Relationship Between Zinc, Selenium, and Magnesium Status and Markers of Metabolically Healthy and Unhealthy Obesity Phenotypes.

Our objective was to investigate the relationship between zinc, selenium, and magnesium status and markers of metabolically healthy and unhealthy obesity phenotypes. This was a cross-sectional study with 140 women: metabolically healthy obese women (n = 35), metabolically unhealthy obese women (n = 28), and normal-weight women (n = 77). We have calculated the body mass index, waist-hip ratio, waist-height ratio and some adiposity indices. Additionally, we evaluated endocrine-metabolic parameters and estimated the dietary intake of energy, macronutrients, zinc, selenium, and magnesium. The mineral concentrations in plasma, erythrocytes, and urine were assessed. In obese patients, there was a significant decrease in dietary zinc, selenium, and magnesium intake per kilogram of body weight, as well as lower mineral concentrations in both plasma and erythrocytes. Additionally, these patients exhibited higher urinary mineral levels compared to the control group, regardless of whether they had healthy or unhealthy phenotypes. We observed a significant correlation between deficiencies in zinc, selenium, and magnesium and obesity-associated metabolic disorders, including dyslipidemias and redox status disturbances. This study highlights a connection between deficiencies in zinc, selenium, and magnesium and metabolic disorders linked to obesity, including dyslipidemias, alterations in redox status, and thyroid hormonal dysfunction.

Evaluation of systemic endothelial-dependent and endothelial-independent microvascular reactivity in metabolically healthy obesity: An observational study.

BACKGROUND: Metabolically healthy obesity (MHO), a phenotype of obesity considered to be of lower cardiovascular risk, is still a controversial concept. This study aimed to investigate the presence of subclinical systemic microvascular dysfunction in individuals with MHO. METHODS: This was a cross-sectional study in which 112 volunteers were allocated into three groups: metabolically healthy normal weight (MHNW), MHO, or metabolically unhealthy obesity (MUO). Obesity was defined as a body mass index (BMI) ≥ 30 kg/m2. MHO was defined as the absence of any component of metabolic syndrome, except waist circumference. Microvascular reactivity was evaluated using cutaneous laser speckle contrast imaging. RESULTS: Mean age was 33.2 ± 7.66 years. The median BMI in the MHNW, MHO and MUO groups was 23.6, 32.8, and 35.8 kg/m2, respectively. Baseline microvascular conductance values were lower in the MUO group (0.25 ± 0.08 APU/mmHg) than in MHO (0.30 ± 0.10 APU/mmHg) and MHNW groups (0.33 ± 0.12 APU/mmHg) (P = 0.0008). There were no significant differences regarding endothelial-dependent (acetylcholine stimulation or postocclusive reactive hyperemia) or endothelial-independent (sodium nitroprusside stimulation) microvascular reactivity among the groups. CONCLUSIONS: Individuals with MUO had lower baseline systemic microvascular flow than those with MHNW or MHO, but endothelium-dependent or endothelium-independent microvascular reactivity were not changed in any of the groups. The relatively young age of the study population, the low frequency of class III obesity, or the strict definition of MHO (absence of any metabolic syndrome criteria) might account for the lack of difference of microvascular reactivity among MHNW, MHO or MUO.

Association between the expression of TLR4, TLR2, and MyD88 with low-grade chronic inflammation in individuals with metabolically healthy obesity.

BACKGROUND: Among the Toll-like receptors (TLR) that are dependent of myeloid response protein (MyD88), the TLR4 and TLR2 are directly associated with low-grade chronic inflammation; however, they are not been investigated in subjects with metabolically healthy obesity (MHO). Thus, the objective of this study was to determine the association between the expression of TLR4, TLR2, and MyD88 with low-grade chronic inflammation in individuals with MHO. METHODS AND RESULTS: Men and women with obesity aged 20 to 55 years were enrolled in a cross-sectional study. Individuals with MHO were allocated into the groups with and without low-grade chronic inflammation. Pregnancy, smoking, alcohol consumption, intense physical activity or sexual intercourse in the previous 72 h, diabetes, high blood pressure, cancer, thyroid disease, acute or chronic infections, renal impairment, and hepatic diseases, were exclusion criteria. The MHO phenotype was defined by a body mass index (BMI ≥ 30 kg/m2) plus one or none of the following cardiovascular risk factors: hyperglycemia, elevated blood pressure, hypertriglyceridemia, and low high-density lipoprotein cholesterol. A total of 64 individuals with MHO were enrolled and allocated into the groups with (n = 37) and without (n = 27) inflammation. The multiple logistic regression analysis indicated that TLR2 expression is significantly associated with inflammation in individuals with MHO. In the subsequent analysis adjusted by BMI, TLR2 expression remained associated with inflammation in individuals with MHO. CONCLUSION: Our results suggest that overexpression of TLR2, but not TLR4 and MyD88, is associated with low-grade chronic inflammation in subjects with MHO.

Prevalence of liver cirrhosis based on the metabolic health and weight criteria: Report from the Korea National Health and Nutrition Examination Survey (KNHANES) data analysis.

INTRODUCTION AND OBJECTIVES: Recent studies have proposed two distinctive types of obesity, metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO), based on various physiological factors. This study sought to explore the relationship between the metabolic obesity types and the incidence of liver cirrhosis (LC) in a large nationally-representative population. MATERIALS AND METHODS: Data on 27,629 adults with MHO or MUHO, were analyzed from the Korea National Health and Nutrition Examination Survey (KNHANES) obtained from 2015 through 2019. Four categories of metabolic health and weight (MHW) were generated for analysis: (1) MHO, (2) MUHO, (3) Metabolically unhealthy normal weight (MUHNW), and (4) Metabolically healthy normal weight (MHNW). Statistical analyzes were performed with univariate and multivariate logistic regression. RESULTS: The prevalence of LC did not show statistically significant differences among the MHW categories: 0.5% in MHO, 0.4% in MUHO, 0.2% in MHNW, and 0.3% in MUHNW. The unadjusted analysis showed a significant association between self-reported LC and MUHO, but this association was not evident in the adjusted analysis. In the adjusted analysis of the prevalence of laboratory LC, a significant association emerged in the MUHO group, followed in descending order of magnitude by the MHO and MUHNW groups. A favorable fasting blood glucose level was the only factor associated with increased prevalence of reported LC in MUHO. CONCLUSIONS: The study demonstrated a difference in the prevalence of LC between MHO and MUHO. Our study concludes that the MHO phenotype is a transient status with regard to metabolic abnormalities, and caution is necessary when evaluating MHO.

The beneficial metabolic actions of prolactin.

The role of prolactin (PRL) favoring metabolic homeostasis is supported by multiple preclinical and clinical studies. PRL levels are key to explaining the direction of its actions. In contrast with the negative outcomes associated with very high (>100 µg/L) and very low (<7 µg/L) PRL levels, moderately high PRL levels, both within but also above the classically considered physiological range are beneficial for metabolism and have been defined as HomeoFIT-PRL. In animal models, HomeoFIT-PRL levels counteract insulin resistance, glucose intolerance, adipose tissue hypertrophy and fatty liver; and in humans associate with reduced prevalence of insulin resistance, fatty liver, glucose intolerance, metabolic syndrome, reduced adipocyte hypertrophy, and protection from type 2 diabetes development. The beneficial actions of PRL can be explained by its positive effects on main metabolic organs including the pancreas, liver, adipose tissue, and hypothalamus. Here, we briefly review work supporting PRL as a promoter of metabolic homeostasis in rodents and humans, the PRL levels associated with metabolic protection, and the proposed mechanisms involved. Finally, we discuss the possibility of using drugs elevating PRL for the treatment of metabolic diseases.

The rs9939609 Variant in FTO Increases the Risk of Hypercholesterolemia in Metabolically Healthy Subjects with Excess Weight.

INTRODUCTION: The fat mass and obesity-associated gene (FTO) is largely/primarily expressed in the hypothalamus. It plays a role in energy balance, regulation of food intake, and adipogenesis. According to metabolic phenotypes, studies have associated the FTO rs9939609 variant with body mass index (BMI), body fat mass, and dietary intake but not with serum lipids. This study aimed to analyze the association of the FTO rs9939609 variant with serum lipids in Mexican adults with different metabolic phenotypes. METHODS: We included 306 subjects aged 18-65 years, classified as normal weight or excess weight (EW) according to their BMI. EW included BMI from 25 to 39.9 kg/m2. Participants were classified into two metabolic phenotypes: metabolically healthy/metabolically unhealthy (MH/MUH). We use the homeostatic model assessment of insulin resistance and NCEP-ATP III cutoffs for glucose, triglycerides, high-density lipoprotein, and blood pressure. Subjects with ≥2 altered parameters were classified as MUH. The variant was determined by allelic discrimination with TaqMan® probes. RESULTS: In subjects with the A allele, significantly higher total cholesterol and low-density-lipoprotein cholesterol were found (p < 0.05). Furthermore, subjects with EW-MH and the AA or AT genotype had a significantly higher odds ratio for hypercholesterolemia (odds ratio 4.48, 95% confidence interval: 1.48-13.59, p = 0.008). CONCLUSION: The FTO rs9939609 variant may influence serum lipid concentrations, increasing the risk of hypercholesterolemia.

Dose-Response Relationship of Resistance Training on Metabolic Phenotypes, Body Composition and Lipid Profile in Menopausal Women.

The relationship between volume training of resistance training (RT), body composition and cardiometabolic profile in menopausal women is poorly understand. This study aimed to evaluate the dose−response relationship of RT on lipid profile, body composition and metabolic phenotypes in menopausal women. A total of 31 women were categorized according to different volume of RT. Body composition was evaluated by DEXA and the cardiometabolic risk by metabolic phenotypes and lipid profile. There was a higher frequency of metabolically unhealthy phenotype in women who practiced RT for less than two years and had a weekly frequency lower than three days a week (p > 0.05). Women with more than two years and a higher weekly frequency of RT had lower trunk fat mass than their counterparties (15.33 ± 7.56 versus 10.57 ± 4.87, p = 0.04; 16.31 ± 7.46 versus 10.98 ± 5.49, p = 0.03, respectively). There was an association between HDL-c and time of RT in years. A moderate correlation was identified between variables of body adiposity, time in years and weekly frequency of RT. The present study concludes that more time in years and weekly frequency of RT practice are associated with lower body adiposity in menopausal women, the first also being associated with HDL-c.

Expression of obesity- and type-2 diabetes-associated genes in omental adipose tissue of individuals with obesity.

AIMS: Obesity and type 2 diabetes mellitus are two pathologies that share metabolic abnormalities in most of the cases; however, there are differences as well. Some studies have reported that approximately 30% of obese patients have normal glucose and lipid levels in blood despite an accumulation of abdominal adipose tissue. Here, we compare the gene expression in adipose tissue of several genes associated with obesity and/or diabetes between obese patients without T2D and obese patients with T2D. METHODS: Omental adipose tissue was collected during the patients elective bariatric surgery. Gene expression was determined by real-time PCR. Phenotypic variables were correlated with gene expression and 2^-ΔΔCt relative expression analysis between groups was performed. RESULTS: The stronger correlations in the obese without T2D or reference group was between ICAM1 and HbA1c; HP and TC and LDL while in the obese with diabetes or case group the correlation occurred between CSF1 and BMI. A correlation between HP and TC was found in the case group as well. The expression of VEGFA, CCND2, IL1R1 and PTEN was downregulated in the obese with T2D group. CONCLUSIONS: This study identified genes whose expression is different between obese subjects with and without diabetes. Those genes are related to inflammation, cholesterol transport, adipocyte differentiation/expansion and browning.

Replication of Integrative Data Analysis for Adipose Tissue Dysfunction, Low-Grade Inflammation, Postprandial Responses and OMICs Signatures in Symptom-Free Adults.

We previously reported preliminary characterization of adipose tissue (AT) dysfunction through the adiponectin/leptin ratio (ALR) and fasting/postprandial (F/P) gene expression in subcutaneous (SQ) adipose tissue (AT) biopsies obtained from participants in the GEMM study, a precision medicine research project. Here we present integrative data replication of previous findings from an increased number of GEMM symptom-free (SF) adults (N = 124) to improve characterization of early biomarkers for cardiovascular (CV)/immunometabolic risk in SF adults with AT dysfunction. We achieved this goal by taking advantage of the rich set of GEMM F/P 5 h time course data and three tissue samples collected at the same time and frequency on each adult participant (F/P blood, biopsies of SQAT and skeletal muscle (SKM)). We classified them with the presence/absence of AT dysfunction: low (<1) or high (>1) ALR. We also examined the presence of metabolically healthy (MH)/unhealthy (MUH) individuals through low-grade chronic subclinical inflammation (high sensitivity C-reactive protein (hsCRP)), whole body insulin sensitivity (Matsuda Index) and Metabolic Syndrome criteria in people with/without AT dysfunction. Molecular data directly measured from three tissues in a subset of participants allowed fine-scale multi-OMIC profiling of individual postprandial responses (RNA-seq in SKM and SQAT, miRNA from plasma exosomes and shotgun lipidomics in blood). Dynamic postprandial immunometabolic molecular endophenotypes were obtained to move towards a personalized, patient-defined medicine. This study offers an example of integrative translational research, which applies bench-to-bedside research to clinical medicine. Our F/P study design has the potential to characterize CV/immunometabolic early risk detection in support of precision medicine and discovery in SF individuals.

Vitamin D is directly associated with favorable glycemic, lipid, and inflammatory profiles in individuals with at least one component of metabolic syndrome irrespective of total adiposity: Pró-Saúde Study, Brazil.

Vitamin D insufficiency has been suggested as a risk factor for several metabolic disorders. The objective of the study was to investigate the association between serum 25 hydroxyvitamin D [25(OH)D] and metabolic health markers of Brazilian individuals with normal-weight, overweight or obesity. We hypothesized that serum 25(OH)D would be inversely associated with glycemic, lipid and inflammatory markers indicative of metabolic abnormality. Data of 511 individuals (33-79 years), recruited from a longitudinal investigation (Pró-Saúde Study), were analyzed cross-sectionally. Anthropometric, biochemical, body composition, socio-demographic and lifestyle data were collected. Based on body mass index (BMI; normal weight, overweight, obesity) and metabolic health (metabolically healthy (MH) and metabolically unhealthy (MU)) categories, the participants were classified into 6 phenotypes. Individuals having zero components of the metabolic syndrome were considered as "MH". MH obesity was frequent in 2.0% of the participants and 56.0% exhibited vitamin D insufficiency (<20 ng/mL). In the subgroups of the same BMI category, there were no significant differences in 25(OH)D concentrations between individuals classified as MH and MU. After adjustments (including %body fat and BMI), an inverse association was observed between 25(OH)D and visceral adipose tissue (B = -6.46, 95% confidence interval, CI: -12.87, -0.04), leptin (B = -0.09, 95% confidence interval, CI: -0.14, -0.03), insulin (B = -0.21, 95%CI: -0.34, -0.07), HOMA-IR (B = -0.06, 95%CI: -0.10, -0.02), triglycerides (B = -2.44, 95%CI: -3.66, -1.22), and TNF-α (B = -0.12, 95%CI: -0.24, -0.005) only in MU individuals. Our results indicate that the association of 25(OH)D concentrations with a favorable biochemical profile (glycemic, lipidic and inflammatory) seems to depend on the individual's overall metabolic health, suggesting more benefits from higher serum vitamin D in MU individuals, regardless of their adiposity.

Influence of dietary patterns on the metabolically healthy obesity phenotype: A systematic review.

AIMS: In many individuals (35%) obesity is not accompanied by cardiometabolic disorders, a condition referred to as metabolically healthy obesity. Since the effectiveness of dietary interventions for this condition is not well established, this study reviews the influence of dietary patterns on the phenotype of metabolically healthy obesity in adults and elderly. DATA SYNTHESIS: The review was carried out following the PRISMA guidelines and registered in the PROSPERO. The search was conducted in the MEDLINE, SCOPUS, Web of Science, Science Direct, LILACS, and SciELO databases. A total of 236 articles were identified, seven of which were selected for synthesis after application of the eligibility criteria. CONCLUSIONS: The overall result found out in this synthesis was that the greater adherence to healthy eating patterns was considered a preventive to the transition from metabolically healthy obesity to metabolic unhealthy obese phenotypes, by improving metabolic health, and reducing the risk of cardiovascular disease and mortality from all causes. In contrast, unhealthy eating patterns resulted in increased inflammation and risks of developing noncommunicable diseases. This review indicates that adherence to healthy eating patterns may interfere with metabolic phenotypes of obesity and positively affect metabolically healthy obesity. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42020159783.

Gut microbiota of adults with different metabolic phenotypes.

OBJECTIVE: The aim of this study was to investigate the gut microbiota of individuals with different metabolic phenotypes and to compare their characteristics. METHODS: This was a cross-sectional study with 109 adults, classified according to metabolic status, by body mass index, and homeostasis model assessment. Anthropometric and biochemical characteristics and blood pressure were evaluated. Level of physical activity was evaluated by means of a questionnaire, and dietary consumption was evaluated using a 3-d food record. Feces samples were collected from each participant, and gut microbiota profile was analyzed by sequencing of the 16S rRNA gene. The Kruskal-Wallis and χ2 tests were used, according to the scale of measurement of the variables, on the statistical program SPSS version 25, with significance level of 5%. RESULTS: Significantly lower values of saturated fat intake and fasting glycemia were observed in metabolically healthy individuals who were overweight and obese compared with their unhealthy counterparts. Diversity and richness of bacterial communities were lower in individuals who were obese and in the unhealthy phenotype. The genus Eubacterium rectale and genera of the family Prevotellaceae were more abundant in the metabolically healthy obese and metabolically healthy overweight groups than in the metabolically healthy normal weight one, whereas Bifidobacterium was more abundant in the metabolically healthy normal weight group. The genera Coprococcus and Ruminococcus were more abundant in the metabolically healthy overweight group than in the metabolically unhealthy overweight one. CONCLUSIONS: We observed distinct characteristics in the gut microbiota of different metabolic phenotypes. The intestines of individuals with unhealthy phenotypes hosted inflammation-associated microbiota, with lower butyrate production potential and reduced bacterial diversity.

Natural course of metabolically healthy phenotype and risk of developing Cardiometabolic diseases: a three years follow-up study.

BACKGROUND: Whether the metabolically healthy obese (MHO) phenotype is a single, stable or a transitional, fluctuating state is currently unknown. The Mexican-Mestizo population has a genetic predisposition for the development of type 2 diabetes (T2D) and other cardiometabolic complications. Little is known about the natural history of metabolic health in this population. The aim of this study was to analyze the transitions over time among individuals with different degrees of metabolic health and body mass index, and evaluate the incidence of cardiometabolic outcomes according to phenotype. METHODS: The study population consisted of a metabolic syndrome cohort with at least 3 years of follow up. Participants were apparently-healthy urban Mexican adults ≥20 years with a body mass index (BMI) ≥20 kg/m2. Metabolically healthy phenotype was defined using the criteria of the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) metabolic syndrome criteria and the subjects were stratified into 4 groups according to their BMI and metabolic health. For cardiometabolic outcomes we estimated the incidence of cardiometabolic outcomes and standardized them per 1, 000 person-years of follow-up. Finally, to evaluate the risk for transition and development of cardiometabolic outcomes, we fitted Cox Proportional Hazard regression models. RESULTS: Amongst the 5541 subjects, 54.2% were classified as metabolically healthy and 45.8% as unhealthy. The MHO prevalence was 39.3%. Up to a third of the population changed from their initial category to another and the higher transition rate was observed in MHO (42.9%). We also found several novel factors associated to transition to metabolically unhealthy phenotype; socioeconomic status, number of pregnancies, a high carbohydrate intake, history of obesity and consumption of sweetened beverages. Similarly, visceral adipose tissue (VAT) was a main predictor of transition; loss of VAT ≥5% was associated with reversion from metabolically unhealthy to metabolically healthy phenotype (hazard ratio (HR) 1.545, 95%CI 1.266-1.886). Finally, we observed higher incidence rates and risk of incident T2D and hypertension in the metabolically unhealthy obesity (MUHO) and metabolically unhealthy lean (MUHL) phenotypes compared to MHO. CONCLUSIONS: Metabolic health is a dynamic and continuous process, at high risk of transition to metabolically unhealthy phenotypes over time. It is imperative to establish effective processes in primary care to prevent such transitions.

Inadequacy of Vitamin D Nutritional Status in Individuals with Metabolically Unhealthy Obesity Phenotype: The Relevance of Insulin Resistance.

PURPOSE: The aim was to evaluate 25(OH)D serum concentrations in metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO) and its relation with biochemical and clinical parameters in both groups according to homeostatic model assessment-insulin resistance (HOMA-IR) definition of the obesity phenotypes. PATIENTS AND METHODS: Descriptive cross-sectional study was conducted with individuals of both genders. Anthropometric data [waist circumference, body mass index (BMI)] and metabolic parameters: blood glucose, glycated hemoglobin, insulin, lipid profile, calcium, phosphorus, parathyroid hormone (PTH) and high-sensitivity c-reactive protein (hs-CRP) and (25(OH)D) were obtained. The cutoff points for vitamin D deficiency and insufficiency were ≤20 and 21-29 ng/mL, respectively. Individuals were classified as MUHO according to HOMA-IR≥2.5. RESULTS: This study comprised 232 individuals with obesity (BMI≥35 kg/m2; 42.6±4.7 kg/m2). The MUHO phenotype was observed in 76.7% of the population. The mean values of glucose (P<0.001), insulin (P<0.001), HOMA-IR (P<0.001), and triglycerides (P=0.049) were significantly higher in the MUHO than in the MHO phenotype group. The mean value of 25(OH)D showed a significant difference between the MHO and MUHO phenotype groups (P=0.011). Additionally, and in line, lower mean 25(OH)D values were found in the MUHO vs the MHO phenotype group in the deficiency (14.5±3.6 ng/mL/17.1±2.7 ng/mL, P=0.004) and insufficiency (24.5±2.9 ng/mL/25.7±2.6 ng/mL, P=0.077) 25(OH)D groups. An increase of 1 ng/mL of vitamin D increased in 1.051 (95% CI= 1.011-1.093, P=0.012) the odds of the healthy phenotype. CONCLUSION: The highest prevalence of inadequacy of serum concentrations of 25(OH)D and greater severity of this deficiency in individuals with MUHO phenotype were observed. Low serum concentrations of this vitamin were associated, mainly, with insulin resistance. Monitoring the nutritional status of vitamin D in individuals with obesity that present with MUHO phenotype may contribute to minimize the occurrence and aggravation of diseases associated with obesity.

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

OBJECTIVES: To 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. METHODS: A 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. RESULTS: Data 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. CONCLUSIONS: Prevalence 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.

Emerging concepts in metabolically healthy obesity.

Obesity is a major risk factor for noncommunicable diseases that is responsible for more than 70% of early deaths in the world. In the 1980's decade, some studies started to describe a "benign" obesity phenotype, named "metabolically healthy obesity" (MHO), which represents obesity without comorbidities such as hypertension, cardiovascular diseases, insulin resistance, diabetes, dyslipidemia or metabolic syndrome. However, it is still unclear if this "benign" obesity phenotype is really favorable or just a transition status to unhealthy obesity and if these subjects presented subclinical levels of cardiovascular risk that are not commonly detected. To further elucidate these issues, the investigation of pathophysiological mechanisms that can increase cardiovascular risk in MHO individuals, such as hormones and cytokines, may offer some responses. In parallel, the evaluation of subclinical cardiovascular derangement, using the systemic microcirculation as a proxy, may be an alternative to anticipate overt cardiovascular disease. Overall, further studies are needed to better understand the pathophysiology of MHO as well as to identify high-risk individuals who deserve more intensive management.

Are young Iranian women with metabolically healthy obesity at increased risk of CVD incidence?

BACKGROUND: The association between the Metabolically Healthy Obese (MHO) phenotype in the absence of metabolic syndrome and subsequent cardiovascular disease remains unclear. OBJECTIVES: We examined the association between MHO and CVD risk in young Iranian women. METHODS: We studied 183 women aged 20-35 years from a population of 308 candidates. We classified participants into 4 phenotypes. We measured body composition, blood pressure, and biochemical factors in all participants. RESULTS: The Metabolically Healthy Normal Weight (MHNW) and Normal Weight Obese (NWO) phenotypes had no statistical differences in any biochemistry variables. FBS, TG, LDL/HDL, Cholesterol/HDL, hs-CRP, and atherogenic index of plasma (AIP) were all higher in Metabolically Unhealthy Obese (MUO) than MHO individuals, whereas HDL was higher in MHO than in MUO individuals. LDL/HDL and hs-CRP were higher in MHO participants than MHNW participants, whereas HDL-c was higher in MHNW than MHO. CONCLUSIONS: Results of the present study demonstrate that young women displaying the MHO phenotype have a favorable metabolic profile as shown by lower FBS, TG, LDL-c/HDL, Cho/HDL, hs-CRP, and AIP and higher HDL levels than the MUO phenotype. However, MHO individuals were still at greater risk of CVD incidence (lower HDL and higher hs-CRP levels) than MHNW individuals.

CONTEXTO: A associação entre o fenótipo obeso metabolicamente saudável (OMS) na ausência de síndrome metabólica e doença cardiovascular subsequente permanece incerta. OBJETIVOS: Examinamos a associação entre o fenótipo OMS e risco de DCV em jovens iranianas. MÉTODOS: Analisamos 183 mulheres com idade de 20-35 anos de uma população de 308 candidatas. Classificamos as participantes em quatro fenótipos. Mensuramos composição corporal, pressão arterial e fatores bioquímicos em todas as participantes. RESULTADOS: Os fenótipos com peso normal metabolicamente saudável (PNMS) e obeso com peso normal não apresentaram diferenças estatísticas em nenhuma das variáveis bioquímicas. Os níveis de glicemia sanguínea em jejum (GSJ), triglicerídeos (TG), relação LDL/HDL, HDL, proteína C reativa ultrassensível (PCR-us) e índice aterogênico do plasma (IAP) foram mais elevados em obesas metabolicamente não saudáveis (OMNS) do que em indivíduos OMSs, enquanto o HDL foi maior em OMSs do que em indivíduos OMNSs. A relação LDL/HDL e o nível de PCR-us foram mais elevados em participantes OMSs do que em participantes com PNMS, enquanto o HDL foi maior naquelas com PNMS do que nas OMSs. CONCLUSÕES: Os resultados do presente estudo demonstram que mulheres jovens com o fenótipo OMS têm um perfil metabólico favorável, conforme demonstrado pelos níveis menores de GSJ, TG, relação LDL/HDL, HDL, PCR-us e IAP e pelos níveis maiores de HDL em comparação às mulheres com o fenótipo OMNS. Entretanto, indivíduos OMSs ainda apresentavam maior risco de DCV incidente (níveis menores de HDL e maiores de PCR-us) do que indivíduos com PNMS.

Comparison between metabolically healthy obesity and metabolically unhealthy obesity by different definitions among Mexican children.

Background There is no consensus on the definition of metabolically healthy obesity (MHO) and the diagnostic criteria in children. Objectives To estimate the prevalence of MHO and compare clinical and biochemical characteristics between MHO and metabolically unhealthy obesity (MUO), and to evaluate the association between MUO and cardiovascular disease (CVD) risk, anthropometrics and family background using different definitions in children. Methods This was a cross-sectional study. Participants included 224 obese children between the years 2007 and 2017. MHO was defined by three different criteria: (i) absence of metabolic syndrome (MHO-MS), (ii) no insulin resistance (IR) by homeostatic model assessment (HOMA) <3.16 cut-off (MHO-IR3.16) and (iii) absence of IR at <95th percentile for Mexican children (MHO-95th). Results The prevalence of MHO-MS, MHO-IR3.16 and MHO-IR95th was 12.9%, 56.3% and 41.5%, respectively. The prevalence of simultaneous MHO-MS plus MHO-IR95th was 5.36%. Children with MHO-MS vs. MUO-MS showed lower height, weight and body mass index (BMI) percentiles; MHO-IR3.16 vs. MUO-IR3.16 showed lower age, acanthosis, Tanner, waist circumference (WC), waist-to-height ratio (WHtR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and glucose; and MHO-IR95th vs. MUO-IR95th showed lower acanthosis, WC, DBP, glucose and high high-density lipoprotein cholesterol (HDL-C). MUO-MS was associated with WC > 90th, type 2 diabetes mellitus (T2DM) in first-degree relatives and obesity in siblings. MUO-IR3.16 was associated with pubertal stages, WC > 90th, WHtR > 0.55 and fasting hyperglycemia. MUO-IR95th was associated with WHtR > 0.55 and HDL < 10th. MHO-MS and MHO-IR3.16 or MHO-IR95th did not have agreement. Conclusions The prevalence of MHO varied depending on the definition, although the real MHO with no MS or IR is very low. Low DBP and high HDL-C in MHO were present in any definition. Association of MUO with anthropometric, biochemical and family background differs across definitions.

Are young Iranian women with metabolically healthy obesity at increased risk of CVD incidence? / Jovens iranianas obesas metabolicamente saudáveis têm maior risco de incidência de DCV?

Abstract Background The association between the Metabolically Healthy Obese (MHO) phenotype in the absence of metabolic syndrome and subsequent cardiovascular disease remains unclear. Objectives We examined the association between MHO and CVD risk in young Iranian women. Methods We studied 183 women aged 20-35 years from a population of 308 candidates. We classified participants into 4 phenotypes. We measured body composition, blood pressure, and biochemical factors in all participants. Results The Metabolically Healthy Normal Weight (MHNW) and Normal Weight Obese (NWO) phenotypes had no statistical differences in any biochemistry variables. FBS, TG, LDL/HDL, Cholesterol/HDL, hs-CRP, and atherogenic index of plasma (AIP) were all higher in Metabolically Unhealthy Obese (MUO) than MHO individuals, whereas HDL was higher in MHO than in MUO individuals. LDL/HDL and hs-CRP were higher in MHO participants than MHNW participants, whereas HDL-c was higher in MHNW than MHO. Conclusions Results of the present study demonstrate that young women displaying the MHO phenotype have a favorable metabolic profile as shown by lower FBS, TG, LDL-c/HDL, Cho/HDL, hs-CRP, and AIP and higher HDL levels than the MUO phenotype. However, MHO individuals were still at greater risk of CVD incidence (lower HDL and higher hs-CRP levels) than MHNW individuals.

Resumo Contexto A associação entre o fenótipo obeso metabolicamente saudável (OMS) na ausência de síndrome metabólica e doença cardiovascular subsequente permanece incerta. Objetivos Examinamos a associação entre o fenótipo OMS e risco de DCV em jovens iranianas. Métodos Analisamos 183 mulheres com idade de 20-35 anos de uma população de 308 candidatas. Classificamos as participantes em quatro fenótipos. Mensuramos composição corporal, pressão arterial e fatores bioquímicos em todas as participantes. Resultados Os fenótipos com peso normal metabolicamente saudável (PNMS) e obeso com peso normal não apresentaram diferenças estatísticas em nenhuma das variáveis bioquímicas. Os níveis de glicemia sanguínea em jejum (GSJ), triglicerídeos (TG), relação LDL/HDL, HDL, proteína C reativa ultrassensível (PCR-us) e índice aterogênico do plasma (IAP) foram mais elevados em obesas metabolicamente não saudáveis (OMNS) do que em indivíduos OMSs, enquanto o HDL foi maior em OMSs do que em indivíduos OMNSs. A relação LDL/HDL e o nível de PCR-us foram mais elevados em participantes OMSs do que em participantes com PNMS, enquanto o HDL foi maior naquelas com PNMS do que nas OMSs. Conclusões Os resultados do presente estudo demonstram que mulheres jovens com o fenótipo OMS têm um perfil metabólico favorável, conforme demonstrado pelos níveis menores de GSJ, TG, relação LDL/HDL, HDL, PCR-us e IAP e pelos níveis maiores de HDL em comparação às mulheres com o fenótipo OMNS. Entretanto, indivíduos OMSs ainda apresentavam maior risco de DCV incidente (níveis menores de HDL e maiores de PCR-us) do que indivíduos com PNMS.

Does the Metabolically Healthy Obese Phenotype Protect Adults with Class III Obesity from Biochemical Alterations Related to Bone Metabolism?

Obesity negatively affects the relationship between markers and micronutrients of bone metabolism. Testing the hypothesis that the metabolically healthy obese phenotype might be protected by those alterations was the aim of this study. A cross-sectional study was carried out in adults with class III obesity classified in Metabolically Healthy Obese (MHO) and Metabolically Unhealthy Obese (MUHO), according to the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP ATP III) criteria. Anthropometric, biochemical, and clinical variables were analyzed for sample characterization. To evaluate bone metabolism, markers (alkaline phosphatase and parathyroid hormone-PTH) and related nutrients (vitamin D, vitamin B12, calcium, phosphorus, magnesium, potassium and zinc) were analyzed. A total of 223 adults with class III obesity aged 41.20 ± 10.15 years were included. The MHO phenotype was identified in 32.73% of the sample. After logistic regression, it was observed that inadequacies of calcium (OR: 4.11; 95% CI: 2.33-6.66), phosphorus (OR: 3.03; 95% CI: 1.98-5.79), vitamin D (OR: 5.01; 95% CI: 2.92-6.71) and PTH (OR: 5.45; 95% CI: 4.49-6.74) were significantly higher in the MUHO group compared to the MHO Group. This study showed that the MHO phenotype does not protect adults from alterations in markers and micronutrients of bone metabolism. However, the MUHO phenotype presents a higher risk for alterations related to bone metabolism, which can favor the emergence of metabolic bone diseases.