Midriff weight gain in mid-life could be the sign of a serious metabolic problem. Ilene Cohen couldn't figure out what was wrong, and neither could her doctors. "I was always tired," she recalls, "working full-time and running a home, on my day off I didn't want to do anything. "I felt I was missing a lot because I only wanted to rest." Cohen, now 42, is just shy of five feet tall. She had been gaining weight too, and was up to 167 pounds. Over the years, she had sought help.

"I had different doctors, and I always complained about being very lethargic, and I went for more thyroid and glucose tolerance tests, and they all came back negative. 'Everything's fine, maybe you're working too much' they said."

Cohen remained baffled and miserable until a friend recommended one more doctor for her to try. An endocrinologist at New York Medical College in Valhalla, Dr. Harriette Mogul had been screening hundreds of women since the college started their Menopause Health Program in 1994. She had quickly begun noticing a cluster of symptoms in a certain type of patient who came in to be evaluated for hormone replacement therapy.

"Among these patients—a narrow range of health-conscious, non-smoking, physically-active women approaching menopause—there were many complaints of weight gain, usually around the waist, after years at a constant weight. When we began seeing these symptoms clustered together with elevated blood pressure and insulin levels, we decided there was a pattern," Dr. Mogul recalls.

Finding the Root
"Ilene came to see me because she had been experiencing weight gain, and she had a particular pattern of weight gain in her waist, and she had been exercising and attempting to diet, and really wasn't able to decrease her weight," Dr. Mogul explains. "In addition, she had some blood pressure changes, she had some abnormalities in the balance of her cholesterol, so she was starting to develop some early risk factors for heart disease."

Dr. Mogul coined the term "Syndrome W" to reflect the weight gain, particularly what she calls "waist gain," and intermittent—or "white-coat"—hypertension, she'd been seeing over and over in patients like Ilene. "Women with the Syndrome also report a detectable increase in appetite, food cravings, and inability to lose weight despite exercise and attempts to diet," she adds.

The key, however, was the women's elevated insulin levels despite normal blood glucose. Dr. Mogul was sure insulin was the root cause of all the other symptoms and realized that Syndrome W was really the manifestation of a potentially lethal phenomenon known as "insulin resistance." Therefore, the name "W" seemed all the more apt because it would likely lead, as it does alphabetically, to the better known Syndrome X.

The Power of Insulin
Also an umbrella term, "Syndrome X" was coined in 1988 by Stanford University Professor of Medicine Gerald Reaven to describe the cardiovascular effects usually observed when insulin levels are persistently elevated, as they are in many diabetics. Syndrome X traits include high blood pressure, abnormalities in the amount and properties of certain blood fats, and abnormalities in blood clotting factors. Together, these are believed to contribute significantly to the unusually high rate of death from heart disease (roughly 75 percent) among diabetics.

Insulin is a powerful hormone that can constrict blood vessels and interfere with several processes in the body. But its primary job is to shepherd incoming nutrients. Released by the pancreas when we eat, insulin guides the amino acids from protein to our muscle cells, and takes fatty acids to the fat cells.

Carbohydrates are first broken down into "blood sugar" glucose, which the body uses for energy. Insulin makes sure there's never too much of that caustic fuel lingering in the bloodstream by storing excess glucose in the liver and fat cells, and shuttling just what's needed for energy at the moment to the various cells of the body. Insulin even unlocks a sort of door on each cell, allowing glucose to enter.

But when cells no longer answer the door to insulin, the body is said to have become "insulin resistant." No one is sure what first triggers the change. Obesity is one factor observed to foster insulin resistance, but heredity also plays a role, and even a thin person can become insulin resistant.