Keeping Metabolic Syndrome in Check

It's not a disease, but it's a precursor to stroke, diabetes, heart disease, and kidney disease. By identifying it early and working to lessen its impact, you can reduce your risk of developing these conditions.

Called metabolic syndrome, it's serious and it's dramatically on the rise - especially among people who are overweight and sedentary, according to Ahmed H. Kissebah, MD, PhD, Medical College of Wisconsin Professor of Medicine. Dr. Kissebah is one of the world's leading researchers in metabolic syndrome.

Metabolic syndrome, a cluster of interrelated conditions that can severely damage a person's health, is characterized by:

• insulin resistance -- a decreased ability to process glucose
• an overweight, apple-shaped body
• high triglycerides and blood cholesterol
• high blood pressure

In the US alone, metabolic syndrome is thought to affect 12% of children, 20% of adults, and 50% of older adults. And with escalating rates of adult and childhood obesity and diabetes, metabolic syndrome is also on the rise. In Wisconsin, childhood obesity and diabetes rates soared 33% in the past decade; records from the Wisconsin Public Health and Health Policy Institute show that 15% to 20% of Wisconsin children are now obese. "Identifying and treating metabolic syndrome early can help prevent or delay serious health risks in children and adults," Dr. Kissebah says.

If you haven't yet heard of metabolic syndrome, it's probably because it's a condition that has only recently been defined by the medical community. "In the past 15 years, it's gone from an observation to a syndrome," notes Dr. Kissebah. "Now it's a worldwide phenomenon."

The World Health Organization published the first internationally accepted definition of metabolic syndrome in 1998, but a more widely accepted criterion was defined in 2001 by the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults.

Factors characteristic of the metabolic syndrome, as stated by the NCEP, are "abdominal obesity, atherogenic dyslipidemia (elevated triglyceride, small LDL particles, low HDL cholesterol), raised blood pressure, insulin resistance (with or without glucose intolerance), and prothrombotic and proinflammatory states."

Researchers at the Medical College of Wisconsin have played a key role in defining metabolic syndrome and continue to figure prominently in researching genetic causes and developing successful early prevention models. One such model was developed by Dr. Kissebah, Gabriele E. Sonnenberg, MD, Professor of Medicine, and Senior Research Scientist Glenn R. Krakower, PhD. "This model details physiological events between obesity and the manifestations of metabolic syndrome," Dr. Kissebah explains. "It highlights the role of numerous factors called adipokines, which are secreted by adipose tissue. Adipokines markedly influence lipid and glocose/insulin metabolism, oxidative stress, and cardiovascular integrity, all of which contribute to metabolic syndrome."

"In the future, this centralized pathway model may guide the search for preventive and therapeutic interventions," says Dr. Kissebhah. "It offers a way to prevent or delay the onset of metabolic syndrome, rather than limiting treatment to specific clinical manifestations such as high blood pressure or insulin resistance."

With the support of a $5 million grant from the National Institutes of Health, Medical College researchers also have teamed with researchers at Children's Hospital of Wisconsin and Froedtert Hospital to create a successful treatment model that incorporates the patient's family. "Treating an adult or child alone with metabolic syndrome doesn't work," Dr. Kissebah says. "To successfully change a patient's lifestyle, which is key to treatment, the whole family must be involved."

Defect in the Metabolic Pathway
Normally, the digestive system breaks down food into blood sugar called glucose, the body's main fuel. The pancreas makes a protein called insulin, which travels the bloodstream and ushers the glucose into the cells, where it releases energy.

In metabolic syndrome, the body becomes resistant to insulin and high levels of glucose remain trapped in the blood. In reaction, the pancreas produces more insulin. The extra insulin temporarily allows glucose to enter the cells, but there are physiological consequences.

"Extra insulin affects cholesterol and trigylceride levels and causes damage to coronary arteries," says Dr. Kissebah. Recent studies show that metabolic syndrome causes an inflammatory process in the blood vessels that leads to arteriosclerosis, or hardening of the arteries. This inflammatory process can be gauged by blood levels of C-reactive protein, or CRP.

"A blood test that measures a person's CRP level gives us an idea of how much inflammation is present," says Dr. Kissebah. "If the CRP level is high, the person with metabolic syndrome is at risk of cardiovascular disease." High insulin levels also can interfere with the kidney's ability to process salt, which can raise blood pressure. Eventually the pancreas cannot overcome the insulin resistance. More glucose builds up in the blood, leading to Type 2 diabetes.

Part Genetic, Part Lifestyle
Poor diet and lack of exercise are the root causes in 50% of cases of metabolic syndrome, according to Dr. Kissebah. Genetics are a factor in another 50%.

Currently, Medical College researchers lead the worldwide search for the genetic components of metabolic syndrome and they have identified five genes that play a part in its development. One gene affects how the body deals with burning fat; a second influences insulin; a third affects the arteries and can promote hardening; a fourth affects lipid levels; and a fifth affects blood pressure. "We have identified members of the gene family, but are still looking for the leader, the head gene," says Dr. Kissebah.

Who is at Risk?
If left untreated, metabolic syndrome can lead to dangerous health consequences. Fortunately, doctors can test us for the four components of the syndrome:

Obesity, a particular problem if the extra weight is carried around the mid-body - often referred to as having an apple-shaped body. "Thirty years ago, we didn't know why obesity was so dangerous and we didn't know certain forms of obesity were worse than others," says Kissebah, who led groundbreaking research at the Medical College in the early '80s on health risks associated with body shapes. "Apple-shaped bodies have the worst impact on health," he says. ("Pear-shaped" people, who carry most of their weight below the waist, have lower risk of negative health effects.)

"In an apple-shaped body, fat is inside the abdomen, among the internal organs. People with apple-shaped bodies tend to have higher rates of insulin resistance and abnormal lipid levels. A waist circumference of 40 inches or more in men, and 35 inches or more in women, indicates an apple-shaped body.

Hypertension is strongly associated with heart disease, stroke and kidney disease. Blood pressure greater than or equal to 130/85 mm Hg is considered high.

Dyslipidemia, or unhealthy levels of cholesterol and lipoproteins, is indicated if HDL (the good cholesterol) is less than 40 mg/dL in men, less than 50 mg/dL in women; or if fasting triglycerides are greater than or equal to 150 mg/dL.

Insulin resistance, indicated by a fasting glucose level greater than or equal to 110 mg/dL.

Self-Care and Medical Treatment
If you have metabolic syndrome, your doctor will work with you to manage self-care strategies. "Diet and exercise are the mainstays of reducing your risk," Dr. Kissebah notes.

• If you're overweight, losing even 10 pounds can make a difference. But quick weight loss has its own dangers. Work with your doctor to develop a diet plan for a lifetime, one that is low in fat and high in fiber, including plenty of fruits and vegetables.
• If you're sedentary, get moving. Aim for 30 minutes of vigorous exercise five days a week. (A mere 8% of people in Wisconsin get regular and vigorous exercise, according to the Wisconsin Behavioral Risk Factor Survey.)
• Stop smoking. Smoking increases insulin resistance and promotes heart disease. Smokers with metabolic syndrome have poorer health outcomes.

Your doctor also may also prescribe medications to control the specific risks you have - high cholesterol, high blood pressure, insulin resistance, and obesity. "There are numerous sites along the pathway where pharmacological intervention can be helpful," says Kissebah.

The bottom line? Even if your genes put you at increased risk for metabolic syndrome and the problems it can bring, your lifestyle choices and behaviors can still make a big difference in improving your health.

Carolyn Alfvin
HealthLink Contributing Writer

MCW Health News presents up-to-date information on patient care and medical research by the physicians of the Medical College of Wisconsin.