The neutrophil to lymphocyte ratio (NLR) positively correlates with the presence and severity of metabolic syndrome in obese adults, but not in obese children/adolescents.

Metabolic syndrome (MetS) associated with obesity is a pathological condition increasing worldwide. Recent studies have demonstrated that the neutrophil to lymphocyte ratio (NLR) can be successfully used to stage MetS in obese adults. The aim of the study was to evaluate NLR values in 552 children/adolescents (M 219, F 333; 14.8 [12.9-16.3] years) and 231 adults (M 88, F 143; 52.3 [36.4-63.3] years) with morbid obesity, subdivided into subgroups according with the presence or absence of MetS. Adult patients with obesity showed a higher prevalence of MetS compared to the pediatric population (71% vs 26%), associated with a greater number of subjects with 3 and 4-5 altered components for MetS. NLR was higher (P-value = 0.041) in adults with MetS compared with those without. NLR values also positively correlated with the severity grade of the syndrome (P-value = 0.032). By contrast, in pediatric subjects with obesity with MetS, NLR values were comparable with those recorded in subjects without MetS (P-value = 0.861), no correlation being found with MetS severity (P-value = 0.441). Our study confirms the importance of NLR as an inflammatory indicator associated with MetS in adult subjects with severe obesity, while it excludes a similar role in children/adolescents.

Ceramide Risk Score in the Evaluation of Metabolic Syndrome: An Additional or Substitutive Biochemical Marker in the Clinical Practice?

Ceramide risk score (CERT1, ceramide test 1), based on specific ceramides (Cers) and their corresponding ratios in the plasma, has been reported as a promising biochemical marker for primary and secondary prediction of cardiovascular disease (CVD) risk in different populations of patients. Thus far, limited attention has been paid to metabolic syndrome, a condition considered at high CVD risk. The aim of the present study was to evaluate CERT1 in a group of obese subjects without (OB-MetS-) and with (OB-MetS+) metabolic syndrome (according to the International Diabetes Federation (IDF) diagnostic criteria), compared to an age- and sex-matched normal-weight (NW) group. In all participants, plasma levels of Cer 16:0, Cer 18:0, Cer 24:1, and Cer 24:0 were measured, and the corresponding ratios Cer 16:0/24:0, Cer 18:0/24:0, and Cer 24:1/24:0 were calculated together with CERT1. Subjects with obesity showed higher CERT1 values than the NW group (p < 0.05), with no difference between OB-MetS- and OB-MetS+ groups. Waist circumference (WC), homeostatic model assessment of insulin-resistance (HOMA-IR) (surrogates of IDF diagnostic criteria for metabolic syndrome), and C reactive protein (CRP) (a marker of inflammation) were predictors of CERT1 (p < 0.05), with the contribution of the other IDF criteria such as arterial hypertension and dyslipidemia being negligible. Adjustment for WC resulted in a loss of the difference in CERT1 between OB-MetS- and NW subjects, with the combination of WC and HOMA-IR or CRP as covariates being necessary to yield the same effect for the difference in CERT1 between OB-MetS+ and NW subjects. Importantly, an association was found between CERT1 and vascular age (VA) (p < 0.05). Proportions of NW, OB-MetS- and OB-MetS+ subjects appeared to be distributed according to the CERT1-based risk groups (i.e., low, moderate, increased, and high risk; p < 0.05), with some OB-MetS- subjects included in the increased/high-risk group and some OB-MetS+ in the low/moderate-risk one. In conclusion, the clinical diagnosis of metabolic syndrome seems to be inaccurate to assess CVD risk in the obese population; however, further studies are needed before considering CERT1 as an additional or substitutive biochemical marker in clinical practice.

Identification of a Specific Plasma Sphingolipid Profile in a Group of Normal-Weight and Obese Subjects: A Novel Approach for a "Biochemical" Diagnosis of Metabolic Syndrome?

Metabolic syndrome is nosographically defined by using clinical diagnostic criteria such as those of the International Diabetes Federation (IDF) ones, including visceral adiposity, blood hypertension, insulin resistance and dyslipidemia. Due to the pathophysiological implications of the cardiometabolic risk of the obese subject, sphingolipids, measured in the plasma, might be used to biochemically support the diagnosis of metabolic syndrome. A total of 84 participants, including normal-weight (NW) and obese subjects without (OB-SIMET-) and with (OB-SIMET+) metabolic syndrome, were included in the study, and sphingolipidomics, including ceramides (Cer), dihydroceramides (DHCer), hexosyl-ceramides (HexCer), lactosyl-ceramides (LacCer), sphingomyelins (SM) and GM3 ganglosides families, and sphingosine-1-phosphate (S1P) and its congeners, was performed in plasma. Only total DHCers and S1P were significantly higher in OB-SIMET+ than NW subjects (p < 0.05), while total Cers decreased in both obese groups, though statistical significance was reached only in OB-SIMET- (vs. NW) subjects (p < 0.05). When considering the comparisons of the single sphingolipid species in the obese groups (OB-SIMET- or OB-SIMET+) vs. NW subjects, Cer 24:0 was significantly decreased (p < 0.05), while Cer 24:1, DHCer 16:0, 18:0, 18:1 and 24:1, and SM 18:0, 18:1 and 24:1 were significantly increased (p < 0.05). Furthermore, taking into account the same groups for comparison, HexCer 22:0 and 24:0, and GM3 22:0 and 24:0 were significantly decreased (p < 0.05), while HexCer 24:1 and S1P were significantly increased (p < 0.05). After having analyzed all data via a PLS-DA-based approach, the subsequent determination of the VIP scores evidenced the existence of a specific cluster of 15 sphingolipids endowed with a high discriminating performance (i.e., VIP score > 1.0) among the three groups, including DHCer 18:0, DHCer 24:1, Cer 18:0, HexCer 22:0, GM3 24:0, Cer C24:1, SM 18:1, SM 18:0, DHCer 18:1, HexCer 24:0, SM 24:1, S1P, SM 16:0, HexCer 24:1 and LacCer 22:0. After having run a series of multiple linear regressions, modeled by inserting each sphingolipid having a VIP score > 1.0 as a dependent variable, and waist circumference (WC), systolic/diastolic blood pressures (SBP/DBP), homeostasis model assessment-estimated insulin resistance (HOMA-IR), high-density lipoprotein (HDL), triglycerides (TG) (surrogates of IDF criteria) and C-reactive protein (CRP) (a marker of inflammation) as independent variables, WC was significantly associated with DHCer 18:0, DHCer 24:1, Cer 18:0, HexCer 22:0, Cer 24:1, SM 18:1, and LacCer 22:0 (p < 0.05); SBP with Cer 18:0, Cer 24:1, and SM 18:0 (p < 0.05); HOMA-IR with DHCer 18:0, DHCer 24:1, Cer 18:0, Cer 24:1, SM 18:1, and SM 18:0 (p < 0.05); HDL with HexCer 22:0, and HexCer 24:0 (p < 0.05); TG with DHCer 18:1, DHCer 24:1, SM 18:1, and SM 16:0 (p < 0.05); CRP with DHCer 18:1, and SP1 (p < 0.05). In conclusion, a cluster of 15 sphingolipid species is able to discriminate, with high performance, NW, OB-SIMET- and OB-SIMET+ groups. Although (surrogates of) the IDF diagnostic criteria seem to predict only partially, but congruently, the observed sphingolipid signature, sphingolipidomics might represent a promising "biochemical" support for the clinical diagnosis of metabolic syndrome.

Complete Blood Count-Derived Inflammation Indexes Are Useful in Predicting Metabolic Syndrome in Children and Adolescents with Severe Obesity.

Background: Childhood obesity is a globally increasing pathological condition leading to long-term health issues such as cardiovascular diseases and metabolic syndrome (MetS). This study aimed to determine the clinical value of the Complete Blood Count-derived inflammation indexes Monocyte/HDL-C ratio (MHR), Lymphocyte/HDL-C ratio (LHR), Neutrophil/HDL-C ratio (NHR), and System Inflammation Response Index (SIRI) to predict the presence of metabolic syndrome and its association with cardiovascular risk markers (HOMA-IR, TG/HDL-C, and non-HDL-C) in children and adolescents with obesity. Methods: The study included a total of 552 children/adolescents with severe obesity (BMI: 36.4 [32.7-40.7] kg/m2; 219 males, 333 females; age: 14.8 [12.9-16.3] years), who were further subdivided based on the presence or absence of metabolic syndrome (MetS+ and MetS respectively). Results: The MHR, LHR, and NHR indexes (p < 0.0001), but not SIRI (p = 0.524), were significantly higher in the MetS+ compared to the MetS- subgroup, showing a positive correlation with the degree of MetS severity (p < 0.0001). Furthermore, MHR, LHR, and NHR were positively associated with cardiometabolic risk biomarkers (HOMA-IR: MHR p = 0.000, LHR p = 0.001, NHR p < 0.0001; TG/HDL-C: MHR, LHR, NHR p < 0.000; non-HDL-C: MHR, LHR p < 0.0001, NHR p = 0.000). Finally, the ROC curve analysis demonstrated that among the analyzed indexes, only MHR, LHR, and NHR had diagnostic value in distinguishing MetS patients among children and adolescents with obesity (MHR: AUC = 0.7045; LHR: AUC = 0.7205; NHR: AUC = 0.6934; p < 0.0001). Conclusions: In conclusion, the MHR, LHR, and NHR indexes, but not the SIRI index, can be considered useful tools for pediatricians to assess the risk of MetS and cardiometabolic diseases in children and adolescents with obesity and to develop multidisciplinary intervention strategies to counteract the widespread disease.

The Lipid Accumulation Product Index (LAP) and the Cardiometabolic Index (CMI) Are Useful for Predicting the Presence and Severity of Metabolic Syndrome in Adult Patients with Obesity.

Background: The concomitant occurrence of obesity and metabolic syndrome (MetS) causes a significant worsening of a patient's clinical condition. Indexes that employ anthropometric measurements alone or associated with blood parameters have been investigated for their ability to identify MetS. This study aimed to evaluate the diagnostic accuracy of three of these indexes, the body adiposity index (BAI), the lipid accumulation product index (LAP), and the cardiometabolic index (CMI), in a cohort of 1912 adult subjects with obesity. Methods and Results: MetS was found in 62.3% of the enrolled subjects, with a higher prevalence in males (72.5%) than females (60.9%). Receiver operating characteristic (ROC) analysis was used to define which index performed better. The BAI was found to be the lowest-performing index, with an ROC area of 0.50, a sensitivity of 30.31%, a specificity of 74.48%, and a likelihood ratio of 1.19. On the contrary, the LAP and the CMI showed a comparable ROC area of 0.82. The LAP had a sensitivity of 63.06%, a specificity of 86.55%, and a likelihood ratio of 4.69, while the CMI had a sensitivity of 67.59%, specificity of 81.55%, and a likelihood ratio of 3.66. The analysis was also performed in the group divided into males and females, with overlapping results. Conclusions: The LAP and the CMI performed better than the BAI in detecting MetS both in the general population with obesity and in the male/female subgroups. In the future, it will be important to validate these useful diagnostic tools in order to employ them in clinical practices.

Complete Blood Count (CBC)-Derived Inflammation Indexes Are Useful in Predicting Metabolic Syndrome in Adults with Severe Obesity.

Background: Metabolic syndrome (MetS) is a globally increasing pathological condition. Recent research highlighted the utility of complete blood count-derived (CBC) inflammation indexes to predict MetS in adults with obesity. Methods: This study examined CBC-derived inflammation indexes (NHR, LHR, MHR, PHR, SIRI, AISI, and SII) in 231 adults with severe obesity (88 males, 143 females; age: 52.3 [36.4-63.3] years), divided based on the presence (MetS+) or absence (MetS-) of MetS. The relationships between the indexes and the cardiometabolic risk biomarkers HOMA-IR, TG/HDL-C, and non-HDL-C were also evaluated. Results: Individuals with metabolic syndrome (MetS+) had significantly higher values of MHR, LHR, NHR, PHR, and SIRI than those without (MetS-) (MHR and NHR: p < 0.0001; LHR: p = 0.001; PHR: p = 0.011; SIRI: p = 0.021). These values were positively correlated with the degree of MetS severity. Logistic regression (MHR and NHR: p = 0.000; LHR: p = 0.002; PHR: p = 0.022; SIRI: p = 0.040) and ROC analysis (MHR: AUC = 0.6604; LHR: AUC = 0.6343; NHR: AUC = 0.6741; PHR: AUC = 0.6054; SIRI: AUC = 0.5955) confirmed the predictive potential of CBC-derived inflammation indexes for MetS in individuals with severe obesity. CBC-derived inflammation indexes also correlated with HOMA-IR (MHR, LHR, and NHR: p < 0.0001; PHR: p < 0.001; SIRI: p = 0.000) and TG/HDL-C (MHR, LHR, NHR and PHR: p < 0.0001; SIRI: p = 0.006). Conclusions: In conclusion, this study validates CBC-derived inflammation indexes for predicting MetS in individuals with severe obesity. The relationships between these indexes and cardiometabolic risk factors can enable clinicians to better grade MetS associated with obesity.

Metabolomic profiling of Prader-Willi syndrome compared with essential obesity.

Introduction: Prader-Willi syndrome (PWS) is a rare disease, which shows a peculiar clinical phenotype, including obesity, which is different from essential obesity (EOB). Metabolomics might represent a valuable tool to reveal the biochemical mechanisms/pathways underlying clinical differences between PWS and EOB. The aim of the present (case-control, retrospective) study was to determine the metabolomic profile that characterizes PWS compared to EOB. Methods: A validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) targeted metabolomic approach was used to measure a total of 188 endogenous metabolites in plasma samples of 32 patients with PWS (F/M = 23/9; age: 31.6 ± 9.2 years; body mass index [BMI]: 42.1 ± 7.0 kg/m2), compared to a sex-, age- and BMI-matched group of patients with EOB (F/M = 23/9; age: 31.4 ± 6.9 years; BMI: 43.5 ± 3.5 kg/m2). Results: Body composition in PWS was different when compared to EOB, with increased fat mass and decreased fat-free mass. Glycemia and HDL cholesterol were higher in patients with PWS than in those with EOB, while insulinemia was lower, as well as heart rate. Resting energy expenditure was lower in the group with PWS than in the one with EOB, a difference that was missed after fat-free mass correction. Carrying out a series of Tobit multivariable linear regressions, adjusted for sex, diastolic blood pressure, and C reactive protein, a total of 28 metabolites was found to be associated with PWS (vs. non-PWS, i.e., EOB), including 9 phosphatidylcholines (PCs) ae, 5 PCs aa, all PCs aa, 7 lysoPCs a, all lysoPCs, 4 acetylcarnitines, and 1 sphingomyelin, all of which were higher in PWS than EOB. Conclusions: PWS exhibits a specific metabolomic profile when compared to EOB, suggesting a different regulation of some biochemical pathways, fundamentally related to lipid metabolism.

Measured vs estimated resting energy expenditure in children and adolescents with obesity.

Pediatric obesity requires early targeted interventions consisting mainly of a low-calorie diet prescribed based on resting energy expenditure (REE), often estimated through predictive equations. The aim of this study was to define the prevalence of "hypo-", "normo-" and "hypermetabolic" in a large cohort of children and adolescents with obesity by comparing measured and estimated REE and to evaluate the characteristics related to these metabolic statuses in both males and females. The study population was divided into the three subgroups by comparing REE measured using indirect calorimetry and estimated using the Molnar equation, and subsequently analyzed. The majority of the participants (60.6%) were normometabolic, 25.5% hypermetabolic and 13.9% hypometabolic. No significant differences in age, Tanner stage, systolic blood pressure, or the presence of metabolic syndrome were found. However, the hypermetabolic subgroup was significantly lighter, shorter, with lower hip and waist circumferences, had a greater amount of fat-free mass and lower fat mass, significantly lower diastolic blood pressure, and a significantly higher frequency of non-alcoholic liver steatosis. Pediatric obesity is more associated with normal or increased REE than with a hypometabolic condition, suggesting that estimation of energy expenditure with predictive equations is still inadequate for prescribing the appropriate diet plan.

The psychosocial functioning in adolescents with severe obesity evaluated throughout the strengths and difficulties questionnaire (SDQ): a preliminary report.

Introduction: Childhood obesity is associated with poor psychological adjustment. Severely impacts the psychological adjustment of young patients. To assess the psychological functioning of children and adolescents, several questionnaires have been proposed so far. Although the Strengths and Difficulties Questionnaire (SDQ) is one of the most well-used tools, its application in obesity research is scarce. The study is aimed at assessing the psychological profile of a sample of Italian children and adolescents seeking an in-hospital multidisciplinary body weight reduction program for obesity, via SDQ. Methods: One hundred and fourteen consecutive Italian children and adolescents with obesity (43 males/71 females, age range: 11-17 years, mean age ± SD: 15.1 ± 1.66, body mass index-BMI ± SD: 37.4 ± 6.13 kg/m2), were recruited at the Division of Auxology, Istituto Auxologico Italiano IRCCS, Piancavallo (VB). Results: Obese Females reported worse conditions of emotional symptoms (t = 5.48; p < 0.001) and peer problems (t = 2.34; p = 0.021), as well as higher which were associated with greater scores of pro-social behaviors than obese males (t = 3.07; p = 0.003). The total difficulties score (t = 4.00; p < 0.001) and the total impact score (t = 4.53; p < 0.001) were significantly higher in females than males. No statistically significant differences in SDQ variables were found in relation to the degree of obesity (BMI SDS: 2-2.99; BMI SDS: > 3). Discussion: These findings can contribute to understand the psychological condition of adolescents with obesity in a better way and also to develop effective interventions for the treatment of pediatric obesity which not only take into account the medical and physical aspects but also the emotional and social difficulties expressed by adolescents with obesity.

A Metabolomics-Based Investigation of the Effects of a Short-Term Body Weight Reduction Program in a Cohort of Adolescents with Obesity: A Prospective Interventional Clinical Study.

Metabolomics applied to assess the response to a body weight reduction program (BWRP) may generate valuable information concerning the biochemical mechanisms/pathways underlying the BWRP-induced cardiometabolic benefits. The aim of the present study was to establish the BWRP-induced changes in the metabolomic profile that characterizes the obese condition. In particular, a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) targeted metabolomic approach was used to determine a total of 188 endogenous metabolites in the plasma samples of a cohort of 42 adolescents with obesity (female/male = 32/10; age = 15.94 ± 1.33 year; body mass index standard deviation score (BMI SDS) = 2.96 ± 0.46) who underwent a 3-week BWRP, including hypocaloric diet, physical exercise, nutritional education, and psychological support. The BWRP was capable of significantly improving body composition (e.g., BMI SDS, p < 0.0001), glucometabolic homeostasis (e.g., glucose, p < 0.0001), and cardiovascular function (e.g., diastolic blood pressure, p = 0.016). A total of 64 metabolites were significantly reduced after the intervention (at least p < 0.05), including 53 glycerophospholipids (23 PCs ae, 21 PCs aa, and 9 lysoPCs), 7 amino acids (tyrosine, phenylalanine, arginine, citrulline, tryptophan, glutamic acid, and leucine), the biogenic amine kynurenine, 2 sphingomyelins, and (free) carnitine (C0). On the contrary, three metabolites were significantly increased after the intervention (at least p < 0.05)-in particular, glutamine, trans-4-hydroxyproline, and the octadecenoyl-carnitine (C18:1). In conclusion, when administered to adolescents with obesity, a short-term BWRP is capable of changing the metabolomic profile in the plasma.

Cardiometabolic Index (CMI) and Visceral Adiposity Index (VAI) Highlight a Higher Risk of Metabolic Syndrome in Women with Severe Obesity.

Recent evidence shows that simple and inexpensive anthropometric measurements can be used to identify, at an early stage, women with obesity at increased risk of developing metabolic syndrome (MetS). Thus, the aim of this study was to compare the accuracy of five different indexes of adiposity and/or body composition in identifying MetS in a group of 876 women (mean age ± SD: 52.1 ± 13.8 years; body mass index (BMI): 43.6 ± 6.1 kg m-2). The following indexes were determined for each subject: waist-to-hip ratio (WHR), waist-to-height ratio (WtHR), body mass fat index (BMFI), visceral adiposity index (VAI), and cardiometabolic index (CMI). Overall, the presence of MetS was detected in 544 patients (62%). Pearson correlation coefficients were calculated to evaluate the relationships between body composition indexes and metabolic characteristics of the women. Receiver operating characteristic (ROC) analysis was used to determine the best predictor for each adiposity index among metabolic risk factors. The ROC analysis showed VAI (AUC = 0.84) and CMI (AUC = 0.86) showed the best performance in predicting MetS. Differences were found between the ROC area of CMI and VAI with all other indexes (p < 0.05). The optimal cutoff point for early diagnosis of MetS was >0.92 for WHR, >0.76 for WtHR, >30.1 kg m-1 for BMFI, >1.94 for VAI, and >0.84 for CMI. In addition, VAI and CMI were the most sensitive and specific indexes compared with other indexes. In conclusion, VAI and CMI represent the most useful and reliable indexes to be used for detecting MetS in women suffering from obesity in clinical practice.

Proteome profiling identifies circulating biomarkers associated with hepatic steatosis in subjects with Prader-Willi syndrome.

Introduction: Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by loss of expression of paternal chromosome 15q11.2-q13 genes. Individuals with PWS exhibit unique physical, endocrine, and metabolic traits associated with severe obesity. Identifying liver steatosis in PWS is challenging, despite its lower prevalence compared to non-syndromic obesity. Reliable biomarkers are crucial for the early detection and management of this condition associated with the complex metabolic profile and cardiovascular risks in PWS. Methods: Circulating proteome profiling was conducted in 29 individuals with PWS (15 with steatosis, 14 without) using the Olink Target 96 metabolism and cardiometabolic panels. Correlation analysis was performed to identify the association between protein biomarkes and clinical variables, while the gene enrichment analysis was conducted to identify pathways linked to deregulated proteins. Receiver operating characteristic (ROC) curves assessed the discriminatory power of circulating protein while a logistic regression model evaluated the potential of a combination of protein biomarkers. Results: CDH2, CTSO, QDPR, CANT1, ALDH1A1, TYMP, ADGRE, KYAT1, MCFD, SEMA3F, THOP1, TXND5, SSC4D, FBP1, and CES1 exhibited a significant differential expression in liver steatosis, with a progressive increase from grade 1 to grade 3. FBP1, CES1, and QDPR showed predominant liver expression. The logistic regression model, -34.19 + 0.85 * QDPR*QDPR + 0.75 * CANT1*TYMP - 0.46 * THOP1*ALDH1A, achieved an AUC of 0.93 (95% CI: 0.63-0.99), with a sensitivity of 93% and specificity of 80% for detecting steatosis in individuals with PWS. These biomarkers showed strong correlations among themselves and were involved in an interconnected network of 62 nodes, related to seven metabolic pathways. They were also significantly associated with cholesterol, LDL, triglycerides, transaminases, HbA1c, FLI, APRI, and HOMA, and showed a negative correlation with HDL levels. Conclusion: The biomarkers identified in this study offer the potential for improved patient stratification and personalized therapeutic protocols.

Cognitive Fusion and Emotional Eating among Adolescents with Obesity: A Preliminary Cross-Sectional Study.

Cognitive fusion and avoidance are supposed to exert a key role in the development and maintenance of disordered eating behaviors related to obesity, such as emotional eating. A large portion of the research has focused on adult populations, while few data are available on adolescents so far. The current cross-sectional study is intended to explore the association between cognitive fusion, avoidance, and emotional eating in a sample of fifty-six Italian adolescents (13-17 years) with obesity (body mass index > 97th centile). For this purpose, participants attending a 3-week body weight reduction program were assessed using demographical, physical, and clinical data. A multivariate linear regression model was performed in order to preliminarily investigate the predictive role of cognitive fusion on emotional eating, controlling for possible confounding factors. Results showed a significant association between cognitive fusion and emotional eating. Regression revealed that cognitive fusion was a significant contributor for explaining emotional eating (controlling for sex) [R2 = 0.551; Adjusted R2 = 0.534; F(2,53) = 32.5; p < 0.001]. Even if preliminary, our findings suggest a predictive role of cognitive fusion on emotional eating, and also suggest that cognitive fusion can be considered a key component in understanding and addressing of disordered eating behaviors related to obesity. Future replications are required to expand the sample and collect longitudinal data. Intervention programs for childhood obesity could benefit from this line of research.

Predictive factors of responsiveness to a body weight reduction program in Prader-Willi patients at 6 years of follow-up.

Prader-Willi syndrome (PWS), a multisystemic disorder caused by lack of expression of genes on the paternally inherited chromosome 15q11.2-q13 region, is characterized by hyperphagia and childhood-onset morbid obesity, A retrospective cohort study of 60 PWS patients, 38 females and 22 males, undergoing a 6-year rehabilitation program was analysed. Mean age at the time of first admission was 27 ± 7 years, body weight (BW) was 97 kg ± 29 kg and height was 1.53 ± 0.09 m. Twenty-four patients (40%) showed BW loss after 6 years of follow-up, seventeen (28%) remained stable and nineteen (32%) gained BW. Responsiveness in term of BW reduction was less frequent in patients with the UPD karyotype, karyotype del15 being more frequent among responsive patients. Furthermore, responsive PWS subjects had a higher BMI (47 vs. 36 kg/m2), waist (123 vs. 106 cm) and hip (136 vs. 118 cm) circumferences than non-responsive at the time of first hospitalization. Baseline body composition and metabolic parameters did not differentiate between responsive and non-responsive patients. Given the rarity of PWS and relative lack of studies, these results can be considered relevant because based on a relatively large number of PWS patients followed up for a long term period.

High Tg/HDL-Cholesterol Ratio Highlights a Higher Risk of Metabolic Syndrome in Children and Adolescents with Severe Obesity.

Few data are currently available on the reliability of the different anthropometric, instrumental and biochemical indexes in recognizing the presence of metabolic syndrome (MetS) in children and adolescents with severe obesity. Therefore, the objective of our study was to find out the simplest and most accurate predictive index of MetS in this population at-risk. In 1065 children and adolescents (563 f, 502 m), aged 14.6 ± 2.1 years (range 10-17), with severe obesity [BMI-SDS 3.50 ± 0.36 (range 3.00-5.17)], the following indexes were evaluated: BMI, BMI-SDS, Tri-Ponderal Mass Index, Waist-to-Height ratio, TG/HDL-Cholesterol ratio, Cardiometabolic Index (CMI), and Visceral Adiposity Index (VAI). For each subject, all the components of MetS, defined according to the IDF criteria, were determined. Overall, the presence of MetS was found in 324 patients (30.4%), 167 males (33.3%) and 157 females (27.9%). According to the ROC analysis, three indexes (VAI, CMI and TG/HDL-Cholesterol ratio), performed significantly better than the other ones in identifying MetS, with no difference among them. In conclusion, the TG/HDL ratio, which just needs the evaluation of two simple biochemical parameters, offers the same accuracy as other more sophisticated indexes in recognizing MetS in children and adolescents with severe obesity, thus making it the best predictor to be easily used.

A three-week in-hospital multidisciplinary body weight reduction program exerts beneficial effects on physical and mental health and fatiguability of elderly patients with obesity.

Introduction: Obesity represents one of the most serious problems of public health affecting elderly populations in an increasingly relevant way. The aim of the current study was to assess the effects of a 3-week in-hospital multidisciplinary body weight reduction program (BWRP) in a sample of elderly patients with obesity on reducing body mass index (BMI), improving fatigue, muscle performance, and psychological well-being. Methods: Two hundred and thirty-seven consecutive elderly in-patients with obesity (males = 84; females = 153; age range = 65-86 yrs.; mean BMI = 43.7) undergoing a three-week multidisciplinary BWRP participated in the study. Data on BMI, fatiguability (measured with the Fatigue Severity Scale, FSS), muscle performance (evaluated with the Stair Climbing Test, SCT), and psychological well-being (assessed with the Psychological General Well- Being Index, PGWBI) were collected before and after the intervention. Results: Results showed that BWRP was capable to reduce BMI [F(1.00, 235.00) = 1226.8; p < 0.001; ƞ 2 = 0.024], improve perceived fatigue [F(1,234) = 296.80125; p < 0.001; ƞ 2 = 0.129], physical performance [F(1.00,158.00) = 119.26; p < 0.001; ƞ 2 = 0.026], and enhance psychological well-being [F(1,235) = 169.0; p < 0.001; ƞ 2 = 0.103] in both males and females. Discussion: Although it will be necessary to demonstrate with further longitudinal studies whether the reported beneficial effects will be maintained over time, the effectiveness of a 3-week BWRP on different aspects involved in determining a level of autonomy and good quality of life of elderly obese patients appears to represent a valid attempt to counteract - at least in part - the unavoidable and progressive disability of these patients.

Changes in DNA Methylation of Clock Genes in Obese Adolescents after a Short-Term Body Weight Reduction Program: A Possible Metabolic and Endocrine Chrono-Resynchronization.

Circadian rhythms are generated by a series of genes, collectively named clock genes, which act as a self-sustained internal 24 h timing system in the body. Many physiological processes, including metabolism and the endocrine system, are regulated by clock genes in coordination with environmental cues. Loss of the circadian rhythms has been reported to contribute to widespread obesity, particularly in the pediatric population, which is increasingly exposed to chronodisruptors in industrialized society. The aim of the present study was to evaluate the DNA methylation status of seven clock genes, namely clock, arntl, per1-3 and cry1-2, in a cohort of chronobiologically characterized obese adolescents (n: 45: F/M: 28/17; age ± SD: 15.8 ± 1.4 yrs; BMI SDS: 2.94 [2.76; 3.12]) hospitalized for a 3-week multidisciplinary body weight reduction program (BWRP), as well as a series of cardiometabolic outcomes and markers of hypothalamo-pituitary-adrenal (HPA) function. At the end of the intervention, an improvement in body composition was observed (decreases in BMI SDS and fat mass), as well as glucometabolic homeostasis (decreases in glucose, insulin, HOMA-IR and Hb1Ac), lipid profiling (decreases in total cholesterol, LDL-C, triglycerides and NEFA) and cardiovascular function (decreases in systolic and diastolic blood pressures and heart rate). Moreover, the BWRP reduced systemic inflammatory status (i.e., decrease in C-reactive protein) and HPA activity (i.e., decreases in plasma ACTH/cortisol and 24 h urinary-free cortisol excretion). Post-BWRP changes in the methylation levels of clock, cry2 and per2 genes occurred in the entire population, together with hypermethylation of clock and per3 genes in males and in subjects with metabolic syndrome. In contrast to the pre-BWRP data, at the end of the intervention, cardiometabolic parameters, such as fat mass, systolic and diastolic blood pressures, triglycerides and HDL-C, were associated with the methylation status of some clock genes. Finally, BWRP induced changes in clock genes that were associated with markers of HPA function. In conclusion, when administered to a chronodisrupted pediatric obese population, a short-term BWRP is capable of producing beneficial cardiometabolic effects, as well as an epigenetic remodeling of specific clock genes, suggesting the occurrence of a post-BWRP metabolic and endocrine chronoresynchronization, which might represent a "biomolecular" predictor of successful antiobesity intervention.

Effect of a 3-Week Multidisciplinary Body Weight Reduction Program on the Epigenetic Age Acceleration in Obese Adults.

Obesity and aging share common molecular and cellular mechanisms underlying the pathophysiology of cardiovascular diseases (CVD), which occur frequently in both conditions. DNA methylation (DNAm) age, a biomarker of the epigenetic clock, has been proposed as a more accurate predictor of biological aging than chronological age. A positive difference between an individual's chronological age and DNAm age is referred to as epigenetic age acceleration. The objective of the present study was to evaluate the effects of a 3-week in-hospital body weight reduction program (BWRP) on the epigenetic age acceleration, as well as on other cardiometabolic outcomes, in a cohort of 72 obese adults (F/M: 43/29; (chronological) age: 51.5 ± 14.5 yrs; BMI: 46.5 ± 6.3 kg/m2). At the end of the BWRP, when considering the entire population, BMI decreased, and changes in body composition were observed. The BWRP also produced beneficial metabolic effects as demonstrated by decreases in glucose, insulin, HOMA-IR, total cholesterol, and LDL cholesterol. A post-BWRP improvement in cardiovascular function was also evident (i.e., decreases in systolic and diastolic blood pressures and heart rate). The BWRP reduced some markers of systemic inflammation, particularly C-reactive protein (CRP). Finally, vascular age (VA) and Framingham risk score (FRS) were reduced after the BWRP. When considering the entire population, DNAm age and epigenetic age acceleration did not differ after the BWRP. However, when subdividing the population into two groups based on each subject's epigenetic age acceleration (i.e., ≤0 yrs or >0 yrs), the BWRP reduced the epigenetic age acceleration only in obese subjects with a value > 0 yrs (thus biologically older than expected). Among all the single demographic, lifestyle, biochemical, and clinical characteristics investigated, only some markers of systemic inflammation, such as CRP, were associated with the epigenetic age acceleration. Moreover, chronological age was correlated with DNAm age and VA; finally, there was a correlation between DNAm age and VA. In conclusion, a 3-week BWRP is capable of reducing the epigenetic age acceleration in obese adults, being the BWRP-induced rejuvenation evident in subjects with an epigenetic age acceleration > 0 yrs. Based on the BWRP-induced decrease in CRP levels, chronic systemic inflammation seems to play a role in mediating obesity-related epigenetic remodeling and biological aging. Thus, due to the strong association of CVD risk with the epigenetic clock and morbidity/mortality, any effort should be made to reduce the low-grade chronic inflammatory state in obesity.

Responsiveness of the Italian version of the Pediatric Quality of Life Multidimensional Fatigue Scale in adult inpatients with obesity.

This study aimed to evaluate the responsiveness of the Italian version of the Paediatric Quality of Life Inventory Multidimensional Fatigue Scale (PedsQL-MFS) to changes in BMI, fatigue and depressive symptoms in adult inpatients with obesity. 198 adults (81% female, mean age = 44.7 years) with obesity completed the PedsQL-MFS, the Fatigue Severity Scale (FFS) and the Centre for Epidemiologic Studies Depression Scale (CESD) before and after completing a 3-week body weight reduction program. Internal responsiveness was measured via paired t-tests, standardized mean response (SMR) and Glass's delta (d). Changes in FFS, CESD and BMI were used as anchors to categorize participants as "improved", "unchanged" or "deteriorated". External Responsiveness was assessed by comparing mean post-intervention PedsQL-MFS scores across change groups, adjusting for pre-intervention PedsQL-MFS scores and in area-under-curve (AUC) analysis. PedsQL-MFS Total, Sleep/Rest Fatigue and Cognitive Fatigue scores demonstrated significant reductions in response to an established body weight reduction program. Post-intervention PedsQL-MFS scale scores were lower among those who had improved on the CESD and FSS than among those whose CESD and FSS scores had not significantly changed. There was no difference in PedsQL-MFS scale scores according to whether participants had reduced their BMI by at least 5%. AUC analyses indicated that change in PedsQL-MFS scores was somewhat more predictive of improvement in CESD than FSS scores. The Italian version of the PedsQL-MFS demonstrated both internal and external responsiveness. It appeared more sensitive to improvement than deterioration in fatigue symptoms and its sensitivity to deterioration in depressive symptoms and weight loss could not be evaluated in the present study as there was no reliable deterioration in CESD scores and weight loss was modest. Future studies should include a control group to assess the sensitivity of the PedsQL-MFS more thoroughly.

Robustness of Distinctive Facial Features in Prader-Willi Syndrome: A Stereophotogrammetric Analysis and Association with Clinical and Biochemical Markers in Adult Individuals.

BACKGROUND: Prader-Willi syndrome (PWS) is a rare genomic imprinting disorder associated to a complex neurodevelopmental phenotype and a distinctive facial appearance. The study investigated the relationships between the quantitative facial dysmorphism in PWS and clinical and biochemical markers of the disease and its treatment. METHODS: Facial images of 15 Caucasian adult individuals with PWS (8 males, 42 ± 5 years; 7 females, 37 ± 8 years; BMI 38.87 ± 8.92 kg/m2) were acquired through stereophotogrammetry. From the 3D coordinates of 38 landmarks, linear distances and angles were calculated; they were expressed as z-score values by referring to 403 healthy subjects matched for age and sex and compared by Student's t-test with Bonferroni correction for multiple testing. Patients underwent auxological and biochemical assessment of endocrine/metabolic dysfunction and nocturnal respiratory function. An exploratory correlation analysis was performed to investigate their associations with the facial phenotype; uncorrected p-values were used. RESULTS AND CONCLUSIONS: Individuals with PWS showed decreased bifrontal diameter, facial depths, palpebral fissures, mandibular ramus length, lower vermillion height, and modified relative position of exocanthia and nasion. Since these characteristics did not show any associations with clinical and biochemical markers of PWS, they could constitute robust distinctive facial features and contribute to the diagnosis of the disorder. Individuals with PWS showed also a larger mandibular width with smaller gonial angles, thinner upper vermillion, greater inclination of the orbit relative to the Frankfurt plane, and a smaller angle of the auricles versus the facial midplane. Relationships between these facial anthropometric features and body composition, glucidic metabolism indexes, nocturnal hypoxemia episodes, or duration of GH treatment were found, suggesting their potentially useful role in the clinical monitoring and management of the disease. However, they need to be confirmed by subsequent dedicated studies.