Link in a deadly chain

More than 30 years ago, when Dr. David Heber was an intern, he asked the senior doctors the same questions over and over:

“How come all my patients have high blood pressure, high cholesterol and diabetes? Are these things linked?” He said his mentors at Beth Israel Deaconess Medical Center in Boston would shrug and say, “Dave, common things occur commonly. Go back to work.”

Today, doctors know Heber’s intuition was right. Type 2 diabetes and heart disease are physiologically linked. What’s more, according to new government figures, 64 million Americans now have what’s called Metabolic Syndrome, also known as insulin resistance, which doubles the risk of heart disease and raises the risk of diabetes by 30%.

“It’s a chain from obesity to diabetes to heart disease,” said Heber, now director of UCLA’s Center for Human Nutrition. “In the next 10 years, 80% of all heart disease will be due to Type 2 diabetes.”

Granted, you may never have heard of Metabolic Syndrome. But you probably have it if you have any three of the following five factors:

* Abdominal obesity, as gauged by a waist circumference of 40 inches or more for men, 35 for women;

* Elevated triglycerides (150 milligrams per deciliter or more);

* Low HDL (high-density lipoprotein), or “good” cholesterol (less than 40 milligrams per deciliter in men, 50 in women);

* High blood pressure (130 millimeters of mercury or higher, over 85 millimeters or higher);

* Moderately elevated fasting blood sugar (110 to 125 milligrams per deciliter).

The pace at which Americans, especially women, are falling prey to these symptoms is increasing at an alarming rate. In this month’s issue of Diabetes Care, researchers from the national Centers for Disease Control and Prevention report that in the years between two studies -- one from 1988 through 1994 and a second in 1999 to 2000 -- there was “a significant increase” in the prevalence of Metabolic Syndrome in adults ages 20 and older.

But while the increase among men was a relatively small 2.2%, among women it was 23.5%, driven in large part by rising obesity. In recent years, tens of millions of female baby boomers have been going through menopause, which typically leads to an upper body weight gain of 12 to 20 pounds.

While heart disease does not cause diabetes, diabetes -- or insulin resistance -- can lead to heart disease. Having diabetes “is the equivalent of already having had a heart attack in terms of the risk of having a new heart attack,” said Dr. Edward S. Horton, vice president and director of clinical research at the Joslin Diabetes Center in Boston.

Metabolic Syndrome “is not a disease, per se,” said Dr. Paul Ridker, director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital in Boston, but “it is an important warning sign that something has to be done.” The term hammers home the point that heart disease and diabetes, “while seemingly different, share a common soil,” he said.

However, Metabolic Syndrome is still being treated piecemeal, as a bunch of symptoms, rather than as one linked problem. Doctors use separate drugs to control blood pressure, cholesterol and triglycerides. Drugs approved to treat diabetes are not yet approved for Metabolic Syndrome -- although trials to gauge their usefulness for this are underway.

The far better approach to treating the overall problem, Ridker and others say, is the difficult, low-tech way: by losing weight through diet and exercise.

The good news is that “you don’t have to lose a ton of weight to partially reverse Metabolic Syndrome,” said Dr. Richard Nesto, chairman of the Department of Cardiovascular Medicine at the Lahey Clinic in Burlington, Mass., and one of the country’s foremost experts on the overlap between heart disease and diabetes.

“You only have to lose 12 to 16 pounds to see marked improvement in cholesterol, blood pressure and CRP,” or C-reactive protein, a marker of inflammation that some doctors believe should be part of the definition of Metabolic Syndrome. The reason losing weight is so crucial, as opposed to just fighting individual symptoms, is that stored fat in the abdomen -- not the subcutaneous kind you can grab with your hands, but the deep fat that wraps itself around internal organs -- pumps out chemicals that drive Type 2 diabetes and heart disease. So-called visceral fat is a biologically active organ. “It’s a little factory in the belly that makes bad hormones,” as Nesto put it.

Here’s what scientists think is going on. Stored fat makes chemicals called cytokines, which trigger inflammation all over the body, including in blood vessel walls. Cytokines raise CRP levels, which in turn increase the risk of heart disease, even in people with normal cholesterol. Cytokines also increase the tendency for blood to clot, triggering potentially fatal heart attacks. They also raise blood pressure and worsen cholesterol profiles, and they cause a narrowing of the arteries, including those that feed the heart and other vital organs.

Just as important, cytokines from fat also mess up the delicate system by which insulin, the hormone that escorts sugar into cells, sends its chemical signals inside cells. Faulty insulin signaling in turn triggers insulin resistance, which forces the pancreas (which makes insulin) to work harder and harder until it finally gives out, resulting in full-blown diabetes.

Meanwhile, fat cells also release free fatty acids, which flock to the liver, where they are linked together into little bundles (triglycerides) and pumped back into the blood. In high enough amounts, triglycerides disrupt cholesterol balance, making levels of “good” cholesterol fall.

“Fatty acids are also toxic in themselves,” said Dr. George L. Blackburn, associate director of nutrition in the Division of Nutrition at Harvard Medical School.

Not a pretty picture. You can take statin drugs such as Lipitor or Zocor to lower LDL (low-density lipoprotein), or “bad” cholesterol, and reduce C-reactive protein levels. You can take diuretics, ACE inhibitors or other drugs to lower blood pressure. You can take Lopid or Tricor to lower triglycerides and Niaspan to boost “good” cholesterol.

You can also take some drugs that are approved for diabetes but not yet for insulin resistance, among them Glucophage, Avandia and Actos.

But the best solution is to take a tape measure and measure your waistline. If your girth is too great, get serious about losing weight.