Redefining Evaluation of Adiposity and Leanness: Broadening Objective Diagnostics for Obesity (REAL-BODY)

Obesity is a disease of excess and abnormal distribution of adipose tissue. Even though negative metabolic outcomes of obesity are driven by adipose tissue, investigators still use body weight (comprised of both fat and fat-free mass) in the calculation of body mass index (weight in kg divided by height in meters squared) to define, subclassify and monitor treatment in people with obesity. Despite this traditional focus on body weight, body composition is an important consideration in the management of people with obesity.

Clinical trials and clinical research often use DXA and MRI to quantify changes in body composition; however these methods are expensive and not easily implemented. It is desirable to monitor fat mass and other body composition outcomes in individuals with obesity taking weight loss medications as well as when new weight management therapeutic drugs are developed.

Most weight loss medications are associated with loss of both fat mass and fat-free mass with the "quality of weight loss" defined as the proportion of weight lost as fat mass, equal to 60-75%. Recognizing that loss of fat-free mass during weight loss is undesirable, several companies are developing lean mass preserving weight loss agents. For these agents, stepping on a weight scale will no longer be an accurate measure of benefit; loss in fat is offset by gains in lean, rendering body weight changes as an inaccurate measure of weight loss quality. Therefore, the application of body composition measurements will be required for patients, physicians, and payors to monitor treatment in people with obesity. In order for this to occur, investigators need scalable body composition measurements for fat mass.

Bioelectrical impedance analysis (BIA) offers a more scalable approach as the time, cost and footprint of BIA devices make them appropriate for a physician's office and for clinical research trials. Traditionally, BIA devices have been deemed to possess insufficient accuracy for body composition quantification. While this decreased accuracy was an obstacle for first generation weight loss medications with less weight loss, it is possible that with the newer generation of weight loss medications that confer greater weight loss, BIA may be adequate to measure changes in body composition occurring over time in individuals losing weight. Additionally, notable technological innovation has occurred in the field of bioimpedance, with several new devices possessing improved hardware and software as compared to previously evaluated analyzers. As such, these devices are expected to outperform traditional BIA systems.

Other accessible technologies that are practical to apply in clinical research and practice have appeared in recent publications. These include three-dimensional optical systems (3DO) housed in smartphones and multi-omics blood tests capable of estimating various body compartments. To the extent that BIA and these newer technologies can serve as useful sufficiently reproducible phenotypic measures of a person's body composition remains largely unknown. In addition to the dichotomy of fat mass vs fat-free mass, not all fat mass is created equal. Superficial or subcutaneous fat mass is thought to be metabolically healthy whereas visceral central fat is thought to be metabolically unhealthy. Furthermore, visceral fat is associated with long-term morbidity and mortality. Therefore, another dimension of body composition is the proportion of fat in the visceral vs subcutaneous compartments.