Association between sex hormones and bone age in boys aged 9-18 years from China.

This study aimed to analyse the association between sex hormones and bone age (BA) in boys aged 9-18 years, both individually and interactively, and further to explore whether nutritional status may influence this association. A retrospective analysis was performed among 1382 Chinese boys with physical measurements, sexual characteristics, BA radiographs and sex hormone indicators from February 2015 to February 2022. A total of 470 (34.0%) boys had advanced BA. BA was positively associated with estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone in both advanced and normal BA groups after adjusting for age, genetic height and body mass index. Multiple logistic regression showed that after adjusting for covariates, estradiol (odds ratio [OR] = 1.66, 95% confidence interval [CI]: 1.14-2.12), LH (OR = 1.43, 95% CI: 1.04-1.96), and testosterone (OR = 1.58, 95% CI: 1.17-2.13) were significantly associated with the increased risk of advanced BA in boys, and the association was reinforced when these hormones were interactively explored. Stratified by nutritional status, the interaction between estradiol, LH, and testosterone showed a strong association with advanced BA in boys with normal weight.

Biomarkers of intestinal permeability are associated with inflammation in metabolically healthy obesity but not normal-weight obesity.

Systemic inflammation is reported in normal-weight obesity (NWO) and metabolically healthy obesity (MHO), which may be linked to their increased cardiovascular disease (CVD) risk. Yet, drivers of this inflammation remain unclear. We characterized factors known to influence inflammatory status (i.e., intestinal permeability, adipose tissue, diet quality, microbiota), and their relationships with measured inflammation, in NWO and MHO, healthy control subjects (CON), and metabolically unhealthy obesity (MUO; N = 80; n = 20/group). Serum indicators of intestinal permeability and inflammation were assessed by ELISA and/or multiplex. Total, visceral, and percent body fat were measured with dual-energy X-ray absorptiometry (DXA). Fecal microbiota composition was assessed via 16S rRNA sequencing (n = 9-10/group). For C-reactive protein (CRP), MUO > NWO > CON (P < 0.0001). In MHO, CRP was intermediate and similar to both MUO and NWO. Lipopolysaccharide binding protein (LBP) and the ratio of LBP to soluble CD14 (sCD14) were higher in MHO and MUO vs. CON/NWO (P < 0.0001). Across correlation and regression analyses, LBP consistently displayed the strongest relationships with CRP in the entire sample (r = 0.78; ß = 0.57; P < 0.0001) and in MHO (r = 0.74; P < 0.01) but not NWO (r = 0.37; P = 0.11). Shannon index was higher in CON compared with MUO (P < 0.05) and inversely correlated with CRP in the full sample (r = -0.37; P < 0.05). These data are consistent with the notion that intestinal permeability is associated with low-grade inflammation in MHO, which could be implicated in this population's reported CVD risk.NEW & NOTEWORTHY This is the first study to our knowledge to examine biomarkers of intestinal permeability in normal-weight obesity and one of few assessing microbiota compositions in this population. Additionally, we report that individuals with metabolically healthy obesity and metabolically unhealthy obesity displayed similar evidence of intestinal permeability, which was more strongly associated with systemic inflammation than total and visceral adipose tissue mass.

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.

A systematic review of physical activity and nutritional interventions for the management of normal weight and overweight obesity.

AIMS: Normal Weight Obesity (NWO) and Overweight Obesity (OWO) are prevalent conditions, yet knowledge of management is limited. This review aims to assess the effectiveness of physical activity and nutritional interventions in the management of NWO and OWO (together defined as BMI <30 kg/m2 with raised body fat). DATA SYNTHESIS: Clinical trials including any physical activity or nutritional interventions, published between 2012 and 2022, evaluating body fat change were selected. Seven trials met inclusion criteria, including one single arm intervention, and six RCTs. A high intensity interval training intervention (high risk of bias) had the largest effect on reducing percentage body fat (MD: -6.8%, SE: 0.06). High protein intake interventions were also found to be effective (MD: -2.8%, SE: 0.27, MD: -2.0%, SE: 0.05). These three interventions led to greater increases in fat free mass. Two energy restricted interventions resulted in the highest mean weight loss (MD: -3.10 kg, SD: 0.87 (intervention only), MD: -2.90 kg, SE: 0.06), but also loss of fat free mass, resulting in low reductions in percentage body fat (MD: -1.10%, SD: 0.57 (intervention only), MD: -0.8%, SE 0.30). There was considerable heterogeneity between studies. CONCLUSIONS: There are physical activity and nutritional interventions that could be efficacious for the management of NWO and OWO. However, there was considerable heterogeneity between studies. The most promising nutritional intervention is high protein intake and the least is energy restriction (without increased protein intake). More high-quality trials are needed to evaluate interventions, and to determine the best tools to measure adiposity.

Relationship between normal weight central obesity and arterial stiffness in Chinese adults with hypertension.

BACKGROUND AND AIMS: Normal weight central obesity (NWCO) is a category of obesity that is characterized by having a normal BMI and presence of abdominal obesity. Recently, studies have reported that NWCO was associated with the cardiovascular diseases. The researches exploring the relationship between NWCO and arterial stiffness are limited. So this study intended to investigate the relationship between NWCO and arterial stiffness in Chinese adults with hypertension. METHODS AND RESULTS: This study is a sub-study of the China H-type Hypertension Registry Study. We included 8580 Chinese hypertensive patients with normal weight (18.5 kg/m2 ≤BMI <24 kg/m2). Central obesity was defined as waist-height ratio ≥0.5, and participants were categorized into two groups: NWCO and normal weight and no central obesity (NWNO). Using the brachial-ankle pulse wave conduction velocity (baPWV) assessed the arterial stiffness. Multiple linear regression analysis was used to evaluate relationship between NWCO and baPWV. Multiple logistic regression analysis was used to evaluate relationship between NWCO and arterial stiffness. Of 8580 participants, 4327 (50.4 %) were NWCO. The multiple linear regression analysis demonstrated that people with NWCO had higher baPWV value (total people: ß = 38.33, 95%CI 22.82-53.84; men: ß = 39.87, 95%CI 18.43-61.32; women: ß = 29.65, 95%CI 7.20-52.09) compared with NWNO. The baPWV ≥1800 cm/s was defined as arterial stiffness, and the multiple logistic regression analysis showed that people with NWCO associated higher arterial stiffness risk (total people: OR = 1.25, 95%CI 1.12-1.39; men: OR = 1.29, 95%CI 1.11-1.50; women: OR = 1.18, 95%CI 1.01-1.38). CONCLUSION: NWCO is significantly related to increased risk of arterial stiffness in Chinese adults with hypertension.

The Normal Weight Obesity (NWO) Problem-Prevalence and Time Changes in Children and Adolescents From Kraków (Poland).

OBJECTIVES: Normal weight obesity can be associated with an increased risk of metabolic abnormalities, systemic inflammation and mortality. The main aim of the study was to analyze the changes in the prevalence of normal weight obesity in 8-18-year-olds from Kraków (Poland) between 2010 and 2020. METHODS: The study was based on two sets of cross-sectional, school-based data obtained in 2010 and 2020. Body height, weight, and fat percentage were obtained. Body mass index was calculated, and only normal-weight individuals were included. Normal weight obesity was defined as normal BMI with adiposity >85 percentile for age and sex. RESULTS: The prevalence of normal weight obesity among Polish children and adolescents has been alarming for at least the last 10 years. Depending on the sex and age, normal weight obesity was present in more than 10% up to even more than 20% of the examined population. CONCLUSIONS: Alarming numbers of Polish children and adolescents suffer from NWO and this problem seems to be present for at least the last decade. A need for a maximally universal definition and cut-offs to diagnose normal weight obesity should also be stressed, as it will be helpful in providing the best prophylaxis and help to persons already suffering from normal weight obesity.

Comparison of novel and traditional anthropometric indices in Eastern-China adults: which is the best indicator of the metabolically obese normal weight phenotype?

BACKGROUND: People with the metabolically obese normal weight (MONW) phenotype have been confirmed to significantly increase the risk of unfavorable health consequences. This study aimed to investigate the relationships between traditional and novel anthropometric indices with the MONW phenotype and compare the predictive ability of different anthropometric indices in identifying individuals with the MONW phenotype. METHODS: This cross-sectional study involved a total of 26,332 participants aged 18 years or older with a normal weight from Nanjing, China. Sociodemographic information, biochemical measurements, and anthropometric indices were collected. The novel body fat anthropometric indices included body shape index (ABSI), body roundness index (BRI), abdominal volume index (AVI), weight-adjusted-waist index (WWI), body adiposity index (BAI), conicity index (CI), waist-hip-height ratio (WHHR), as well as traditional indices such as waist circumference (WC), hip circumference (HC), body mass index (BMI), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR).The prevalence ratio (PR) from modified poisson regression and area under the receiver-operating characteristic curve (AUC) were conducted to compare the association and predictive capacity of different obesity indicators for the MONW phenotype. All analyses were stratified by sex. RESULTS: Modified poisson regression analyses revealed that weight, WC, HC, BMI, WHR, WHtR, ABSI, BRI, AVI, WWI, BAI, CI, and WHHR were independently associated with higher risk of the MONW phenotype, regardless of whether they were treated as a continuous or categorical variable (P < 0.05). Notably, BRI demonstrated the strongest association in both men (highest quartile VS lowest quartile; PR = 3.14, 95%CI, 2.49, 3.96; P < 0.001) and women (PR = 4.63, 95%CI, 3.81, 5.62; P < 0.001). Receiver operating characteristic analysis indicated that AUC for the different anthropometric indices ranged from 0.50 to 0.80. BRI and WHtR had the largest AUC in both males (both AUC = 0.733; 95% CI, 0.717, 0.750) and females (both AUC = 0.773; 95% CI, 0.761, 0.786). The optimal cut-off points for BRI, determined by maximizing the Youden's index, were 3.102 (sensitivity: 63.2%, specificity: 36.2%) in males and 3.136 (sensitivity: 68.9%, specificity: 44.2%) in females. Moreover, BRI and WHtR exhibited the highest diagnostic accuracy in younger age groups, specifically those aged 18-34 in both sexes. CONCLUSIONS: BRI emerged as the optimal predictor and independent determinant of the MONW phenotype, regardless of gender. This association was particularly pronounced in young individuals.

Cardiorespiratory fitness and submaximal exercise dynamics in normal-weight obesity and metabolically healthy obesity.

PURPOSE: Cardiorespiratory fitness (CRF) is critical for cardiovascular health. Normal-weight obesity (NWO) and metabolically healthy obesity (MHO) may be at increased risk for cardiovascular disease, but a comparison of CRF and submaximal exercise dynamics against rigorously defined low- and high-risk groups is lacking. METHODS: Four groups (N = 40; 10/group) based on body mass index (BMI), body fat %, and metabolic syndrome (MetS) risk factors were recruited: healthy controls (CON; BMI 18.5-24.9 kg/m2, body fat < 25% [M] or < 35% [F], 0-1 risk factors), NWO (BMI 18.5-24.9 kg/m2, body fat ≥ 25% [M] or ≥ 35% [F]), MHO (BMI > 30 kg/m2, body fat ≥ 25% [M] or ≥ 35% [F], 0-1 risk factors), or metabolically unhealthy obesity (MUO; BMI > 30 kg/m2, body fat ≥ 25% [M] or ≥ 35% [F], 2 + risk factors). All participants completed a V ˙ O2peak test on a cycle ergometer. RESULTS: V ˙ O2peak was similarly low in NWO (27.0 ± 4.8 mL/kg/min), MHO (25.4 ± 6.7 mL/kg/min) and MUO (24.6 ± 10.0 mL/kg/min) relative to CON (44.2 ± 11.0 mL/kg/min) when normalized to total body mass (p's < 0.01), and adjusting for fat mass or lean mass did not alter these results. This same differential V ˙ O2 pattern was apparent beginning at 25% of the exercise test (PGroup*Time < 0.01). CONCLUSIONS: NWO and MHO had similar peak and submaximal CRF to MUO, despite some favorable health traits. Our work adds clarity to the notion that excess adiposity hinders CRF across BMI categories. CLINICALTRIALS: gov registration: NCT05008952.

Cyclomodulins-harboring Escherichia coli isolated from obese and normal-weight subjects induces intestinal dysplasia in a mouse model.

Recently, cyclomodulins have been identified in Escherichia coli (E. coli), which can induce dysplastic damage. This work aimed to determine the dysplastic activity of cyclomodulin-harboring E. coli isolated from CRC patients, obese and normal-weight subjects in a mouse model. Forty-two mice were pretreated with streptomycin, azoxymethane, and dextran sodium sulfate. Mice were infected with E. coli pks + isolated from a CRC patient, with E. coli pks + cif + isolated from obese or normal-weight subjects, or with E. coli HB101. The presence of cyclomodulin-harboring E. coli in the feces, weight loss, changes in fecal consistency, and the presence of blood in the feces were monitored and used to assess the disease activity index (DAI). After 62 days, the mice were sacrificed to evaluate the presence of intestinal polyps and dysplastic damage by histologic sections. Cyclomodulin-harboring E. coli colonized the mice; these mice exhibited weight loss and watery diarrhea, and isolated normal-weight E. coli had a higher DAI. Polyps were observed in mice infected with cyclomodulin-harboring E. coli in the ileum but to a greater extent in obese isolates. E. coli isolated from CRC showed more significant endothelial damage associated with dysplasia in the ileum in equal proportions from obese and normal-weight isolates. In conclusion, E. coli harboring cyclomodulins isolated from CRC, obesity, or normal weight can cause dysplastic damage in the ileum of mice and may be a risk factor for CRC development.

Risk Factors of Metabolic Syndrome among Normal Weight Adolescents in Lagos, Nigeria.

BACKGROUND: In the last few decades, the global disease epidemiology shift has resulted in the preponderance of noncommunicable diseases such as Metabolic Syndrome (MetS). Globally, an increasing prevalence is reported among children and adolescents in whom the condition was once rare. There is a dearth of data in Nigeria on MetS, especially among normal-weight adolescents. OBJECTIVE: To determine the prevalence and risk factors of MetS among normal-weight adolescents attending secondary schools at Mushin Local Government, Lagos. METHODS: This descriptive cross-sectional study recruited adolescents using a multi-stage sampling technique. Self-administered questionnaires were used to obtain data on socio-demographic characteristics, physical activity, medical, family and dietary history. Waist circumference (WC), was measured from the midpoint between the lowest rib and the top of the iliac crest to determine central obesity, Body mass index was calculated as weight (in kilograms) divided by height (in meters2), and the World Health Organization (WHO) growth charts were used to determine their BMI percentiles. An appropriately sized bladder cuff of a sphygmomanometer was used in obtaining the blood pressure. RESULTS: A total of 259 normal-weight adolescents were recruited. The mean ± SD of participants was 13.6 ± 2.3 years. The prevalence of MetS among participants was 2.7%. The most common cardiometabolic risk factors were central obesity and elevated blood pressure in 7.7% and 7.3% of participants. Physical activity was significantly associated with a lower prevalence of MetS. A family history of hypertension and diabetes in first-degree relatives was significantly associated with MetS. CONCLUSION: Metabolic syndrome was documented among apparently healthy normal-weight adolescent. A family history of hypertension or diabetes and physical inactivity were significantly associated with metabolic syndrome in study participants.

CONTEXTE: Au cours des dernières décennies, le changement épidémiologique mondial des maladies a entraîné la prépondérance des maladies non transmissibles telles que le syndrome métabolique (MetS). À l'échelle mondiale, une prévalence croissante est signalée chez les enfants et les adolescents chez qui cette maladie était autrefois rare. Il y a une pénurie de données au Nigeria sur le MetS, en particulier chez les adolescents de poids normal. OBJECTIF: Déterminer la prévalence et les facteurs de risque du MetS chez les adolescents de poids normal fréquentant les écoles secondaires du gouvernement local de Mushin, à Lagos. METHODES: Cette étude transversale descriptive a recruté des adolescents à l'aide d'une technique d'échantillonnage à plusieurs degrés. Des questionnaires auto-administrés ont été utilisés pour obtenir des données sur les caractéristiques sociodémographiques, l'activité physique, les antécédents médicaux, familiaux et alimentaires. Le tour de taille (WC) a été mesuré à partir du point médian entre la côte la plus basse et le haut de la crête iliaque pour déterminer l'obésité centrale. L'indice de masse corporelle a été calculé comme le poids (en kilogrammes) divisé par la taille (en mètres2), et l'indice mondial de santé Les courbes de croissance des organisations (OMS) ont été utilisées pour déterminer leurs centiles d'IMC. Un brassard vésical de taille appropriée d'un sphygmomanomètre a été utilisé pour obtenir la tension artérielle. RESULTATS: Au total, 259 adolescents de poids normal ont été recrutés. La moyenne ± écart-type des participants était de 13,6 ± 2,3 ans. La prévalence du MetS parmi les participants était de 2,7 %. Les facteurs de risque cardiométaboliques les plus courants étaient l'obésité centrale et l'hypertension artérielle chez 7,7 % et 7,3 % des participants. L'activité physique était significativement associée à une prévalence plus faible du MetS. Des antécédents familiaux d'hypertension et de diabète chez des parents au premier degré étaient significativement associés au MetS. CONCLUSION: Un syndrome métabolique a été documenté chez des adolescents de poids normal apparemment en bonne santé. Des antécédents familiaux d'hypertension ou de diabète et l'inactivité physique étaient significativement associés au syndrome métabolique chez les participants à l'étude. MOTS CLES: Syndrome métabolique ; Adolescents ; Poids normal; facteurs de risque cardiométaboliques.

Consumption of a Byproduct of Chia Seed Oil Extraction by Cold Pressing Ameliorates Cardiovascular Risks Factors in an Experimental Model of Metabolically Unhealthy Normal Weight.

The byproduct of Salvia hispanica (chia) seed oil extraction by cold pressing, also known as expeller, possesses a high nutritional value. It is rich in proteins, fibers, minerals, and has a residual oil content of 7-11%, which is rich in omega 3 linolenic acid (ALA). However, this byproduct has been historically undervalued. Thus, the aim of current work was to study the effects of consuming of a rich in chia expeller diet on a rabbit model of metabolically unhealthy normal weight to validate their use as a functional food. Rabbits were fed different diets for a period of 6 weeks: a standard diet (CD), a high-fat diet (HFD), a rich in expeller CD (Exp-CD) and a rich in expeller HFD (Exp-HFD). The Exp-HFD attenuated the rise in basal glucose, TyG index, triglycerides, cholesterol and non-HDL cholesterol induced by the HFD. Both rich in expeller diets reduced mean arterial blood pressure (MAP) and increase liver and fat ALA levels compared to their respective controls. Furthermore, the angiotensin converting enzyme (ACE) activity was lower in the lungs of animals fed on rich in expeller diets compared to their respective controls. In vitro studies showed that ALA inhibited ACE activity. The evaluation of vascular reactivity revealed that rich in expeller diets improved angiotensin II affinity and reduced contractile response to noradrenaline. In conclusion, the consumption of rich in expeller diets showed beneficial effects in preventing cardiovascular risk factors such as insulin resistance, dyslipidemia and MAP. Therefore, its use as functional ingredient holds significant promise.

Ramadan Intermittent Fasting and Plasma Volume Variations in Individuals with Different Body Weights.

Background: There is increasing awareness of the physiological effects of Ramadan intermittent fasting (RIF) in obese subjects. However, there are no data on the effects of RIF on plasma volume changes (ΔPV) in individuals with different body weights. Background and Objectives: This study investigated the effects of RIF on ΔPV in normal-weight (NW) and overweight (OW) adult men, and adult men with obesity (OB) and severe obesity (SO). Materials and Methods: Thirty-two male subjects (32) were divided into four groups (n = 8 per group) according to their body mass index (BMI): normal weight (NW) (BMI < 25 kg/m2; age = 27.4 ± 3.8), overweight (OW) (BMI between 25 and 29.9 kg/m2; age = 26.8 ± 3.7), obese subjects (OB) (BMI between 30 and 34.9 kg/m2; age = 25.6 ± 2.9), and severely obesity (SO) (BMI between 35 and 40 kg/m2; age = 24.0 ± 4.1). Blood samples were collected for 24 h on 4 different occasions, at T0 before the start of the Ramadan month, at T1 15 days after the start of Ramadan, at T2 one day after the end of Ramadan, and at T3 on the 21st day after the end of Ramadan to determine ΔPV. All groups completed their fasting rituals for the 30 days of Ramadan. Results: A significant group × time effect occurred for body mass (p = 0.001; ES = 0.53), BMI (p = 0.001; ES = 0.53), and body fat percentage (p = 0.001; ES = 0.52). Post hoc tests indicated reductions in body mass in OB and SO at T1 (p = 0.03; ES = 0.21 and p = 0.002; ES = 0.12) and T2 (p = 0.03; ES = 0.31 and p = 0.02; ES = 0.23), reductions in BMI in OB and SO at T1 (p = 0.04; ES = 0.35 and p = 0.03; ES = 0.42) and T2 (p = 0.03; ES = 0.52 and p = 0.005; ES = 0.48), and reductions in body fat percentage only in OB AT T1 (p = 0.002; ES = 0.31) and T2 (p = 0.001; ES = 0.17). A significant group × time effect occurred for hematocrit (p = 0.02; ES = 0.34), hemoglobin (p = 0.01; ES = 0.35), and ΔPV (p = 0.02; ES = 0.18). Post hoc tests indicated increases in hematocrit in OB at T2 (p = 0.03; ES = 0.36) and hemoglobin in OB and SO at T1 (p = 0.03; ES = 0.35 and p = 0.002; ES = 0.32) and T2 (p = 0.003; ES = 0.21 and p = 0.002; ES = 0.33). There were also increases in ΔPV in OB at T1 and T2 (p = 0.002; ES = 0.25 and p = 0.003; ES = 0.22) and in SO only at T2 (p = 0.02; ES = 0.37). Contrast analysis indicated that NW was significantly lower than the grand mean of OW, Ob, and SO for all anthropometric and PVV variables (all p < 0.05). Conclusions: The effects of RIF on ΔPV and anthropometric characters was greater in obese individuals compared to normal-weight and overweight participants, suggesting that the improvements in body composition and ΔPV produced by RIF could positively influence obesity.

Strength training is more effective than aerobic exercise for improving glycaemic control and body composition in people with normal-weight type 2 diabetes: a randomised controlled trial.

AIMS/HYPOTHESIS: Type 2 diabetes in people in the healthy weight BMI category (<25 kg/m2), herein defined as 'normal-weight type 2 diabetes', is associated with sarcopenia (low muscle mass). Given this unique body composition, the optimal exercise regimen for this population is unknown. METHODS: We conducted a parallel-group RCT in individuals with type 2 diabetes (age 18-80 years, HbA1c 47.5-118.56 mmol/mol [6.5-13.0%]) and BMI <25 kg/m2). Participants were recruited in outpatient clinics or through advertisements and randomly assigned to a 9 month exercise programme of strength training alone (ST), aerobic training alone (AER) or both interventions combined (COMB). We used stratified block randomisation with a randomly selected block size. Researchers and caregivers were blinded to participants' treatment group; however, participants themselves were not. Exercise interventions were conducted at community-based fitness centres. The primary outcome was absolute change in HbA1c level within and across the three groups at 3, 6 and 9 months. Secondary outcomes included changes in body composition at 9 months. Per adherence to recommended exercise protocol (PP) analysis included participants who completed at least 50% of the sessions. RESULTS: Among 186 individuals (ST, n=63; AER, n=58; COMB, n=65) analysed, the median (IQR) age was 59 (53-66) years, 60% were men and 83% were Asian. The mean (SD) HbA1c level at baseline was 59.6 (13.1) mmol/mol (7.6% [1.2%]). In intention-to-treat analysis, the ST group showed a significant decrease in HbA1c levels (mean [95% CI] -0.44 percentage points [-0.78, -0.12], p=0.002), while no significant change was observed in either the COMB group (-0.35 percentage points, p=0.13) or the AER group (-0.24 percentage points, p=0.10). The ST group had a greater improvement in HbA1c levels than the AER group (p=0.01). Appendicular lean mass relative to fat mass increased only in the ST group (p=0.0008), which was an independent predictor of HbA1c change (beta coefficient -7.16, p=0.01). Similar results were observed in PP analysis. Only one adverse event, in the COMB group, was considered to be possibly associated with the exercise intervention. CONCLUSIONS/INTERPRETATION: In normal-weight type 2 diabetes, strength training was superior to aerobic training alone, while no significant difference was observed between strength training and combination training for HbA1c reduction. Increased lean mass relative to decreased fat mass was an independent predictor of reduction in HbA1c level. TRIAL REGISTRATION: ClinicalTrials.gov NCT02448498. FUNDING: This study was funded by the National Institutes of Health (NIH; R01DK081371).

Left atrial epicardial adipose tissue exacerbates electrical conduction disturbance in normal-weight patients undergoing pulmonary vein isolation for atrial fibrillation.

INTRODUCTION: Epicardial adipose tissue (EAT) exacerbates both electrical and structural remodeling in obese atrial fibrillation (AF) patients, but the impacts of EAT on atrial arrhythmogenicity remain unclear in normal-weight AF patients. Therefore, we sought to investigate this issue using electroanatomic mapping. METHODS AND RESULTS: We enrolled drug-refractory 105 paroxysmal AF patients in the normal body mass index range (18.5-24.9 kg/m2 ), who had undergone electroanatomic mapping after pulmonary vein isolation (PVI). One day before PVI, we assessed P-wave duration in a 12-lead electrocardiogram and left atrial (LA)-EAT volumes using contrast-enhanced computed tomography. The patients were divided into two groups based on the median LA-EAT volume (16.0 ml); the high LA-EAT group (≥16.0 ml, n = 53) and low LA-EAT group (<16.0 ml, n = 52). We compared P-wave duration, LA conduction velocity and bipolar voltage, the presence of low-voltage zone (<0.5 mV), and LA volume index on echocardiography between the two groups. The LA bipolar voltage, low-voltage zone, and LA volume index were not different between the high and low LA-EAT groups. However, P-wave duration was significantly longer in the high group than in the low group (p < .001). Additionally, the LA conduction velocity was significantly more depressed in the high group than in the low group (p < .001). Multivariate linear regression analysis revealed that LA-EAT volume was correlated with P-wave duration (ß = .367, p < .001) and conduction velocity (ß = -.566, p < .001), respectively. CONCLUSIONS: Increased LA-EAT volumes were associated with electrical conduction disturbance after PVI in normal-weight patients with AF. P-wave duration may be a clinically useful predictor of LA-EAT.

Normal-weight visceral obesity promotes a higher 10-year atherosclerotic cardiovascular disease risk in patients with type 2 diabetes mellitus-a multicenter study in China.

BACKGROUND: Visceral obesity is associated with high cardiovascular events risk in type 2 diabetes mellitus (T2DM). Whether normal-weight visceral obesity will pose a higher atherosclerotic cardiovascular disease (ASCVD) risk than body mass index (BMI)-defined overweight or obese counterparts with or without visceral obesity remains unclear. We aimed to explore the relationship between general obesity and visceral obesity and 10-year ASCVD risk in patients with T2DM. METHODS: Patients with T2DM (6997) who satisfied the requirements for inclusion were enrolled. Patients were considered to have normal weight when 18.5 kg/m2 ≤ BMI < 24 kg/m2; overweight when 24 kg/m2 ≤ BMI < 28 kg/m2; and obesity when BMI ≥ 28 kg/m2. Visceral obesity was defined as a visceral fat area (VFA) ≥ 100 cm2. Patients were separated into six groups based on BMI and VFA. The odd ratios (OR) for a high 10-year ASCVD risk for different combinations of BMI and VFA were analysed using stepwise logistic regression. Receiver operating characteristic (ROC) curves for diagnosing the high 10-year ASCVD risk were constructed, and areas under the ROC curves were estimated. Potential non-linear relationships between VFA levels and high 10-year ASCVD risk were examined using restricted cubic splines (knot = 4). Multilinear regression was used to identify factors affecting VFA in patients with T2DM. RESULTS: In patients with T2DM, subjects with normal-weight visceral obesity had the highest 10-year ASCVD risk among the six groups, which had more than a 2-fold or 3-fold higher OR than those who were overweight or obese according to BMI but did not have visceral obesity (all P < 0.05). The VFA threshold for high 10-year ASCVD risk was 90 cm2. Multilinear regression showed significant differences in the effect of age, hypertension, drinking, fasting serum insulin, fasting plasma glucose, 2 h postprandial C-peptide, triglyceride, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol on VFA in patients with T2DM (all P < 0.05). CONCLUSIONS: T2DM patients with normal-weight visceral obesity had a higher 10-year ASCVD risk than BMI-defined overweight or obese counterparts with or without visceral obesity, which should initiate standardised management for ASCVD primary prevention.

Normal-weight central obesity and risk of cardiovascular and microvascular events in adults with prediabetes or diabetes: Chinese and British cohorts.

OBJECTIVE: To investigate the relationship between body fat distribution and risk of cardiometabolic and microvascular events among individuals with prediabetes or diabetes with normal body mass index (BMI). METHODS: A total of 17,232 participants with prediabetes or diabetes from UK Biobank (UKB) with 12-year follow-up and 499 diabetic participants from China with 2-year follow-up with normal BMI were included. Anthropometric measurements of waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR), and body fat composition assessment of trunk-to-leg fat ratio (TLFR) were obtained. Outcomes included incident all-cause and cardiovascular mortality and macrovascular and microvascular diseases. RESULTS: In British cohort, participants with central obesity defined by WHR had 27%-54% higher risk of incident all-cause mortality (hazard ratio (HR) 1.42, 95% confidence interval (CI): 1.23-1.64), cardiovascular mortality (HR 1.54 [1.15-2.07]), myocardial infarction (HR = 1.43 [1.15, 1.78]), stroke (HR 1.26 [0.90, 1.75]), heart failure (HR = 1.27 [1.00, 1.61]), diabetic nephropathy (HR 1.33 [1.07, 1.65]), and diabetic retinopathy (DR) (HR = 1.48 [1.12, 1.96]) than those without obesity. Central obesity defined by WC and WHtR was associated with 40%-44% and 23%-98% higher risks of developing diabetic events, respectively. In the Chinese cohort, individuals with abdominal obesity, defined by WC (HR 1.44) or WHtR (HR 1.43) but not by WHR, carried more than 40% higher risk of developing DR than those without it. Higher TLFR carried 1.30-2.85 times higher risk of CVD and microvascular diseases among the dysglycemic population. CONCLUSIONS: Body fat distribution diseases among individuals with prediabetes or diabetes are associated with an increased risk of cardiometabolic and microvascular diseases independent of BMI.

Dietary determinants of healthy/unhealthy metabolic phenotype in individuals with normal weight or overweight/obesity: a systematic review.

Objectives: Nutritional factors are amongst the major determinants in the onset and development of obesity and metabolic complications. Nevertheless, the dietary determinants of metabolic health are not completely elucidated. The aim of this systematic review is to investigate nutritional and dietary factors that may contribute to metabolic heterogeneity in individuals with obesity or normal weight. Methods: A literature search was performed in PubMed, Scopus, EMBASE, and google scholar databases until August 2021, to locate studies that examined metabolic health and its association with intakes of specific foods or food groups, nutrient intakes or status, as well as adherence to certain dietary patterns. Two researchers had independently screened titles and abstracts, examined full-text studies, conducted data extraction, and evaluated their quality using the Newcastle-Ottawa Scale. Results: Twenty-seven studies, with a total of 39518 subjects, were included. Of these studies, 11 articles evaluated the association between different dietary patterns and metabolic phenotypes, while 15 had investigated the association of single food/nutrients intakes or nutrient status with metabolic phenotype, and one paper evaluated the association of dietary inflammatory index with metabolic health. The findings of these studies propose that healthy dietary patterns such as the Mediterranean pattern, Dietary Approaches to Stop Hypertension, and population-derived patterns (such as the "Healthy" and "Fruit and vegetable" patterns) were associated with higher odds of the metabolically healthy phenotype. Higher intakes of fruits, vegetables, dairy products, coffee/tea, vitamin D, magnesium, and flavonoids, were suggested to lower the risk of developing metabolically unhealthy phenotype, while, higher consumption of saturated fat, carbohydrate and sugar-sweetened beverages, fast foods, organ meats, and a pro-inflammatory diet increased the risk. Conclusion: Results from published studies, which were mostly cross-sectional, suggest that higher adherence to unhealthier dietary patterns, characterized by the consumption of refined and processed foods, was associated with a lower likelihood of having a healthy metabolic phenotype, while the opposite was observed for healthier dietary patterns. Findings may be used in developing nutritional strategies aimed at improving metabolic health in the population.

Association of normal-weight central obesity with hypertension: a cross-sectional study from the China health and nutrition survey.

BACKGROUND: Central obesity is associated with an increased risk of hypertension in the general population. However, little is known regarding the potential relationship between central obesity and the risk of hypertension among adults with a normal body mass index (BMI). Our aim was to assess the risk of hypertension among individuals with normal weight central obesity (NWCO) in a large Chinese population. METHODS: We identified 10 719 individuals aged 18 years or older from the China Health and Nutrition Survey 2015. Hypertension was defined by blood pressure measurements, physician diagnosis, or the use of antihypertensive treatment. Multivariable logistic regression was used to assess the association of obesity patterns, defined by BMI, waist circumference (WC) and waist hip ratio (WHR), with hypertension after adjusting for confounding factors. RESULTS: The patients' mean age was 53.6 ± 14.5 years, and 54.2% were women. Compared with individuals with a normal BMI but no central obesity, subjects with NWCO had a greater risk of hypertension (WC: OR, 1.49, 95% CI 1.14-1.95; WHR: OR, 1.33, 95% CI 1.08-1.65). Overweight-obese subjects with central obesity demonstrated the highest risk of hypertension after adjustment for potential confounders (WC: OR, 3.01, 95% CI 2.59-3.49; WHR: OR, 3.08, CI 2.6-3.65). Subgroup analyses showed that the combination of BMI with WC had similar findings to the overall population except for female and nonsmoking persons; when BMI was combined with WHR, a significant association of NWCO with hypertension was observed only in younger persons and nondrinkers. CONCLUSIONS: Central obesity, as defined by WC or WHR, is associated with an increased risk of hypertension in Chinese adults with normal BMI, highlighting the need to combine measures in obesity-related risk assessment.

Effects of Weight Gain During Pregnancy in Normal-Weight Women on Changes in the Gut Microbiota of Pregnant Women in the Third Trimester.

With the improvement of living standards and the lack of nutrition awareness during pregnancy, the phenomenon of excessive weight gain (EWG) of pregnancy is increasing. EWG during pregnancy has profound effects on the health of mother and offspring. The role of intestinal flora in regulating metabolic diseases has gradually attracted attention in recent years. The study explored the effect of EWG during pregnancy on gut microbiota, and analyzed the diversity and composition of gut microbiota in pregnant women in third trimester. Fecal samples were collected and divided into: insufficient weight gain (IWG) during pregnancy (group A1, N = 4), and appropriate weight gain (AWG) during pregnancy (group A2, N = 9), and EWG during pregnancy (N = 9 in A3 group). MiSeq high-throughput sequencing technology and bioinformatics analysis were introduced to investigate relationship of gestational weight gain and maternal gut microbiota. General data analysis showed that gestational weight gain and delivery mode have significant differences among the three groups. The overall level and diversity of intestinal microbiota in A1 and A3 group were increased. Composition of gut microbiota has no difference among three groups at the phylum level, but species of gut microbiota were different. Alpha diversity index analysis showed that the richness of A3 group was increased versus A2 group. EWG during pregnancy affects the abundance and proportion of gut microbiota in the third trimester. Therefore, maintaining moderate weight gain during pregnancy helps to maintain intestinal homeostasis.

Ultra-processed foods consumption and the risk of metabolically unhealthy phenotype in normal-weight and overweight/obese adults: a prospective investigation.

This study investigated the association between ultra-processed foods (UPF) and the risk of metabolically unhealthy normal weight (MUNW) and metabolically unhealthy overweight/obese (MUO). We included 512 normal-weight and 787 overweight/obese adults with a metabolically healthy phenotype from the Tehran and Lipid Glucose Study, who were followed from the third (baseline) to the sixth study examinations. Each 10% increase in energy intake from UPF was related to a 54% (95% CI = 21-96%) and 2% (95% CI = 1-3%) higher risk of MUNW and MUO, respectively. The risk of MUNW was significantly higher in quartile 4 compared to quartile 1. The restricted cubic splines suggested that the risk of MUNW increases monotonically when UPF accounts for at least 20% of energy intake. No non-linear association was observed between UPF and the risk of MUO. Energy intake from UPF was positively related to the risk of MUNW and MUO.