Elsevier

Metabolism

Volume 63, Issue 9, September 2014, Pages 1084-1092
Metabolism

Review
Metabolically healthy obesity from childhood to adulthood — Does weight status alone matter?

https://doi.org/10.1016/j.metabol.2014.06.009Get rights and content

Abstract

Up to 30% of obese people do not display the “typical” metabolic obesity-associated complications. For this group of patients, the term “metabolically healthy obese (MHO)” has been established during the past years and has been the focus of research activities. The development and severity of insulin resistance as well as (subclinical) inflammations seems to play a key role in distinguishing metabolically healthy from metabolically non-healthy individuals. However, an internationally consistent and accepted classification that might also include inflammatory markers as well as features of non-alcoholic fatty liver disease is missing to date, and available data – in terms of prevalence, definition and severity – are heterogeneous, both during childhood/adolescence and during adulthood. In addition, the impact of MHO on future morbidity and mortality compared to obese, metabolically non-healthy as well as normal weight, metabolically healthy individuals is absolutely not clear to date and even conflicting. This review summarizes salient literature related to that topic and provides insight into our current understanding of MHO, covering all age spans from childhood to adulthood.

Introduction

Obesity prevalence has nearly doubled worldwide between 1980 and 2008 and still continues to increase. The largest increase in prevalence rates, especially during childhood and adolescence, has been lately seen in the African region as well as Europe [1].

Almost 10% of the world’s adult population presents with diabetes, with highest prevalence rates in the Eastern Mediterranean region as well as the American region [1].

Obesity is in general associated with significantly higher all-cause mortality during adulthood [2], and obesity during childhood and adolescence has been shown to significantly increase the risk for morbidity and mortality later in life [3]. Especially visceral obesity, defined as increased waist circumference and accumulation of adipose tissue in the abdomen, significantly increases the risk for cardiovascular or metabolic diseases, starting as soon as during puberty [4]. However, there is emerging evidence that some obese patients do not have the typical obesity-associated metabolic disorders, such as insulin resistance and glucose intolerance, arterial hypertension, or dyslipidemia. The phenomenon of metabolically healthy obese patients has been described almost 15 years ago [5], and prevalence rates for the MHO phenotype have been reported to vary between 10% and 34% [5], [6], [7], [8], [9]. MHO seems to be more prevalent in women than in men, and prevalence of MHO seems to decrease with age in both genders [10].

The aim of this review is to discuss the current literature and our current understanding of metabolically healthy obesity as well as underlying mechanisms and its effect on obesity-associated (long-term) morbidity from childhood over adolescence to adulthood.

Section snippets

Definition of metabolically healthy obesity

In most studies, metabolically healthy obesity has been suggested to be defined as obesity (BMI  30 kg/m2) with no indication for associated metabolic disorders, such as type 2 diabetes or dyslipidemia [5], [11], [12]. One classification presented within a review article suggests to use body fat content > 25% in men and 30% in women instead of BMI to define obesity [6]. One of the first studies to define the MHO phenotype has defined percentage body fat and insulin resistance as key components to

Underlying mechanisms defining disease or health

There is increasing evidence suggesting that (subclinical) inflammation could be the underlying mechanism that determines whether an obese individual is metabolically healthy or not and that categorizes the differences in metabolic profiles between subgroups of obesity [18]. (Subclinical) inflammation is associated with insulin resistance, and CRP has emerged as one of the best predictors of (vascular) inflammation, cardiovascular disease and the metabolic syndrome [22]. There is a strong

Healthy obese — Is there a pathophysiological explanation?

Human fat depots consist of several compartments, namely subcutaneous adipose tissue which is the most prominent, visceral fat covering the viscerum (omentum majus and around the liver and kidney) and intrahepatic fat as well as brown adipose tissue. Compared to subcutaneous fat which is mostly metabolically inactive, the visceral adipose tissue is endocrinologically active [36]. To date, more than 200 hormones are known to be secreted by the visceral adipocytes (so-called adipokines), and the

Different interventions strategies for MHO and non-MHO patients?

Such a concept would have direct impact on the development of appropriate interventions for healthy and non-healthy obese patients [39], [40]. One might hypothesize that metabolically healthy obese subjects do not need an intervention at all, whereas non-healthy obese or even metabolically non-healthy normal weight patients (if they have a substantial amount of visceral or hepatic fat) might require a lifestyle intervention. Recent studies show that aerobic exercise or hypocaloric diet may help

Metabolically healthy obesity during childhood and adolescence

Available data related to the MHO phenotype are mainly derived from studies in adults, as studies that have focused on MHO during childhood and adolescence are very limited to date. As in adult patients, there is no homogenous definition of MHO for the pediatric population: Suggested definitions for MHO in childhood and adolescence include (a) quartiles based on levels of insulin resistance determined by HOMA-IR index [46], (b) no or 1 cardiometabolic risk factor (MHO) or ≥ 1 (or ≥ 2,

Maintaining the MHO phenotype from childhood to adulthood — Are the beneficial effects later in life?

The longitudinal Bogalusa Heart study has examined 1098 individuals who participated as both children (aged 5–17 years) and adults (aged 24–43 years) between 1997 and 2002. Participants with the MHO phenotype during childhood were more likely to retain MHO status in adulthood. Despite the fact that the level of obesity and fat mass was still markedly increased in childhood and in adulthood, this group of MHO individuals (both, during childhood and in adulthood) showed a cardiometabolic profile

Metabolically healthy obesity during adulthood and impact on morbidity and mortality — Results from a meta-analysis

According to our current understanding, the classification of “metabolically benign obesity” or “metabolically healthy obesity” does only refer to metabolic or cardiovascular complications and does not take into account, that obesity may be associated with other, non-metabolic complications, such as orthopedic problems, pulmonary complications, psychological conditions, or others.

It is absolutely unclear to date, whether the MHO phenotype may modify or even resolve morbidity and mortality

Conclusion and future directive

To date, definition of metabolically healthy obesity is very heterogeneous, making comparison between studies difficult. A consistent, robust and standardized definition of metabolically healthy obesity is urgently needed, which should consider – beside features of the metabolic syndrome – the degree of visceral obesity, insulin sensitivity, inflammatory markers as well as the degree of liver fat (NAFLD). This may have important implications for clinical research and patient care alike.

Acknowledgment

Part of the work was supported by the Federal Ministry of Education and Research, Germany (Integrated Research and Treatment Center IFB “Adiposity Diseases”, FKZ: 01E01001).

References (61)

  • K. Flegal et al.

    Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis

    JAMA

    (2013)
  • M. Juonala et al.

    Childhood adiposity, adult adiposity, and cardiovascular risk factors

    N Engl J Med

    (2011)
  • S. Blüher et al.

    Body mass index, waist circumference, and waist-to-height ratio as predictors of cardiometabolic risk in childhood obesity depending on pubertal development

    J Clin Endocrinol Metab

    (2013)
  • L. Roberson et al.

    Beyond BMI: The “Metabolically healthy obese” phenotype & its association with clinical/subclinical cardiovascular disease and all-cause mortality — a systematic review

    BMC Public Health

    (2014)
  • R. Wildman et al.

    The obese without cardiometabolic risk factor clustering and the normal weight with cardiometabolic risk factor clustering: prevalence and correlates of 2 phenotypes among the US population (NHANES 1999–2004)

    Arch Intern Med

    (2008)
  • P. Pajunen et al.

    Metabolically healthy and unhealthy obesity phenotypes in the general population: the FIN-D2D survey

    BMC Public Health

    (2011)
  • J. Shea et al.

    The prevalence of metabolically healthy obese subjects defined by BMI and dual-energy X-ray absorptiometry

    Obesity (Silver Spring)

    (2011)
  • J. van Vliet-Ostaptchouk et al.

    The prevalence of metabolic syndrome and metabolically healthy obesity in Europe: a collaborative analysis of ten large cohort studies

    BMC Endocr Disord

    (2014)
  • M. Blüher

    The distinction of metabolically ‘healthy’ from ‘unhealthy’ obese individuals

    Curr Opin Lipidol

    (2010)
  • M. Brochu et al.

    What are the physical characteristics associated with a normal metabolic profile despite a high level of obesity in postmenopausal women?

    J Clin Endocrinol Metab

    (2001)
  • A. Karelis et al.

    The metabolically healthy but obese individual presents a favorable inflammation profile

    J Clin Endocrinol Metab

    (2005)
  • K. Kantartzis et al.

    Effects of a lifestyle intervention in metabolically benign and malign obesity

    Diabetologia

    (2011)
  • N. Stefan et al.

    Identification and characterization of metabolically benign obesity in humans

    Arch Intern Med

    (2008)
  • S. Camhi et al.

    Differences in body composition between metabolically healthy obese and metabolically abnormal obese adults

    Int J Obes (Lond)

    (2013)
  • A. Karelis et al.

    Obesity: can inflammatory status define metabolic health?

    Nat Rev Endocrinol

    (2013)
  • E. Bobbioni-Harsch et al.

    From metabolic normality to cardiometabolic risk factors in subjects with obesity

    Obesity (Silver Spring)

    (2012)
  • C. Aguilar-Salinas et al.

    High adiponectin concentrations are associated with the metabolically healthy obese phenotype

    J Clin Endocrinol Metab

    (2008)
  • M. Hamer et al.

    Metabolically healthy obesity and risk of all-cause and cardiovascular disease mortality

    J Clin Endocrinol Metab

    (2012)
  • J. Sutherland et al.

    The metabolic syndrome and inflammation

    Metab Syndr Relat Disord

    (2004)
  • C. Phillips et al.

    Does inflammation determine metabolic health status in obese and nonobese adults?

    J Clin Endocrinol Metab

    (2013)
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