Elsevier

Metabolism

Volume 92, March 2019, Pages 61-70
Metabolism

Diagnosis of obesity and use of obesity biomarkers in science and clinical medicine

https://doi.org/10.1016/j.metabol.2018.12.006Get rights and content

Highlights

  • Obesity is associated with cardiovascular disease, cancer and lower life expectancy.

  • Obesity is traditionally classified based on the body mass index (BMI).

  • Taking body fat distribution into account may improve disease prediction.

  • Insulin/IGF axis and chronic inflammation are major pathophysiological pathways.

  • A biomarker-guided obesity definition may enable personalized prevention.

Abstract

The global epidemic of obesity is a major public health problem today. Obesity increases the risk of many chronic diseases, such as type 2 diabetes, coronary heart disease, and certain types of cancer, and is associated with lower life expectancy. The body mass index (BMI), which is currently used to classify obesity, is only an imperfect measure of abnormal or excessive body fat accumulation. Studies have shown that waist circumference as a measure of fat distribution may improve disease prediction. More elaborate techniques such as magnetic resonance imaging are increasingly available to assess body fat distribution, but these measures are not readily available in routine clinical practice, and health-relevant cut-offs not yet been established. The measurement of biomarkers that reflect the underlying biological mechanisms for the increased disease risk may be an alternative approach to characterize the relevant obesity phenotype. The insulin/insulin-like growth factor (IGF) axis and chronic low-grade inflammation have been identified as major pathways. In addition, specific adipokines such as leptin, adiponectin and resistin have been related to obesity-associated health outcomes. This biomarker research, which is currently further developed with the application of high throughput methods, gives important insights in obesity-related disease etiology and pathophysiological pathways and may be used to better characterize obese persons at high risk of disease development and target disease-causing biomarkers in personalized prevention strategies.

Introduction

The global epidemic of obesity is on the rise in almost all countries worldwide and further increases are expected for the future [1]. Highest obesity prevalence is observed for men in Western high income countries and for women in Central Asia, the Middle East and North Africa [1]. Obesity is a risk factor for a number of chronic diseases, most notably type 2 diabetes, coronary heart disease and certain types of cancer [2,3] and is associated with lower life expectancy [4]. Thus, obesity poses one of the major public health problems of our times and has a great relevance to both the healthcare system as well as individual health. Obesity is classically defined based on body mass index (BMI), although the BMI is known to be an imperfect measure of excessive or abnormal body fat accumulation, and studies have shown that taking body fat distribution with measures such as waist circumference into account may improve disease prediction [5]. Investigations into the underlying biological processes of the association between adiposity and chronic disease have suggested several biomarkers as potential mediators. These obesity biomarkers include circulating hormones and cytokines such as adipokines, which are hormones secreted by adipose tissue, as well as markers at other biological levels such as genetic or transcriptomic markers that have been recently brought forward by newer omics technologies. Besides providing knowledge about causes and mechanisms, obesity biomarkers also have the potential to be used for an alternative or extended more precise characterization of the obesity phenotype that is relevant for disease. Ultimately, such a biomarker-guided obesity definition may be the basis for personalized prevention identifying persons at high risk of disease development for refined monitoring and intervention programs.

In this review, we first discuss the strengths and limitations of currently used anthropometric measures to diagnose obesity and summarize the epidemiological evidence regarding the association between obesity defined by classical anthropometric measures and risk of chronic diseases and mortality. Subsequently, we introduce obesity biomarkers and summarize the current evidence from epidemiological studies relating these biomarkers to chronic disease risk. Regarding “obesity biomarkers”, we focus on molecular markers that (1) have been associated with obesity and (2) have been proposed to describe parts of the disease-causing biological mechanisms by describing the link between obesity and chronic disease, or the molecular processes contributing to obesity.

Section snippets

Diagnosis of Obesity

The World Health Organization (WHO) defines obesity as “a condition of abnormal or excessive fat accumulation in adipose tissue, to the extent that health may be impaired” [6]. Traditionally, obesity is classified based on the body mass index (BMI) calculated as weight in kilograms divided by height squared in meters. According to WHO and most current guidelines for Western populations, obesity is defined as a BMI ≥30 kg/m2 [6,7]. This classification is based on the higher risk of mortality

Obesity Defined by Classical Anthropometric Markers and Risk of Major Chronic Diseases and Mortality

General obesity as defined by BMI as well as abdominal obesity have been related to a number of chronic diseases including but not limited to type 2 diabetes, coronary heart disease, stroke, hypertension and certain types of cancer in a huge number of epidemiological studies. Today, there is condensed information available from both study-level as well as individual-level meta-analyses from consortia of prospective cohort studies, which are useful to judge the overall available evidence.

Obesity Biomarkers

While there is strong evidence from epidemiological studies on the detrimental effects of obesity defined by classical anthropometric measures on health outcomes, the underlying biological mechanisms are less understood. The endocrine function of adipose tissue, in particular visceral adipose tissue, and the hereby secreted various cytokines and adipokines have been proposed as a biological link between obesity and chronic diseases. The measurement of obesity-related biomarkers in

Conclusion

Anthropometric measurements such as BMI for general obesity and waist circumference for abdominal obesity are the predominant measures to diagnose obesity in the clinical context as well as in epidemiological research. Their strong and consistent association with health outcomes such as type 2 diabetes, coronary heart disease and certain types of cancer underlines that these are reasonable, simple instruments. For the detailed investigation on the role of body fat composition in disease

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Conflict-of-Interest/Financial Disclosure Statement

Nothing to disclose.

Author Contributions

KN drafted the article. SK and TP revised the article critically for important intellectual content. All authors participated in the conception and design of the article and approved the final version to be submitted.

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