Metabolically healthy obesity, transition to unhealthy phenotypes, and type 2 diabetes in 0.5 million Chinese adults: the China Kadoorie Biobank.

OBJECTIVES: To prospectively assess the association of metabolic health status and its transition with incident diabetes risk across BMI categories. DESIGN: Cohort study based on the China Kadoorie Biobank (CKB). METHODS: The CKB study enrolled 512 715 adults aged 30-79 years from ten diverse areas in China during 2004-2008. After exclusion, 432 763 participants were cross-classified by BMI categories and the metabolic status was followed up for incident diabetes disease. The changes in BMI and metabolic health status were defined from baseline to the second resurvey. RESULTS: Type 2 diabetes risk is higher for metabolically healthy obese (MHO) subjects than metabolically healthy normal weight (MHN) individuals (HR: 3.97, 95% CI: 3.64-3.66), and it is highest for those affected by metabolically unhealthy obese (MUO) (HR: 6.47, 95% CI: 6.17-6.79). About 15.26% of participants with MHN converted to metabolically healthy overweight or obesity (MHOO), whereas 48.40% of MHOO remained unconverted throughout the follow-up. In obese or overweight people, the conversion from metabolically healthy to unhealthy might increase the chances of developing diabetes as compared to those with a stable metabolic healthy state (HR: 3.70, 95% CI: 2.99-4.59), while those with persistent metabolic disorders are most likely to have diabetes (HR: 8.32, 95% CI: 7.08-9.78). CONCLUSIONS: Metabolic healthy is a transient state, and individuals converted from metabolically healthy status to unhealthy phenotypes across all BMI categories might raise the risk of diabetes.

Impact of the Definition of Metabolically Healthy Obesity on the Association with Incident Cardiovascular Disease.

Background: Whether subjects with metabolically healthy obesity (MHO) have an increased risk of cardiovascular disease (CVD) is controversial. Some of this discrepancy could be due to differences in the definition of MHO. Therefore, we investigated how the definition of MHO affected the risk of CVD. Methods: In the Uppsala Longitudinal Study of Adult Men (ULSAM) cohort (total n = 2122, mean age 50 years), obese (n = 134), overweight (n = 845), and normal weight (n = 1143) individuals were subdivided according to the number of Metabolic Syndrome (MetS) risk factors (excluding waist circumference). During a median follow-up of 28.0 years, 877 individuals experienced a CVD event (defined as fatal or nonfatal myocardial infarction, stroke, or heart failure). Results: All obese groups, except that without any MetS risk factors (n = 3), showed an increased risk compared to the control group of normal weight without any MetS risk factors (n = 235), ranging from a hazard ratio (HR) of 3.0 (95% confidence interval [CI] 1.7-5.3, P = 0.0002) in those with one MetS risk factor to HR 5.5 (95% CI 3.0-9.8, P < 0.00001) in those with four MetS risk factors. The overweight group without any MetS risk factor (n = 74) showed a similar risk of incident CVD as the normal weight group, whereas all other overweight groups showed an increased risk with increasing number of MetS risk factors. Conclusions: The results suggest that the definition of MHO played a major role on the risk of CVD. No increased risk was seen in overweight/obese individuals with no MetS risk factor, but they were very rare.

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.

Fate of the metabolically healthy obese-is this term a misnomer? A study from the Clinical Practice Research Datalink.

INTRODUCTION: The metabolically healthy obese (MHO) phenotype may express typical characteristics on long-term follow-up. Little is known about the initiation of this phenotypes and its future stability. AIM: The Clinical Practice Research Datalink (CPRD) is a large-scale primary care database. The aim of this study was to assess the stability of, and evaluate the factors associated with a transition into an unhealthy outcome in, a MHO population in the UK. METHODS: The CPRD was interrogated for a diagnosis of 'obesity' and cross-referenced with a body mass index (BMI) ≥35 kg/m2; participants were further classified as MH using a clinical diagnostic code or a relative therapeutic code. A hazard cox regression univariate and multivariate analysis evaluated the time to transition for independent variables. RESULTS: There were 231,399 patients with a recorded BMI of 35 kg/m2 or greater. Incomplete records were eliminated and follow-up limited to 300 months, the cohort was reduced to 180,560 patients. The prevalence of MHO within the obese population from the CPRD was 128,191/180,560 (71%). MHO individuals, who were of male gender (hazard ratio (HR) 1.23 (1.21-1.25), p = < 0.01), older age group (HR 3.93 (3.82-4.04), p = < 0.01), BMI of 50-60 kg/m2 at baseline (HR 1.32(1.26-1.38), p = 0.01), smokers (HR 1.07(1.05-1.09), p = < 0.01) and regionally from North West England (HR 1.15(1.09-1.21), p = < 0.01) were more prone to an unhealthy transition (to develop comorbidities). Overall, of those MH at baseline, 71,485/128,191(55.8%) remained healthy on follow-up, with a mean follow-up of 113.5 (standard deviations (SD) 78.6) months or 9.4 (SD 6.6) years. CONCLUSIONS: From this unique large data set, there is a greater prevalence of MHO individuals in the UK population than in published literature elsewhere. Female gender, younger age group, and lower initial weight and BMI were found to be significant predictors of sustained metabolic health in this cohort. However, there remains a steady progressive transition from a healthy baseline over the years.

Is metabolically healthy obesity a useful concept?

Obesity poses significant public health concerns, including Type 2 diabetes mellitus, cardiovascular disease and stroke. Although deleterious metabolic profiles typically accompany individuals with obesity, various epidemiological studies have identified a subset of patients with a favourable metabolic phenotype referred to as the metabolically healthy obese. Metabolically healthy obesity is a novel concept that stratifies obese individuals according to their respective metabolic status. It has important implications for healthcare policies, particularly the efficient allocation of resources in the targeted treatment of obesity and prevention of metabolic ill-health. However, conflicting evidence in the literature regarding its risk profile questions its clinical relevance. In addition, the lack of a unified definition of metabolically healthy obesity and agreement on its progression further impede its utility as a stratification strategy. This review aims to describe current concepts of metabolically healthy obesity within the literature, evidence of this metabolic phenotype, the clinical implications of patient stratification and limitations of the concept.

Somatotype characteristics of normal-weight and obese women among different metabolic subtypes.

BACKGROUND: Obesity is a well known risk factor for the development of metabolic abnormalities. However, some obese people are healthy and on the other hand some people with normal weight have adverse metabolic profile, therefore it can be assumed that there is a difference in physical characteristics amongst these people. The aim of this study was to establish whether there are somatotype differences between metabolically healthy and metabolically obese women who are obese or of normal weight. SUBJECTS AND METHODS: Study included 230 women aged 44.76 ± 11.21y. Metabolic status was assessed according to IDF criteria, while somatotype was obtained using Heath & Carter method. RESULTS: Significant somatotype differences were observed in the group of women with normal-weight: metabolically healthy women had significantly lower endomorphy, mesomorphy and higher ectomorphy compared to metabolically obese normal-weight women (5.84-3.97-2.21 vs. 8.69-6.47-0.65). Metabolically healthy obese women had lower values of endomorphy and mesomorphy and higher values of ectomorphy compared to 'at risk' obese women but the differences were not statistically significant (7.59-5.76-0.63 vs. 8.51-6.58-0.5). Ectomorphy was shown as an important determinant of the favorable metabolic profile (cutoff point was 0.80). CONCLUSION: We concluded that, in addition to fat mass, metabolic profile could be predicted by the structure of lean body mass, and in particular by body linearity.

Somatotype characteristics of normal-weight and obese women among different metabolic subtypes

ABSTRACT Background Obesity is a well known risk factor for the development of metabolic abnormalities. However, some obese people are healthy and on the other hand some people with normal weight have adverse metabolic profile, therefore it can be assumed that there is a difference in physical characteristics amongst these people. The aim of this study was to establish whether there are somatotype differences between metabolically healthy and metabolically obese women who are obese or of normal weight. Subjects and methods Study included 230 women aged 44.76 ± 11.21y. Metabolic status was assessed according to IDF criteria, while somatotype was obtained using Heath & Carter method. Results Significant somatotype differences were observed in the group of women with normal-weight: metabolically healthy women had significantly lower endomorphy, mesomorphy and higher ectomorphy compared to metabolically obese normal-weight women (5.84-3.97-2.21 vs. 8.69-6.47-0.65). Metabolically healthy obese women had lower values of endomorphy and mesomorphy and higher values of ectomorphy compared to ‘at risk’ obese women but the differences were not statistically significant (7.59-5.76-0.63 vs. 8.51-6.58-0.5). Ectomorphy was shown as an important determinant of the favorable metabolic profile (cutoff point was 0.80). Conclusion We concluded that, in addition to fat mass, metabolic profile could be predicted by the structure of lean body mass, and in particular by body linearity.

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

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