Obesity-rated illnesses are set to overtake smoking as the leading cause of death in the US, warned a recent study. As the overwhelming statistics call for urgent action, however, many scientists are questioning the clinical standards for diagnosing the disorders.

For public health purposes, the body mass index (BMI)—albeit an imperfect measure—is used to assess risk of diabetes and cardiovascular disease (see page 325). But several studies now suggest that the 'metabolic syndrome' is a better clinical benchmark for those diseases (Circulation 109, 42–46 and 706–713; 2004).

Among physicians, “I think the word [about metabolic syndrome] is buzzing around,” says Prakash Deedwania, chief of cardiology at the Veterans Administration Central California Health Care System in Fresno. Studies suggest that more than 20% of Americans and about 45% of those over 50 have the syndrome (JAMA 287, 356–359; 2002). But most people who have it don't know about it, Deedwania says. “I think there needs to be more of a unified public health message,” he says.

Even among scientists, there is confusion about the exact criteria for the syndrome, says Gerald Reaven, professor of medicine at Stanford University. Reaven in 1988 coined the term 'Syndrome X' to define a similar constellation of symptoms associated with cardiovascular risk.

Definitions of the metabolic syndrome continue to change nearly as rapidly as the average waist size in the US. One definition established by a panel of experts in 2001 describes the syndrome as a large waist circumference combined with hypertension, low levels of high-density cholesterol, and high levels of glucose and triglycerides. The World Health Organization's definition uses the BMI instead of waist circumference, and some other researchers feel that neither the BMI nor waist circumference is particularly useful.

There is increasing evidence that rather than a high BMI or an expansive waist, other components of the metabolic syndrome—such as high triglycerides—are more predictive of cardiovascular risk. Indeed, many people with the syndrome appear healthy, and many are not overweight.

For instance, the metabolic syndrome is closely related to insulin resistance, but the risk for insulin resistance is highly dependent on genetics, Reaven says. About 25% of the risk comes from a lack of exercise, and only 25% from being overweight. Individuals from specific ethnic groups—such as Asian Indians—have the highest risk of developing insulin resistance, although many appear thin.

“People need to look beyond the scale,” says Oscar Marroquin, a cardiologist at the University of Pittsburgh. “Is [the culprit] really obesity or metabolic abnormalities associated with obesity?”