Past the Tipping Point
To Handelsman, who can methodically recount the syndrome's genesis, as a parent recounts the maturation of a child, that was
the tipping point. "Nothing helped metabolic syndrome more than the establishment of the ICD9 code."
The"Make the Link" campaign, sponsored by the American College of Cardiology and the American Diabetes Association, is an
example of the type of cross-pollination of specialties emerging in metabolic syndrome.
Pharma then opened its floodgates and began to publicly fund market development initiatives to make physicians more aware
of the role of insulin resistance in diabetes and heart disease. Although physicians knew that the two often existed in the
same patients, the initiatives helped to cross-pollinate cardiologists and endocrinologists. Some of those initiatives included:
- Partners Against Insulin Resistance, an educational program underwritten by Takeda Pharmaceuticals North America and Eli Lilly,
designed to promote awareness about insulin resistance.
- The first professorship at the University of Liverpool dedicated to obesity research, funded by AstraZeneca-an early mover
in the field, having backed "Future Forum," a physician website targeting metabolic and vascular disease management, in 1999.
- "Insulin Resistance: Cardiovascular Risks and Therapeutic Interventions," an interactive satellite videoconference presented
by the Endocrine Society and funded by GSK.
The scope of research on metabolic syndrome has widened, and today scientists cite mounting evidence that insulin resistance
is related to breast, prostate, and colon cancer, polycystic ovarian syndrome, and nonalcoholic liver disease, among other
Communications about the new disease have achieved a critical mass. "Today, if you scan the medical journals, there are plenty
of articles on metabolic syndrome," says Richard Nesto, MD, chairman of the department of cardiovascular medicine at the Lahey
Clinic Medical Center in Burlington, Massachusetts; associate professor of medicine at Harvard Medical School; and co-principal
investigator of BARI 2D, a trial evaluating treatment strategies to improve survival in type 2 diabetic patients with coronary
artery disease. "And if you look at the websites that have anything to do with high blood pressure, diabetes, cholesterol-many
of them supported by drug companies-you'll see there is enough out there that the average mindful physician should have heard
That is fortunate, since by all accounts, physicians are seeing an enormous number of patients with metabolic syndrome, and
the number is expected to grow.
What's in a Name?
Population at Risk
Cardiologist Mark McGovern, MD, chief medical officer of Kos Pharmaceuticals, says that the US obesity epidemic is driving
metabolic syndrome, and, therefore, increases in type 2 diabetes and heart disease. "It's estimated that 20 percent of the
adult population has metabolic syndrome," says McGovern. "Similarly, 20 percent of adults are obese. Within the next decade,
by some estimates, obesity will climb to 40 percent of the population. Another frightful statistic from the NIH is that for
an American born in the year 2000, the lifetime odds of developing diabetes will be one in three. The American College of
Cardiology made another estimate: the prevalence of heart disease will double by the year 2040."
According to some estimates, 86 million Americans will have metabolic syndrome by 2025. Many are already being treated for
type 2 diabetes or heart disease. (It is estimated that metabolic syndrome raises the likelihood of heart attack between four
and 20 times.) But the real challenge is to find a way to prevent millions of at-risk patients from developing type 2 diabetes
and heart disease in the first place.
"In metabolic syndrome, the risk for type 2 diabetes has been there for years before the person becomes formally diagnosed,"
says Nesto. "So you may see a 60-year-old diabetic who had a heart attack at age 50. But that heart attack may actually have
been an early manifestation of this underlying metabolic condition. CVD begins well before the person loses the ability to
manage their glucose.
"It used to be that patients who have family histories of early heart attacks had 'bad genes.' But if you look at families
with premature heart attacks or strokes, very often they have metabolic syndrome."
Nesto talks to his patients about metabolic syndrome-but he may be one of the few. John Buse, MD, chairperson of the ADA diabetes/cardiovascular
disease initiative, which fueled the "Make the Link" campaign, says some doctors wouldn't recognize metabolic syndrome "if
it bit them in the face." But others ignore it intentionally because there's not yet enough clinical evidence to determine
what to do for patients.
"Until we learn more about the root causes and can test some of these new hypotheses, we're still left with treating individual
entities-one drug for hypertension, one to treat lipids, one to treat glucose abnormalities," says Gunnar Olsson, global vice-president
of cardiovascular therapy area for AstraZeneca. "So you end up with a cocktail of therapies, unless some of these drugs in
development that treat glucose and lipids simultaneously come to fruition." (See "PPAR Pipeline," page 54.)
Even though there are no FDA-approved treatments for the group of symptoms suffered by metabolic syndrome patients, there
is still value in communicating to physicians about it. "The problem comes when you have a lot of 'milds'-mild hypertension,
mild disturbances in cholesterol, and mild obesity," says Nesto. "No one bothers to treat them because, individually, the
risk factors don't look so bad. With metabolic syndrome, you have a collection of mild risk factors, but the risk of that
collection is greater than the sum of the parts."
A recent flood of research including the Diabetes Prevention Program (DPP), STOP-NIDM, and the Troglitazone in Prevention
of Diabetes (TRIPOD) proved that diabetes drugs administered to high-risk patients can prevent or delay the onset of type
2 diabetes. The Xenical in the Prevention of Diabetes in Obese Subjects (XENDOS) study demonstrated that pharmacotherapy plus
improved diet delayed or prevented the development of type 2 diabetes more than lifestyle modification alone.
"What remains to be tested," says Olsson, "is if any of the therapies treating different parts of metabolic syndrome could
have a broader effect on one or more of the risk factors, which could simplify treatment."