Metabolically Obese Normal Weight Research Articles

Interaction between early environment and genetic predisposition instigates the metabolically obese, normal weight phenotype in children: findings from the BCAMS study.

A subset of normal-weight individuals appears predisposed to obesity-related cardiometabolic abnormalities. Studies of this metabolically obese, normal weight (MONW) phenotype in youth are scarce. We aimed to identify early environmental and genetic factors associated with MONW in children. Overall, 1475 normal-weight Chinese children aged 6-18 were recruited from the Beijing Children and Adolescents Metabolic Syndrome study cohort. Birthweight, childhood lifestyle, socio-economic factors, and 20 genetic variants previously shown to be associated with BMI or glucose metabolism in East Asian adults were examined for their association with the MONW phenotype. MONW was defined by exhibiting any metabolic syndrome component. After adjusting for covariates including BMI, low birthweight and low levels of physical activity, fruit consumption, parental education and household income, as well as CDKAL1 rs2206734 genotype were independent predictors of the MONW phenotype (all P < 0.05). Moreover, rs2206734 interacted with birthweight to predict the MONW phenotype (Pinteraction = 0.0008). Among high (>75th percentile) birthweight individuals, each C allele at this locus was associated with a 62% reduced risk of MONW (OR = 0.38; 95% CI = 0.26-0.58; P = 5.71 × 10-6), while no such genetic associations were found in intermediate or low birthweight individuals (P > 0.1). This CDKAL1-MONW relationship in high birthweight individuals was especially strong in the presence of favorable childhood environmental factors (high levels of physical activity, fruit consumption, parental education and household income) (Pinteraction = 0.013). Our findings provided the novel evidence that early environment (especially birthweight) and genetics, along with their interaction with one another, play important roles in predicting the MONW phenotype among children.

Abstract P528: Normal Weight Metabolic Obesity and Risk of Coronary Artery Disease: The Million Veteran Program

Introduction: Obesity and metabolic dysfunction, individually, are known risk factors of stroke, coronary artery disease (CAD), and mortality. However, few studies have examined the long-term risk for CAD among non-obese people with metabolic dysfunction, and no studies have been conducted for Veterans of the United States. Hypothesis: Veterans who are metabolically obese normal weight (MONW) at baseline have an increased risk of developing CAD compared to metabolically healthy normal weight (MHNW) veterans enrolled in the Million Veteran Program (MVP). Methods: We included MVP participants who had a stable normal body mass index (18.5-25kg/m 2 ) five years prior to enrollment. Metabolic obesity was defined as having three or more of the Adult Treatment Panel III criteria [diabetes, hypertension, low HDL-C (≤40 mg/dl for men, ≤50 mg/dl for women), and high triglycerides (≥150 mg/dl)] at enrollment. CAD was defined as non-fatal myocardial infarction, ischemic heart disease or angina pectoris. Participants with prevalent CAD, major cancers and incomplete lifestyle information were excluded. Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for CAD incidence. In secondary analyses, we stratified by sex and race to evaluate possible effect modification. Results: Of the 16,764 people identified as normal weight with complete data, 15% were MONW, 84.5% were male, 84.4% were White and the mean age was 63.1 ± 14.2. Over a median follow up of 3.6 (IQR 1.8-5.2) years, there were 847 incident CAD events observed. MONW individuals had a 64% (95% CI: 40 -91%) higher risk of CAD compared to normal weight individuals, controlling for age, race, sex, education, smoking status, physical activity, alcohol use and diet. In secondary analyses, we observed a nominally higher risk among women who were MONW [HR (95% CI): 2.74 (1.30-5.77) for women vs. 1.60 (1.37-1.88) for men], however the interaction of MONW and sex was not statistically significant (interaction p=0.19). Similarly, the interaction of MONW and race was not statistically significant [1.62 (1.37-1.92) for White, 1.55 (0.97-2.48) for Black, and 2.26 (1.03-4.95) for other, interaction p=0.83)]. Conclusions: MONW Veterans had a higher risk of CAD compared to MHNW Veterans. This risk was magnified in female Veterans and attenuated in White and Black Veterans compared to other races (Asian, Pacific Islander, Native American, other). These findings will need to be validated in future studies.

The triglycerides and glucose index is associated with cardiovascular risk factors in metabolically obese normal-weight subjects.

The aim of this study was to determine whether the triglycerides and glucose (TyG) index is associated with the presence of metabolically obese normal-weight (MONW) phenotype and related cardiovascular risk factors. Apparently healthy men and non-pregnant women aged 20-65years were enrolled in a population-based cross-sectional study. Overweight, obesity, smoking, alcohol consumption, pregnancy, diagnosis of hypertension, diabetes, cardiovascular disease, liver disease, renal disease, malignancy, and medical treatment were exclusion criteria. Subjects were allocated into the MONW or normal-weight groups. MONW phenotype was defined by normal weight and the presence of at least one of the following cardiovascular risk factors: elevated blood pressure, hyperglycemia, hypertriglyceridemia, and low HDL cholesterol. A total of 542 subjects were enrolled and allocated into the MONW (n = 354) and normal-weight (n = 188) groups. The adjusted logistic regression analysis showed that the elevated TyG index is significantly associated with the presence of MONW phenotype (OR = 11.14; 95% CI 6.04-20.57), hyperglycemia (OR = 3.18; 95% CI 1.95-5.21), hypertriglyceridemia (OR = 399.19; 95% CI 94.01-1694.98), and low HDL-C (OR = 2.60; 95% CI 1.74-3.87), but not with elevated blood pressure (OR = 1.55; 95% CI 0.93-2.60). Results of this study support that the TyG index may be a useful indicator to detect MONW phenotype and associated cardiovascular risk factors.

Role of Metabolic Obesity and Body Mass Index in Patients with Coronary Artery Diseases

Obesity and its related consequences are some of the most alarming health problems the world is currently facing. Studies have shown that a little more than a fourth of the adults all over the world are overweight and a little more than a tenth are obese. Also, Obesity is considered as an independent risk factor for determining the severity of a Coronary Artery Disease (CAD). The aim of this paper is to determine the role of Metabolic Obesity and Body Mass Index in Patients with Coronary Artery Diseases. We train a model capable of predicting the GENSINI score which determines the severity of CAD in four health groups, namely Metabolically Healthy and Normal Weight (MHNW), Metabolically Obese Normal Weight (MONW), Metabolically Healthy Obese (MHO) and Metabolically Abnormally Obese (MAO). Several factors like Glycated Hemoglobin (HBA1C), Triglyceride and Insulin Resistance are considered. Ridge Regression, Lasso regression, and Neural Networks are the mechanisms used to train a model for predicting the GENSINI score based upon health statistics of patients

Tipe tubuh (somatotype) dengan sindrom metabolik pada wanita dewasa non-obesitas usia 25 – 40 tahun

Body type (somatotype) with metabolic syndrome among non-obese woman aged 25-40 years oldBackground: The prevalence of central obesity was found high in women, not only in obese individuals but also occur in non-obese individuals or metabolically obese normal weight (MONW). Endomorph marked by higher fat mass, which will lead to metabolic disorders.Objective: This study aimed to describe the correlation of somatotype with metabolic syndrome in a non-obese woman.Methods: Cross-sectional observational study, subjects were selected using purposive sampling involving 46 women 25-40 years old with BMI 18.5-24.9 kg/m2 in several offices in the City of Semarang, consist of Balai Besar Teknologi Pencegahan dan Pencemaran Industri, Dinas Pekerjaan Umum, and Dinas Perindustrian dan Perdagangan Central Java. Somatotype data is measured in three components, namely endomorph, mesomorph, and ectomorph. The resulting value of each component is calculated using the Heath-Carter formula. Triglycerides, HDL, and fasting blood glucose measured by enzymatic colorimetric methods. Blood pressure measured by aneroid sphygmomanometer. Syndrome metabolic was defined as metabolic syndrome risk score (cMetS). Data were analyzed by Rank Spearman and Pearson.Results: The subject's body type is endomorph as much as 91.3% and ectomorph-endomorph (8.7%). Central obesity (50%), low HDL levels (28%), hypertriglyceridemia (2%), normal GDP levels (100%), hypertension (15%), metabolic syndrome (13%), and metabolic pre-syndromes (47, 8%) found in the subject of this study. There were correlation between endomorph (p=0.005; r=0.4) and ectomorph (p=0.000; r=-0.53) with waist circumference. There was a significant correlation between endomorph with metabolic syndrome risk score (p=0.05; r=0.129).Conclusions: Endomorph was associated with a metabolic syndrome risk score. Higher endomorph tends to have higher metabolic syndrome risk scores.

Altered serum Zinc and Copper in Iranian Adults who were of normal weight but metabolically obese

Metabolically obese normal weight (MONW) individuals are potentially at increased risk of developing metabolic syndrome. Serum zinc and copper concentrations were assessed in individuals with MONW to determine whether MONW is associated with altered serum zinc and/or copper status. Normal weight subjects (total n = 2419; 1298 men and 1121 women), were recruited as part of Mashhad Stroke and Heart Association Disorder (MASHAD) Study cohort. They were divided into two groups according to the presence or absence of MetS, defined using IDF criteria. Serum zinc and copper concentrations were determined by atomic absorption. Of the 2419 normal weight adults, 377 had MetS. Of this group, 53.7% and 49.7% had a serum zinc <70 µg/dl (Q1) (p = 0.001) or a serum copper <79 µg/dl (Q1) respectively. Furthermore, 27.3% had a serum copper >131 µg/dl (Q4) (p = 0.034), and 18.8% had a serum zinc >95 µg/dl (Q4). Logistic regression analysis was performed to determine the odds ratio (OR) for an association of serum zinc, copper and zinc to copper ratio with MetS in normal weight subjects. The subjects with a serum zinc >95 µg/dl (Q4) had 0.386 [OR: 0.614(95%CI 0.457–0.823)] lower chance of MetS (p = 0.001) and the subjects with a serum copper >131 (Q4) had OR 1.423 (95% CI: 1.09–1.857) higher chance of MetS (p = 0.009). These data remained significant after adjustment for age and sex, for serum zinc and copper, respectively. Furthermore, our results strongly suggested that zinc and copper were the independent risk factor for metabolic syndrome in normal weight subjects. There is an imbalance between serum copper and zinc concentrations among individuals with MONW when compared with normal BMI individuals without MetS. This may increase the risk of individuals with MONW developing conditions associated with this imbalance, such as diabetes and cardiovascular disease.

1322-P: Early Environment and Genetic Predisposition to Metabolically Obese Normal-Weight Phenotype in Children: Findings from a Cohort Study

Some normal-weight individuals are predisposed to obesity-related cardiometabolic abnormalities, namely, metabolically obese normal weight (MONW). Studies of the MONW phenotype in youths are scarce. We aimed to identify early environmental and genetic factors associated with MONW in children. Overall, 1,484 normal-weight Chinese children aged 6-18, including 588 subjects with MONW phenotype, were recruited from the Beijing Children and Adolescents Metabolic Syndrome cohort. Birth weight (BW) childhood lifestyle and socio-economic factors, and 20 genetic variants which had been previously shown to be associated with BMI or T2D in East Asian adults were examined for the associations with pediatric MONW phenotype. Metabolically unhealthy was defined as having any metabolic syndrome component or HOMA-IR≥3.0. Independent risk factors for MONW phenotype were low BW, increased BMI, and lower levels of physical activity, maternal education and family income (all P&amp;lt;0.05), while amongst genetic variants, CDKAL1 rs2206734 shown the strongest association with MONW (OR per C allele=0.81, 95% CI=0.70-0.95; P=0.008). Moreover, rs2206734 interacted with BW on MONW phenotype (P interaction=0.005). Every C allele was associated with a 50% reduced risk of MONW in high (&amp;gt;75th percentile) BW (95% CI=0.34-0.72; P=0.0002), while the genetic associations were nonsignificant in intermediate and low (≤75th percentile) BW (P&amp;gt;0.1). The effect of high BW on the CDKAL1-MONW relationship could be further augmented by the combined impact of beneficial childhood environmental factors (physically active, high maternal education and family income) (Pinteraction=0.017). In conclusion, both early environments, particularly BW, and genetic predisposition plus their interaction were associated with MONW in children. Our study provides new insights into MONW and suggests a long-term prevention strategy, especially in genetically susceptible individuals. Disclosure M. Li: None. G. Li: None. S. Gao: None. S.M. Willi: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Roche Diagnostic USA. Research Support; Self; Jaeb Center for Health Research, National Institute of Allergy and Infectious Diseases, Sanofi-Aventis. Other Relationship; Self; National Institute of Diabetes and Digestive and Kidney Diseases. Funding National Key Research Program of China (2016YFC1304801); Beijing Municipal Science &amp; Technology Commission (D111100000611001, D111100000611002); Beijing Natural Science Foundation (7172169); Beijing Science &amp; Technology Star Program (2004A027), Novo Nordisk (2011A002); National Key Program of Clinical Science (WBYZ 2011-873); Central Research Institute Fund of Chinese Academy of Medical Sciences (2017PT32020, 2018PT32001)

Host genetics and diet composition interact to modulate gut microbiota and predisposition to metabolic syndrome in spontaneously hypertensive stroke-prone rats.

Metabolic syndrome encompasses obesity, glucose intolerance, hypertension, and dyslipidemia; however, the interactions between diet and host physiology that predispose to metabolic syndrome are incompletely understood. Here, we explored the effects of a high-fat diet (HFD) on energy balance, gut microbiota, and risk factors of metabolic syndrome in spontaneously hypertensive stroke-prone (SHRSP) and Wistar-Kyoto (WKY) rats. We found that the SHRSP rats were hypertensive, hyperphagic, less sensitive to hypophagic effects of exendin-4, and expended more energy with diminished sensitivity to sympathetic blockade compared to WKY rats. Notably, key thermogenic markers in brown and retroperitoneal adipose tissues and skeletal muscle were up-regulated in SHRSP than WKY rats. Although HFD promoted weight gain, adiposity, glucose intolerance, hypertriglyceridemia, hepatic lipidosis, and hyperleptinemia in both SHRSP and WKY rats, the SHRSP rats weighed less but had comparable percent adiposity to WKY rats, which supports the use of HFD-fed SHRSP rats as a unique model for studying the metabolically obese normal weight (MONW) phenotype in humans. Despite distinct strain differences in gut microbiota composition, diet had a preponderant impact on gut flora with some of the taxa being strongly associated with key metabolic parameters. Together, we provide evidence that interactions between host genetics and diet modulate gut microbiota and predispose SHRSP rats to develop metabolic syndrome.-Singh, A., Zapata, R. C., Pezeshki, A., Workentine, M. L., Chelikani, P. K. Host genetics and diet composition interact to modulate gut microbiota and predisposition to metabolic syndrome in spontaneously hypertensive stroke-prone rats.

Metabolic Phenotyping Using Metabolic Syndrome Criteria and Cardiometabolic Disabilities Criteria in Bangladeshi Adult Population

Obesity has become a global epidemic and has been found to be associated with numerous comorbidities. Body mass index (BMI) based classification of obesity is simple but co-morbidities do not affect all obese and overweight people. The present study was aimed to find out the frequency of metabolic phenotypes in different BMI groups using metabolic syndrome (MetS) criteria and cardiometabolic disabilities (CA) criteria and also to find out an appropriate method for defining metabolic health among adult population attending out patient department of Bangabandhu Sheikh Mujib Medical University (BSMMU). This cross-sectional analytical study was carried out in the Department of Biochemistry, Bangabandhu Sheikh Mujib Medical University (BSMMU) from March 2016 to February 2017. By non probability sampling, a total of 1023 study subjects were selected from apparently healthy adult individuals attending outpatient department of BSMMU. The study subjects were grouped into three body mass index classes and also further categorized into six groups according to metabolically unhealthy or healthy phenotypes by presence or absence of metabolic syndrome (MetS) criteria as well as cardiometabolic disabilities (CA) criteria respectively. Then agreement among different metabolic phenotypes based on these two criteria were observed. Frequency of different metabolic phenotypes i,e metabolically healthy normal weight (MHNW), metabolically obese normal weight (MONW), metabolically healthy over weight (MHOW), metabolically obese over weight (MOOW), metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO) were 12.3%, 6.9%, 21.4%, 27.7%, 7.7%, 23.9% by MetS criteria and 7.7%, 11.5%, 11.6%, 37.4%, 6.1%, 25.6% by CA criteria respectively. MOOW followed by MUO were found to be predominant among all phenotypes. Fare agreement was found between two criteria in case of normal weight and overweight groups and good agreement was found in case of obese groups. From this study, it may be concluded that, attention should be given to the metabolically obese phenotypes in different BMI classes to reduce co-morbidities.&#x0D; Bangladesh J Med Biochem 2018; 11(1): 1-8

Incidence of Prostate Cancer according to Metabolic Health Status: a Nationwide Cohort Study

BackgroundWe assessed the association between metabolic health status and incidence of prostate cancer using the National Health Check-ups (NHC) database of Korea.MethodsA total of 11,771,252 men who participated in the NHC between 2009 and 2012 and 56,552 men who were newly diagnosed with prostate cancer were analyzed. Normal-weight and obesity were defined as body mass index (BMI) < 25 kg/m2 and ≥ 25 kg/m2, respectively. Metabolic obesity was defined as the presence ≥ 3 components of the metabolic syndrome. Participants were stratified into 4 groups: metabolically healthy, normal-weight; metabolically obese, normal-weight (MONW); metabolically healthy, obese (MHO); and metabolically obese, obese. Multivariate Cox regression analysis was performed to examine the relationship between metabolic health status and incidence of prostate cancer.ResultsDuring a mean 5.4 ± 1.1 years of follow-up, 56,552 patients were registered with a diagnosis of prostate cancer. When analyzed according to metabolic health status classification, the multivariable-adjusted hazard ratio (HR) was 1.143 for the MONW group, 1.097 for the MHO group, showing the HR for the MONW group was higher than that for the MHO group. As the number of metabolic syndrome components increased, HR increased significantly. When stratified based on BMI, metabolically obese patients showed significantly higher HR than metabolically healthy patients in all BMI groups.ConclusionThis population-based nationwide study revealed an association between metabolic health status and the incidence of prostate cancer, and the risk increased according to the number of components of the metabolic syndrome.

Abstract 16865: Debunking the Concept That the “Metabolically Obese Normal Weight” Phenotype is Independent of Fat: It is All About Central Obesity

Background: The Metabolically Obese Normal Weight (MONW) phenotype has been described as a unique subgroup of individuals with metabolic dysregulation similar to obese individuals, but not considered obese per se . In theory, these individuals have an adiposity-independent substrate predisposing them to metabolic dysregulation. We tested whether central obesity explains the metabolic abnormalities in persons with MONW in a prospective population-based cohort in the Czech Republic. Methods: We used data from Kardiovize Brno 2030 study, a prospective community-based cohort in Central Europe. We defined obesity using World Health Organization categories for body mass index (BMI) and central obesity by waist circumference (WC≥ 94 cm in men and ≥ 80 cm in women). Metabolically obese (MO) was defined using AHA criteria by having three or more of the following: Hypertriglyceridemia (≥ 1.7 mmol/l); HDL cholesterol level &lt;1.0 mmol/l in men or &lt;1.3 mmol/l in women; elevated blood pressure (systolic ≥ 130 mmHg and/or diastolic ≥ 85 mmHg) or antihypertensive drug treatment or history of hypertension; elevated fasting plasma glucose ≥ 5.6 mmol/l; or drug treatment and central obesity. Results: Of the 2,056 participants (46% men; mean age= 47.2 years, SD=11.2) included in the current analysis, 975 (47.4%) had normal weight and 696 (33.8%) were overweight. Prevalence of MO in the overall sample was 20.6% (n=424), 3.7% (n=36) among those with normal BMI and 9.9% (n=204) among overweight individuals. From the 36 subjects with MONW, 33 (91.6%) had central obesity by WC, while 201/204 (98.5%) with metabolically obese overweight, had central obesity by WC. Remarkably, in a subgroup of people with no metabolic obesity factors nobody had central obesity, see Figure . Conclusions: Metabolic dysregulation in people labeled as MONW can be explained by excessive visceral adiposity and not by an inherent predisposition, independent of adiposity.These findings underscore the importance of identifying central obesity in clinical practice even if BMI is below the obese criteria.

Genes that make you fat, but keep you healthy.

Obesity prevalence continues to rise worldwide, posing a substantial burden on people's health. However, up to 45% of obese individuals do not suffer from cardiometabolic complications, also called the metabolically healthy obese (MHO). Concurrently, up to 30% of normal-weight individuals demonstrate cardiometabolic risk factors that are generally observed in obese individuals, the metabolically obese normal weight (MONW). Besides lifestyle, environmental factors and demographic factors, innate biological mechanisms are known to contribute to the aetiology of the MHO and MONW phenotypes, as well. Experimental studies in animal models have shown that adipose tissue expandability, fat distribution, adipogenesis, adipose tissue vascularization, inflammation and fibrosis, and mitochondrial function are the main mechanisms that uncouple adiposity from its cardiometabolic comorbidities. We reviewed current genetic association studies to expand insights into the biology of MHO/MONW phenotypes. At least four genetic loci were identified through genome-wide association studies for body fat percentage (BF%) of which the BF%-increasing allele was associated with a protective effect on glycemic and lipid outcomes. For some, this association was mediated through favourable effects on body fat distribution. Other studies that characterized the genetic susceptibility of insulin resistance found that a higher susceptibility was associated with lower overall adiposity due to less fat accumulation at hips and legs, suggesting that an impaired capacity to store fat subcutaneously or a preferential storage in the intra-abdominal cavity may be metabolically harmful. Clearly, more work remains to be done in this field, first through gene discovery and subsequently through functional follow-up of identified genes.

Regulation of glucose metabolism in nondiabetic, metabolically obese normal-weight Asians

Type 2 diabetes in Asia occurs largely in the absence of obesity. The metabolically obese normal-weight (MONW) phenotype refers to lean subjects with metabolic dysfunction that is typically observed in people with obesity and is associated with increased risk for diabetes. Previous studies evaluated MONW subjects who had greater body mass index (BMI) or total body fat than respective control groups, making interpretation of the results difficult. We evaluated insulin sensitivity (hyperinsulinemic-euglycemic clamp); insulin secretion (mixed meal with oral minimal modeling); intra-abdominal, muscle, and liver fat contents (magnetic resonance); and fasting and postprandial glucose and insulin concentrations in 18 MONW subjects and 18 metabolically healthy controls matched for age (43 ± 3 and 40 ± 3 yr; P = 0.52), BMI (both 22 ± 1 kg/m2; P = 0.69), total body fat (17 ± 1 and 16 ± 1 kg; P = 0.33), and sex (9 men and 9 women in each group). Compared with controls, MONW subjects had an approximately twofold greater visceral adipose tissue volume and an approximately fourfold greater intrahepatic fat content (but similar muscle fat), 20-30% lower glucose disposal rates and insulin sensitivity, and 30-40% greater insulin secretion rates (all P < 0.05). The disposition index, fasting glucose, and HbA1c concentrations were not different between groups, whereas postprandial glucose and insulin concentrations were ~15% and ~65% greater, respectively, in MONW than control subjects (both P < 0.05). We conclude that the MONW phenotype is associated with accumulation of fat in the intra-abdominal area and the liver, profound insulin resistance, but also a robust β-cell insulin secretion response that compensates for insulin resistance and helps maintain glucose homeostasis.

Evidence of genetic predisposition for metabolically healthy obesity and metabolically obese normal weight.

Obesity has evolved into a global pandemic that constitutes a major threat to public health. The majority of obesity-related health care costs are due to cardiometabolic complications, such as insulin resistance, dyslipidemia, and hypertension, which are risk factors for Type 2 diabetes and cardiovascular disease. However, many obese individuals, often called metabolically healthy obese (MHO), seem to be protected from these cardiometabolic complications. Conversely, there is a group of individuals who suffer from cardiometabolic complications despite being of normal weight; a condition termed metabolically obese normal weight (MONW). Recent large-scale genomic studies have provided evidence that a number of genetic variants show an association with increased adiposity but a favorable cardiometabolic profile, an indicator for the genetic basis of the MHO and MONW phenotypes. Many of these loci are located in or near genes that implicate pathways involved in adipogenesis, fat distribution, insulin signaling, and insulin resistance. It has been suggested that a threshold for subcutaneous adipose tissue expandability may be at play in the manifestation of MHO and MONW, where expiry of adipose tissue storage capacity could lead to ectopic lipid accumulation in non-adipose tissues such as liver, muscle, heart, and pancreatic beta cells. Understanding the genetic aspects of the mechanisms that underpin MHO and MONW is crucial to define appropriate public health action points and to develop effective intervention measures.

Obesity phenotypes: normal-weight individuals with metabolic disorders versus metabolically healthy obese

According to recent studies, adipose tissue secretes a large number of bioactive proteins, which affect the whole body metabolism. The amount of adipose tissue is the main factor that explains metabolic disorders; however, obesity is not necessarily the result of increased body weight. Interestingly, there is a subgroup of patients with normal weight and high-risk metabolic profile. Consequently, they are significantly more likely to have metabolic disorders or cardiovascular disease (CVD). Conversely, some individuals, called metabolically healthy obese (MHO), demonstrate a favourable metabolic profile despite having high BMI index and excessive adipose tissue. The aim of this paper is to review recent studies about obesity phenotypes. Better understanding of differences between metabolically obese normal-weight (MONW) and MHO may improve the therapy and treatment of metabolic health in all obese patients. Equally importantly, it may lead to an increase in early detection of individuals with metabolic disorders, regardless of their body mass value or BMI.

Comparison of insulin resistance and metabolic syndrome criteria in metabolically obese, normal weight (MONW) individuals in the prediction of cardiovascular disease risk: analysis of the Korean National Health and Nutrition Examination Survey (KNHANES) in 2010–2012

Body mass index is considered to be insufficient to diagnose obesity in population with metabolic abnormalities. In this study, we aimed to determine the optimal criteria for metabolically obese, normal weight (MONW) with insulin resistance or with metabolic syndrome to provide reliable diagnostic tool for obesity, especially targeting Korean population. This is a cross-sectional study based on the data extracted from the Korean National Health and Nutrition Examination Survey in 2010–2012. A total of 6274 adults with the normal weight were enrolled, and each subject was classified into either MONW with insulin resistance (MONW-IR) or MONW with metabolic syndrome (MONW-Mets) in order to analyze the risk of cardiovascular events. The Framingham risk score (FRS) and atherosclerotic cardiovascular disease risk equation (ASCVD) were used in the process. The odds ratio for the cardiovascular disease risk based on the FRS in the MONW-IR group (1.132; 95% confidence interval (CI), 0.854–1.502) was not significantly elevated whereas the odds ratio for the cardiovascular disease risk using the ASCVD in the MONW-IR group (1.809; 95% CI, 1.410–2.322) was significantly increased. The odds ratio for the cardiovascular disease risk in the MONW-Mets group was both significantly increased (2.93; 95% CI, 2.19–3.91 by FRS, 8.44; 95% CI, 6.19–11.49 by ASCVD) as well. However, the risk of cardiovascular disease was not significantly increased after excluding the subjects with diabetes mellitus that were the majority of MONW-IR group. Metabolic syndrome criteria can be considered more useful tool in diagnosing MONW in the Korean population. However, further prospective studies are needed to confirm our findings.

Lean, but not healthy: the 'metabolically obese, normal-weight' phenotype.

Obesity is commonly associated with metabolic dysfunction but there are obese persons who are metabolically healthy. On the opposite side of the coin, there are lean persons who carry multiple cardiometabolic risk factors, typically referred to as metabolically obese, normal-weight (MONW). This has called into question our understanding of obesity and metabolic dysfunction, as an appearance of normal weight may mask significant comorbidities and delay health interventions. High heterogeneity in MONW prevalence rates has been observed, with estimates ranging from as low as 5% to as high as 45%. Reasons for this include sample size effects, differences in MONW definition, social and demographic factors, as well as assumptions made in establishing normal weight. MONW study participants are often characterized by excess visceral adipose tissue and ectopic fat deposition, adipose tissue inflammation, altered inflammatory and adipokine profiles, reduced skeletal muscle mass and low cardiorespiratory fitness. However, more often than not, groups of MONW study participants have been somewhat 'fatter' than the control groups of metabolically healthy lean study participants, which in itself could be responsible for some of the observed differences. Very limited data are available regarding interventions to improve metabolic function in MONW study participants. There is a need for more research to better understand the characteristics of the MONW phenotype, the cause of metabolic dysfunction in the absence of obesity, and evaluate potential therapies so as to facilitate the establishment of clinical guidelines.

Diet Quality and Mortality Risk in Metabolically Obese Normal-Weight Adults

ObjectiveTo examine the associations among the Dietary Approaches to Stop Hypertension (DASH)–style diet, the Healthy Eating Index (HEI), and mortality risk in metabolically obese normal-weight (MONW) adults. Patients and MethodsData were from normal-weight (body mass index of 18.5 to <25) adults aged 30 to 90 years at baseline in the Third National Health and Nutrition Examination Survey, October 18, 1988, through October 15, 1994, followed up for deaths (all-cause, cardiovascular, and cancer related) until December 31, 2011. A total of 2103 participants without known cardiovascular disease and cancer at baseline were included in this prospective cohort study. Metabolic obesity was defined as having 2 or more of the following: high glucose, blood pressure, triglyceride, C-reactive protein, and insulin resistance values and low high-density lipoprotein cholesterol levels; metabolic healthy status was defined as having 0 or 1 of these metabolic derangements. ResultsDuring median follow-up of 18.6 years, there were 344 and 296 deaths in the MONW and metabolically healthy normal-weight (MHNW) phenotypes, respectively. In MONW individuals, a 1-SD increment in adherence to a DASH diet (2 points) or HEI (14 points) was significantly associated with reductions (17% [hazard ratio (HR), 0.83; 95% CI, 0.72-0.97] and 22% [HR, 0.78; 95% CI, 0.68-0.90], respectively) in the risk of all-cause mortality, after adjustment for potential confounders. The corresponding HRs for cardiovascular disease mortality were 0.72 (95% CI, 0.55-0.94) and 0.79 (95% CI, 0.65-0.97), respectively. In addition, reduction of cancer mortality was observed with 1-SD increment of HEI (HR, 0.63; 95% CI, 0.46-0.88). However, no association was observed in the MHNW phenotype. Sensitivity analyses suggested relationships robust to different definitions of MONW and also dose responses with the number of metabolic derangements. ConclusionHigher diet quality scores were associated with lower risk of mortality in normal-weight individuals with metabolic abnormalities.

Mediterranean diet, Dietary Approaches to Stop Hypertension (DASH) style diet, and metabolic health in U.S. adults

There is sparse evidence on the relationship between the Mediterranean diet, Dietary Approaches to Stop Hypertension (DASH) style diet, and metabolic health, especially comparing cardiometabolic phenotypes among in normal weight and obese populations. We aimed to investigate the association of the Mediterranean diet scores (MDS) and DASH index with metabolically healthy obese (MHO) and metabolically obese normal weight (MONW) phenotypes in a representative U.S. MDS and DASH index were calculated using dietary data from 2767 adults aged 20-90 years without any prior diagnosis of cancer or cardiovascular disease from the National Health and Nutrition Examination Survey III, 1988-1994. MHO and MONW individuals were identified using fasting glucose, insulin resistance, blood pressure, triglycerides, C-reactive protein, and high-density lipoprotein-cholesterol. Higher MDS was associated with higher odds of MHO phenotype (odds ratio (OR)T3 vs T1, 2.57 [95% confidence interval (CI), 1.04-6.35]; P trend=0.04), and higher DASH index was associated with lower odds of MONW phenotype (ORT3 vs T1, 0.59 [95% CI, 0.38-0.93]; P trend=0.03) only in the younger age group (<45 years for men or premenopausal women). No significant associations of MDS and DASH index with MHO and MONW phenotypes were observed in the older age group (≥45 years for men or postmenopausal women). Adherence to Mediterranean diet or DASH style diet was favorably associated with MHO and MONW phenotypes only in the younger age group, suggesting that potential dietary intervention to prevent cardiometabolic disease differ by age group.

OP.2A.03] METABOLICALLY HEALTHY OBESITY AND METABOLICALLY OBESE NORMAL WEIGHT IN RUSSIAN POPULATION

Objective: Metabolic health can be the determinant factor of the cardiovascular diseases independently of presence of obesity. The study estimates prevalence of metabolically healthy obesity (MHO) and metabolically obese normal weight (MONW) phenotypes in regions of Russian Federation. Design and method: A novel epidemiology survey of cardiovascular risk in regions of RF with different climatic, geographic, economic and demographic characteristics (ESSE-RF) was performed in a multi-step stratified random sample of approximately 1600 participants aged 25–65 years in every 13 selected region (Volgograd, Vologda, Voronezh, Vladivostok, Ivanovo, Kemerovo, Krasnoyarsk, Samara, Orenburg, Tomsk, Tyumen, Saint-Petersburg and Northern Osetia-Alania). Totally 22249 participants were recruited (8536 males (38,4%) and 13713 females (61,6%)). All subjects signed informed consent and filled out validated questionnaires regarding lifestyle risk factors, concomitant diseases and medication. Anthropometry (height, weight with body mass index (BMI) calculation, and waist circumference (WC)), fasting blood-tests: glucose, lipids were performed. Office BP was registered by OMRON (Japan). Obesity was detected as BMI more (or equal) than 30 kg/m2. Markers of metabolic unhealthy state: HDL less 1.30/1.04 mmol/l; triglycerides higher 1.7 mmol/l; glucose higher 5.6 mmol/l or treatment; BP higher 130/85 mmHg or therapy and WC higher 102(M)/88(F) cm. MHO was diagnosed in obese with less (or equal) 2 markers and MONW in lean with more (or equal) 2 markers. Statistical analysis was performed using SPSS Statistics 20. Results: Data analysis was possible in 22080 participants, results are presented in table 1. Table 1. Prevalence of MHO and MONW and associations with gender, age, cardiovascular complicationsodds ratio (OR) for region was adjusted for age and gender Conclusions: The prevalence of metabolically healthy obesity is rather high in Russian population without gender difference. Normal weight with metabolic abnormalities was detected in the third of lean participants with bias to male gender. Aging is decreasing number of MHO and increasing MONW. Also interregional difference was revealed.