Endocrinol Metab.  2020 Sep;35(3):487-493. 10.3803/EnM.2020.301.

Metabolically Healthy and Unhealthy Normal Weight and Obesity

Affiliations
  • 1Department of Internal Medicine IV, University Hospital of Tübingen, Tübingen, Germany
  • 2Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich, Tübingen, Germany
  • 3German Center for Diabetes Research (DZD), Neuherberg, Germany

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.

Keyword

Obesity; Normal weight; Metabolic health; Fatty liver; Obesity, abdominal; Insulin resistance; Subclinical inflammation; Diabetes mellitus, type 2; Cardiovascular diseases

Figure

  • Fig. 1. Fat distribution, fatty liver and main lifestyle and genetic determinants of metabolically unhealthy normal weight and obesity. The arrows indicate whether the prevalence of fat distribution and fatty liver is increased or decreased in the metabolically unhealthy condition. Modified from Stefan et al. [8]. IRS1, insulin receptor substrate 1; GRB14, growth factor receptor-bound protein 14; PPARG, peroxisome proliferator activated receptor gamma; LYPLAL1, lysophospholipase like 1; FTO, fat mass and obesity-associated; MC4R, melanocortin-4 receptor.

  • Fig. 2. Transition from metabolic healthy to unhealthy phenotypes and association with cardiovascular disease (CVD) risk across body mass index categories in 90,257 women of the Nurses’ Health Study. Risk of CVD in women with normal weight and obesity, stratified by metabolic health status. Hazard ratios (HRs) are adjusted for age, race, highest degree, alcohol consumption, postmenopausal status, physical examinations for screening purposes, family history of myocardial infarction and diabetes, aspirin use, smoking status change, physical activity. The data are from Eckel et al. [30], with permission from Elsevier. CI, confidence interval.


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