Obese but metabolically healthy people have a significantly lower risk of cardiovascular disease and death compared to metabolically unhealthy people with obesity. Unexpectedly, their risk is only slightly higher compared to lean, metabolically healthy people. A recent review article in 'Nature Reviews Endocrinology' by DZD researchers Matthias Schulze and Norbert Stefan shows that studies support the concept of metabolically healthy obesity (MHO) and emphasise the role of fat distribution. These findings are important for guiding treatment goals and intervention strategies in clinical practice.

High blood pressure, obesity and elevated fasting blood glucose are among the most important global health risks. These and other known factors, such as low HDL cholesterol and high triglycerides, are used to assess metabolic health. Normally, individuals are considered metabolically healthy if they have less than two of these risk factors and are not being treated with medication. Interestingly, research has identified specific subgroups, such as metabolically unhealthy normal weight (MUHNW) and metabolically healthy obesity (MHO). These groups show considerable differences in their risk of cardiovascular disease and death.

Determining metabolic health is important for targeting treatment goals and intervention strategies in clinical practice. © Matthias Schulze (created with BioRender.com)

People with MHO and favourable fat distribution do not have an increased risk of mortality from cardiovascular disease
In several meta-analyses, these two groups were compared with metabolically healthy normal weight (MHNW) individuals. According to these meta-analyses, the risk of cardiovascular disease is around 50 per cent higher in people with MHO than in people with MHNW. However, people with MUHNW have a significantly higher risk: in the meta-analyses, this is usually at least twice as high as the risk for people with MHNW. Obesity appears to increase the risk of heart failure in particular – even in metabolically healthy people. In their current review article, the two DZD researchers not only present the historical knowledge about these correlations, but also discuss their new definition of metabolic health. Taking into account the risk factors of high blood pressure, type 2 diabetes and a high waist-to-hip ratio – the so-called waist-to-hip index – when analysing data from the US National Health and Nutrition Examination Survey III and UK Biobank study, they found that the risk of mortality from cardiovascular disease was not increased in people with MHO, in contrast to a greatly increased risk in metabolically obese individuals. "These data support that body fat distribution should be taken into account when defining metabolic health," says Matthias Schulze, who heads the Department of Molecular Epidemiology at the German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE).

Fat distribution influences the risk of cardiovascular disease
Norbert Stefan, Professor of Clinical Experimental Diabetology at the University Hospital of Tübingen, adds: "BMI does not adequately reflect the metabolic abnormalities associated with the accumulation of internal abdominal fat and fat in the liver in both people with obesity and those of normal weight." To illustrate the importance of fat distribution, the authors of this review article discuss the results of different research approaches. For example, genetic analyses show that the body's reduced ability to store fat in the buttocks and thighs is a very strong and independent determinant of an increased risk of cardiovascular disease.

Preventive lifestyle interventions
On the other hand, people with MHO have a higher risk of developing type 2 diabetes compared to people with MHNW, and for many, the metabolically healthy state is of a temporary nature. This fact emphasises the importance of preventive lifestyle interventions in both MHO and MUHO. The authors emphasise that the concept of metabolic health has an easy applicability by the treating physicians and supports the communication of cardiometabolic risk with the patients. Using the concept of metabolic health, patients with obesity can easily self-assess whether their degree of weight loss has been sufficient to achieve or maintain metabolic health.

Increase metabolic health through weight reduction, healthy eating and more exercise
People with MUHO may require greater weight loss to achieve a similar low-risk state as people with MHO, requiring greater intensity and therefore more resources for weight management therapy. However, interventions should not be limited to weight control alone. Increasing physical activity and the quality of diet can help to improve or maintain metabolic health. The transformation from a metabolically unhealthy to a metabolically healthy state or the maintenance of a metabolically healthy state, regardless of lifestyle intervention and the extent of weight loss, could provide a strong motivation for patients to continue their efforts to maintain a healthy lifestyle.

Abbreviations:

Publication:
Schulze MB, Stefan N. Metabolically Healthy Obesity: From Epidemiology and Pathophysiology to Clinical Implications. Nat Rev Endocrinol. 2024, DOI: 10.1038/s41574-024-01008-5

Scientific Contact:
Prof. Dr. Matthias Schulze
Department of Molecular Epidemiology
German Institute of Human Nutrition Potsdam-Rehbruecke
Phone: +49 33200-882434
E-Mail: mschulze(at)dife.de
 

Prof. Dr. Norbert Stefan
German Center for Diabetes Research
Helmholtz Center Munich
Department of Internal Medicine IV
Tübingen University Hospital
Phone: +49 7071-2980390
E-Mail: norbert.stefan(at)med.uni-tuebingen.de

German Institute of Human Nutrition Potsdam-Rehbruecke 
The DIfE is a member of the Leibniz Association. It investigates the causes of diet-related diseases in order to develop new strategies for prevention and therapy and to provide dietary recommendations. Its research focus includes the causes and consequences of the metabolic syndrome, which is a combination of obesity, high blood pressure, insulin resistance and lipid metabolism disorder, as well as the role of diet in healthy aging and the biological basis of food choices and eating habits. www.dife.de/en

Helmholtz Munich is a leading biomedical research center. Its mission is to develop breakthrough solutions for better health in a rapidly changing world. Interdisciplinary research teams focus on environmentally triggered diseases, especially the therapy and prevention of diabetes, obesity, allergies and chronic lung diseases. www.helmholtz-munich.de/en

The German Center for Diabetes Research (DZD) is one of eight German Centers for Health Research. It brings together experts in the field of diabetes research and combines basic research, translational research, epidemiology and clinical applications. The aim is to develop novel strategies for personalized prevention and treatment of diabetes. www.dzd-ev.de/en