 126 or higher on a fasting test). Everyone should have a fasting blood-sugar test every 3 years after age 45; but if you have IRS, ask your doc about more frequent checks.

HIGH BLOOD PRESSURE AND KIDNEY DAMAGE High insulin levels raise hypertension risk, possibly by encouraging your kidneys to retain sodium and water. New Tulane University research also links IRS with a 2 1/2-times-higher risk of kidney damage that leads to kidney failure.

BEST PLAN NOW If you have IRS, ask your doc about the merits of a urine test for microalbumin. It measures tiny amounts of protein leaking from your kidneys into your urine, an early sign of kidney malfunction. Researchers do not yet know for certain if reversing IRS will protect kidneys, but they suspect it may, says study author ling Chen, MD, a Tulane kidney disease specialist.

ALZHEIMER'S DISEASE AND DEMENTIA Researchers have long known that both diabetes and overweight raise the risk for Alzheimer's and other kinds of dementia. Now, an intriguing lab study from the Joslin Diabetes Center suggests that the malfunctioning insulin receptors that mimic IRS may be a link between those disorders. The brains of specially bred lab mice showed the same biochemical changes seen in Alzheimer's disease, says Kahn, one of the study's authors. "We can say that based on this evidence, people with insulin resistance might be at risk for developing these kinds of brain changes. We should think about this because IRS is becoming so prevalent."

BEST PLAN NOW The diet and exercise changes in "Your Best Anti-IRS Strategies", could help. "Most insulin resistance is reversible," Kahn says.

He cautions that no one has yet tested the next question for researchers in this cutting-edge field: Will reducing insulin resistance, with drugs or lifestyle changes, truly lower Alzheimer's risk?
Health Tool of the Future?

Experts are beginning to talk about IRS not just as a scary force, but as a tool for preventing heartbreaking health problems from ever happening. "We know how to find it. We know how to treat it," Handelsman notes. "It is very powerful."

To learn more about The Sugar Solution, go to www.prevention.com or call 800-848-4735.

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By Sarí Harrar

Senior Health News Editor Sarí Harrar covers diabetes and heart health for Prevention. She last wrote about young women and stroke.

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