Metabolically Healthy Normal Weight Group Research Articles

Association between different metabolic phenotypes and the development of hypothyroidism: 9 years follow-up of Tehran thyroid study.

The association between metabolic phenotypes and thyroid function has not yet been established; therefore, this study examined whether different metabolic phenotypes are associated with the development of hypothyroidism. Study participants were selected from the Tehran Thyroid Study (TTS). A total of 3338 euthyroid adults were included and categorized into four obesity phenotype groups: metabolically healthy normal weight (MHNW), metabolically healthy obese (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy obese (MUO). The participants were assessed at baseline and during three follow-up studies at three-year intervals. Multiple logistic regression analysis was used to examine the relationship between metabolic phenotypes and the development of hypothyroidism. In the total population, the chi-square test was only significant (P=0.008) in 3rd year with a higher prevalence of hypothyroidism in the MUNW phenotype, followed by MHO, MUO, and MHNW. Moreover, in the 3rd and 9th years of follow-up, hypothyroidism was more prevalent in MUO only in male subjects (P=0.002 and 0.035, respectively). In the unadjusted model, the MHO phenotype increased the odds of hypothyroidism compared with the MHNW phenotype (OR=1.51; 95% CI=1.04, 2.18; P-value=0.031). After adjusting for confounding factors, the odds of hypothyroidism were higher in the MUNW (OR=1.86; 95% CI=1.17, 2.96; P-value=0.008), MHO (OR=1.71; 95% CI=1.09, 2.67; P-value=0.018), and MUO (OR=1.64; 95% CI=1.03, 2.62; P-value=0.036) phenotypes than in the MHNW group. The MUNW phenotype increased the risk of hypothyroidism compared to MHNW, only in males. However, in females, the MHO phenotype increased the risk of hypothyroidism compared to MHNW. Both obesity and metabolic abnormalities are associated with hyperthyroidism. Healthy metabolic and weight maintenance were associated with a lower risk of hypothyroidism in males and females.

Association between metabolic phenotype and urinary albumin‐creatinine ratio in Chinese community adults: A cross‐sectional study

BackgroundUrinary albumin‐creatinine ratio (UACR) is a sensitive marker of kidney injury. This study analyzed the prevalence of different metabolic phenotypes and investigated their relationship with UACR in Chinese community adults.MethodsThis study involved 33 303 participants over 40 years old from seven centers across China. They were stratified into six groups according to their body mass index (BMI) and metabolic status: metabolically healthy normal weight (MHNW), metabolically healthy overweight (MHOW), metabolically healthy obesity (MHO), metabolically unhealthy normal weight (MUNW), metabolically unhealthy overweight (MUOW), and metabolically unhealthy obesity (MUO). Increased albuminuria was defined as a UACR ≥30 mg/g.ResultsThe percentages of MHNW, MHOW, MHO, MUNW, MUOW, and MUO were 27.6%, 15.9%, 4.1%, 19.8%, 22.5%, and 9.6%, respectively. Multiple logistic regression analysis showed that the MHO group (odds ratio [OR] 1.205; 95% CI, 1.081‐1.343), MUNW group (OR 1.232; 95% CI, 1.021‐1.486), MUOW group (OR 1.447; 95% CI, 1.303‐1.607), and MUO group (OR 1.912; 95% CI, 1.680‐2.176) were at higher risk of increased albuminuria compared to the MHNW group. Subgroup analysis indicated that the risk of increased albuminuria was further elevated among regular smokers in men aged 40 to 55 years old with abdominal obesity.ConclusionsAmong Chinese community adults, increased albuminuria was associated with increased BMI whether metabolism was normal or not, and those with abnormal metabolism were at greater risk of increased albuminuria than those with normal metabolism. These findings suggest that overweight or obesity or metabolic abnormalities are risk factors for chronic kidney disease.

Association between metabolic body composition status and vitamin D deficiency: A cross-sectional study.

This study aimed to investigate the risk of vitamin D deficiency in a relatively healthy Asian population, with (i) metabolically healthy normal weight (MHNW) (homeostasis model assessment-insulin resistance [HOMA-IR] < 2. 5 without metabolic syndrome [MS], body mass index [BMI] < 25), (ii) metabolically healthy obesity (MHO) (HOMA-IR < 2.5, without MS, BMI ≥ 25), (iii) metabolically unhealthy normal weight (MUNW) (HOMA-IR ≥ 2.5, or with MS, BMI < 25), and (iv) metabolically unhealthy obesity (MUO) (HOMA-IR ≥ 2.5, or with MS, BMI ≥ 25) stratified by age and sex. This cross-sectional study involved 6,655 participants aged ≥ 18 years who underwent health checkups between 2013 and 2016 at the Chang Gung Memorial Hospital. Cardiometabolic and inflammatory markers including anthropometric variables, glycemic indices, lipid profiles, high-sensitivity C-reactive protein (hs-CRP), and serum 25-hydroxy vitamin D levels, were retrospectively investigated. Compared to the MHNW group, the MHO group showed a higher odds ratio (OR) [1.35, 95% confidence interval (CI) 1.05–1.73] for vitamin D deficiency in men aged < 50 years. By contrast, in men aged > 50 years, the risk of vitamin D deficiency was higher in the MUO group (OR 1.44, 95% CI 1.05–1.97). Among women aged < and ≥ 50 years, the MUO group demonstrated the highest risk for vitamin D deficiency, OR 2.33 vs. 1.54, respectively. Our study revealed that in women of all ages and men aged > 50 years, MUO is associated with vitamin D deficiency and elevated levels of metabolic biomarkers. Among men aged < 50 years, MHO had the highest OR for vitamin D deficiency.

The Metabolic Profiles of Metabolically Healthy Obese and Metabolically Unhealthy Obese South African Adults over 10 Years.

Obesity is associated with an increased cardiometabolic risk, but some individuals maintain metabolically healthy obesity (MHO). The aims were to follow a cohort of black South African adults over a period of 10 years to determine the proportion of the group that maintained MHO over 10 years, and to compare the metabolic profiles of the metabolically healthy and metabolically unhealthy groups after the follow-up period. The participants were South African men (n = 275) and women (n = 642) from the North West province. The prevalence of obesity and the metabolic syndrome increased significantly. About half of the metabolically healthy obese (MHO) adults maintained MHO over 10 years, while 46% of the women and 43% of men became metabolically unhealthy overweight/obese (MUO) at the end of the study. The metabolic profiles of these MHO adults were similar to those of the metabolically healthy normal weight (MHNW) group in terms of most metabolic syndrome criteria, but they were more insulin resistant; their CRP, fibrinogen, and PAI-1act were higher and HDL-cholesterol was lower than the MHNW group. Although the metabolic profiles of the MUO group were less favourable than those of their counterparts, MHO is a transient state and is associated with increased cardiometabolic risk.

Metabolically unhealthy individuals, either with obesity or not, have a higher risk of critical coronavirus disease 2019 outcomes than metabolically healthy individuals without obesity

BackgroundThis study aimed to determine the relative and independent contributions of impaired metabolic health and obesity to critical coronavirus disease 2019 (COVID-19). MethodsWe analyzed 4069 COVID-19 patients between January and June 2020 in South Korea, classified into four groups according to metabolic health status and body mass index (BMI): metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy obesity (MHO), and metabolically unhealthy obesity (MUO). The primary outcome was a composite of intensive care unit (ICU) admission, invasive mechanical ventilation (IMV), extracorporeal membrane oxygenation (ECMO), and death. Multivariable Cox proportional hazard regression models were used to estimate the hazard ratio (HR) for the outcome. ResultsThe incidence rate (per 100 person-months) of critical COVID-19 was the lowest in the MHNW group (0.90), followed by the MHO (1.64), MUNW (3.37), and MUO (3.37) groups. Compared with MHNW, a significantly increased risk of critical COVID-19 was observed in MUNW (HR, 1.41; 95% CI, 1.01–1.98) and MUO (HR, 1.77; 95% CI, 1.39–2.44) but not in MHO (HR, 1.48; 95% CI, 0.98–2.23). The risk of ICU admission or IMV/ECMO was increased only in MUO; however, the risk of death was significantly higher in MUNW and MUO. The risk of critical COVID-19 increased insignificantly by 2% per 1 kg/m2 BMI increase but significantly by 13% per 1 metabolically unhealthy component increase, even after mutually adjusting for BMI and metabolic health status. ConclusionsMetabolic health is more important to COVID-19 outcomes than obesity itself, suggesting that metabolic health status should be considered for a precise and tailored management of COVID-19 patients.

Combined Associations of Serum Ferritin and Body Size Phenotypes With Cardiovascular Risk Profiles: A Chinese Population-Based Study.

Background: Serum ferritin (SF) has been correlated with one or more metabolic syndrome features associated with an increased risk for cardiovascular disease (CVD). This study explored the associations between SF and CVD risk factors among different body size phenotypes that were based on metabolic status and body mass index (BMI) categories.Methods: A cross-sectional study was performed using a cohort of 7,549 Chinese adults from the China Health and Nutrition Survey. Participants did not exhibit acute inflammation, were not underweight and were stratified based on their metabolic status and BMI categories. The metabolically at-risk status was defined as having two or more criteria of the Adult Treatment Panel-III metabolic syndrome definition, excluding waist circumference.Results: Compared with individuals without high SF, subjects with high SF had an increased risk of diabetes in the metabolically at-risk normal-weight (MANW) and metabolically at-risk overweight/obesity (MAO) groups. The multivariate-adjusted odds ratios (ORs) were 1.52 [95% confidence interval (Cls): 1.02, 2.28] and 1.63 (95% Cls: 1.27, 2.09), respectively. Adjusted ORs for hyperuricemia from high SF in metabolically healthy normal-weight (MHNW), metabolically healthy overweight/obesity (MHO), MANW, and MAO phenotypes were 1.78 (95% Cls: 1.26, 2.53), 1.42 (95% Cls: 1.03, 1.95), 1.66 (95% Cls: 1.17, 2.36), and 1.42 (95% Cls: 1.17, 1.73), respectively. Similarly, positive correlations of high SF with triglycerides, non-high-density lipoprotein cholesterol, and apolipoprotein B100 were observed in all phenotypes. No association between high SF and elevated low-density lipoprotein cholesterol were observed among participants who were metabolically at-risk, regardless of their BMI categories. However, the ORs for elevated low-density lipoprotein cholesterol from high SF were 1.64 (95% Cls: 1.29, 2.08) in the MHNW group and 1.52 (95% Cls:1.22, 1.91) in the MHO group, significantly. This study demonstrated that the highest ORs were in MAO with a high SF group for all unfavorable CVD risk factors except low-density lipoprotein cholesterol (all p < 0.001).Conclusions: The associations of high SF with the prevalence of CVD risk factors, including diabetes, dyslipidemia, and hyperuricemia, vary in individuals among different body size phenotypes. In the MAO group, subjects with high SF levels exhibited worse CVD risk profiles than individuals without high SF.

Association of Metabolic Obesity Phenotypes and Total Testosterone in Chinese Male Population.

ObjectiveObesity and metabolic syndrome have been reported to exert an impact on the male reproductive system with decreasing levels of serum total testosterone (TT); however, the effect of different metabolic obesity phenotypes on testosterone has been poorly studied. We aimed to evaluate the association of metabolic obesity phenotypes and total testosterone levels in a Chinese male population.MethodsWe performed a retrospective study based on an epidemiological investigation, a total of 4,081 male individuals aged from 40–75 years old were recruited. The population was classified as metabolically healthy normal weight (MHNW), metabolically healthy overweight/obese (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy overweight/obese (MUO) according to normal weight (BMI<25.0) and overweight/obesity (BMI≥25.0) with or without metabolic syndrome.ResultsWe collected 563 hypotestosteronemia among 4,081 male individuals. The odds ratios (ORs) (95% CIs) of hypotestosteronemia in obesity and metabolic syndrome were 3.072 (2.414–3.911) and 3.294 (2.631–4.125), respectively, after adjusting for age, luteinizing hormone, smoking status, and alcohol consumption. Compared to the MHNW group, male subjects in MHO, MUNW, and MUO groups had decreased serum TT levels. Additionally, the MUO group had a lowest concentration of serum TT and a highest proportion of hypotestosteronemia. There was no significant difference of TT levels between the MHO and MUNW groups.ConclusionObesity and metabolic syndrome are independent risk factors of hypotestosteronemia in Chinese male populations. Our study also suggested that individuals with MHO, MUNW, and MUO have a higher risk of developing hypotestosteronemia.

Schizophrenia patients with a metabolically abnormal obese phenotype have milder negative symptoms

BackgroundSchizophrenia patients with a metabolically abnormal obese (MAO) phenotype have been shown poor cardiovascular outcomes, but the characteristics of their current psychiatric symptoms have not been characterized. This study mainly explored the psychiatric symptoms of schizophrenia patients with the MAO phenotype.MethodsA total of 329 patients with schizophrenia and 175 sex- and age-matched people without schizophrenia from Anhui Province in China were enrolled. The Positive and Negative Syndrome Scale (PANSS) was used to evaluate the mental symptoms of the schizophrenia patients. The MAO phenotype was defined as meeting 1–4 metabolic syndrome criteria (excluding waist circumference) and having a body mass index (BMI) ≥ 28 kg/m2. And, metabolically healthy normal-weight (MHNW) phenotype was defined as meeting 0 criteria for metabolic syndrome and 18.5 ≤ BMI < 24 kg/m2.ResultsOverall, 15.8% of the schizophrenia patients and 9.1% of the control group were consistent with the MAO phenotype, and the prevalence of MAO in the schizophrenia group was higher than that in the control group. Among the patients with schizophrenia, the MAO group had lower negative factor, cognitive factor and total PANSS scores than the MHNW group. However, when confounding factors were controlled, only the negative factor remained lower significantly.ConclusionWe found that schizophrenia patients with the MAO phenotype had reduced negative symptoms, which may indicate an internal mechanism linking metabolic disorders and negative symptoms.Trial registrationThis study was registered in the China Clinical Trial Registration Center (No. chiCTR 1,800,017,044).

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.

Associations between obesity and metabolic health with nonalcoholic fatty liver disease in elderly Chinese

BackgroundNonalcoholic fatty liver disease (NAFLD) is closely associated with obesity. However, this association could be influenced by the coexisting metabolic abnormalities. This study aimed to investigate the role of obesity and metabolic abnormalities in NAFLD among elderly Chinese. MethodsA cross-sectional study was performed among elderly residents who took their annual health checkups during 2016 in Keqiao District, Shaoxing, China. ResultsA total of 3359 elderly adults were retrospectively included in this study. The overall prevalence of NAFLD was 28.7%. The prevalence of NAFLD were 7.14%, 27.92%, 34.80%, and 61.02% in participants with metabolically healthy normal weight (MHNW), metabolically abnormal normal weight (MANW), metabolically healthy obese (MHO), and metabolically abnormal obese (MAO), respectively. NAFLD patients in MHO group had more unfavorable metabolic profiles than those in MHNW group. Logistic regression analysis showed that sex, body mass index (BMI), fasting blood glucose, and serum uric acid were the risk factors of NAFLD. ConclusionsBoth obesity and metabolic health were significantly associated with NAFLD in elderly Chinese. Screening for obesity and other metabolic abnormalities should be routinely performed for early risk stratification of NAFLD.

The Impact of BMI Categories on Metabolic Abnormality Development in Chinese Adults Who are Metabolically Healthy: A 7-Year Prospective Study.

PurposeTo determine what metabolic abnormalities develop frequently among metabolically healthy adults over time according to different baseline body mass index (BMI) categories.Patients and MethodsA prospective cohort study was performed on 10,805 adults, who were metabolically healthy at the time of the 2008 survey. Participants were divided into four groups: metabolically healthy obese (MHO), metabolically healthy overweight (MHOW), metabolically healthy normal-weight (MHN), and metabolically healthy underweight (MHU). Modified Poisson regression models were used to evaluate the relationship of BMI with the development of metabolic abnormalities. Association rule mining was used to identify the most frequent abnormalities that developed over time.ResultsCompared with the MHN group, the adjusted relative risks of the MHO group were 1.57 (95% CI: 1.09–2.27) and 2.08 (95% CI: 1.59–2.73) for developing elevated fasting glucose and elevated blood pressure, respectively, after adjusting for lifestyle behaviours and dietary factors. At the end of follow-up, 33 (19.1%) MHO subjects and 342 (16.6%) MHOW subjects had elevated blood pressure as the predominant metabolic syndrome component, whereas 236 (9.0%) MHU subjects had elevated plasma glucose. The results were similar after stratification by sex.ConclusionMHO and MHOW subjects developed elevated blood pressure most frequently, and MHU subjects developed elevated blood glucose most commonly, regardless of sex.

The Presence of Urinary Ketones according to Metabolic Status and Obesity.

BackgroundRecently, new concepts about obesity and normal weight subtypes with metabolic conditions are rising and ketone bodies are emerging as a significant indicator of metabolic health. This study aimed to find a relationship between ketonuria and those subtypes.MethodsThe data of 19,036 subjects were analyzed in this cross-sectional study (2013–2017 Korea National Health and Nutrition Examination Survey, KNHANES). Based on body mass index and adult treatment panel III with modification of waist circumference, individuals were categorized into 4 groups: metabolically healthy normal weight (MHNW), metabolically healthy obese (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy obese (MUO). Individuals were divided into 2 groups, positive and negative ketonuria groups, and the metabolic parameters were compared.ResultsThe metabolic indicators of the positive ketonuria group showed better results than those of the negative ketonuria group and the MHNW group showed the highest proportion of positive ketonuria. The MHNW group showed higher urinary ketones than the MUO group (odds ratio [OR], 0.391; 95% confidence interval [CI], 0.254–0.601) in men. In women, OR of having ketonuria was 0.698 (95% CI, 0.486–1.002) in the MHO group and 0.467 (95% CI, 0.226–0.966) in the MUNW group compared to the MHNW group, respectively.ConclusionCompared to the MHNW group, the MUO group showed lower presence of ketonuria in men, and tendency to have less ketonuria in women.

Different metabolic/obesity phenotypes are differentially associated with development of prediabetes in adults: Results from a 14-year cohort study

BACKGROUNDThe risk of developing prediabetes based on the metabolic/obesity phenotypes has been poorly investigated.AIMTo examine the association of baseline metabolic/obesity phenotypes and their changes over time with the risk of prediabetes development.METHODSIn a population-based cohort study, 1741 adults (aged > 19 years) with normal blood glucose were followed for 14 years. Anthropometric and biochemical measures were evaluated regularly during the follow-up period. According to body mass index and metabolic health status, participants were categorized into four groups: Metabolically healthy normal weight (MHNW), metabolically healthy obese (MHO), metabolically unhealthy normal weight (MUNW) and metabolically unhealthy obese (MUO). Multivariable Cox regression analysis was used to measure the risk of prediabetes according to the baseline metabolic/obesity phenotype and their changes during the follow-up.RESULTSIn the whole population with a mean (95CCI for mean) follow up duration of 12.7 years (12.6-12.9), all three MUNW, MHO, MUO groups were at higher risk for developing prediabetes compared to the MHNW group (P = 0.022). The MUNW group had the highest risk for developing prediabetes (hazard ratio (HR): 3.84, 95%CI: 1.20, 12.27). In stratified analysis by sex, no significant association was found in men, while women in the MUNW group were at the greatest risk for prediabetes (HR: 6.74, 95%CI: 1.53, 29.66). Transforming from each phenotype to MHNW or MHO was not related to the risk of prediabetes development, whereas transforming from each phenotype to MUO was associated with an increased risk of prediabetes (HR > 1; P < 0.05).CONCLUSIONOur findings indicate that MHO is not a high risk, unless it transforms into MUO over time. However, people in the MUNW group have the greatest risk for developing prediabetes, and therefore, they should be screened and treated.

The long-term prognosis of heart diseases for different metabolic phenotypes: a systematic review and meta-analysis of prospective cohort studies.

This meta-analysis aimed to assess the association of different categories of weight and metabolic status with risk of heart diseases including myocardial infarction (MI), cardiovascular diseases (CVDs), and heart failure (HF). Data from relevant studies were identified systematically by searching PubMed and Scopus search engines up to 29 May 2018. Prospective studies were included in the analyses with metabolically healthy normal weight (MHNW) as the reference. Pooled RRs and 95% CI were calculated using random-effects or fixed-effect models when appropriate. Subgroup analysis was applied to define possible sources of heterogeneity. Overall, 21 studies (n = 778,401 participants) were eligible for the present meta-analysis. Generally, the risk of CVDs for all metabolic phenotypes in metabolically unhealthy obese increased compared with the MHNW group. A significant positive association between all metabolic phenotypes and the risk of HF was also observed expect for MHOW (RR = 1.10, 95% CI: 0.60-2.00, P = 0.76) and MHO phenotypes (RR = 0.96, 95% CI: 0.25-3.77, P = 0.95). Moreover, MUHO phenotype was associated with greater risk of MI compared with the MHNW phenotype (RR = 1.82, 95% CI: 1.50-2.22, P < 0.001, respectively). Our findings showed that all metabolically unhealthy phenotypes in different categories of weight were associated with increased incident of CVDs/HF and MI. Furthermore, healthy overweight and obese subjects had increased risk of CVDs.

Impact of the Dynamic Change of Metabolic Health Status on the Incident Type 2 Diabetes: A Nationwide Population-Based Cohort Study.

BackgroundMetabolically healthy obese (MHO) is regarded as a transient concept. We examined the effect of the dynamic change of metabolic health status on the incidence of type 2 diabetes mellitus (T2DM) both in obese and normal weight individuals.MethodsWe analyzed 3,479,514 metabolically healthy subjects aged over 20 years from the Korean National Health Screening Program, who underwent health examination between 2009 and 2010, with a follow-up after 4 years. The relative risk for T2DM incidence until the December 2017 was compared among the four groups: stable metabolically healthy normal weight (MHNW), unstable MHNW, stable MHO, and unstable MHO.ResultsDuring the 4 years, 11.1% of subjects in the MHNW group, and 31.5% in the MHO group converted to a metabolically unhealthy phenotype. In the multivariate adjusted model, the unstable MHO group showed the highest risk of T2DM (hazard ratio [HR], 4.67; 95% confidence interval [CI], 4.58 to 4.77). The unstable MHNW group had a higher risk of T2DM than stable MHO group ([HR, 3.23; 95% CI, 3.16 to 3.30] vs. [HR, 1.81; 95% CI, 1.76 to 1.85]). The stable MHO group showed a higher risk of T2DM than the stable MHNW group. The influence of the transition into a metabolically unhealthy phenotype on T2DM incidence was greater in subjects with aged <65 years, women, and those with weight gain.ConclusionMetabolically healthy phenotype was transient both in normal weight and obese individuals. Maintaining metabolic health was critical for the prevention of T2DM, irrespective of their baseline body mass index.

Risk of ischemic stroke in metabolically healthy obesity: A nationwide population-based study.

BackgroundWhether metabolically healthy obese (MHO) individuals are at increased risk of ischemic stroke is not well known. We investigated the association of the MHO phenotype with ischemic stroke.MethodsA total of 354,083 adults (age 45.8 ± 14.2 years) from the Korean National Health Insurance Service–National Sample Cohort enrolled in 2004–2008 were followed-up for incident ischemic stroke until 2013. Subjects meeting none of the metabolic syndrome criteria were classified as ‘metabolically healthy’. The cohort was categorized into four groups according to obesity and metabolic status: metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), MHO, and metabolically unhealthy obese (MUO).ResultsIschemic stroke was newly diagnosed in 4,884 (1.4%) individuals during a mean follow-up of 7.4 ± 1.5 years. Stroke incidence rates for the MHNW, MUNW, MHO, and MUO groups were 0.56, 2.61, 0.61, and 2.76 per 1,000 person-years, respectively. While risk for stroke increased significantly in metabolically unhealthy groups, it was not increased in MHO compared to the MHNW group on multivariate analysis. In metabolically healthy individuals, obesity did not increase the risk for ischemic stroke, regardless of the severity of obesity. Meanwhile, in metabolically unhealthy individuals, being obese was significantly associated with increased risk of stroke.ConclusionsMHO individuals were not at increased risk for ischemic stroke. However, obesity increased risk for ischemic stroke in persons with metabolic risk factors; therefore, maintaining normal weight may be more important for this population. Also, metabolic unhealthiness showed greater association than obesity with stroke.

Vascular Inflammation in Metabolically Abnormal but Normal-Weight and Metabolically Healthy Obese Individuals Analyzed With 18F-Fluorodeoxyglucose Positron Emission Tomography

Recent studies have suggested that body size phenotype may contribute to atherosclerosis and cardiovascular disease. (18)F-fluorodeoxyglucose (FDG) positron emission tomography is a useful imaging technique for detecting vascular inflammation that may reflect plaque vulnerability. Therefore, we analyzed which body size phenotypes cause the increased vascular inflammation using FDG positron emission tomography. We compared (18)F-FDG uptake, measured using the blood-normalized standardized uptake value, known as the target-to-background ratio (TBR), along with various cardiometabolic risk parameters in 250 participants without a history of cardiovascular disease. Body size phenotypes were classified according to body mass index and the presence/absence of metabolic syndrome. Cardiometabolic risk factors were significantly different among the body size phenotype groups. In particular, the maximum TBR (maxTBR) values in the metabolically abnormal but normal-weight, metabolically healthy obese (MHO), and metabolically abnormal obese groups were significantly greater than those of the metabolically healthy normal-weight (MHNW) group. Components of metabolic syndrome, insulin resistance, high-sensitivity C-reactive protein, and Framingham Risk Score were associated with maxTBR value. Interestingly, although the Framingham Risk Score of the MHO group was almost similar to that of the MHNW group, maxTBR value of MHO subjects was significantly higher than that of MHNW subjects (1.38 [1.20, 1.50] vs 1.22 [1.12, 1.37], p= 0.006). In conclusion, the present study suggests that unique subsets of body size phenotype, such as MHO or metabolically abnormal but normal weight, may have distinct effects on vascular inflammation.

Metabolically healthy obesity, presence or absence of fatty liver, and risk of type 2 diabetes in Japanese individuals: Toranomon Hospital Health Management Center Study 20 (TOPICS 20).

We investigated whether the metabolically healthy obese (MHO) phenotype was associated with an increased risk of the development of diabetes. If so, we aimed to determine what factors could explain this finding. Studied were 8090 Japanese individuals without diabetes. Metabolic health status was assessed by common clinical markers: blood pressure, triglycerides, high-density lipoprotein-cholesterol, and fasting glucose concentrations. The cutoff value for obesity or normal weight (NW) was a body mass index of 25.0 kg/m(2). The 5-year incidence rate of diabetes was 1.2% (n = 58 of 4749) in metabolically healthy NW (MHNW) individuals, 2.8% (n = 20 of 719) in MHO individuals, 6.0% (n = 102 of 1709) in metabolically abnormal NW individuals, and 10.3% (n = 94 of 913) in metabolically abnormal obese individuals. Although MHO individuals had no or one metabolic factor, 47.8% had ultrasonographic fatty liver (FL). The MHO group had a significantly increased risk of diabetes compared with the MHNW group [multivariate adjusted odds ratio (OR) 2.23 (95% confidence interval [CI] 1.33, 3.75)], but this risk was attenuated after adjustment for FL. Compared with the MHNW/non-FL group, the risk of diabetes in the MHO/non-FL group was not significantly elevated [OR 1.01 (95% CI 0.35, 2.88)]. However, the MHO/FL and MHNW/FL groups had similarly elevated risks of diabetes [OR 4.09 (95% CI 2.20, 7.60) and 3.16 (1.78, 5.62), respectively]. Almost half of the MHO participants had FL, which partially explained the increased risk of diabetes among the obese phenotypes. The presence of FL should be evaluated to assess whether an individual was actually in a metabolically benign state for the prediction of diabetes.

Association of metabolically abnormal but normal weight (MANW) and metabolically healthy but obese (MHO) individuals with arterial stiffness and carotid atherosclerosis

ObjectiveDespite recent interest in differential impact of body size phenotypes on cardiovascular outcomes and mortality, studies evaluating the association between body size phenotypes and indicators of atherosclerosis are limited. This study investigated the relationship of metabolically abnormal but normal weight (MANW) and metabolically healthy but obese (MHO) individuals with arterial stiffness and carotid atherosclerosis in Korean adults without cardiovascular disease. MethodsA total of 1012 participants (575 men and 437 women, mean age 50.8 years), who underwent a health examination between April 2012 and May 2013 were prospectively enrolled based on inclusion and exclusion criteria. Study subjects were classified according to body mass index (BMI) and the presence/absence of metabolic syndrome. ResultsThe prevalence of metabolically healthy normal weight (MHNW), MANW, MHO, and metabolically abnormal obese (MAO) were 54.84%, 6.42%, 22.83%, and 15.91%, respectively. Individuals with MANW had significantly higher brachial-ankle pulse wave velocity and maximal carotid intima-media thickness values than those with MHO, after adjusting for age and gender (P = 0.026 and P = 0.018, respectively). The odds ratio (OR) of arterial stiffness and carotid atherosclerosis in the MANW group were significantly higher than in the MHNW group in unadjusted models. Furthermore, multivariable models showed that increased OR of carotid atherosclerosis in the MANW group persisted even after adjusting for confounding factors (OR = 2.98, 95% CI = [1.54, 5.73], P = 0.011). ConclusionsCompared to MHNW or MHO subjects, Korean men and women with the MANW phenotype exhibited increased arterial stiffness and carotid atherosclerosis. Clinical trials noNCT01594710.