This article originally appeared in the June 2006 Harvard Women’s Health Watch and is provided courtesy of Harvard Health Publications.

The metabolic syndrome: Diagnosis

Although it’s only been recognized since 1988, this looming threat to America’s health has already been known by several names — Syndrome X, the Insulin Resistance Syndrome, and the Deadly Quartet. Each name has some merit; the disorder has several components, is deadly, may depend largely on insulin, and is still somewhat mysterious. But as researchers have learned more, they’ve settled on a name that’s less punchy but more accurate.

What is the metabolic syndrome, and what does it mean for your health?

The fearsome five
Although the metabolic syndrome was originally classified as a quartet of abnormalities, doctors have now identified five components. The table below displays the most widely accepted criteria for the diagnosis.

People who have as few as three of the five abnormalities qualify for the diagnosis; the presence of four or five makes the outlook even worse. Here is a rundown of the individual factors.

1. Obesity. It’s the fundamental factor in the metabolic syndrome, and the rapid increase in America’s girth accounts for the rapid emergence of the syndrome.

Fewer than 15% of men with healthy body weights have the problem, but the risk rises to 22% in overweight men and to 60% in those who are obese. Since about a third of all American adults are overweight and another third obese, it’s easy to see that the metabolic syndrome is on the rise.

All forms of obesity are troublesome, but upper body obesity is the most troublesome of all. Abdominal obesity is more common in men (the “beer belly” or “apple shape”) than women (the “pear shape”). The easiest way to find out if you have abdominal obesity is to measure your waist at the navel, measure your hips at their widest, then divide your waist size by your hip size. A man’s risk of heart attack and stroke rises progressively with waist-to-hip ratios above 1.0 (for women, risk rises above 0.85). The math is simple enough, but it’s even simpler to find out if you have enough body fat to meet the first criterion for the metabolic syndrome: Just measure your waist. Forty inches put you where you don’t want to be.

2. Triglycerides have been the most controversial and confusing of the blood fats. Since they transport fatty acids through the bloodstream after they’re absorbed from food, a fasting blood sample is required for an accurate measurement. Doctors are still not sure whether a high triglyceride level increases the risk of heart disease if it’s the only thing that’s abnormal. But it’s now clear that high triglyceride levels are risky indeed when they are part of the metabolic syndrome.

3. HDL cholesterol has been called the “good” cholesterol because high levels are associated with a reduced risk of heart attack and stroke. HDL is protective because it represents cholesterol molecules that are being carried away from arteries to the liver, which disposes of them by dumping them into the bile.

The higher your HDL, the better. Normal values for men begin at 35 mg/dL, but even a “normal” level of 40 will increase risk when it’s part of the metabolic syndrome.

4. Blood pressure. Experts have been progressively lowering their goals for healthy blood pressure readings as they’ve learned more about blood pressure and the risk of stroke, heart disease, and kidney failure. Even with these changes, however, the diagnosis of hypertension still depends on readings of 140/90 or higher. But although a pressure of 130/85 is only in the range of “prehypertension,” it’s enough to contribute to a diagnosis of the metabolic syndrome.

5. Blood sugar is a kind of shorthand for the role of insulin when it comes to diagnosing the metabolic syndrome.

Glucose is the sugar that fuels the body’s metabolism. Blood sugar (glucose) levels rise after a meal. In response, the pancreas pours insulin into the blood. The hormone allows glucose to get into cells; blood sugar levels fall, and the body gets the energy it needs. In healthy people, insulin levels reflect the amount of carbohydrate in a meal and the length of time it takes the intestines to break down the carbs into the glucose that’s absorbed into the blood.
An elevated blood sugar level is the hallmark of diabetes. In type 1 diabetes, the problem is a lack of insulin. In contrast, most patients with the much more common type 2 form of the disease can produce insulin; the problem is that their tissues don’t respond properly — they have insulin resistance.

Fasting blood sugar levels below 100 mg/dL are considered normal, and levels of 126 or higher establish a diagnosis of diabetes. But values between 100 and 126 generally indicate insulin resistance, and modest elevations of 110 or higher are enough to be counted toward a diagnosis of the metabolic syndrome.

Is it common?
Yes.

According to the Third National Health and Nutrition Examination Survey, the prevalence of the metabolic syndrome rises progressively with age. Only 7% of 20- to 29-year-olds have the problem, but by age 60 the prevalence is above 40%. In all, 24% of American men and 23% of American women have the problem.

Is it dangerous?
Yes.

The metabolic syndrome is a cluster of cardiovascular risk factors. With the possible exception of triglycerides, each is important in its own right — but when they occur in a package, the total risk is greater than the sum of the parts. And that risk is substantial. An important 13-year study of 6,255 adults found that people with the problem were two times more likely to die from coronary artery disease than people without it. According to research published in 2005, hostility adds to the risk of the syndrome, quadrupling the chances of suffering a heart attack. Similarly, a study of over 1,000 men reported that the metabolic syndrome doubles the risk of stroke. And results suggest that the syndrome contributes to cognitive decline, kidney disease, and liver disease.

What fuels the fire?
Scientists have learned how to identify the metabolic syndrome, but they have not fully unraveled its mysteries. All five components are closely related aspects of the body’s metabolism. According to one theory, insulin is the driving force behind a vicious cycle of damage. The body seems to compensate for excessive insulin levels by producing more adrenaline, cortisol, and other stress hormones. These chemicals have two major effects. First, they boost the blood levels of free fatty acids and glucose; high glucose levels trigger more insulin release, perpetuating the cycle. Second, the stress hormones act with high sugar levels and insulin itself to raise the blood pressure, damage the sensitive endothelial cells that line the arteries, and trigger the blood clots that can form on cholesterol-laden plaques to produce heart attacks and strokes.

More research is needed to gain a fuller understanding of how the metabolic syndrome does its damage. But even now, scientists can measure that damage as it progresses. C-reactive protein (CRP) is produced by the liver in response to inflammation anywhere in the body. The high-sensitivity test for CRP can measure the subtle increases that reflect vascular inflammation caused by atherosclerosis. The higher the CRP, the greater the risk of heart attack and stroke. And a study of almost 15,000 apparently healthy women found a clear link between the metabolic syndrome and CRP levels. When none of the five abnormalities was present, the average CRP was just 0.68 mg/L, but it rose progressively to 1.09, 1.93, 3.01, 3.88, and 5.75 when two, three, four, or five criteria were present.

Problems and progress
It’s taken more than 15 years for doctors to define the metabolic syndrome and to recognize it as a major risk factor for heart attack and stroke. Research on the treatment is just hitting its stride, but we can’t afford to wait another 15 years for the answers — nor do we have to; although it will take time to clarify the role of medication, it’s already clear that lifestyle therapy can help.

Stress and metabolic syndrome
A 2006 study of 10,308 British civil servants linked work stress to a 2.2-fold increase in the risk of the metabolic syndrome, probably because of unhealthy lifestyles. It’s another example of the way stress can impair health.