Metabolic abnormalities,but not obesity per se,associated with chronic kidney disease in a Taiwanese population

Background and aimsIt is inconclusive whether obesity itself or metabolic abnormalities are linked to chronic kidney disease (CKD). The aim of this study was to examine the association between different subtypes of obesity and metabolic abnormalities with CKD in adults.Methods and resultsThis study enrolled 14,983 eligible subjects stratified into 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) according to body mass index and metabolic syndrome status (ATP-III criteria). The metabolic healthy phenotype was defined as the absence of both metabolic syndrome and any known diabetes, coronary artery disease, stroke, hypertension or dyslipidemia. Early and advanced CKD were defined as eGFR<60, proteinuria, or structural abnormalities as detected by renal sonography. The prevalence of CKD was 2.5, 3.0, 4.0, 10.6, 9.5, and 10.5% in subjects with MHNW, MHOW, MHO, MUNW, MUOW, and MUO, respectively. In the multivariate analysis, the MUNW (OR:2.22, P < 0.001), MUOW (OR:2.22, P < 0.001), and MUO (OR:2.45, P < 0.001) groups were associated with early CKD. For advanced CKD, the OR was 2.56 (P < 0.001), 2.31 (P < 0.001), and 3.49 (P < 0.001) in the MUNW, MUOW, and MUO groups, respectively. The associated risks of early and advanced CKD were not significant in the MHOW and MHO group. MUOW and MUO were associated with higher risk of CKD compared with MHOW and MHO after adjusting other variables.ConclusionsMetabolic abnormalities, but neither overweight nor obesity, were associated with a higher risk of CKD in adults.     

Contribution of 20-year body mass index and waist circumference history to poor cardiometabolic health in overweight/obese and normal weight adults: A cohort study

Background and aimsWe investigated the associations of 20-year body mass index (BMI) and waist circumference (WC) histories with risk of being 1) metabolically unhealthy overweight/obese (MUOO) vs metabolically healthy overweight/obese (MHOO) and 2) metabolically unhealthy normal weight (MUNW) vs metabolically healthy normal weight (MHNW).Methods and resultsParticipants comprised 3018 adults (2280 males; 738 females) with BMI and WC measured, every ~5 years, in 1991–1994, 1997–1999, 2002–2004, 2007–2009, and 2012–2013. Mean age in 2012–2013 was 69.3 years, with a range of 59.7–82.2 years. Duration was defined as the number of times a person was overweight/obese (or centrally obese) across the 5 visits, severity as each person's mean BMI (or WC), and variability as the within-person standard deviation of BMI (or WC). At the 2013–2013 visit, participants were categorised based on their weight (overweight/obese or normal weight; body mass index (BMI) ≥25 kg/m²) and health status (healthy or unhealthy; two or more of hypertension, low high-density lipoprotein cholesterol, high triglycerides, high glucose, and high homeostatic model assessment of insulin resistance). Logistic regression was used to estimate associations with the risk of being MUNW (reference MHNW) and MUOO (reference MHOO) at the last visit. BMI and WC severity were each related to increased risk of being unhealthy, with estimates being stronger among normal weight than overweight/obese adults. The estimates for variability exposures became null upon adjustment for severity. Individuals who were overweight/obese at all 5 time points had a 1.60 (0.96–2.67) times higher risk of being MUOO than MHOO compared to those who were only overweight/obese at one (i.e., the last) time point. The corresponding estimate for central obesity was 4.20 (2.88–6.12). Greater duration was also related to higher risk of MUNW than MHNW.ConclusionBeing overweight/obese yet healthy seems to be partially attributable to lower exposure to adiposity across 20 years of adulthood. The results highlight the importance of maintaining optimum and stable BMI and WC, both in adults who become and do not become overweight/obese.     

Coffee and metabolic phenotypes: A cross-sectional analysis of the Japan multi-institutional collaborative cohort (J-MICC) study

Background and aimsTo date, the relationship between coffee consumption and metabolic phenotypes has hardly been investigated and remains controversial. Therefore, the aim of this cross-sectional study is to examine the associations between coffee consumption and metabolic phenotypes in a Japanese population.Methods and resultsWe analyzed the data of 26,363 subjects (aged 35–69 years) in the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study. Coffee consumption was assessed using a questionnaire. Metabolic Syndrome (MetS) was defined according to the Joint Interim Statement Criteria of 2009, using body mass index (BMI) instead of waist circumference. Subjects stratified by the presence or absence of obesity (normal weight: BMI <25 kg/m²; obesity: BMI ≥25 kg/m²) were classified by the number of MetS components (metabolically healthy: no components; metabolically unhealthy: one or more components) other than BMI.In multiple logistic regression analyses adjusted for sex, age, and other potential confounders, high coffee consumption (≥3 cups/day) was associated with a lower prevalence of MetS and metabolically unhealthy phenotypes both in normal weight (OR 0.83, 95% CI 0.76–0.90) and obese subjects (OR 0.83, 95% CI 0.69–0.99). Filtered/instant coffee consumption was inversely associated with the prevalence of MetS and metabolically unhealthy phenotypes, whereas canned/bottled/packed coffee consumption was not.ConclusionThe present results suggest that high coffee consumption, particularly filtered/instant coffee, is inversely associated with the prevalence of metabolically unhealthy phenotypes in both normal weight and obese Japanese adults.     

Impact of metabolically healthy obesity on carotid intima-media thickness - The Brazilian Longitudinal Study of Adult Health

Background and aimsObesity increases the risk of metabolic abnormalities, which contributes to elevated cardiovascular risk. However, the independent role of obesity in the development of cardiovascular disease is still debatable. There are individuals with an obesity phenotype without metabolic abnormalities: “metabolically healthy obesity” (MHO). This study evaluates the association between MHO and carotid intima-media thickness (CIMT), an early marker of subclinical atherosclerosis.Methods and resultsThis is a cross-sectional analysis of the baseline data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). We used a strict definition to classify MHO: body mass index ≥30 kg/m² and meeting none of the four metabolic syndrome criteria. Data from 10,335 participants were analyzed. The obesity prevalence in our population was 21.2% (n = 2191). The prevalence of MHO was 5.6% (n = 124). When individuals were stratified according to metabolic health, we found the metabolically healthy individuals were younger, more likely to be women and never smokers. The mean CIMT of the sample was 0.81 mm (±0.20). The mean CIMT of the metabolically healthy subsample was 0.70 mm (±0.13) in individuals without obesity and 0.76 mm (±0.13) in individuals with obesity (p < 0.001). The mean CIMT of the metabolically unhealthy subsample was 0.81 mm (±0.20) in individuals without obesity and 0.88 mm (±0.20) in individuals with obesity (p < 0.001). These findings remained essentially unchanged after multivariate adjustment for confounding factors.ConclusionThe concept of MHO, even with the strict definition, seems inadequate, as even in this population, obesity is associated with higher CIMT levels.     

Lifestyle factors associated with the transition from healthy to unhealthy adiposity among black South African adults over 10 years

Background and aimsObesity is associated with an increasing prevalence of cardiovascular diseases in Africa, but some obese individuals maintain cardiometabolic health. The aims were to track metabolically healthy overweight or obesity (MHO) over 10 years in African adults and to identify factors associated with a transition to metabolically unhealthy overweight or obesity (MUO).Methods and resultsThe participants were the South African cohort of the international Prospective Urban and Rural Epidemiological study. From the baseline data of 1937 adults, 649 women and 274 men were followed for 10 years. The combined overweight and obesity prevalence of men (19.2%–23.8%, p = .02) and women (58%–64.7%, p < .001), and the prevalence of the metabolic syndrome in all participants (25.4%–40.2%, p < .001) increased significantly. More than a quarter (26.2%) of the women and 10.9% of men were MHO at baseline, 11.4% of women and 5.1% of men maintained MHO over 10 years, while similar proportions (12.3% of women, 4.7% of men) transitioned to MUO. Female sex, age, and total fat intake were positively associated with a transition to MUO over 10 years, while physical activity was negatively associated with the transition. HIV positive participants were more likely to be MHO at follow-up than their HIV negative counterparts.ConclusionsOne in two black adults with BMI ≥25 kg/m² maintained MHO over 10 years, while a similar proportion transitioned into MUO. Interventions should focus on lower fat intakes and higher physical activity to prevent the transition to MUO.     

Association of cumulative excess weight and waist circumference exposure with transition from metabolically healthy obesity to metabolically unhealthy

Background and aimsThe association between obesity severity and duration with the transition from metabolically healthy obese/overweight (MHO) phenotype to metabolically unhealthy obese (MUO) phenotype is not well understood.Methods and resultsThis study includes the Tehran Lipid and Glucose Study participants who were initially classed as MHO. Cumulative excess weight (CEW) and cumulative excess waist circumference (CEWC) scores, which represent the accumulation of body mass index and waist circumference deviations from expected values over time (kg/m² 1 y and cm 1 y, respectively), were calculated until the transition from MHO to MUO or the end of follow-up. The sex-stratified association of CEW and CWEC with the transition from MHO to MUO was investigated by time-dependent Cox models, adjusting for confounders. Out of 2525 participants, 1732 (68.5%) were women. During 15 years of follow-up, 1886 (74.6%) participants transitioned from MHO to MUO. A significant association was found between CEW and CEWC quartiles with the development of MUO among women participants (fully adjusted hazard ratios in the fourth quartile of CEW and CEWC [95% (CI)]:1.65 [1.37–1.98] and [95% CI]: 1.83 [1.53–2.19]). There was no significant association between CEW and CEWC with the MHO transition to MUO among men participants.ConclusionOver 15 years of follow-up in TLGS, general and central obesity accumulation was associated with the increased transition from MHO to MUO among women participants. More research with a larger sample size is needed to confirm and explain why the results are different for men and women.     

Adiposity,hepatic steatosis,and metabolic health transitions in people with obesity: Influences of age and sex

Background and aimsMetabolically healthy (MHO) and unhealthy obesity (MUO) may be transient conditions. This study aimed to quantify and identify predictive factors of metabolic transitions in obesity, exploring influences of age and sex.Methods and resultsWe retrospectively evaluated adults with obesity who underwent routine health evaluation. In a cross-sectional analysis of 12,118 individuals (80% male, age 44.3 ± 9.9 years), 16.8% had MHO. In a longitudinal evaluation of 4483 participants, 45.2% of individuals with MHO at baseline had dysmetabolism after a median follow-up of 3.0 (IQR 1.8–5.2) years, whereas 13.3% MUO participants became metabolically healthy (MH). Development of hepatic steatosis (HS, ultrasound) was an independent predictor of MHO conversion to dysmetabolism (OR 2.36; 95% CI 1.43, 3.91; p < 0.001), while HS persistence was inversely associated with transition from MUO to MH status (OR 0.63; 95% CI 0.47, 0.83; p = 0.001). Female sex and older age were associated with a lower chance of MUO regression. A 5% increment in body mass index (BMI) over time increased the likelihood of metabolic deterioration by 33% (p = 0.002) in females and 16% (p = 0.018) in males with MHO. A 5% reduction in BMI was associated with a 39% and 66% higher chance of MUO resolution in females and males, respectively (both p < 0.001).ConclusionThe findings support a pathophysiological role of ectopic fat depots in metabolic transitions in obesity and identify female sex as an aggravating factor for adiposity-induced dysmetabolism, which has implications for personalized medicine.     

Frequency of insulin resistance in nondiabetic adult Bangladeshi individuals of different obesity phenotypes

Insulin resistance (IR) is the corner stone of metabolic obesity. This cross-sectional analytical study was aimed to find out the frequency of IR in non-diabetic adult individuals of different obesity phenotypes that would help to implement preventive measures to avoid the cardiometabolic catastrophes.MethodsTotal 955 nondiabetic adult individuals were selected and categorized into six metabolic phenotypes by metabolic syndrome criteria in each BMI group (18.5–24.9-normal weight, 25-29.9-overweight, ≥30-obese). From them, metabolically obese normal weight, metabolically obese overweight, metabolically healthy obese and metabolically unhealthy obese were selected as Obesity phenotypes (N = 616).ResultsThe frequency of IR was found to be very high (60.2%) in total nondiabetic adult obese individuals (N = 616). Highest frequency of IR was found in MUO phenotype (76.3%), lowest frequency of IR was found in MONW phenotype (37.1%) and frequency of IR in MOOW and MHO phenotypes found to be identical but significantly (p < 0.0001) less than MUO and significantly (p < 0.0001) more than MONW phenotype. Among the obesity phenotypes, females were more insulin resistant than males (67.5% vs 48.1% respectively, p < 0.05). Frequency of IR found significantly (p < 0.05) more in female than male in all obesity phenotypes except in MUO phenotype where males found to show significantly (p < 0.05) higher frequency than females. Frequency of IR was significantly higher in younger (20–39 yrs) age group than 40–60 yrs age group (63.2% vs 53.5% respectively, p < 0.05).ConclusionIR is alarmingly high (60.2%) in nondiabetic adult obese individuals. Among different obesity phenotypes, it is highest (76.3%) in MUO and lowest (37.1%) in MONW.     

Metabolic Health,Obesity, and Cardiovascular Disease: 2015–2016 National Health and Nutrition Examination Survey

BackgroundThe metabolically unhealthy normal weight (MUN) and metabolically healthy obese (MHO) phenotypes are abnormal metabolic states. The purpose of this study was to report the frequency of the strictly defined MHO and MUN phenotypes and the association between metabolic phenotype and 10-year Framingham cardiovascular disease (CVD) risk score using a sample taken from the 2015–2016 National Health and Nutrition Examination Survey.MethodsA cross-sectional sample of 2,316 participants age 18–79 years with complete metabolic health information were selected from the 2015–2016 dataset and included in the present analysis. Metabolic health was defined as the absence of all metabolic abnormalities as outlined by the National Cholesterol Education Program Adult Treatment Panel III criteria, excluding waist circumference. Obesity was defined as body mass index ≥30 kg/m² or waist > 88.9 cm for females or > 101.6 cm for males.ResultsFrequency of the MHO phenotype was 5.5% and the MUN was 44.3%. After adjustment for all covariates, Framingham CVD risk score was higher in the MUN (b = 1.74,p < 0.001) and metabolically unhealthy obese (b = 3.32,p < 0.001) phenotypes that used BMI to define obesity, and the MHO phenotype had a slight protective effect (b = -2.25,p < 0.001) when waist circumference was used as the measure of obesity.ConclusionsMetabolically unhealthy phenotypes had higher CVD risk, while the MHO phenotype was not at any greater risk than the metabolically healthy normal weight.     

Myocardial Tissue-Level Characteristics of Adults With Metabolically Healthy Obesity

BackgroundIt remains unclear whether adults with metabolically healthy obesity (MHO) have altered myocardial tissue-level characteristics.ObjectivesThis study aims to assess the subclinical myocardial tissue-level characteristics of adults with MHO.MethodsThe EARLY-MYO-OBESITY (EARLY Assessment of MYOcardial Tissue Characteristics in OBESITY; NCT05277779) registry was a prospective, 3-center, cardiac imaging study of obese nondiabetic individuals without cardiac symptoms who underwent cardiac magnetic resonance. Myocardial tissue-level characteristics, including extracellular volume fraction (ECV) and native T2 values, were measured as indicators of myocardial fibrosis and edema. Global longitudinal peak systolic strain and early diastolic longitudinal strain rate were assessed by tissue tracking analysis to detect subclinical systolic and diastolic dysfunction.ResultsA total of 120 participants were included: MHO (n = 32; mean age, 38 years; 41% men), metabolically healthy controls without obesity (n = 32; mean age: 37 years; 41% men), and metabolically unhealthy obesity (MUHO) (n = 56; mean age: 37 years; 55% men). The MHO group had higher ECV and native T2 values than healthy controls (both P < 0.001); furthermore, the ECV was higher in the MUHO group than in the MHO group (P = 0.002). The prevalence of myocardial fibrosis was 44% (14 of 32) in the MHO group and 71% (40 of 56) in the MUHO group. Although there was no intergroup difference in left ventricular ejection fraction, the MHO group had reduced global longitudinal peak systolic and early diastolic longitudinal strain rates, indicating subclinical systolic and diastolic dysfunction. Multivariate regression analysis identified increased body mass index to be an independent risk factor for myocardial fibrosis (OR: 6.28 [95% CI: 3.17-12.47]; P < 0.001).ConclusionsThis study provides the first evidence of subclinical myocardial tissue-level remodeling in adults with obesity, regardless of metabolic health. Early identification of cardiac impairment may facilitate preventive strategies against heart failure in the MHO population. (EARLY Assessment of MYOcardial Tissue Characteristics in OBESITY [EARLY-MYO-OBESITY]; NCT05277779)     

New obesity classification criteria as a tool for bariatric surgery indication

Obesity plays relevant pathophysiological role in the development of health problems, arising as result of complex interaction of genetic, nutritional, and metabolic factors. Due to the role of adipose tissue in lipid and glucose metabolism, and low grade inflammation, it is necessary to classify obesity on the basis of body fat composition and distribution, rather than the simply increase of body weight, and the Body Mass Index. The new term of adiposopathy(‘‘sick fat') clearly defines the pathogenic role of adipose tissue. Four phenotypes of obese individuals have been described:(1) normal weight obese(NWO);(2) metabolically obese normal weight;(3) metabolically healthy obese; and(4) metabolically unhealthy obese or "at risk" obese. Moreover, sarcopenic obesity has been related to all the phenotypes. The category of normal weight lean, represented by metabolically healthy normal weight has been classified to distinguish from NWO. It is crucial to recommend a bariatric surgery taking into account adiposopathy and sick fat that occurs with the expansion of fat mass, changing the inflammatory and metabolic profile of the patient. Body fat percentage and genetic polymorphism have to be evaluated to personalize the best bariatric surgery intervention.     

The risk of metabolic derangements is higher in children and adolescents with overweight or obesity born small for gestational age

Background and aimsBirth weight (BW) has been associated with the risk of obesity and metabolic derangements in children and adults. The aims of this study were: i. to evaluate the distribution of BW in a sample of overweight and obese children and adolescents compared with the general reference population; ii. to explore the relationship between the BW and insulin resistance and other cardiometabolic derangements in a population of children and adolescents with overweight and obesity.Methods and results710 overweight and obese children and adolescents were recruited and categorized into small (SGA), appropriate (AGA), and large (LGA) for gestational age, according to the BW percentile. Arterial blood pressure, lipid profile, glucose metabolism and hepatic steatosis were evaluated to assess cardiometabolic obesity-related derangements. The distribution of BW categories in our population was significantly different compared with the general population (SGA 6.9% vs. 8.6%, AGA 74.6% vs. 81.4%, LGA 18.5% vs. 10%; p < 0.0001). We found a higher frequency of prediabetes conditions (21.7% vs 8.9%, OR 2.97, 95% CI 1.38–6.38, p = 0.005) and borderline/high low-density lipoprotein cholesterol (31.8% vs 18.6%, OR 2.13, 95% CI 1.09–4.18, p = 0.033) in overweight and obese children born SGA compared to those born non-SGA, independently of age, sex, and BMI.ConclusionsBW is a risk factor of cardiometabolic derangements in a population of children and adolescents with overweight and obesity. Therefore, adequate obesity prevention strategies should be planned for children born SGA to minimize their risk to become obese and to reduce their short- and long-term cardiometabolic risks.     

Association of metabolic health phenotypes,obesity, and hepatocellular carcinoma risk

BackgroundThe obesity and hepatocellular carcinoma (HCC) risk association may differ by individuals’ metabolic health status.AimTo investigate the association between obesity categories and HCC risk among individuals with different metabolic health phenotypes.MethodsA case-control study among 518 HCC cases and 1,036 frequency-matched controls was conducted. Body mass index (BMI) was assessed before diagnosis. Pre-diagnosis data on dyslipidemia, hypertension, and diabetes were used to categorize participants as metabolically healthy or metabolically unhealthy. Participants were further categorized into metabolically healthy normal weight (MHNW), metabolically healthy overweight (MHOW), metabolically healthy obese (MHO), metabolically unhealthy normal weight (MUNW), metabolically unhealthy overweight (MUOW), and metabolically unhealthy obese (MHO). We used logistic regression to calculate multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs).ResultsBeing overweight (OR=1.68, 95%CI=1.21–2.34) or obese (OR=1.49, 95%CI=1.11–1.89) was associated with higher HCC risk. Among metabolically healthy participants, no association was found between being overweight or obese and HCC risk. However, among the metabolically unhealthy participants, being overweight (OR=1.89, 95%CI=1.31–2.72) or obese (OR=1.50, 95%CI=1.07–2.09) was associated with higher HCC risk. Compared to the MHNW phenotype, no association was found between the MHOW and MHO phenotypes and HCC risk, but the MUNW (OR=1.94, 95%CI=1.09–3.43), MUOW (OR=3.78, 95%CI=2.15–6.65), and MUO (OR=2.93, 95%CI=1.70–5.05) phenotypes were associated with higher HCC risk.ConclusionThe association between BMI and HCC appears to be restricted to individuals with underlying metabolic abnormalities.     

The association between early-life famine exposure and adulthood obesity on the risk of dyslipidemia

Background and aimsThe joint effect of famine exposure and adulthood obesity on risk of dyslipidemia remains unclear. Thus, we aim to explore the joint effect of famine exposure and adulthood obesity on the risk of dyslipidemia, and the potential effect of adult general or abdominal obesity on the association between famine exposure and dyslipidemia.Methods and resultsWe conducted a community-based cohort study in 8880 subjects aged 40 years or older. Participants were divided into nonexposed, fetal-exposed, childhood-exposed, adolescent-exposed according to birth date. General obesity and abdominal obesity were defined according to body mass index (BMI: overweight≥24.0 kg/m², obesity≥28.0 kg/m²) and waist-to-hip ratio (WHR, men/women: moderate≥0.90/0.85, high≥0.95/0.90). Dyslipidemia was defined using the National Cholesterol Education Program Adult Treatment Panel III criteria. Compared with nonexposed participants, fetal-exposed individuals had significantly increased risk of dyslipidemia (OR:1.24, 95%CI: 1.03–1.50) in the whole study. Significant increased risk of dyslipidemia related to famine exposure was observed in women [ORs (95%CIs) were 1.36 (1.05–1.76) and 1.70 (1.22–2.37) for the fetal and childhood-exposed group, respectively] but not in men. Moreover, both general and central obesity had significant multiplicative interactions with famine exposure for the risk of dyslipidemia (P for interaction = 0.0001 and < 0.0001, respectively). Significant additive interaction was found between famine exposure and WHR on risk of dyslipidemia in women, with the relative excess risk due to interaction (RERI) and 95% CI of 0.43 (0.10–0.76).ConclusionCoexistence of early-life undernutrition and adulthood obesity was associated with a higher risk of dyslipidemia in later life.     

Metabolically obese phenotype and its dynamic change are associated with increased carotid intima-media thickness: Results from a cohort study

Background and aimsTo examine associations between metabolically obese phenotypes or their changes and increased carotid intima-media thickness (CIMT).Methods and resultsThis prospective cohort included 13,681 Chinese adults aged 20–80 years who completed follow-up health examination with carotid ultrasound and were divided according to metabolic and weight status: metabolically healthy and normal weight (MHNW); metabolically obese but normal weight (MONW); metabolically healthy but obese (MHO); metabolically abnormal and obese (MAO). Cox and logistic regression were used to evaluate the associations of the phenotypes or their changes with increased CIMT.During a mean follow-up of 33 months, 1927 participants developed increased CIMT. After adjusting for age, sex and potential biochemical confounders, MAO was significantly associated with increased CIMT (HR 1.22, 95% CI [1.07, 1.4]); the association remained significant in those 40 years or older. Compared with stable MHNW, increased CIMT risk was higher for stable MAO (OR 1.35 [1.16, 1.57]), transitional MAO from MONW (OR 1.44 [1.04, 1.97]), and transitional MHO from MHNW (OR 1.59 [1.10, 2.26]) in demographic adjusted models; only stable MAO remained significant in the multivariate adjusted model (OR 1.23 [1.05, 1.45]).ConclusionMAO significantly elevated the risk of increased CIMT. Stable MAO and obese transitions also promoted CIMT progression.     

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.     

Changes in (poly)phenols intake and metabolic syndrome risk over ten years from adolescence to adulthood

Background and aims(Poly)phenols might contribute to prevent cardiovascular disease, but limited prospective studies exist among adolescents. This study aimed to evaluate within-subject longitudinal changes in (poly)phenols intakes and food group contributors while also exploring the association with metabolic syndrome risk (MetS) during 10 years of follow up in European adolescents becoming young adults.Methods and resultsIn 164 participants (58% girls, 13-18 y at baseline) from Ghent, Zaragoza and Lille, longitudinal data (2006–2016) on (poly)phenol intake was retrieved via 2 or 3 24 h recalls. Linear and logistic longitudinal regression tested the association of (poly)phenols intake (total and classes) with Mets risk or its components (waist-height-ratio, HDL cholesterol, LDL cholesterol, triglycerides, blood pressure and insulin resistance index), adjusted for age, sex, country and other nutrient intakes. The total (poly)phenols intake was 421 ± 107 mg/day (192 mg/1000 kcal/day) at baseline, while 610 ± 101 mg/day (311 mg/1000 kcal/day) at follow-up. The three major food sources for (poly)phenols were ‘chocolate’, ‘fruit and vegetable juices’, ‘cakes and biscuits’ during adolescence and ‘coffee’, ‘tea’ and ‘chocolate’ during adulthood. Phenolic acid intake was associated with less LDL increase over time, while stilbene intake with a steeper increase in triglycerides over time.ConclusionsDifferences in major (poly)phenols contributors over time were partially explained by age-specific dietary changes like increased coffee and tea during adulthood. Some significant (poly)phenols-MetS associations might argue for nutrition-based disease prevention during adolescence, especially since adolescents had low (poly)phenols intake.     

Preclinical vascular alterations in obese adolescents detected by Laser-Doppler Flowmetry technique

Background and aimsChildhood obesity promotes adverse changes in cardiovascular structure and function. This study evaluated whether alterations in skin microcirculation were already present in obese adolescents in a pre-clinical phase of cardiovascular disease.Methods and resultsAfter an overnight fasting 22 obese adolescents and 24 normal-weight controls of similar age and gender distribution underwent clinical and blood examination and assessment of microvascular function by using two non-invasive techniques such as Peripheral Artery Tonometry (PAT) and Laser-Doppler Flowmetry (LDF).As compared to normal weight subjects, obese children had higher blood pressure, were significantly more hyper-insulinemic and insulin resistant, showing significantly higher plasma total cholesterol, LDL cholesterol, triglycerides and alanine aminotransferase (ALT).LDF showed lower pre- and post-occlusion forearm skin perfusion (perfusion units/second (PU/sec); median [IQR]) in obese than in normal weight subjects (pre-occlusion: 1633.8 [1023.5] vs. 2281.1 [1344.2]; p = 0.015. Post-occlusion: 4811.3 [4068.9] vs. 7072.8 [7298.8]; p = 0.021), while PAT revealed similar values of reactive hyperemia index (RHI).In entire population, fat mass % (FM%) was an independent determinant of both pre-and post-occlusion skin perfusion. Finally, being obese was associated with a higher risk to have a reduction of both pre- and post-occlusion skin perfusion (OR = 5,82 and 9,27, respectively).ConclusionLDF showed very early, pre-clinical, vascular involvement in obese adolescents, characterized by impaired skin microcirculation, possibly reflecting a more diffuse microvascular dysfunction to other body tissues. Whether changing life style and improving weight may reverse such pre-clinical alterations remains to be established.     

Growth patterns in early childhood and cardiovascular structure and function at 4 years old: A prospective cohort study

Background and aimsChildhood overweight and obesity are lifetime risk factors for cardiovascular disease but the relationship between dynamic body mass index (BMI) change and cardiovascular structure and function in early childhood remains unclear.Methods and resultsThis cohort study consisted 525 participants with 6 distinct representative growth patterns to examine the associations between BMI growth patterns and subsequent cardiovascular structure and function at age 4. BMIs were obtained at birth, 2 and 4 years old. Cardiovascular assessments were performed, including blood pressure (BP), cardiac geometric parameters, left ventricular (LV) function, speckle-tracking, integrated backscatter analysis and carotid intima-media thickness. Compared to the stable normal BMI pattern, children with the stable overweight (OW) pattern had significantly greater LV anatomic parameters in fully adjusted models. Children with the catch-up (CU) pattern revealed a uniform trend and had poorer strain. LV diameters and integrated backscatter signals were larger for those with BMI gain and lose pattern. Children with BMI lose pattern showed improved tendency involving LV mass index and BP. Both OW and CU patterns were associated with high systolic BP [odds ratio (95% CI): OW: 3.67 (1.08, 12.47); CU: 4.24 (1.75, 10.28)]. Compared to static BMI measurements at birth, 2 and 4 years old, dynamic BMI growth patterns were more predictive of cardiovascular structure and function at 4.ConclusionsChildren with overweight-related BMI growth patterns in early childhood experienced undesirable cardiovascular functional or structural changes as early as 4 years old, indicating that early intervention is needed and potentially beneficial.     

Alterations of cholesterol synthesis and absorption in obstructive sleep apnea: Influence of obesity and disease severity

Background and aimsObstructive sleep apnea (OSA) is closely linked to obesity and related adverse metabolic changes, including dyslipidemia. However, it is not clear whether OSA is an independent contributing factor to dyslipidemia, or the observed association is a reflection of a concomitant presence of obesity. Additionally, dyslipidemia is usually evaluated through measurement of parameters of routine lipid status, while more precise evaluation of lipid homeostasis is rarely performed in OSA. In this study, we analyzed markers of cholesterol synthesis and absorption in patients with OSA with respect to the presence of obesity and the disease severity.Methods and resultsThis study enrolled 116 OSA patients. Concentrations of non-cholesterol sterols (NCS), measured by LC-MS/MS, were used as markers of cholesterol synthesis and absorption. Apnea-hypopnea index (AHI) and oxygen saturation (SaO₂) were utilized as markers of OSA severity. Serum lipid status parameters were determined by routine enzymatic methods. Markers of cholesterol synthesis were increased (P = 0.005), whilst markers of cholesterol absorption decreased (P = 0.001) in obese OSA patients. Cholesterol synthesis/absorption ratio was elevated in obese subjects (P < 0.001). Concentration of cholesterol synthesis marker lathosterol was significantly higher in subjects with severe OSA (P = 0.014) and we observed a trend of decreased cholesterol absorption in these patients. AHI was revealed as an independent determinant of lathosterol concentration (P = 0.022).ConclusionsOur results suggest that the presence of obesity and severe forms of OSA is characterized by elevated endogenous cholesterol synthesis. AHI was singled out as an independent determinant of the serum level of cholesterol synthesis marker lathosterol.