THE DANGERS OF VISCERAL FAT

Most physicians have experienced this apparent contradiction: Jane Doe carries so much weight on her hips and thighs that it pushes her body mass index (BMI) into the obese range. Yet her blood sugar, lipids, and other metabolic tests remain normal. John Doe’s BMI classifies him as overweight but not obese, perhaps thanks to his thin arms and thin legs. All his fat is around his middle. And it is the nonobese John Doe who develops diabetes.

The key difference could lie in whether they carry their extra weight in the body types called “apples” or “pears.” Apples are big in the abdomen, with visceral fat wrapped around their vital organs. Pears expand out farther down, their extra calories taking the form of less metabolically active subcutaneous fat.

The risks of overweight and obesity—diabetes, heart disease, stroke, and metabolic syndrome—are well-known, but researchers are making progress in understanding why these risks increase greatly when fat is added inside the peritoneal cavity as visceral fat. The easiest and most accepted indicator of visceral fat is waist circumference, and although many studies have shown that it is no better than BMI in predicting problems such as cardiovascular risk, many experts see it as a better measure of metabolic risk, especially in women.

Latest Guideline

Th at belief is reflected in guidelines that have adopted waist circumference over BMI, including the National Cholesterol Education Program Adult Treatment Panel III guideline for identifying metabolic syndrome, which recommends that a waist circumference at or above 102 cm (40 inches) for men and 88 cm (35 inches) for women be considered a risk factor. The Endocrine Society Guideline on Metabolic Risk recommends these cutoffs for most patients, but drops them in East Asian and South Asian patients to 90 cm (35.5 inches) for men and 80 cm (31.5 inches) for women.

Waist circumference measurement is not difficult, but because it is not as routine as height and weight, both nurses and patients can be resistant or at least unaccustomed to it, said Daniel Bessesen, M.D., chief of endocrinology at Denver Health Medical Center. The proper procedure is to measure at the top of the hip bone with the tape measure parallel to the floor at the end of a relaxed expiration.

The waist-to-hip ratio has been proposed as another abdominal alternative, but there is no evidence that is better than waist circumference or BMI, and it is a more complicated measurement and calculation.

None of these anthropometric measures can distinguish between subcutaneous fat located around the waist and visceral, also known as intra-abdominal, fat. Only an expensive procedure like magnetic resonance spectroscopy or imaging can visualize the fat in its specific depots.

Visceral fat is associated with a constellation of metabolic abnormalities, including insulin resistance, hyperinsulinemia, glucose intolerance, type 2 diabetes, high triglycerides, dyslipidemia, inflammation, and altered cytokine profile. (Its relationships with other obesity-related problems like arthritis and cancer are not well known.) To investigate whether central adiposity is a root cause of these problems or is simply a marker of deeper abnormalities, researchers tested the effects of removing the fat surgically.

Liposuction Outcomes

Samuel Klein, M.D., professor of medicine and nutritional science and director of the Center for Human Nutrition at Washington University School of Medicine in St. Louis, and his colleagues used liposuction to remove large amounts of abdominal subcutaneous adipose tissue, corresponding to a 10 percent reduction in total body fat and a 7 percent reduction in weight. In contrast to what would be expected from a similar weight loss by dieting, the fat reduction did not improve metabolic outcomes such as insulin sensitivity, blood pressure, plasma triglycerides, and cholesterol.

But that was subcutaneous fat, so Klein worked with another group that did a more invasive procedure to remove visceral adipose tissue by surgically removing the omentum. The surgery did not improve insulin sensitivity or other measures of metabolic function in patients who also had Roux-en-Y gastric bypass surgery or on its own in obese subjects with type 2 diabetes.

“It is not the loss of fat that’s important, but how you lose the fat that’s important,” Klein told Endocrine News. “When you remove fat by eating less and being more physically active, you shrink your fat cells to a smaller size and you eliminate fat in other organs like muscle tissue [and] liver tissue, as well as reducing visceral fat. When you remove fat by liposuction, you remove billions of subcutaneous fat cells without changing any of the other parameters, and some of those other parameters are probably important to improve metabolic function.”

Energy Balance

Gastric bypass patients’ diabetes can go into remission after surgery but before they have lost much weight, providing more evidence that the fat itself may not be the issue. The highly cited recent studies of Roy Taylor, M.D., of Newcastle University in the United Kingdom showed that obese patients who restrict their intake to 600 calories a day can resolve their type 2 diabetes within weeks. Magnetic resonance imaging scans revealed that fat levels in these patients’ pancreases and livers declined to normal levels, and their pancreases regained their ability to make insulin. “We believe this shows that type 2 diabetes is all about energy balance in the body,” Taylor said. “If you are eating more than you burn, then the excess is stored in the liver and pancreas as fat, which can lead to type 2 diabetes in some people.”

Klein said his studies have also showed that fat in the liver is very sensitive to small changes in energy balance, and “within 48 hours we found that you can reduce fat in the liver by 25 percent by just calorie restriction.” But he cautioned that whether liver fat is a marker or a cause is not known.

Another line of inquiry proposes that the excess visceral adiposity is caused by an overactivated hypothalamic-pituitary-adrenal axis leading to increased control of carbohydrate and lipid metabolism by glucocorticoids. Because visceral adipocytes have more glucocorticoid receptors than subcutaneous adipose cells, the activated axis could promote visceral fat deposition while inducing insulin resistance in the liver and skeletal muscle.

Visceral fat cells differ from subcutaneous fat cells in other ways with negative metabolic consequences—they secrete less leptin and are associated with higher levels of cortisol.

Weight Redistribution

Why some fat cells go to the thighs and some go to the belly is not known, but part of the reason may be hormonal—when women go through menopause, some of their weight redistributes to the abdomen, with accompanying adverse changes in metabolic tests. And there is undoubtedly a genetic component, said Naveed Sattar, M.D., Ph.D., professor of metabolic medicine at the University of Glasgow in the United Kingdom. People vary in the amounts that their subcutaneous fat depots can hold, and evidently once that capacity is exhausted “you start to put fat centrally, and your visceral fat accumulation, and that of associated organs such as liver, goes up,” he said.

Although Sattar notes that waist circumference is the “best anthropometric predictor of visceral fat,” and might be better in terms of predicting metabolic risks such as diabetes, he was part of a group that published a study last year in the Lancet that found that measures such as BMI and waist circumference do not significantly improve assessment of cardiovascular risk when metabolic information is already available on “downstream” measures such blood pressure, diabetes status, and lipid levels.

A rather simple measure of the risk has been proposed by one of the leaders in the field, Jean-Pierre Després, Ph.D., of the Université Laval in Quebec City, Canada. His studies show that an elevated fasting triglyceride level and enlarged waistline are “predictive of excess visceral adiposity, a clinical phenotype that we first described as ‘hypertriglyceridemic waist’.” These simple markers could allow cardiologists and primary-care physicians to identify patients wiThexcess visceral fat putting them at increased cardiovascular risk, he concluded in a recent issue of Circulation.

Another reason for relying on indicators such as insulin sensitivity and lipids is that they reveal what is happening in the body, which can vary greatly at the same levels of fat. For example, some normal weight people are “metabolically obese” in these measures, and conversely, the tests of patients who are “fat and fit” can remain in the normal range despite their weight, evidently because they are active and in good aerobic condition.

Simple Treatment

Researchers can debate ultimate causes, but there is no doubt that a major underlying driver is too many calories. And that means that whether an overweight patient has visceral or subcutaneous fat, the frontline treatment is the same: The patient should eat less, exercise more, and adopt a healthier lifestyle. The value of waist circumference may be that it provides one more argument to convince a patient of this necessity—or, in extreme cases, of the need for bariatric surgery or weight-loss drugs.

“Numbers do have power for a patient,” Bessesen told Endocrine News. “I often have a patient who says, ‘I just cannot weigh 200 pounds. My weight is 201 pounds, and that’s unacceptable’, as though 198 is OK, but 201 is not. It ultimately comes down to somebody deciding to take action. The factor that ultimately tips somebody over is often a number.”

And one advantage that waist circumference offers over weight is that a patient who exercises can lose fat but gain muscle to weigh about the same. But bringing the belt in a notch is unequivocal evidence of progress.

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