Identifying Metabolically Healthy but Obese Individuals in Sedentary Postmenopausal Women

Abstract

IntroductIonObesity is widely recognized as an important risk factor for the development of metabolic complications such as insulin resistance, hypertension, and dyslipidemia, which may increase the risk of cardiovascular diseases and type 2 diabetes (1-3). However, the presence of these obesity-related metabolic disturbances varies widely among obese individuals (4-8). Accordingly, a unique subset of obese individuals has been described in the medical literature that appears to be protected or more resistant to the development of metabolic abnormalities associated with obesity (9-11). These individuals, now known as "metabolically healthy but obese" (MHO), despite having excessive body fatness, display a favorable metabolic profile characterized by high levels of insulin sensitivity, no hypertension as well as normal lipid, inflammation, hormonal and immune profiles (12-16). Moreover, a recent longitudinal study reported that the protective metabolic profile observed in MHO individuals was associated with lower incidences of type 2 diabetes and cardiovascular diseases (17). Furthermore, evidence suggests that MHO individuals may account for as much as 30-40% of the obese population (4,5,10,18,19 The purpose of this study was to compare different methods to identify metabolically healthy but obese (MHO) individuals in a cohort of obese postmenopausal women. We examined the anthropometric and metabolic characteristics of 113 obese (age: 57.3 ± 4.8 years; BMI: 34.2 ± 2.7 kg/m 2 ), sedentary postmenopausal women. The following methods were used to identify MHO subjects: the hyperinsulinemic-euglycemic clamp (MHO: upper quartile of glucose disposal rates); the Matsuda index (MHO: upper quartile of the Matsuda index); the homeostasis model assessment (HOMA) index (MHO: lower quartile of the HOMA index); having 0-1 cardiometabolic abnormalities (systolic/diastolic blood pressure ≥130/85 mm Hg, triglycerides (TG) ≥1.7 mmol/l, glucose ≥5.6 mmol/l, HOMA >5.13, high-sensitive C-reactive protein (hsCRP) >0.1 mg/l, high-density lipoprotein-cholesterol (HDL-C) <1.3 mmol/l); and meeting four out of five metabolic factors (HOMA ≤2.7, TG ≤1.7 mmol/l, HDL-C ≥1.3 mmol/l, low-density lipoproteincholesterol ≤2.6 mmol/l, hsCRP ≤3.0 mg/l). Thereafter, we measured insulin sensitivity, body composition (dual-energy X-ray absorptiometry), body fat distribution (computed tomography scan), energy expenditure, plasma lipids, inflammation markers, resting blood pressure, and cardiorespiratory fitness. We found significant differences in body composition (i.e., peripheral fat mass, central lean body mass (LBM)) and metabolic risk factors (i.e., HDL-C, hsCRP) between MHO and at risk individuals using the different methods to identify both groups. In addition, significant differences between MHO subjects using the different methods to identify MHO individuals were observed such as age, TG/HDL, hsCRP, and fasting insulin. However, independently of the methods used, we noted some recurrent characteristics that identify MHO subjects such as TG, a...

The association between inflammatory biomarkers and metabolically healthy obesity depends of the definition used

“…Again, our findings are partly in agreement with the literature (Koster et al, 2010) and may be related to differing body fat content according to the definition of MHO used (Messier et al, 2010). Still, the differences in TNF-a levels among some MHO definitions remained significant after adjusting for waist or body fat percentage ( Table 6), suggesting that metabolic pathways other than differing fat content might intervene.…”

“…Conversely, the MHO definition of Meigs includes many components (waist, systolic blood pressure, diastolic blood pressure), which are significantly associated with inflammatory markers, thus, explaining the differences between MHO and non-MHO subjects. Overall, our findings suggest that the lower levels of inflammatory biomarkers found among MHO subjects could be due to a lower or different fat mass distribution (higher subcutaneous and lower visceral; Messier et al, 2010), a different genetic background or simply a selection bias (criteria used to define MHO). Nevertheless, further studies are needed to assess which of these hypotheses (and possibly others) are actually true.…”

“…Overall, our data are in agreement with the results of previous studies (Park et al, 2005;Di Renzo et al, 2008), which suggested that increased IL-6 is associated with increased body fat content. Hence, the lower IL-6 levels found for some MHO definitions appear to be associated with a decreased body fat content in MHO subjects using these definitions (Messier et al, 2010) and not to a specific effect in MHO on IL-6 levels.…”

Metabolically healthy obesity: different prevalences using different criteria

“…Our findings suggest that the prevalence of MHO varies considerably according to the obesity markers and the criteria used to define metabolic abnormalities, thus raising the question of which criteria and obesity markers to use, and the comparability between studies. Furthermore, o5% of all obese subjects (irrespective of the anthropometric marker used to define obesity) were considered as MHO by all six definitions used, a finding also reported in another study, where no MHO subject was identified within the five methods used (Messier et al, 2009 Using BMI to define obesity, the prevalence of MHO was lower than reported in other studies (Figure 3). An exception was the prevalence of MHO in women defined by the criteria of Karelis et al (2004), which showed a good agreement with the previously published data.…”

“…Metabolic abnormalities were defined using different criteria (see Table 1 for details). Prevalence of metabolically healthy obesity S Velho et al (Messier et al, 2009), still our data suggest that an increased waist is negatively related with MHO among BMI-defined obese subjects. Nevertheless, the wide range of MHO prevalence according to the set of criteria used observed in this study stresses the need for an expert consensus to standardize the identification of MHO subjects, as suggested previously (Messier et al, 2009).…”