Metabolically Healthy and Unhealthy Normal Weight and Obesity

Abstract

Increased fat mass is an established risk factor for the cardiometabolic diseases type 2 diabetes and cardiovascular disease (CVD) and is associated with increased risk of all-cause and CVD mortality. However, also very low fat mass associates with such an increased risk. Whether impaired metabolic health, characterized by hypertension, dyslipidemia, hyperglycemia, insulin resistance, and subclinical inflammation, may explain part of the elevated risk of cardiometabolic diseases that is found in many subjects with very low fat mass, as it does in many obese subjects, is unknown. An important pathomechanism of impaired metabolic health is disproportionate fat distribution. In this article the risk of cardiometabolic diseases and mortality in subjects with metabolically healthy and unhealthy normal weight and obesity is summarized. Furthermore, the change of metabolic health during a longer period of follow-up and its impact on cardiometabolic diseases is being discussed. Finally, the implementation of the concept of metabolic health in daily clinical practice is being highlighted.

Metabolically unhealthy individuals, either with obesity or not, have a higher risk of critical coronavirus disease 2019 outcomes than metabolically healthy individuals without obesity

“…This partly explains hyperimmune response to infectious insult including SARS-CoV-2 and adverse outcomes of COVID-19 in MUNW people. Another possible factor is reduced muscle mass characteristic of MUNW individuals [ 16 ]. Reduced muscle mass has been proposed to be independently associated with insulin resistance and increased susceptibility to adverse respiratory outcomes, including pneumonia and sepsis [ 28 , 29 ].…”

“…This observation directed much interest to metabolically unhealthy without obesity phenotypes. However, metabolically healthy with obesity phenotypes have also been observed [ 16 ].…”

Relationships Between Metabolic Body Composition Status and Rapid Kidney Function Decline in a Community-Based Population: A Prospective Observational Study

“…Many methods used to evaluate body fat distribution, such as computed tomography (CT) and magnetic resonance imaging (MRI), are expensive and not feasible in clinical practice. The concept of metabolic body composition status (MBCS), which may reflect different patterns of body fat distribution (9)(10)(11), has been proposed to describe six different phenotypes (12), namely metabolically healthy normal weight (MHNW), metabolically healthy overweight (MHOW), metabolically healthy obesity (MHO), metabolically unhealthy normal weight (MUNW), metabolically unhealthy overweight (MUOW), and metabolically unhealthy obesity (MUO). In recent years, several studies have indicated the importance of MBCS in assessing the risk of diabetes and cardiovascular disease (13,14).…”

Insulin and cancer: a tangled web

“…However, large epidemiological studies have shown that metabolically healthy obese individuals have greater all-cause mortality than metabolically healthy lean individuals [ 63 ], and that metabolically healthy obese individuals have greater odds of developing cancer than metabolically healthy lean individuals [ 64 ]. Conversely, there exist individuals with a BMI between 18.5 and 25 kg/m 2 who nevertheless exhibit elevated cardiometabolic risk factors with decreased skeletal muscle mass and elevated visceral fat mass, referred to as metabolically unhealthy normal-weight individuals [ 65 ], who have higher risk for diabetes [ 66 ], a three-folder high risk of all-cause mortality/cardiovascular disease [ 67 ], and an increased risk of cancer [ 58 ].…”