Metabolically healthy obesity: epidemiology, mechanisms, and clinical implications

Stefan, Norbert; Häring, Hans‐Ulrich; Hu, Frank B.; Schulze, Matthias B.

doi:10.1016/s2213-8587(13)70062-7

Cited by 667 publications

(645 citation statements)

References 73 publications

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“…Indeed, it is remarkable that obese individuals are not all alike in terms of susceptibility to metabolic diseases and, hence, cardiovascular risk. 45 When visceral adipose tissues of 7 severely obese men with and without metabolic syndrome were compared by pathway analysis of differentially methylated genes, the most significant differences were related to genes encoding cell membrane components, and genes controlling immunity, cell cycle regulation, and inflammation. 46 As stated above, hyperglycemia can stimulate inflammation and the latter can facilitate diabetes onset and progression ( Fig.…”

Section: B-cell Development and Functionmentioning

confidence: 99%

Clinical relevance of epigenetics in the onset and management of type 2 diabetes mellitus

et al. 2017

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Epigenetics is involved in the altered expression of gene networks that underlie insulin resistance and insufficiency. Major genes controlling b-cell differentiation and function, such as PAX4, PDX1, and GLP1 receptor, are epigenetically controlled. Epigenetics can cause insulin resistance through immunomediated pro-inflammatory actions related to several factors, such as NF-kB, osteopontin, and Toll-like receptors. Hereafter, we provide a critical and comprehensive summary on this topic with a particular emphasis on translational and clinical aspects. We discuss the effect of epigenetics on b-cell regeneration for cell replacement therapy, the emerging bioinformatics approaches for analyzing the epigenetic contribution to type 2 diabetes mellitus (T2DM), the epigenetic core of the transgenerational inheritance hypothesis in T2DM, and the epigenetic clinical trials on T2DM. Therefore, prevention or reversion of the epigenetic changes occurring during T2DM development may reduce the individual and societal burden of the disease.

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Section: B-cell Development and Functionmentioning

confidence: 99%

Clinical relevance of epigenetics in the onset and management of type 2 diabetes mellitus

et al. 2017

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“…Termed 'metabolically healthy obesity,' it is unclear if the healthy obese phenotype is a stable trait or a transitional stage prior to the onset of metabolic dysfunction (1). This instability may explain the inconsistency in findings between studies with shorter and longer follow-up periods in relation to healthy obesity and the risk of incident type 2 diabetes and cardiovascular disease (2,3).…”

Section: Introductionmentioning

confidence: 99%

Stability of metabolically healthy obesity over 8 years: the English Longitudinal Study of Ageing

Hamer

Bell

Sabia

et al. 2015

European Journal of Endocrinology

116

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Objective: Metabolically healthy obesity possibly reflects a transitional stage before the onset of metabolic dysfunction, but few studies have characterised this transition. We examined the behavioural and biological characteristics of healthy obese adults that progressed to an unhealthy state over 8 years follow-up. Methods: Participants were 2422 men and women (aged 63.3G7.7 years, 44.2% men) from the English Longitudinal Study of Ageing. Obesity was defined as BMI R30 kg/m 2 . Based on blood pressure (BP), HDL-cholesterol, triglycerides, HbA1c and C-reactive protein (CRP) participants were classified as 'healthy' (0 or 1 metabolic abnormality) or 'unhealthy' (R2 metabolic abnormalities). Results: Over 8 years follow-up, 44.5% of healthy obese subjects had transitioned into an unhealthy state, compared to only 16.6 and 26.2% of healthy normal-weight and overweight adults respectively. Compared with healthy obese adults who remained stable, those who progressed to an unhealthy state were more likely to have high BP (75.0% vs 37.0%, age-and sex-adjusted odds ratio (OR) 8.9, 95% CI 4.7-17.0), high CRP (53.7% vs 17.0%, ORZ8.6, 95% CI 4.1-18.0), high HbA1c (46.3% vs 5.9%, ORZ13.8, 95% CI 6.1-31.2) and high triglycerides (45.4% vs 11.9%, ORZ5.9, 95% CI 2.9-12.0) at follow-up, with excess risk remaining independent of lifestyle factors including self-reported physical activity. Progression to an unhealthy state was also linked with significant gains in waist circumference (BZ2.7, 95% CI, 0.5-4.9 cm). Conclusion: These data show that a healthy obesity phenotype is relatively unstable. Transition to an unhealthy state is characterised by multiple biological changes that are not fully explained by lifestyle risk factors.

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“…Clearly, increased BMI cannot be included as a criterion for MH in an analysis of MH OW or OB, and this extends to increased waist circumference which displays marked co-linearity with BMI (4) and has been excluded from the majority of definitions of MH OW or OB (7,10,11,12). Other readily available criteria then include plasma lipid, lipoprotein and glucose concentrations and blood pressure.…”

Section: Definition Of Metabolic Healthmentioning

confidence: 99%

“…Problems consistently raised in commentaries on MH OW and OB have included the lack of an agreed definition of metabolic health and the fact that a continuum of variation in metabolic disturbance extends across all levels of adiposity (5,6,7,8). Nevertheless, if a pragmatic definition of MH could be agreed, it might yet be used to identify OW or OB individuals who need not benefit from intensive weight loss.…”

Section: Introductionmentioning

confidence: 99%

“…Nevertheless, if a pragmatic definition of MH could be agreed, it might yet be used to identify OW or OB individuals who need not benefit from intensive weight loss. In a detailed review, Stefan et al distinguished three types of investigation, differing according to whether MHO had been defined with reference to insulin sensitivity, cardiorespiratory fitness or a putative 'metabolic syndrome' (7). Measures of insulin sensitivity and cardiorespiratory fitness (and inflammatory markers, which have also been used to define MH) are not routinely available.…”

Section: Introductionmentioning

confidence: 99%

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Does metabolic health in overweight and obesity persist? – Individual variation and cardiovascular mortality over two decades

Kaur

Johnston

Godsland

2016

European Journal of Endocrinology

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Objective: Overweight and obese individuals may be metabolically healthy, but attention needs to be given to long-term persistence of this trait and any associated variation in cardiovascular risk. Design: Cross-sectional and longitudinal variation in metabolic health and associated cardiovascular mortality were analysed in 1099 white European-origin normal-weight and overweight or obese males followed for 20 years. Methods: Definitions of metabolic health were based on LDL and HDL cholesterol, triglycerides, blood pressure, fasting glucose and cardiovascular risk. Insulin resistance (e.g. HOMA-IR) and sub-clinical inflammation (ESR and white blood cell count) were explored. Cardiovascular mortality risks and persistence of metabolic health status were evaluated. Results: There were 87 cardiovascular deaths. Insulin resistance was increased in metabolically healthy overweight or obese participants (median HOMA-IR 2.63, 95% CI: 1.79-3.65, P < 0.001) relative to normal-weight participants (median HOMA-IR 1.67, 95% CI: 1.08-2.67, P < 0.001) as was sub-clinical inflammation but metabolically healthy overweight or obese individuals were not at increased risk of cardiovascular mortality compared with the metabolically healthy normal-weight individuals (hazard ratio 1.13, 95% CI: 0.34-3.72, P = 0.8). The proportions of initially metabolically healthy overweight or obese who remained metabolically healthy for visits 2, 3 and 4 were 54, 48 and 39% respectively, and for initially normal-weight individuals, 68, 51 and 41%. A lower proportion of metabolically healthy overweight or obese individuals remained metabolically healthy at visit 2 compared with normal-weight individuals (P = 0.007), but proportions converged thereafter. Conclusions: Despite being insulin resistant and having greater sub-clinical inflammation, and despite instability in metabolic health status, metabolically healthy overweight or obese individuals were at no greater risk of cardiovascular mortality than their normal-weight equivalents.

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Metabolically healthy obesity: epidemiology, mechanisms, and clinical implications

Cited by 667 publications

References 73 publications

Clinical relevance of epigenetics in the onset and management of type 2 diabetes mellitus

Clinical relevance of epigenetics in the onset and management of type 2 diabetes mellitus

Stability of metabolically healthy obesity over 8 years: the English Longitudinal Study of Ageing

Does metabolic health in overweight and obesity persist? – Individual variation and cardiovascular mortality over two decades

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