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Medical News & Perspectives
June 27, 2018

What’s the Best Way to Treat Normal-Weight People With Metabolic Abnormalities?

JAMA. Published online June 27, 2018. doi:10.1001/jama.2018.8188

Metabolically obese normal weight or, as some prefer, normal-weight obesity sounds like an oxymoron. But according to an article in JAMA, 23.5% of normal-weight US adults ages 20 years or older were metabolically abnormal.

And such individuals account for an even a bigger percentage of the population in Asian countries. In India, for example, 40% of people considered to be normal weight by virtue of their body mass index (BMI) have metabolic dysfunction, such as high glucose and high triglycerides, said Faidon Magkos, PhD, a self-described metabolist who holds a joint appointment at the Singapore Institute for Clinical Sciences and the Yong Loo Lin School.

These metabolically obese normal-weight (MONW) individuals appear to be healthy but have a high risk of cardiometabolic disease, such as diabetes and coronary artery disease, and, possibly, cancer, although less research has been conducted into that subject, Magkos said.

While Magkos and others have used the word lean to describe MONW individuals, Francisco Lopez-Jimenez, MD, a cardiologist at the Mayo Clinic in Rochester, Minnesota, calls that a misnomer.

“People might have excessive body fat despite a normal BMI,” said Lopez-Jimenez, who studies what he prefers to call normal-weight obesity defined as a normal BMI with high body fat content (however, as he has noted, there is no consensus on how to define obesity using fat percentage or fat mass calculation).

He and his colleagues have shown that among men and women whose BMI is in the normal range, those with the highest percentage of body fat—in his study, more than 23.1% for men and more than 33.3% for women—were 4 times more likely to have metabolic syndrome, a cluster of metabolic disorders such as hypertension, high triglycerides, and high fasting glucose levels.

And in a recent article, Lopez-Jimenez and his coauthors found that among patients with known coronary artery disease, higher body fat percentage, but not BMI, was associated with a greater risk of major adverse cardiovascular events. “The problem is that we have been diagnosing obesity on the basis of BMI,” he said. “At the individual level, the accuracy of BMI is not very good.”

The notion of normal or ideal body weight dates back to 1943, when the Metropolitan Life Insurance Company introduced new height-weight tables for men and women. Ideal body weight was defined as the weight associated with the lowest mortality. Height-weight tables, and, eventually, BMI became attractive tools for diagnosing obesity because it was difficult and expensive to measure body fat mass.

However, 1 reason BMI isn’t always the best indicator of obesity is because it doesn’t account for the amount and distribution of body fat, which can vary markedly among people with normal BMI. Location is key when it comes to body fat. As a recent article pointed out, fat in the abdominal cavity, whether it be visceral or ectopic (ie, in the liver or other organs), “is a major contributor to cardiovascular and metabolic risk above and beyond the body mass index.” Magkos and others have reported that MONW individuals have a greater accumulation of visceral fat and fat in the liver and greater insulin resistance—the hallmark of the MONW phenotype—than metabolically healthy normal-weight people. On the other hand, peripheral fat, such as in the legs, appears to be protective against insulin resistance.

Waist circumference can serve as a useful tool in assessing abdominal fat; in his practice, Lopez-Jimenez said, patients with normal-weight obesity typically present with above normal waist circumference.

How Low Should You Go?

When overweight or obese individuals have metabolic dysfunction, physicians dole out straightforward lifestyle advice: Lose weight by eating less and moving more. But what about patients with metabolic dysfunction whose BMI falls in the normal range? Could they also benefit from losing weight?

Magkos and his colleagues had previously shown that body composition and metabolic function improved when obese individuals lost just 5% of their weight, so they decided to conduct a study to see if the same held true for MONW individuals.

“These people are lean, so they don’t think that they need to lose weight,” Magkos said. “I tried losing 5%. It’s not the easiest thing for a person who doesn’t have that much weight to lose.”

Still, he and his coauthors were able to recruit 11 metabolically unhealthy men and women of Chinese and Indian descent to participate in their study. The participants were aged 23 to 59 years, and their BMI ranged from 19.5 to 24.2 (the normal range for BMI, calculated as weight in kilograms divided by height in meters squared, is 18.5-24.9).

At baseline, the researchers measured their participants’ total body fat, visceral fat, and subcutaneous abdominal adipose tissue volumes. On average, their total body fat percentage was 32.8%. In addition, Magkos and his coauthors assessed the participants’ lipids, insulin sensitivity, glucose tolerance, and postprandial insulin secretion and clearance rates.

Until they lost 5% of their weight, study participants were asked to replace their usual daily lunch or dinner with low-calorie meals prepared according to their preferences by a Singapore company and delivered to their homes weekly. They were contacted regularly by telephone to make sure they were complying with the researchers’ instructions and met biweekly with a dietitian to weigh in and receive counseling.

It took the participants 6 to 16 weeks to lose 5% of their weight. When they reached that goal, a weight maintenance diet was prescribed for at least 2 weeks before repeat testing was performed.

That small amount of weight loss, approximately 7 pounds on average, had multiple beneficial effects. Compared with baseline, the 5% weight loss trimmed participants’ total fat mass by about 9%, visceral adipose tissue by about 11%, intrahepatic fat by about half, and subcutaneous abdominal adipose tissue by about 17%. Their fasting plasma insulin, triglyceride, and total cholesterol concentrations were also reduced, and their insulin sensitivity increased by 21% to 26%. There was a significant inverse correlation between changes in visceral fat volume and insulin sensitivity.

The researchers did not follow-up with their participants to see if they maintained their weight loss and improved metabolic function, Magkos said. “I am presuming a return of body weight to baseline will also return their metabolic function to baseline.”

While diet-induced weight loss was effective for treating metabolic dysfunction in MONW individuals, “even small amounts of weight loss may not be a feasible, or even the optimal, recommendation; this may be particularly true for older MONW subjects,” the authors concluded.

Weighing Other Approaches

Lopez-Jimenez prefers to focus on physical activity and nutrition, not weight, when counseling MONW patients. Weight fluctuates too much to be a useful measurement in people who need to lose only a few pounds, he said.

Exercise, especially strength training, builds muscle mass, so patients might not see any difference on the scale if they follow his advice to increase physical activity, he said. Instead, Lopez-Jimenez and his patients measure success with a blood pressure cuff, a hemoglobin A1c test, and other tools that assess metabolic function. “I tell these patients the main goal is to improve the metabolic parameters,” he said

Magkos doesn’t disagree. “Exercise, whether you are metabolically healthy or unhealthy, will improve your metabolic health,” he said. While Magkos and his coauthors asked participants not to change their activity level while losing weight, the researchers did not collect information about physical activity.

When it comes to diet, the quality of calories consumed, not just the quantity, plays a role in reducing the risk of chronic disease and death in MONW individuals, research suggests.

An analysis of data from the National Health and Nutrition Examination Survey (NHANES) found an association between a higher-quality diet, such as the DASH diet, and a lower mortality risk among MONW adults during an average follow-up of 18.6 years. The researchers did not find such an association among adults who had a normal BMI and were metabolically healthy. Previous studies assessing the effect of a healthful diet on the risk of chronic disease had focused on individuals whose BMI classified them as obese, the authors noted.

Although their BMIs were normal and, on average, similar, there was a notable difference between the metabolically healthy and metabolically unhealthy individuals, coauthor Anwar Merchant, ScD, MPH, DMD, said. The average waist circumference for the healthy group was 31.8 inches, compared with 34.1 inches for the unhealthy group, said Merchant, an epidemiology and biostatistics professor at the University of South Carolina’s Arnold School of Public Health.

Related research by Merchant and his coauthors suggested that improvements in metabolic health associated with a higher-quality diet are mediated by reductions in abdominal obesity.

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