Metabolically Healthy But Obese Phenotype Research Articles

Metabolically Healthy, but Obese Individuals and Associations with Echocardiographic Parameters and Inflammatory Biomarkers: Results from the CARLA Study.

IntroductionThe research on heterogeneity among obese individuals has identified the metabolically healthy, but obese (MHO) phenotype as a distinct group that does not experience the typical cardiovascular-related diseases (CVD). It is unclear if this group differs with regard to preconditions for CVDs. Our aim was to assess differences in echocardiographic parameters and inflammatory biomarkers between MHO and metabolically healthy, normal weight individuals (MHNW).MethodsThe analyses used data from 1412 elderly participants from a German population-based cohort study (CARLA), which collected detailed information on demographic, biochemical, and echocardiographic variables. Participants were subdivided into four groups (MHNW, MHO, MUNW (metabolically unhealthy, normal weight) and MUO (metabolically unhealthy, obese)) based on BMI≥30 kg/m2 (obese or normal weight) and presence of components of the metabolic syndrome. The clinical characteristics of the 4 groups were compared with ANOVA or Chi-Square test, in addition to two linear regression models for 16 echocardiographic parameters. The difference in inflammatory biomarkers (hsCRP, IL-6 and sTNF-RI) between the groups was examined with a multinomial logistic regression model.ResultsThe MHO individuals were on average 64.2±8.4 years old, with a higher proportion of women (71.6%), low percentage of smokers, larger waist circumference (109.3±10.5 cm vs 89.1±10.8 cm, p<0.0001) and higher odds ratios for hsCRP, IL-6 and sTNF-RI compared to MHNW individuals. Linear regression models revealed greater left atrial (LA) diameter (2.73 (95% CI: 1.35–4.11) mm), LA volume (7.86 (95% CI: 2.88–12.83) mL), and left ventricular mass index (LVMI) (11.82 (95% CI: 4.43–19.22) g/m1.7) in the MHO group compared to the MHNW group.ConclusionThe MHO phenotype is associated with echocardiographic markers of cardiac remodeling (LA diameter, volume and LVMI) and higher odds ratios for inflammatory biomarkers.

Characterization of the metabolically healthy phenotype in overweight and obese British men

We calculated the prevalence of the metabolically healthy but obese (MHO) phenotype in (n=9177) British men (age 48.9±7.4years) attending preventive health screening between 2000 and 2009. We examined differences in cardiorespiratory fitness (Fitness) and self-reported physical activity levels, according to whether the men were metabolically healthy (<2 components of the metabolic syndrome), and by BMI category (normal-weight, overweight, obese). Fitness was estimated from treadmill exercise as VO2peak and classified as: Low, Moderate, or High using age-specific cut-offs. We identified 21.6% of our sample as obese, of whom 83.1% were metabolically healthy. Compared with the metabolic unhealthy obese (MUO; 3.7% of sample), MHO phenotypes were fitter (effect size d=0.21) and were more physically active (d=0.31). Logistic regression showed high fitness (OR=2.40, 95% CI 1.38–4.19), and being physically active (OR=1.71, 95% CI 1.14–2.56) to be independently associated with the MHO phenotype. Our findings agree with US data suggesting that higher cardiorespiratory fitness is a characteristic of the MHO phenotype. Our finding that meeting physical activity guidelines was associated with the MHO phenotype independent of fitness is, however, novel. If confirmed, our findings indicate that public health messages that encourage active lifestyles to promote fitness should be encouraged regardless of weight status.

Obesity and Cardiovascular Disease.

The prevalence of obesity has increased worldwide over the past few decades. In 2013, the prevalence of obesity exceeded the 50% of the adult population in some countries from Oceania, North Africa, and Middle East. Lower but still alarmingly high prevalence was observed in North America (≈30%) and in Western Europe (≈20%). These figures are of serious concern because of the strong link between obesity and disease. In the present review, we summarize the current evidence on the relationship of obesity with cardiovascular disease (CVD), discussing how both the degree and the duration of obesity affect CVD. Although in the general population, obesity and, especially, severe obesity are consistently and strongly related with higher risk of CVD incidence and mortality, the one-size-fits-all approach should not be used with obesity. There are relevant factors largely affecting the CVD prognosis of obese individuals. In this context, we thoroughly discuss important concepts such as the fat-but-fit paradigm, the metabolically healthy but obese (MHO) phenotype and the obesity paradox in patients with CVD. About the MHO phenotype and its CVD prognosis, available data have provided mixed findings, what could be partially because of the adjustment or not for key confounders such as cardiorespiratory fitness, and to the lack of consensus on the MHO definition. In the present review, we propose a scientifically based harmonized definition of MHO, which will hopefully contribute to more comparable data in the future and a better understanding on the MHO subgroup and its CVD prognosis.

Role of Fitness in the Metabolically Healthy but Obese Phenotype: A Review and Update

Despite the strong and consistent evidence supporting that a high physical fitness (PF) level at any age is a major predictor of a healthier metabolic profile, major studies focused on the metabolically healthy but obese (MHO) phenotype have ignored the role of PF when examining this phenotype and its prognosis. Particularly, the role of its main health-related components such as higher cardiorespiratory fitness (CRF) and muscular fitness in the MHO phenotype needs to be reviewed in depth. The present review aimed to: 1) contribute to the characterization of the MHO phenotype by examining whether MHO individuals are fitter than metabolically abnormal obese (MAO) individuals in terms of CRF and other PF components; 2) review the role of CRF and other PF components in the prognosis of MHO. The studies reviewed suggest that a higher CRF level should be considered a characteristic of the MHO phenotype. Likewise, CRF seems to play a key role in the prognosis of the MHO individuals, yet this statement is based on a single study and future studies need to confirm or contrast these findings. Comparability of studies is difficult due to the different definitions used for MHO; consequently, the present review makes a proposal for harmonizing this definition in adults and in youth. Obesity is still related to an important number of comorbidities; therefore, the public health message remains to fight against both obesity and low CRF in both adult and pediatric populations.

Prevalence and characteristics of individuals without diabetes and hypertension who underwent bariatric surgery: lessons learned about metabolically healthy obese

BackgroundRecent studies describe a unique subset of obese individuals with normal metabolic profiles despite having excess weight called “metabolically healthy but obese (MHO)”. Our aim was to determine the prevalence of individuals without diabetes and hypertension and risk factors associated with the MHO phenotype among bariatric surgery patients. MethodsWe conducted a retrospective study of 710 adults who underwent bariatric surgery at Johns Hopkins between 2008 and 2010. In the first analysis of 523 individuals, we identified 150 individuals without diabetes and hypertension; in the second analysis of 260 individuals, we identified 44 individuals without diabetes, hypertension and hypertriglyceridemia. We used multivariable logistic regression to examine the association between each group and potential risk factors including age, sex, race, body mass index, and presence of liver disease on liver biopsy. ResultsThe prevalence of individuals without diabetes and hypertension was 28.7%; among these individuals 88.7% had liver steatosis, 7.3% nonalcoholic steatohepatitis (NASH), and 19.3% liver fibrosis. These individuals were significantly more likely to be white OR = 1.9 (95% CI: 1.1–3.1), younger OR = 4.1 (95% CI = 2.6–6.3), and female OR = 2.1, (95% CI = 1.2–3.6) and less likely to have liver steatosis OR = 0.4 (95% CI = 0.2–0.9) or NASH OR = 0.3 (95% CI = 0.2–0.6). ConclusionAmong bariatric surgery patients, almost a third of patients do not have diabetes and hypertension and could be probably considered “MHO” and were more likely to be white, young, female, and have less liver injury. The high prevalence of liver steatosis in MHO individuals among bariatric surgery patients challenges the notion of MHO as a truly metabolically healthy entity.

Abstract 09: A Community-Based Exercise Intervention Transitions Metabolically Abnormal Obese Adults to a Metabolically Healthy Obese Phenotype

Introduction: It has been estimated that 32% of obese adults in the US are metabolically healthy. This subset of individuals, referred to as metabolically healthy but obese (MHO), appear to be more resistant to the adverse cardiometabolic consequences faced by their metabolically abnormal obese (MAO) counterparts. Cross-sectional observations indicate that increased physical activity and higher fitness contribute to the protective metabolic characteristics in this subset of obese individuals. However, to date no study has investigated whether a community-based exercise intervention designed to increase exercise volume and fitness can transition MAO adults to a MHO phenotype. Identifying the therapeutic dose of exercise required to convert a MAO person to metabolically healthy would yield important clinical information for the primary prevention of cardiovascular disease. Hypothesis: We assessed the following hypotheses: (1) community-based exercise training would transition MAO adults to metabolically healthy, and (2) the odds of successful transition to a metabolically healthy phenotype would be larger for obese individuals who [[Unable to Display Character: &amp;#8211;]] (a) performed the highest volume of exercise, and (b) experienced the greatest increase in fitness. Methods: Three-hundred thirty-two healthy adults (190 women, 142 men; aged 28-88 years) engaged in a supervised 14-week community-based exercise program designed to favorably modify cardiovascular disease risk factors. Components of the metabolic syndrome (National Cholesterol Education Program ATP III criteria) were measured before and after the exercise program. Obese (BMI ≥ 30 kg·m 2 ) adults who met 2-4 criteria for metabolic syndrome were classified as metabolically abnormal. Metabolically healthy was defined if obese adults met 0 to 1 criteria for metabolic syndrome. Results: Baseline point prevalence of MAO was 20.5% (N = 68). There was a significant reduction (p&lt;0.05) in point prevalence of MAO to 12.3% by post program as 27/68 individuals (40%) transitioned to MHO. Compared to the lowest quartiles of relative energy expenditure and change in fitness, participants in the highest quartiles were 21.8 (95% CI 4.4[[Unable to Display Character: &amp;#8211;]]108.0; p&lt;0.05) and 8.2 (95% CI 3.1[[Unable to Display Character: &amp;#8211;]]21.6; p&lt;0.05) times more likely to transition from MAO to MHO, respectively. Conclusions: These findings indicate that supervised community exercise can transition MAO adults to a MHO phenotype. MAO adults who engaged in higher volumes of exercise and those who demonstrated greater improvements in fitness were significantly more likely to become metabolically healthy. Importantly, the unfavourable metabolic characteristics of obesity are not irreversible. Community exercise should be considered an effective model for the primary prevention of cardiovascular disease in MAO adults.

Current issues in the identification and treatment of metabolically healthy but obese individuals

A unique subset of obese individuals who appear to be protected from the development of metabolic disturbances has been identified in the medical literature and is termed metabolically healthy but obese (MHO). Part of the issue is that there are no clear accepted criteria on the definition of MHO and the biological mechanisms to explain this phenotype are still unknown which render findings and/or conclusions difficult to interpret and making the application of this concept difficult in clinical practice. With the current definitions, the true prevalence of the MHO phenotype in the general population varies widely from approximately 3–57% of obese adults. In several prospective studies, the MHO individual has been associated with a similar risk of developing type 2 diabetes, cardiovascular disease and mortality when compared to healthy normal weight subjects; however, there is evidence to refute this concept. Furthermore, the current evidence cannot confirm that MHO subjects are permanently protected from the risk of developing metabolic disturbances associated with obesity. Currently, no standard practice guidelines for the treatment of MHO can be proposed, however, a regular surveillance of the waist circumference and cardio-metabolic risk factors such as elevated triglycerides, glycaemia, HOMA, C-reactive protein and low HDL, as well as the prevention of any further weight gain seem to represent the most prudent and sound attitude in the management of MHO subjects.

Liver enzymes and vitamin D levels in metabolically healthy but obese individuals: Korean National Health and Nutrition Examination Survey

ObjectiveIncreased liver enzymes and decreased vitamin D levels are associated with insulin resistance and type 2 diabetes. We examined liver enzymes and vitamin D levels in metabolically healthy but obese (MHO) individuals and compared the values with those of other body size phenotypes in the Korean population. Materials/MethodsA total of 16,190 people over the age of 18years were analyzed using data from the Fourth Korean National Health and Nutrition Examination Survey, which is a nationally representative survey. Body size phenotypes were classified into four groups by body mass index (BMI) and number of metabolic syndrome components. ResultsThe prevalence of MHO was 14.9% in the entire population and 47.7% in the obese population. In a correlation analysis adjusted for age, sex, and BMI, AST and ALT levels were positively correlated with insulin resistance and cardiometabolic risk factors of the metabolic syndrome, whereas vitamin D level was negatively correlated with these variables. MHO individuals had significantly lower concentrations of AST and ALT compared to metabolically abnormal obese (MAO) subjects, although vitamin D levels were not significantly different. Furthermore, a multiple logistic regression analysis revealed that MHO individuals had lower risk of liver enzyme abnormality compared to MAO after adjusting for potential confounding factors. However, the risk of vitamin D deficiency was not significantly different among groups with different body size phenotypes. ConclusionsAlthough both liver enzymes and vitamin D levels are related to insulin resistance and metabolic syndrome, only liver enzymes were independently associated with MHO phenotype.

The Metabolically Healthy But Obese Phenotype in African Americans

Obesity has become one of the leading public health concerns in the United States and worldwide. While obesity is associated with the metabolic syndrome, some obese individuals do not possess the constellation of the metabolic abnormalities and are referred to as metabolically healthy but obese (MHO) persons. Limited data exist on the prevalence and characteristics of the MHO in African Americans. The authors studied 126 obese African Americans and defined the MHO phenotype as an individual with a body mass index ≥30 kg/m(2) , high-density lipoprotein cholesterol ≥40 mg/dL, absence of type 2 diabetes mellitus, and absence of arterial hypertension. The correlates of the MHO phenotype with anthropometrical and metabolic indices were examined, as well as the effect of age on these correlates. Results showed that 36 (28.5%) of the individuals were identified with the MHO phenotype. Waist circumference (WC) and waist-to-hip ratio (WHR) were significantly lower (P<.05) in MHO than in non-MHO patients. While there were significant lower levels of low-density lipoprotein and triglycerides in MHO among patients younger than 40 years, the significance was lost among patients 40 years or older. This study indicates that increased WC and WHR may be early premetabolic syndrome markers in obese individuals and should warrant aggressive risk factor reduction therapy to prevent future development of related cardiovascular conditions.

The metabolically healthy but obese postmenopausal woman presents a favourable heart rate variability profile

Objective. The purpose of this study was to investigate the heart rate variability (HRV) profile in obese women displaying the metabolically healthy but obese (MHO) phenotype. Design. We studied 47 obese, sedentary postmenopausal women. Subjects were classified as MHO or at risk based on insulin resistance as assessed with the homeostatic model assessment (HOMA) index. Subjects were divided into tertiles according to HOMA values. Subjects in the lower tertile were categorised as MHO while subjects in the upper 2 tertiles represented at risk subjects. Outcome measures were heart rate variability factors (RR intervals, SDNN, LF, HF, pNN50, RMSSD), body temperature, body composition (DEXA) and a lipid profile as well as glucose and insulin. Results. MHO individuals had significantly lower resting heart rate, body temperature, lean body mass as well as fasting insulin and HOMA levels compared to at risk subjects (p < 0.05). In addition, RR intervals, SDNN and LF were significantly higher in MHO individuals (p < 0.05). Moreover, stepwise regression analysis showed that SDNN was an independent predictor of the variation in HOMA in our cohort. Conclusion. Results of the present study indicate that postmenopausal women displaying the MHO phenotype present a favourable HRV profile. Therefore, higher HRV could be associated, at least in part, in the protective profile of MHO individuals.

Identifying Metabolically Healthy but Obese Individuals in Sedentary Postmenopausal Women

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 > or =130/85 mm Hg, triglycerides (TG) > or =1.7 mmol/l, glucose > or =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 < or =2.7, TG < or =1.7 mmol/l, HDL-C > or =1.3 mmol/l, low-density lipoprotein-cholesterol < or =2.6 mmol/l, hsCRP < or =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, apolipoprotein B, and ferritin. In conclusion, the present study shows variations in body composition and metabolic profile based on the methods studied to define the MHO phenotype. Therefore, an expert consensus may be needed to standardize the identification of MHO individuals.

Metabolically healthy but obese individuals: relationship with hepatic enzymes

The purpose of this study was to investigate the level of plasma hepatic enzymes in obese women displaying the metabolically healthy but obese (MHO) phenotype. We studied 104 obese, sedentary, postmenopausal women. Subjects were classified as MHO or at risk based on insulin sensitivity as assessed with the oral glucose tolerance test–derived Matsuda index. Subjects were divided into quartiles according to insulin sensitivity values. Subjects in the upper quartile were categorized as MHO, whereas subjects in the lower 3 quartiles represented at-risk subjects. Outcome measures were hepatic enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase, and γ-glutamyltransferase [GGT]], high-density lipoprotein cholesterol, triglycerides, triglycerides to high-density lipoprotein cholesterol ratio, apolipoprotein B, fatty liver index, body composition (dual-energy x-ray absorptiometry), and visceral adipose tissue (computed tomography). The MHO individuals had significantly lower concentrations of ALT, AST, and GGT as well as a lower fatty liver index compared with at-risk subjects ( P < .05). In addition, lean body mass index and visceral adipose tissue were significantly lower in MHO individuals ( P < .05). Moreover, stepwise regression analysis showed that ALT explained 17.9% of the variation in insulin sensitivity in our cohort, which accounted for the greatest source of unique variance. Results of the present study indicate that postmenopausal women displaying the MHO phenotype present favorable levels of ALT, AST, and GGT. Lower concentrations of hepatic enzymes, in particular, lower circulating ALT levels, in MHO individuals may reflect lower hepatic insulin resistance and lower liver fat content; and this could be involved, at least in part, in the protective profile of MHO individuals.

Metabolically obese but normal weight (MONW) and metabolically healthy but obese (MHO) phenotypes in Koreans: characteristics and health behaviors.

The purpose of this study was to estimate the prevalence of 'metabolically obese, but normal-weight' (MONW) and 'metabolically healthy, but obese' (MHO) phenotypes in Korean adults and identify the characteristics and health behaviors related to both phenotypes. Of the 5267 participants (2227 men, 3040 women) from the 3rd Korean National Health and Nutrition Examination Survey, the MONW phenotype (8.7% of total subjects, 12.7% of normal-weight subjects) was defined as individuals of normal weight (BMI<25) with the metabolic syndrome (MS), and the MHO phenotype (15.2% of total subjects, 47.9% of obese subject) was defined as obese individuals (BMI>or=25) without the MS. The odds ratio for MONW phenotype was significantly higher for those at older age, those with lower education, those who had moderate alcohol consumption, and time spent participating in moderate-intensity exercise. The odds ratio for MHO phenotype was significantly lower for those at older age, men, those with lower education, and former/current smokers. In conclusion, regardless of weight status, health behaviors should be modified to prevent MS.