Two recent studies from The Journal of Clinical Endocrinology & Metabolism emphasize the negative metabolic effects of fat mass compared with lean muscle mass on adolescent cardiovascular health and bone health.

Several recent studies have highlighted the importance of lean muscle mass versus the dangers of fat mass in children and adolescents — and suggest that adolescence could be a particularly important time to interrupt an individual’s trend toward the morbidities associated with obesity.

Studies often rely on body mass index (BMI) alone as a measure of obesity, but BMI can be misleading because it does not differentiate lean mass from fat mass, according to Andrew O. Agbaje, MD, PhD, MPH, a pediatric clinical epidemiologist at the Institute of Public Health and Clinical Nutrition at the University of Eastern Finland.

To differentiate the effects of muscle mass versus fat mass, Agbaje led a team that studied more than 3,000 adolescents from the U.K. Avon Longitudinal Study of Parents and Children (ALSPAC) who had complete dual-energy x-ray absorptiometry measurements and fasting blood samples taken at ages 15, 17, and 24 years.

“Fat mass drives insulin resistance, but muscle mass appears to reverse it in a very small way. If we only use BMI, we will not be able to see that muscle mass is beneficial in lowering insulin resistance. …abdominal fat is twice as dangerous as total body fat. Every increase in abdominal fat raised the risk of insulin resistance, not just at the time point but progressively from age 15 to 24.”

Andrew O. Agbaje, MD, MPH, FESC, Institute of Public Health and Clinical Nutrition, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, Kuopio

Published in The Journal of Clinical Endocrinology & Metabolism, the study analyzed the longitudinal association of total fat mass, trunk fat mass, lean mass, and BMI with the cumulative risk of hyperglycemia, hyperinsulinemia, and high insulin resistance at those ages.

“Each 1-kilogram cumulative increase in total fat mass from ages 15 through 24 years was associated with a progressively worsening risk of high insulin resistance as well as hyperglycemia and hyperinsulinemia,” the study found.

“Fat mass drives insulin resistance, but muscle mass appears to reverse it in a very small way,” Agbaje says. “If we only use BMI, we will not be able to see that muscle mass is beneficial in lowering insulin resistance.”

Agbaje added that the study was also able to differentiate the effects of kinds of fat, such that “abdominal fat is twice as dangerous as total body fat. Every increase in abdominal fat raised the risk of insulin resistance, not just at the time point but progressively from age 15 to 24.”

A Key Time to Intervene?

The temporal nature of the study — following each subject for nine years — enabled Agbaje to conclude that “this age 15 to 17 is a very critical point, where physiology appears to become pathology. The vicious cycle of insulin resistance and fat mass reinforcing each other begins at the age of 17 years.”

The timing of the start of this “vicious cycle” led the study authors to conclude: “Mid-adolescence may be an optimal time for interrupting the worsening fat mass-insulin resistance pathologic cycle and attenuating the risk of progressively worsening metabolic dysfunction before young adulthood.”

Cardiovascular Evidence

Agbaje says that a study he published in Atherosclerosis on the effects of lipids on the cardiovascular system provides further evidence of how early pathological damage can begin.

This study analyzed findings from almost 1,600 adolescents in the ALSPAC cohort who had their lipids levels measured at ages 17 and 24 along with echocardiography measurements. The study found that “each 1 mmol increase in total cholesterol was associated with higher odds of worsening left ventricular hypertrophy progression over seven years.”

The study concluded: “Increasing lipid levels from adolescence through young adulthood independently associated with the risk of progressively worsening changes in cardiac structure and function and premature cardiac damage in asymptomatic youth. Evidence of cardiac damage attributable to high lipid levels may be seen two decades earlier in the mid-twenties than the current level of evidence in the mid-forties. Increased fat mass, systolic blood pressure, and insulin are potential pathways through which increased lipids may contribute to cardiac damage.” 

Agbaje noted that these findings could indicate a need for lipid screening to begin at a much earlier age than called for in current guidelines.  

Bone Mass Can’t Keep Up

Looking at another part of the body that obesity can affect, children with obesity have higher bone mineral density and bone mineral content compared with children of average weight, yet those with obesity have a 25% higher risk of extremity fracture than children of average weight.

Intrigued by this paradox, researchers led by pediatric endocrinologist Regis Coutant, MD, of the Specialized Center for Obesity at University Hospital in Angers, France, explored the underlying mechanisms in a study published in JCEM.

The researchers used dual energy x-ray absorptiometry (DXA) to measure the bone mineral content and bone mineral density of about 250 boys with obesity between the ages of 8 and 18 years at Angers Hospital.  

They matched them by height and age with boys without obesity (whom the researchers termed “lean boys”) using data from the U.S. National Health and Nutrition Examination Study (NHANES).

The study found that each 1-point increase in BMI (1 kg/m²) was associated with an average 39-gram increase in bone mineral content in lean boys compared with a 25-gram increase in boys with obesity — a 40% difference. Each 1-point increase in lean BMI was associated with an average 78-gram increase in bone mineral content in both boys of average weight and boys with obesity, whereas a 1-point increase in fat mass index was associated with an average decrease of 9 grams of bone mineral content.

“One critical point is that when people with obesity lose weight, it is very important that they do so by exercise to keep up the lean body mass. By keeping the lean body mass, they will protect their bones.”

Regis Coutant, MD, Specialized Center for Obesity, University Hospital, Angers, France

“When you increase the mechanical load with the weight, you have to increase the bone mineral content,” Coutant says. “But the increase in the bone mineral content in boys with obesity is significantly less than it is in lean boys. So our study suggests that the increase in the bone mineral content associated with the increased weight in obese boys is not enough to support the mechanical load, so it may explain the relative bone frailty of obese boys.”

Although the study did not address treatment, Coutant says that the results suggest the importance of ensuring that children with obesity receive enough calcium and vitamin D to support bone health.

He also highlighted the important association between lean body mass and bone mineral content:

“One critical point is that when people with obesity lose weight, it is very important that they do so by exercise to keep up the lean body mass. By keeping the lean body mass, they will protect their bones.”

Seaborg is a freelance writer based in Charlottesville, Va. In the November 2023 issue, he wrote about efforts to reduce the risk of hypoglycemia in older adults with diabetes.