Transition from metabolically benign to metabolically unhealthy obesity and 10-year cardiovascular disease incidence: The ATTICA cohort study.

BACKGROUND/OBJECTIVES: Metabolically benign obesity remains a scientific field of considerable debate. The aim of the present work was to evaluate whether metabolically healthy obese (MHO) status is a transient condition which propagates 10-year cardiovascular disease (CVD) onset. METHODS: A prospective longitudinal study was conducted during 2001-2012, the ATTICA study studying 1514 (49.8%) men and 1528 (50.2%) women (aged >18 years old) free of CVD and residing in the greater Athens area, Greece. Follow-up assessment of first combined CVD event (2011-2012) was achieved in n = 2020 participants; of them, 317 (15.7%) incident cases were identified. Obesity was defined as body mass index ≥30 kg/m2 and healthy metabolic status as absence of all NCEP ATP III (2005) metabolic syndrome components (excluding waist circumference). RESULTS: The MHO prevalence was 4.8% (n = 146) with 28.2% of obese participants presenting metabolically healthy status at baseline. Within this group, 52% developed unhealthy metabolic status during the 10-year follow up. MHO vs. metabolically healthy non-obese participants had a higher likelihood of presenting with 10-year CVD events, yet only the subset of them who lost their baseline status reached the level of significance (Hazard Ratio (HR) = 1.43, 95% Confidence Interval (95% CI) 1.02, 2.01). Sensitivity analyses revealed that MHO status was independently associated with elevated CVD risk in women and participants with low adherence to the Mediterranean diet, low grade inflammation, and insulin resistance. CONCLUSIONS: MHO status is a transient condition where weight management is demanded to prevent the establishment of unhealthy cardiometabolic features. The existence of obese persons who remain "longitudinally" resilient to metabolic abnormalities is an emerging area of future research.

Metabolically healthy obesity: the low-hanging fruit in obesity treatment?

Obesity increases the risk of several other chronic diseases and, because of its epidemic proportions, has become a major public health problem worldwide. Alarmingly, a lower proportion of adults have tried to lose weight during the past decade than during the mid-1980s to 1990s. The first-line treatment option for obesity is lifestyle intervention. Although this approach can decrease fat mass in the short term, these beneficial effects typically do not persist. If a large amount of weight loss is not an easily achievable goal, other goals that might motivate people with obesity to adopt a healthy lifestyle should be considered. In this setting, the concept of metabolically healthy obesity is useful. Accumulating evidence suggests that, although the risk of all-cause mortality and cardiovascular events might be higher in people with metabolically healthy obesity compared with metabolically healthy people of a normal weight, the risk is substantially lower than in individuals with metabolically unhealthy obesity. Therefore, every person with obesity should be motivated to achieve a normal weight in the long term, but more moderate weight loss sufficient for the transition from metabolically unhealthy obesity to metabolically healthy obesity might also lower the risk of adverse outcomes. However, how much weight needs to be lost for this transition to occur is under debate. This transition might be supported by lifestyle factors-such as the Mediterranean diet-that affect cardiovascular risk, independent of body fat. In this Series paper, we summarise available information about the concept of metabolically healthy obesity, highlight gaps in research, and discuss how this concept can be implemented in clinical care.

A High Rate of Non-Compliance Confounds the Study of Whole Grains and Weight Maintenance in a Randomised Intervention Trial-The Case for Greater Use of Dietary Biomarkers in Nutrition Intervention Studies.

Observational studies consistently find an inverse relationship between whole-grain intake and weight gain. We aimed to confirm this in an open-label researcher-blinded parallel design randomised trial. A total of 179 overweight/obese women with a habitually low whole-grain intake (<16 g/day) were randomised to a weight maintenance diet with refined-grain (RG) or whole-grain (WG) foods (80 g/day) for 12 weeks after an initial weight loss program over 8 weeks. Body weight and composition was assessed at baseline, after the initial weight loss, and after the 12-week dietary intervention. During the 12-week dietary intervention phase, there were no group differences in changes in body weight and total fat mass %, whereas abdominal fat mass tended to increase more during the dietary intervention phase in the WG compared to the RG group (0.7 (SD 3.6) vs. -0.3 (SD 3.8) %; p = 0.052). Plasma alkylresorcinol concentrations, biomarkers of wholegrain wheat and rye intake, indicated poor compliance, particularly in the WG group, where >60% of participants had alkylresorcinol concentrations below 70 nmol/L, a concentration indicating low or no intake of whole-grain wheat. Further, weight regain was lower than expected in both intervention groups, further supporting a lack of compliance to the post-weight-loss diet. The rate of compliance was too low to conclude any effect of whole grain on weight maintenance, and reinforces the need to use objective measures of compliance in nutrition intervention studies.

Metabolically Healthy Overweight and Obesity Is Associated with Higher Adherence to a Traditional Dietary Pattern: A Cross-Sectional Study among Adults in Lebanon.

This study aimed to examine the proportion and socio-demographic correlates of Metabolically Healthy Overweight and Obesity (MHOv/O) among Lebanese adults and to investigate the independent effect of previously identified dietary patterns on odds of MHOv/O. Data were drawn from the National Nutrition and Non-Communicable Disease Risk Factor Survey (Lebanon 2008-2009). Out of the 337 adult participants who had complete socio-demographic, lifestyle, dietary as well as anthropometric and biochemical data, 196 had a BMI ≥ 25 kg/m² and their data were included in this study. MHOv/O was identified using the Adult Treatment Panel criteria. Dietary patterns previously derived in this study population were: Fast Food/Dessert, Traditional-Lebanese and High-Protein. The proportion of MHOv/O in the study sample was 37.2%. Females, higher education and high level of physical activity were positively associated with odds of MHOv/O. Subjects with higher adherence to the Traditional-Lebanese pattern had higher odds of MHOv/O (OR: 1.83, 95% CI: 1.09-3.91). No significant associations were observed between the Fast Food/Dessert and the high-protein patterns with MHOv/O. Follow-up studies are needed to confirm those findings and understand the mechanisms by which the Traditional-Lebanese pattern may exert a protective effect in this subgroup of overweight and obese adults.

Mediterranean diet and mortality risk in metabolically healthy obese and metabolically unhealthy obese phenotypes.

BACKGROUND: The Mediterranean diet has been consistently associated with reduced mortality risk. Few prospective studies have examined whether the benefits from a Mediterranean diet are equally shared by obese individuals with varying metabolic health. OBJECTIVE: The objective of this study was to investigate the association between Mediterranean diet, metabolic phenotypes and mortality risk in a representative obese US population. METHODS: Data from 1739 adults aged 20-88 years were analyzed from participants of the National Health and Nutrition Examination Survey III, 1988-1994 followed up for deaths until 31 December 2011 in a prospective cohort analysis. Mediterranean Diet Scores (MDS) were created to assess the adherence to Mediterranean diet. Participants were classified as metabolically healthy obese (MHO) phenotype (0 or 1 metabolic abnormality) or metabolically unhealthy obese (MUO) phenotype (two or more metabolic abnormalities), based on high glucose, insulin resistance, blood pressure, triglycerides, C-reactive protein and low high-density lipoprotein cholesterol. RESULTS: The MHO phenotype (n=598) was observed in 34.8% (s.e., 1.7%) of those who were obese (mean body mass index was 33.4 and 34.8 in MHO and MUO phenotypes, respectively). During a median follow-up of 18.5 years, there were 77 (12.9%) and 309 (27.1%) deaths in MHO and MUO individuals, respectively. In MHO individuals, the multivariable-adjusted hazard ratio (HR) of all-cause mortality in the highest tertile compared with the first tertile of MDS was 0.44 (95% confidence interval (CI), 0.26-0.75; P for trend <0.001), after adjustment for potential confounders. A five-point (1 s.d.) increment in the adherence to MDS was associated with a 41% reduction in the risk of all-cause mortality (HR, 0.59; 95% CI, 0.37-0.94). Similar findings were obtained when we restricted our analyses to those with or without prevalent diabetes mellitus and hypertension. We did not observe mortality risk reduction in either individuals with MUO phenotype or all obese participants combined. CONCLUSIONS: Adherence to a Mediterranean dietary pattern appears to reduce mortality in the MHO phenotype, but not among the MUO phenotype in an obese population.

Is the metabolically healthy obesity phenotype an irrelevant artifact for public health?

Some obese persons do not develop (at least in the short term) the metabolic complications of obesity that are thought to be causally linked to cardiovascular events or premature mortality. This phenomenon has been termed "metabolically healthy obesity" (MHO), and it has received much attention recently, to the extent that some authors argue that "new metrics" must be developed to estimate the risk associated with obesity beyond body mass index. In this commentary, we argue that the MHO phenotype is not benign and as such has very limited relevance as a public health target. More efforts must be allocated to reducing the distal and actual causal agents that lead to weight gain, instead of the current disproportionate scientific interest in the biological processes that explain the heterogeneity of obesity.