Phenotyping obesity: A focus on metabolically healthy obesity and metabolically unhealthy normal weight

Over the past 4 decades, research has shown that having a normal body weight does not automatically imply preserved metabolic health and a considerable number of lean individuals harbour metabolic abnormalities typically associated with obesity. Conversely, excess adiposity does not always equate with an abnormal metabolic profile. In fact, evidence exists for the presence of a metabolically unhealthy normal weight (MUHNW) and a metabolically healthy obese (MHO) phenotype. It has become increasingly recognised that different fat depots exert different effects on the metabolic profile of each individual by virtue of their location, structure and function, giving rise to these different body composition phenotypes. Furthermore, other factors have been implicated in the aetiopathogenesis of the body composition phenotypes, including genetics, ethnicity, age and lifestyle/behavioural factors. Even though to date both MHO and MUHNW have been widely investigated and documented in the literature, studies report different outcomes on long-term cardiometabolic morbidity and mortality. Future large-scale, observational and population-based studies are required for better profiling of these phenotypes as well as to further elucidate the pathophysiological role of the adipocyte in the onset of metabolic disorders to allow for better risk stratification and a personalised treatment paradigm.     

代谢健康型肥胖与动脉粥样硬化的相关性研究

目的探讨在40岁以上的中国社区人群中,代谢健康型肥胖与动脉粥样硬化患病风险的相关性。方法来自上海嘉定社区共9525名不伴有心血管疾病的居民(男性3621名、女性5904名)参与了本项研究。每位参与者均完成了调查问卷、体格检查[包括肱踝脉搏波传导速度(brachial-ankle pulse wave velocity,baPWV)和血压(blood pressure,BP)的测量],以及实验室检查。根据体重指数(body mass index,BMI)和代谢水平,将参与者分为4组,分别是代谢健康型非肥胖(metabolically healthy non-obese,MHNO)、代谢不健康型非肥胖(metabolically unhealthy non-obese,MUNO)、代谢健康型肥胖(metabolically healthy obese,MHO)和代谢不健康型肥胖(metabolically unhealthy obese,MUO)。baPWV>1400 mm/s被定义为高baPWV水平,脉压差(pulse pressure,PP)高于人群上四分位数被定义为高PP水平。利用多元logistic回归分析模型探究MHO与高baPWV水平以及高PP水平之间的相关性。结果多元logistic回归分析显示,在校正性别、年龄、当前吸烟、当前饮酒及受教育程度之后,与MHNO组比较,MHO组人群与高baPWV水平(OR=1.18,95%CI 1.02~1.37)和高PP水平(OR=1.72,95%CI 1.43~2.08)有显著相关性。另外,MUNO和MUO组人群的高baPWV水平(MUNO为OR=3.02,95%CI 2.60~3.50;MUO为OR=3.26,95%CI 2.87~3.70)和高PP水平(MUNO为OR=2.56,95%CI 2.17~3.02;MUO为OR=3.49,95%CI 3.01~4.06)患病风险显著升高。结论中国社区中老年人群中,MHO与动脉粥样硬化患病风险升高有显著相关性。     

Prevalence and determinants of metabolically healthy obesity in Spain

Background and aims

Obesity is a heterogeneous disorder, so some obese individuals do not have cardiometabolic abnormalities (CA) which mediate the association between obesity and coronary heart disease. This study assessed the prevalence of metabolically healthy obesity and its determinants in Spain.

Methods

The data were taken from a cross-sectional study conducted in 2008–2010 among 11,520 individuals representative of the population of Spain aged ≥18 years. Normal-weight was defined as body mass index (BMI) <25 kg/m², and obesity as BMI ≥30 kg/m². Six CA were considered: elevated blood pressure, low high-density lipoprotein cholesterol, and elevated levels of triglycerides, fasting glucose, homeostasis model assessment of insulin resistance value, and C-reactive protein. Then, two phenotypes were defined: healthy (0–1 CA) and abnormal (≥2 CA).

Results

The prevalence of metabolically healthy obesity was 6.5% overall (95% confidence interval: 6.0–7.1), and corresponds to 28.9% of obese individuals. Lower age, being female, current smoking, moderate alcohol consumption, and high level of physical activity were independently associated with the healthy phenotype among the obese. The prevalence of normal weight with a metabolically abnormal phenotype was 6.4% overall (95% confidence interval: 5.8–6.9) and corresponds to 16.8% of normal-weight subjects. Factors associated with this phenotype in normal-weight persons were higher age, being male, never smoking, no alcohol consumption and larger waist circumference.

Conclusion

Metabolically healthy obesity represents almost one-third of the obese population in Spain. Since this was a cross-sectional study, the association of metabolic healthy obesity with smoking consumption, alcohol intake and physical activity warrants more research.     

Fasting plasma total ghrelin concentrations in monozygotic twins discordant for obesity

Ghrelin is a hormone that is involved in the regulation of food intake. Neuronal, endocrine, and genetic factors have been shown to regulate plasma ghrelin levels; but the determinants of fasting ghrelin concentrations are not yet fully understood. The main aim was to explore the roles of adiposity and genetic differences in determining fasting plasma total ghrelin levels. We measured total ghrelin levels in a population of 23 monozygotic twin pairs discordant for obesity. In addition, 2 variants of ghrelin gene, namely, Arg51Gln and Leu72Met, were genotyped in 3 populations of monozygotic twin pairs: 23 obesity-discordant, 43 lean-concordant, and 46 obesity-concordant twin pairs. In discordant twins, lean co-twins had higher fasting plasma total ghrelin levels (950 pg/mL, SD = 328 pg/mL) than obese twins (720 pg/mL, SD = 143 pg/mL; P = .003). Arg51Gln-polymorphism of the ghrelin gene was equally distributed between the twin groups. However, there were significant differences in genotype frequencies at the Leu72Met polymorphism between the discordant and obese-concordant groups (P = .003) and between the discordant and lean-concordant groups (P = .011), but not between the 2 concordant groups. In the discordant group, there were fewer Met carriers (4%) than among the obese (17%) or the lean-concordant groups (15%). Plasma total ghrelin levels are affected by acquired obesity independent of genetic background. The Leu72 allele is particularly common among monozygotic twins discordant for obesity, suggesting that this ghrelin allele is more permissive in the regulation of energy balance. The ghrelin gene may thus play a role in the regulation of variability of body weight, such that Leu72 allele carriers are more prone to weight variability in response to environmental factors.     

Achalasia in monozygotic twins

Summary The familial occurrence of achalasia has been previously recorded and a genetic origin for the disease has been postulated. We present the first case of achalasia in monozygotic twins and suggest that concordance for the disease is consistent with a genetic factor in the etiology of achalasia.     

Epidemiology and pathophysiology of the association between NAFLD and metabolically healthy or metabolically unhealthy obesity

The prevalence of nonalcoholic fatty liver disease (NAFLD) is continuing to rise in many countries, paralleling the epidemic of obesity worldwide. In the last years, the concept of metabolically healthy obesity [MHO, generally defined as obesity without metabolic syndrome (MetS)] has raised considerable scientific interest. MHO is a complex phenotype with risks intermediate between metabolically healthy individuals with normal-weight (NWMH) and patients who are obese and metabolically unhealthy (MUO, i.e. obesity with MetS). In this review we aimed to examine the association and pathophysiological link of NAFLD with MHO and MUO. Compared to NWMH individuals, patients with obesity, regardless of the presence of MetS features, are at higher risk of all-cause mortality and cardiovascular events. Moreover, MHO patients have a greater risk of NAFLD development and progression compared to NWMH individuals. However, this risk is generally lower than that of MUO patients, suggesting a stronger adverse effect of coexisting MetS disorders than obesity per se on the severity of NAFLD. Nevertheless, since MHO is a dynamic state (with a significant proportion of MHO subjects progressing to MUO over time) and NAFLD itself may predict the transition from MHO to MUO, we believe that any effort should be made to identify NAFLD in all obese individuals, although they appear to be “metabolically healthy”. Future research is needed to better understand the role of NAFLD and other pathogenic factors potentially involved in the transition from MHO to MUO and to elucidate how this transition may affect the presence and severity of NAFLD.     

Focal myositis in monozygotic twins

Focal myositis is a rare disease with unknown etiology and a broad spectrum. Here, we present two cases in monozygotic twins who complained of recurrent pain of their calves and showed histological signs of inflammation and MRI image compatible with the diagnosis of focal myositis. The occurrence of twin cases not living in the same household suggests a genetic susceptibility to the disease.     

Tetralogy of Fallot in monozygotic twins

A pair of monozygotic twins having tetralogy of Fallot is reported for the first time in the Indian literature. This case report will help in further enriching the existing data on genetic hypothesis of congenital heart defects.     

Occurrence of scleroderma in monozygotic twins

Familial occurrence of scleroderma is rare and concordance for the disease in twins has been reported exceptionally. We describe 2 female identical twin pairs concordant for scleroderma. The first twin pair was diagnosed with the systemic form of scleroderma, the second pair with the localized form.     

Tracheobronchial clearance in asthma-discordant monozygotic twins

Tracheobronchial clearance and bronchial reactivity were studied in 6 asthma-discordant monozygotic twin pairs, and in 3 concordant pairs as controls. Clearance of 6-microns Teflon particles labeled with 99mTc was followed for 2 h. The results indicate that clearance in the larger airways is usually not severely impaired in mild to moderate asthma, and that it may be increased as well as decreased. Bronchial reactivity correlated with clearance in the nonasthmatics.     

Bicuspid aortic valves in monozygotic twins

Identical bicuspid valve anomalies were found in monozygotic twins. Screening echocardiography should be considered for first-degree relatives of patients with bicuspid aortic valve.     

Hepatitis C virus in monozygotic twins

A case of a pregnant patient with chronic hepatitis C who gave birth to monozygotic twins that were infected with HCV is reported. One of the newborns was positive for HCV-RNA in blood sample collected 12 hours after delivery. The other newborn was negative for HCV-RNA at birth, but was detected HCV viremia at three months of age. The results have led to the conclusion that one of the twins was probably contaminated in the intrauterine period, while the other acquired the infection in the perinatal period. Both were negative for HCV-RNA and for anti-HCV in the serum samples collected at nine months of age. The report describes the changes in the laboratory tests conducted in mother and twins until 29 months after delivery.     

Multiple rhabdomyomas in monozygotic twins.

Rhabdomyoma is the most frequent primary cardiac tumor seen during infancy. We report multiple rhabdomyomas diagnosed in twins in the neo natal period. To the best of our knowledge, this is the first instance of this happening.     

Comparison of criteria for metabolically healthy overweight/obesity in Shanghai Changfeng study

<正>Objective To establish a more suitable and practicable criterion of metabolically healthy overweight/obesity (MHO/O) in Chinese,a comparison study on different criteria of MHO/O was conducted in subjects aged over 45-year-old in Shanghai Changfeng Community. Method A total of 3301 overweight/obese subjects over 45 years old (men 1 521,women 1 789)in Shanghai Changfeng Community were included in the study. According to the inclusion or exclusion of waist circumference (WC),homeostasis mo...