Metabolically Obese Normal Weight Research Articles

Triglyceride-glucose index is capable of identifying metabolically obese, normal-weight older individuals

BackgroundThe concept of metabolically obese, normal weight (MONW) has emerged to describe individuals with a normal body mass index (BMI) who are at a relatively high risk of chronic diseases. However, BMI itself is a suboptimal index for the assessment of the health risks associated with visceral fat. The triglyceride-glucose (TyG) index is considered to be a reliable and cost-effective marker of insulin resistance. Therefore, in the present study, we aimed to determine the TyG index cut-off values that could be used to define MONW in older people and to determine the usefulness of these values for the prediction of chronic diseases.MethodsA total of 4,721 participants in the Korea National Health and Nutritional Examination Survey who were ≥ 60 years of age and did not have underweight or obesity were included. MONW was defined using the criteria for metabolic syndrome (MS), and the TyG index was calculated on the basis of the fasting plasma triglyceride and glucose concentrations. Chronic diseases, including T2DM, hypertension, and non-alcoholic fatty liver disease (NAFLD), were diagnosed.ResultsThe prevalence of MS increased from the lowest to the highest TyG index tertile. The cut-off values of the TyG index for MONW were calculated as 8.88 and 8.80 for males and females, respectively. MONW, defined using these cut-off values, was associated with high odds ratios for NAFLD, T2DM, and hypertension in both males and females.ConclusionsThe TyG index cut-off values calculated in the present study can be used to discriminate individuals with MONW from other older individuals without obesity and to predict the risk of chronic diseases. These findings show that the TyG index is an effective and cost-efficient method of assessing the risk of chronic diseases in people with MONW.

The Metabolically Obese, Normal-Weight Phenotype in Young Rats Is Associated with Cognitive Impairment and Partially Preventable with Leptin Intake during Lactation.

The intake of high-fat diets (HFDs) and obesity are linked to cognitive impairment. Here, we aimed to investigate whether an early metabolically obese, normal-weight (MONW) phenotype, induced with an HFD in young rats, also leads to cognitive dysfunction and to evaluate the potential cognitive benefits of neonatal intake of leptin. To achieve this, Wistar rats orally received physiological doses of leptin or its vehicle during lactation, followed by 11 weeks of pair-feeding with an HFD or control diet post-weaning. Working memory was assessed using a T-maze, and gene expression in the hippocampus and peripheral blood mononuclear cells (PBMCs) was assessed with real-time RT-qPCR to identify cognition biomarkers. Young MONW-like rats showed hippocampal gene expression changes and decreased working memory. Animals receiving leptin during lactation presented similar gene expression changes but preserved working memory despite HFD intake, partly due to improved insulin sensitivity. Notably, PBMC Syn1 expression appears as an accessible biomarker of cognitive health, reflecting both the detrimental effect of HFD intake at early ages despite the absence of obesity and the positive effects of neonatal leptin treatment on cognition. Thus, the MONW phenotype developed at a young age is linked to cognitive dysfunction, which is reflected at the transcriptomic level in PBMCs. Neonatal leptin intake can partly counteract this impaired cognition resulting from early HFD consumption.

The Role of Adipokines and Myokines in the Pathogenesis of Different Obesity Phenotypes-New Perspectives.

Obesity is a characteristic disease of the twenty-first century that is affecting an increasing percentage of society. Obesity expresses itself in different phenotypes: normal-weight obesity (NWO), metabolically obese normal-weight (MONW), metabolically healthy obesity (MHO), and metabolically unhealthy obesity (MUO). A range of pathophysiological mechanisms underlie the occurrence of obesity, including inflammation, oxidative stress, adipokine secretion, and other processes related to the pathophysiology of adipose tissue (AT). Body mass index (BMI) is the key indicator in the diagnosis of obesity; however, in the case of the NWO and MONW phenotypes, the metabolic disturbances are present despite BMI being within the normal range. On the other hand, MHO subjects with elevated BMI values do not present metabolic abnormalities. The MUO phenotype involves both a high BMI value and an abnormal metabolic profile. In this regard, attention has been focused on the variety of molecules produced by AT and their role in the development of obesity. Nesfatin-1, neuregulin 4, myonectin, irisin, and brain-derived neurotrophic factor (BDNF) all seem to have protective effects against obesity. The primary mechanism underlying the action of nesfatin-1 involves an increase in insulin sensitivity and reduced food intake. Neuregulin 4 sup-presses lipogenesis, decreases lipid accumulation, and reduces chronic low-grade inflammation. Myonectin lowers the amount of fatty acids in the bloodstream by increasing their absorption in the liver and AT. Irisin stimulates the browning of white adipose tissue (WAT) and consequently in-creases energy expenditure, additionally regulating glucose metabolism. Another molecule, BDNF, has anorexigenic effects. Decorin protects against the development of hyperglycemia, but may also contribute to proinflammatory processes. Similar effects are shown in the case of visfatin and chemerin, which may predispose to obesity. Visfatin increases adipogenesis, causes cholesterol accumulation in macrophages, and contributes to the development of glucose intolerance. Chemerin induces angiogenesis, which promotes the expansion of AT. This review aims to discuss the role of adipokines and myokines in the pathogenesis of the different obesity phenotypes.

Abstract 13909: It’s All About the Fat: Most Subjects With Metabolically Obese Normal Weight Have Either High Body Fat or Central Obesity

Introduction: Metabolically obese normal weight (MONW) refers to metabolic abnormalities despite normal body mass index (BMI). Hypothesis: Because obesity is generally defined by BMI, it is assumed that people with MONW do not have excessive adiposity but still have the metabolic dysregulation associated with adiposity. Methods: We included participants aged 20-65 of the National Health and Nutrition Examination Surveys from 1999-2006 and 2011-2018 with normal BMI (18.5-25 kg/m 2 ), fasting blood samples, and DEXA data. According to the AHA criteria, MONW was defined having ≥3 of the following criteria, besides a normal BMI: Hypertriglyceridemia (≥ 150 mg/dL) or treatment for elevated triglycerides; HDL cholesterol level < 40 mg/dL in men or <50 mg/dL in women or treatment for reduced HDL-C; elevated blood pressure (systolic ≥ 130 mmHg and/or diastolic ≥ 85 mmHg) or antihypertensive treatment or history of hypertension; elevated fasting plasma glucose ≥ 100 mg/dL or insulin/oral hypoglycemic treatment and central obesity by waist circumference (≥ 94 cm in men and ≥ 80 cm in women). High fat percentage was defined as ≥25% in men, ≥35% in women. Weighted logistic regression was performed to test the relation between MONW and high fat%, central obesity. Results: Of the 7,887 participants (53.6% men; mean age±SE was 39.23±0.24 years), 2433 (33.4%) had normal BMI included in the analysis. Among these, 148 had MONW (5%). Mean Fat% was 26.08±0.36% in those with MONW versus 21.90±0.17% in those without MONW for men, and 37.02±0.35% versus 33.31±0.21% for women. MONW subjects were 2.21 times more likely to have either central obesity or high fat % (OR 12.09, 95%CI: 6.18-23.67, p<0.01) and 2.18 times more likely to have high fat % (OR=2.84, 95%CI: 1.72-4.67, p<0.01) (see Figure). Conclusions: Most individuals with MONW have either increased fat content, central deposition of fat, or both. That highlights people with normal BMI may still have metabolic complications of adiposity.

Obesity, obesities and gastrointestinal cancers

Obesity has been recognized to be increasing globally and is designated a disease with adverse consequences requiring early detection and appropriate care. In addition to being related to metabolic syndrome disorders such as type 2 diabetes, hypertension, stroke, and premature coronary artery disease. Obesity is also etiologically linked to several cancers. The non-gastrointestinal cancers are breast, uterus, kidneys, ovaries, thyroid, meningioma, and thyroid. Gastrointestinal (GI) cancers are adenocarcinoma of the esophagus, liver, pancreas, gallbladder, and colorectal. The brighter side of the problem is that being overweight and obese and cigarette smoking are mostly preventable causes of cancers.Epidemiology and clinical studies have revealed that obesity is heterogeneous in clinical manifestations. In clinical practice, BMI is calculated by dividing a person's weight in kilograms by the square of the person's height in square meters (kg/m2). A BMI above 30 kg/m2 (defining obesity in many guidelines) is considered obesity. However, obesity is heterogeneous. There are subdivisions for obesity, and not all obesities are equally pathogenic.Adipose tissue, in particular, visceral adipose tissue (VAT), is endocrine and abdominal obesity (a surrogate for VAT) is evaluated by waist-hip measurements or just waist measures. Visceral Obesity, through several hormonal mechanisms, induces a low-grade chronic inflammatory state, insulin resistance, components of metabolic syndrome, and cancers. Metabolically obese, normal-weight (MONW) individuals in several Asian countries may have BMI below normal levels to diagnose obesity but suffer from many obesity-related complications. Conversely, some people have high BMI but are generally healthy with no features of metabolic syndrome. Many clinicians advise weight loss by dieting and exercise to metabolically healthy obese with large body habitus than to individuals with metabolic obesity but normal BMI.The GI cancers (esophagus, pancreas, gallbladder, liver, and colorectal) are individually discussed, emphasizing the incidence, possible pathogenesis, and preventive measures.From 2005 to 2014, most cancers associated with overweight and Obesity increased in the United States, while cancers related to other factors decreased. The standard recommendation is to offer or refer adults with a body mass index (BMI) of 30 or more to intensive, multicomponent behavioral interventions. However, the clinicians have to go beyond. They should critically evaluate BMI with due consideration for ethnicity, body habitus, and other factors that influence the type of obesity and obesity-related risks. In 2001, the Surgeon General's ``Call to Action to Prevent and Decrease Overweight and Obesity'' identified obesity as a critical public health priority for the United States. At government levels reducing obesity requires policy changes that improve the food and physical activity for all. However, implementing some policies with the most significant potential benefit to public health is politically tricky. The primary care physician, as well as subspecialists, should identify overweight and Obesity based on all the variable factors in the diagnosis. The medical community should address the prevention of overweight and Obesity as an essential part of medical care as much as vaccination in preventing infectious diseases at all levels- from childhood, to adolescence, and adults.

A non-coding variant linked to metabolic obesity with normal weight affects actin remodelling in subcutaneous adipocytes.

Recent large-scale genomic association studies found evidence for a genetic link between increased risk of type 2 diabetes and decreased risk for adiposity-related traits, reminiscent of metabolically obese normal weight (MONW) association signatures. However, the target genes and cellular mechanisms driving such MONW associations remain to be identified. Here, we systematically identify the cellular programmes of one of the top-scoring MONW risk loci, the 2q24.3 risk locus, in subcutaneous adipocytes. We identify a causal genetic variant, rs6712203, an intronic single-nucleotide polymorphism in the COBLL1 gene, which changes the conserved transcription factor motif of POU domain, class 2, transcription factor 2, and leads to differential COBLL1 gene expression by altering the enhancer activity at the locus in subcutaneous adipocytes. We then establish the cellular programme under the genetic control of the 2q24.3 MONW risk locus and the effector gene COBLL1, which is characterized by impaired actin cytoskeleton remodelling in differentiating subcutaneous adipocytes and subsequent failure of these cells to accumulate lipids and develop into metabolically active and insulin-sensitive adipocytes. Finally, we show that perturbations of the effector gene Cobll1 in a mouse model result in organismal phenotypes matching the MONW association signature, including decreased subcutaneous body fat mass and body weight along with impaired glucose tolerance. Taken together, our results provide a mechanistic link between the genetic risk for insulin resistance and low adiposity, providing a potential therapeutic hypothesis and a framework for future identification of causal relationships between genome associations and cellular programmes in other disorders.

Metabolically Obese Normal-Weight Phenotype as a Risk Factor for High Blood Pressure: A Five-Year Cohort

Background: The metabolically obese normal-weight (MONW) phenotype has been considered a risk factor for different chronic diseases, but its role in high blood pressure (HBP) is still unclear. The aim of the study is to determine if the MONW phenotype constitutes a risk factor for hypertension in Peruvian adults belonging to a 5-year cohort. Methods: This is a retrospective cohort study. A secondary analysis from the database of the PERU MIGRANT study was carried out from the MONW and non-MONW cohorts; after a 5-year follow-up, the appearance of HBP was evaluated in the subjects of both cohorts. To assess the strength and magnitude of the association, a Poisson regression model (crude and adjusted) with robust variance was used. The measure of association was the relative risk (RR). Results: The incidence of HBP was 11.30%. In the multivariable analysis, subjects with the MONW phenotype had a 2.879-fold risk of presenting HBP in 5 years compared with those who were not MONW at the beginning of the study; this was adjusted for categorized age, sex, group, and state of smoker and alcohol drinker (RR: 2.055; 95% confidence interval (CI): 1.118 - 3.777; P = 0.020). Conclusions: The presence of the MONW phenotype doubled the incidence of HBP, even after adjusting for other covariates. However, studies in this field should continue. If these findings are confirmed, it should be considered that presenting an adequate weight for height should not be interpreted as a condition free of metabolic alterations, so screening for hypertension should be carried out regardless of whether or not the body mass index obtained is considered normal. J Endocrinol Metab. 2023;13(1):13-19 doi: https://doi.org/10.14740/jem855

Changes in BMI and physical activity from youth to adulthood distinguish normal-weight, metabolically obese adults from those who remain healthy.

HighlightsAdults with MONW have a lower BMI during youth until young adulthood, but higher BMI after this than adults with metabolically healthy normal weight. Adults with MONW have a greater decrease in physical activity from youth to adulthood than other adults. Healthy lifestyle is important in the prevention of metabolic disorders, particularly in individuals who are slim in childhood.BackgroundIndividuals with metabolically obese normal-weight (MONW) have higher risk of cardiovascular events than those with obesity but a metabolically healthy status. Etiological factors leading to MONW are not well known. We hypothesized distinct trajectories of changes in BMI and physical activity may modify metabolic risk and distinguish individuals with MONW from those who remain healthy.MethodsWe compared the mean levels of BMI and physical activity at eight time points (1980, 1983, 1986, 1989, 1992, 2001, 2007, 2011) between MONW and healthy normal-weight adults using linear mixed-model analysis. The analyses included 1180 participants of the Cardiovascular Risk in Young Finns study, a population-based study that represents six different age cohorts 3, 6, 9, 12, 15 and 18 years of age at baseline.ResultsIndividuals with adult MONW had significantly lower BMI in childhood and young adulthood, but their BMI increased more than in other adults after this age (p<0.001for interaction between time and MONW status). Physical activity decreased relatively more since youth in individuals with adult MONW (p<0.001).ConclusionsRelative leanness in youth and subsequent weight gain in young adulthood, and a gradual decrease in physical activity levels from youth to adulthood, predispose normal-weight individuals to metabolic impairments. The results highlight the importance of a healthy lifestyle in the prevention of metabolic disorders, particularly in individuals who are slim in childhood.

Hyperuricemia is Associated with the Presence of Metabolically Obese Normal-Weight and Metabolically Healthy Obese Phenotypes

ABSTRACT Background It is well-recognized that hyperuricemia is a common abnormality among individuals with metabolic syndrome. Aims The objective of this study was to determine whether hyperuricemia is associated with the metabolically obese normal-weight (MONW) and metabolically healthy obese (MHO) phenotypes. Methods Men and women equal or greater than 18 years of age were enrolled in a cross-sectional study. Normal-weight subjects were allocated into the MONW or healthy normal-weight (HNW) groups; while obese individuals were divided into the MHO and metabolically unhealthy obese (MUO) subgroups. MONW phenotype was defined by body mass index (BMI) <25.0 kg/m2 accompanied by at least one cardiovascular risk factor (hyperglycemia, elevated blood pressure, hypertriglyceridemia, and low high-density lipoprotein cholesterol), and MHO phenotype was considered in obese subjects (BMI ≥30 kg/m2) without metabolic abnormalities. Results A total of 567 individuals were enrolled; of them, normal-weight subjects were allocated into the MONW (n = 101) and control (n = 72) groups, whereas obese individuals into the MHO (n = 61) and MUO (n = 333) groups. The multiple logistic regression analysis adjusted by age, gender, and body mass index revealed that hyperuricemia is significantly associated with MONW (OR = 5.14; 95% CI: 1.37–19.29) and MHO (OR = 0.34; 95% CI: 0.14–0.82) phenotypes. Conclusion Results of our study showed that hyperuricemia is associated with both MONW and MHO phenotypes.

Perinatal Treatment with Leptin, but Not Celastrol, Protects from Metabolically Obese, Normal-Weight Phenotype in Rats

Perinatal nutrition has a well-known influence on obesity susceptibility. We previously demonstrated the protective anti-obesity effects of perinatal leptin administration. Celastrol is a natural compound acting as a leptin sensitizer with anti-obesity effects when administered in adult animals. Here, we aimed to determine if perinatal treatment with leptin, celastrol, or their combination was able to improve metabolic health in animals fed an isocaloric high-fat (HF) diet. Leptin and/or celastrol or their vehicle were administered orally to rats during the suckling period. After weaning, animals were chronically pair-fed with an HF diet provided isocaloric to the intake of a normal-fat diet by control animals to avoid obesity. Isocaloric HF feeding in vehicle-treated animals resulted in metabolic features characteristic of the metabolically obese, normal-weight (MONW) phenotype, i.e., obesity-related disturbances without increased body weight. Leptin treatment prevented liver fat deposition and insulin resistance, induced greater insulin and leptin signaling capacity, decreased gene expression of orexigenic signals at the hypothalamic level, and induced browning in retroperitoneal adipose tissue. However, celastrol treatment did not provide any protective effect and resulted in greater size of the retroperitoneal adipose depot, higher circulating glucose and insulin levels, and decreased leptin sensitivity capacity in adipose tissue. The co-administration of leptin ameliorated the negative effects of celastrol on the retroperitoneal depot, inducing browning and decreasing its size. In conclusion, the perinatal administration of leptin, but not celastrol, provided protection against the consequences of dietary unbalances leading to an MONW phenotype in adulthood.

Sex Differences in the TyG Index and Cardiovascular Risk Factors in Metabolically Obese Normal Weight Phenotype.

Background The triglyceride glucose (TyG) index is a novel surrogate marker of insulin resistance and increases cardiovascular disease risk. We sought to explore sex differences in the relationship between TyG and cardiovascular (CV) risk factors in metabolically obese normal weight (MONW) phenotype. Method We analyzed data of 1208 healthy men and nonpregnant women enrolled in a population-based longitudinal study from January 2017–June 2020. MONW phenotype was defined by normal body mass index (BMI: 18–<25 kg/m2) with at least one of the following metabolic disorders (MONW phenotype): elevated blood pressure (BP), hypertriglyceridemia, hyperglycemia, and low HDL cholesterol. Multiple logistic regression analysis was performed to assess the association between elevated TyG index and the CV risk factors in women and men and was presented in odds ratio (OR) with 95% confidence interval (CI). Results Of 1208 subjects, 350 (29%) were MONW phenotype (mean age (years): male: 43.5 ± 12.4 and female: 43.1 ± 12.7) and 858 were metabolically healthy normal weight (MHNW; n = 858 (71%)). MONW women had higher mean values of the TyG index (8.03 ± 5.07) than men (7.47 ± 4.68). Multivariate analysis revealed that the elevated TyG index is significantly associated with MONW phenotype in women (adjusted OR: 8.73, 95% CI: 5.62–13.57) and men (aOR: 5.90, 95% CI: 4.23–8.23). TyG was found to be an excellent predictor of MONW status in both women (receiver operating characteristic (ROC) area under the curve (AUC): 0.979, 95% CI: 0.969–0.988) and men (ROC-AUC: 0.968, 95% CI: 0.952–0.983). Conclusion Our study revealed that the TyG index may represent a cost-effective and informative screening tool for the high-risk MONW phenotype.

Anthropometric and body composition parameters in adolescents with the metabolically obese normal-weight phenotype.

We aimed to investigate the anthropometric and body composition parameters associated with the metabolically obese normal-weight (MONW) phenotype. This cross-sectional study was conducted with 506 adolescents in Brazil (aged 10-19 y). The MONW phenotype was defined as normal-weight, according to BMI/age, and at least one metabolic alteration. Anthropometric measurements were obtained and the DEXA was used for body composition analysis. Crude and adjusted Poisson regression models with robust variance were used to estimate the associations. The phenotype was positively associated with waist circumference (male: prevalence ratio (PR) = 1·05; 95% CI 1·01, 1·09; female: PR = 1·06; 95% CI 1·02, 1·09), waist:height ratio (male: PR = 1·26; 95% CI 1·07, 1·49; female: PR = 1·29; 95% CI 1·07, 1·56) and android:gynoid fat ratio (male: PR = 1·25; 95% CI 1·03, 1·51; female: PR = 1·39; 95% CI 1·20, 1·62), in both sexes. Furthermore, there was a positive association of phenotype with waist:hip ratio (PR = 1·32; 95% CI 1·06, 1·65) and trunk:arm fat ratio (PR = 1·13; 95% CI 1·02, 1·24) only in males and with trunk:leg fat ratio (PR = 2·84; 95% CI 1·46, 5·53), BAIp (PR = 1·06; 95% CI 1·01, 1·12), fat mass index (PR = 1·24; 95% CI 1·10, 1·41) and regional indices of metabolic load and capacity (PR = 1·29; 95% CI 1·09, 1·53), in females. Anthropometric and body composition parameters indicative of central and total fat are associated with the MONW phenotype.

Prevalence and characteristics of the metabolically healthy obese phenotype in children and adolescents in a Mexican state

ObjectivesTo determine the prevalence of the Metabolically Healthy Obesity (MHO), and Metabolically Obese Normal-Weight (MONW) phenotypes in a sample of children and adolescents. To evaluate which clinical and laboratory variables are related to the MONW and MHO phenotypes. MethodsA cross-sectional study was carried out in children and adolescents aged 6-18 years old, presumably healthy. Somatometry, glucose, insulin, triglycerides, HDL-cholesterol, LDL-cholesterol, HOMA-IR, triglycerides/HDL ratio, triglycerides and glucose index, and leptin/adiponectin, were determined. ResultsData from 620 children and adolescents were included (50.65% were males); the median age was 11 years. The prevalence of the MONW phenotype was 22.85% (95%CI 16.85%-29.79%), and the MHO phenotype 27.61% (95%CI 22.60%-33.06%). The variables that significantly explained the possibility of presenting the MONW and MHO phenotype were triglycerides/HDL ratio, and product of triglycerides and glucose. Insulin and HOMA-IR were significantly associated with the MHO phenotype but not with the MONW phenotype. ConclusionsPrevalence of metabolically healthy obese phenotype is lower in the Mexican population compared to European studies; thus, future studies should determine if this difference relies upon genetic profile or lifestyle. The indices to assess the action of insulin based on lipids can help identify children and adolescents with the MHO and MONW phenotypes.

Prevalence and characteristics of the metabolically healthy obese phenotype in children and adolescents in a Mexican state

ObjectivesTo determine the prevalence of the Metabolically Healthy Obesity (MHO), and Metabolically Obese Normal-Weight (MONW) phenotypes in a sample of children and adolescents. To evaluate which clinical and laboratory variables are related to the MONW and MHO phenotypes. MethodsA cross-sectional study was carried out in children and adolescents aged 6-18 years old, presumably healthy. Somatometry, glucose, insulin, triglycerides, HDL-cholesterol, LDL-cholesterol, HOMA-IR, triglycerides/HDL ratio, triglycerides and glucose index, and leptin/adiponectin, were determined. ResultsData from 620 children and adolescents were included (50.65% were males); the median age was 11 years. The prevalence of the MONW phenotype was 22.85% (95%CI 16.85%-29.79%), and the MHO phenotype 27.61% (95%CI 22.60%-33.06%). The variables that significantly explained the possibility of presenting the MONW and MHO phenotype were triglycerides/HDL ratio, and product of triglycerides and glucose. Insulin and HOMA-IR were significantly associated with the MHO phenotype but not with the MONW phenotype. ConclusionsPrevalence of metabolically healthy obese phenotype is lower in the Mexican population compared to European studies; thus, future studies should determine if this difference relies upon genetic profile or lifestyle. The indices to assess the action of insulin based on lipids can help identify children and adolescents with the MHO and MONW phenotypes.

Cardiometabolic index: a new tool for screening the metabolically obese normal weight phenotype.

People with the metabolically obese normal weight (MONW) phenotype are considered as an extremely high-risk group for unfavorable health consequences, but they are frequently undetected due to deceptive body mass index (BMI) and complex assessment. This study aimed to explore the clinical usefulness of cardiometabolic index (CMI) in identifying MONW individuals. This cross-sectional study involved a total of 47,683 normal-weight subjects aged ≥ 18years. Participants underwent anthropometrics, routine biochemical tests, and questionnaires for a full evaluation of the metabolic profile. The odds ratio (OR) of CMI and MONW phenotype was determined by the Logistic regression models and the diagnostic accuracy of CMI was evaluated by the receiver operating characteristic (ROC) curve analysis. The prevalence of MONW phenotype was 11.0%. After multivariate adjustment, the ORs for MONW in the highest compared with the lowest quartile of CMI was 71.20 (95% CI 55.19-91.86), and 1-SD increment of CMI brought a 54% additional risk. In ROC analysis, compared with BMI and waist circumference, CMI showed superior performance for identifying MONW individuals with an AUC of 0.853 (95% CI 0.847-0.860) in men and 0.912 (95% CI 0.906-0.918) in women, respectively. Moreover, CMI exhibited the highest diagnostic accuracy in younger age groups (aged 18-34 for men; aged 18-34 and 35-44 for women), in which AUCs surpassed 0.9 in both sexes. CMI could be served as a valuable indicator to identify MONW phenotype of Chinese adults, particularly for young people.

Increased incidence of bladder cancer with metabolically unhealthy status: analysis from the National Health Checkup database in Korea

We assessed the association between metabolic health status and the incidence of bladder cancer using nationally representative data from the National Health Insurance System and National Health Checkups (NHC) databases in South Korea. Data for 11,781,768 men who participated in the NHC between 2009 and 2012 were analysed. The normal-weight and physically obese categories were defined as body mass indexes (BMI) < 25 and ≥25 kg/m2, respectively. Metabolically obese was defined as the presence of ≥3 components of metabolic syndrome. The participants were stratified into metabolically healthy, normal-weight (MHNW); metabolically obese, normal-weight (MONW); metabolically healthy, obese (MHO); metabolically obese, obese (MOO). Multivariate-adjusted Cox regression analysis was conducted to examine the association between metabolic health status and the incidence of bladder cancer. The study participants included 17,777 men newly registered with bladder cancer. Analysis according to metabolic health status classification revealed a higher multivariable-adjusted hazard ratio in the MOO, MONW group than in the MHO group (1.307 [95% CI: 1.258–1.358], 1.183 [95% CI: 1.137–1.231] and 1.066 [95% CI: 1.017–1.119], respectively; hazard ratios given relative to MHNW group) We found an association between metabolic health status and the incidence of bladder cancer, with an increasing risk according to the number of metabolic health status components.

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