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.

Evaluation of adherence to pharmacological treatments by undocumented migrants with chronic diseases: a 10-year retrospective cohort study.

OBJECTIVES: To investigate the time course of medication adherence and some of the factors involved in this process in undocumented migrants with chronic diseases. DESIGN: Retrospective cohort study. SETTING: A big non-governmental organisation in Milano, Italy, giving medical assistance to undocumented migrants. PARTICIPANTS: 1918 patients, 998 females and 920 males, with at least one chronic condition (diabetes, cardiovascular diseases (CVDs), mental health disorders) seen over a period of 10 years (2011-2020). Their mean age was 49.2±13 years. RESULTS: Adherence to medications decreased over 1 year in all patients. This was more evident during the first 2 months of treatment. Patients on only one medication were less adherent than those on more than one medication; at 6 months the percentage of patients with high adherence was 33% vs 57% (p<0.0001) for diabetes, 15% vs 46% (p<0.0001) for mental disorders and 35% vs 59% (p<0.0001) for CVDs. Patients with mental disorders had the lowest adherence: 25% at 6 months and 3% at 1 year. Mental disorders, when present as comorbidities, greatly reduced the probability of being highly adherent: risk ratio (RR) 0.72 (95% CI 0.57 to 0.91; p=0.006) at 3 months, RR 0.77, (95% CI 0.59 to 1.01; p=0.06) at 6 months, RR 0.35 (95% CI 0.13 to 0.94; p=0.04) at 1 year. This was especially evident for patients with CVDs, whose percentage of high adherents decreased to 30% (p=0.0008) at 6 months and to 3% (p=0.01) at 1 year. We also noted that highly adherent patients usually were those most frequently seen by a doctor. CONCLUSIONS: Interventions to increase medication adherence of undocumented migrants with chronic diseases are necessary, particularly in the first 2 months after beginning treatment. These should be aimed at people-centred care and include more outpatient consultations. Educational interventions should especially be taken into consideration for patients on monotherapy.

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.

Characterizing non-communicable disease trends in undocumented migrants over a period of 10 years in Italy.

Undocumented migrants represent a large part of the population in Countries of the European Union (EU) such as Italy. Their health burden is not fully understood and likely to be related mainly to chronic conditions. Information on their health needs and conditions may help to target public health interventions but is not found in national public health databases. We conducted a retrospective observational study of non-communicable disease (NCD) burden and management in undocumented migrants receiving medical care from Opera San Francesco, a non-governmental organization (NGO) in Milan, Italy. We analyzed the health records of 53,683 clients over a period of 10 years and collected data on demographics, diagnosis and pharmacological treatments prescribed. 17,292 (32.2%) of clients had one or more NCD diagnosis. The proportion of clients suffering from at least one NCD increased from 2011 to 2020. The risk of having an NCD was lower in men than women (RR = 0.88, 95% CI 0.86-0.89), increased with age (p for trend < 0.001) and changed with ethnicity. African and Asian migrants had a lower risk than Europeans of cardiovascular diseases (RR 0.62 CI 0.58-0.67, RR 0.85 CI 0.78-0.92 respectively) and mental health disorders (RR 0.66 CI 0.61-0.71, RR 0.60 CI 0.54-0.67 respectively), while the risk was higher in Latin American people (RR 1.07 CI 1.01-1.13, RR 1.18 CI 1.11-1.25). There was a higher risk of diabetes in those from Asia and Latin America (RR 1.68 CI 1.44-1.97, RR 1.39 CI 1.21-1.60). Overall, migrants from Latin America had the greatest risk of chronic disease and this was true for diabetes, cardiovascular diseases and mental health disorders. Undocumented migrants demonstrate a significantly different health burden of NCDs, which varies with ethnicity and background. Data from NGOs providing them with medical assistance should be included in structuring public health interventions aimed at the prevention and treatment of NCDs. This could help to better allocate resources and address their health needs.

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.

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.

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.

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.

Correction: Rigamonti et al. The Role of Aspartate Transaminase to Platelet Ratio Index (APRI) for the Prediction of Non-Alcoholic Fatty Liver Disease (NAFLD) in Severely Obese Children and Adolescents. Metabolites 2022, 12, 155.

In the original publication [...].

The Role of Aspartate Transaminase to Platelet Ratio Index (APRI) for the Prediction of Non-Alcoholic Fatty Liver Disease (NAFLD) in Severely Obese Children and Adolescents.

The aspartate transaminase to platelet ratio index (APRI) has been proposed as an easy-to-use biochemical marker in obese adults with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatotic hepatitis (NASH). The objective of the present study was to evaluate the clinical and predictive value of APRI in a paediatric obese population. Seven hundred fifty-seven obese children and adolescents (BMI standard deviation score, SDS: >2.0; age range: 10-18.5 years), not consuming alcohol and without hepatitis B or C, were recruited after having been screened for NAFLD by ultrasonography. A series of demographic, biochemical and clinical parameters was compared between the two subgroups (with or without NAFLD); the same parameters were correlated with APRI; and finally, univariable and multivariable logistic regression was used to evaluate the predictors of NAFLD. NAFLD was diagnosed in about 39% of the entire paediatric population, predominantly in males and in subjects suffering from metabolic syndrome. APRI was correlated with the waist circumference (WC), high-density lipoprotein cholesterol (HDL-C), uric acid, total bilirubin, C reactive protein (CRP) and systolic blood pressure (SBP). Furthermore, APRI was higher in males than females, but independent from steatosis severity and metabolic syndrome. With the univariable analysis, the BMI SDS, triglycerides (TG), insulin, homeostatic model assessment for insulin resistance (HOMA-IR), APRI, uric acid and metabolic syndrome were positive predictors of NAFLD, with female sex being negative predictor. At multivariable analysis; however, only BMI SDS, TG, HOMA-IR and APRI were positive predictors of NAFLD, with female sex being a negative predictor. The accuracy of APRI as a biochemical marker of NAFLD was about 60%.In conclusion, in a large (Italian) paediatric obese population, parameters, such as BMI SDS, TG, HOMA-IR and APRI, were positive predictors of NAFLD, with female sex being a negative predictor and most of the prediction explained by APRI. Nevertheless, APRI appears to be a simple biochemical marker of liver injury rather than of NAFLD/NASH and, moreover, is endowed with a limited accuracy for the prediction/diagnosis of NAFLD.

Pharmacological Treatment of Type-2-Diabetes and Cardiovascular Comorbidities: Differences between Undocumented Migrants and Natives in Italy.

Diabetes prevalence is growing worldwide, especially in some populations. Though migrations seem to contribute to the presence in host countries of a significant number of patients with diabetes and its comorbidities, very little is known about the health conditions of undocumented migrants. We retrospectively studied 838 patients with type 2 diabetes mellitus (T2DM), 425 Italians followed by the diabetes clinic of a university hospital, and 413 undocumented migrants receiving assistance from a non-governmental organization. We analyzed their demographic and clinical data together with the medications they were on. The prevalence of the use of specific classes of drugs was compared between undocumented migrants and Italians by fitting a Poisson regression model, and the results were reported as prevalence rate ratios (PRRs) with a 95% confidence interval. Undocumented migrants with T2DM received fewer medications for cardiovascular (CV) conditions (PRR: 0.68, 0.60 to 0.76) than Italians, after correcting for confounding factors. Only sulfonylureas were more frequently used in undocumented migrants. The causes of these differences are not completely clear, but social, cultural, and economic factors can have an important role. More efforts are needed to provide appropriate treatment of diabetes and its CV comorbidities to undocumented migrants.

Frequent Medical Supervision Increases the Effectiveness of a Longitudinal Multidisciplinary Body Weight Reduction Program: A Real-World Experience in a Population of Children and Adolescents with Obesity.

Regular medical supervision represents a fundamental component of the clinical management of obesity. In fact, when frequently supplied it reduces the risk of failure associated with any body weight reduction program (BWRP), resulting in body weight gain. The aim of the present study was to establish the potential beneficial effects of increasing medical supervision on weight loss and other auxometric and cardiometabolic parameters in a population of children and adolescents with obesity (n = 158; F/M = 94/64; age range 9.7-17.3 years; body mass index, BMI = 37.8 ± 6.9 kg/m2), followed up for one year in a real-world setting, after and before a 3-week in-hospital BWRP. Weight loss was significantly associated with medical supervision and changes in several auxometric and cardiometabolic parameters such as fat mass, fat-free mass, waist and hip circumferences, total and LDL cholesterols, triglycerides, glucose, insulin, HOMA-IR, systolic blood pressure and IDF criteria for the diagnosis of metabolic syndrome. As expected, weight loss and, congruently, medical supervision, were significantly higher in responsive and stable subjects than in those belonging to the non-responsive group and in responsive subjects than those belonging to the stable group. While weight loss was significantly higher in subjects having class 2 and 3 obesity than those belonging to class 1 obesity group, medical supervision was significantly higher in subjects having class 3 than those having class 1 obesity. Weight loss was significantly higher in subjects suffering from metabolic syndrome than those without; nevertheless, no significant difference was found in medical supervision between these groups. Finally, sex was associated with no differences in weight loss and medical supervision. In conclusion, based on the results of a real-world experience, frequent medical supervision increases the weight loss associated with a longitudinal multidisciplinary BWRP, with a parallel improvement of a set of auxometric and cardiometabolic parameters. Prospectively, incentivising regular medical supervision should reduce the risk of BWRP failure and body weight gain, thus contributing to counteract the detrimental transition from simple obesity to metabolic syndrome in pediatric patients.

The Age-Dependent Increase of Metabolic Syndrome Requires More Extensive and Aggressive Non-Pharmacological and Pharmacological Interventions: A Cross-Sectional Study in an Italian Cohort of Obese Women.

BACKGROUND: Metabolic syndrome is a combination of cardiovascular risk factors (i.e., visceral obesity, dyslipidaemia, glucose intolerance, and hypertension), which entails critical issues in terms of medical management and public health. METHODS: The aim of the present cross-sectional study was to investigate the age-related changes of the single IDF (International Diabetes Federation) diagnostic criteria for metabolic syndrome (waist circumference, WC; high-density lipoprotein cholesterol, HDL-C; triglycerides; glucose; systolic and diastolic blood pressure, SBP and DBP) in a large population of (Italian) obese women (n = 1.000; body mass index, BMI >30 kg/m2; age: 18-83 yrs), subdivided into two subgroups depending on the presence (n = 630) or absence (n = 370) of metabolic syndrome. Parallelly, the percentages of treatment with hypolipidaemic drugs, hypoglycaemics, and antihypertensives and, among the treated subjects, of control of the underlying condition in accordance with the cut-offs of IDF criteria for dyslipidaemia, hyperglycaemia, and hypertension were determined over six age ranges (i.e., 18-30, 31-40, 41-50, 51-60, 61-70, and > 70 yrs). RESULTS: The prevalence of metabolic syndrome increased with advancing age. In the subgroup with metabolic syndrome, an age-dependent increase in HDL-C, glycaemia, and SBP occurred, while the visceral adiposity was stable. In the same subgroup, triglycerides and DBP decreased age-dependently. In the subgroup without metabolic syndrome, an age-dependent increase in WC, HDL-C, glycaemia, SBP, and DBP was observed. A progressive age-dependent increase in the percentage of patients pharmacologically treated for the cardiometabolic abnormalities was detected in patients with metabolic syndrome, a similar trend being also observed in patients without metabolic syndrome only for the antihypertensives. A clear-cut disproportion between treated versus adequately controlled women (with pharmacotherapy) was detected in the whole population. CONCLUSIONS: At least in an Italian context of obese females, the age-dependent worsening of glycaemia and BP exerts a fundamental pathophysiological role in the progressive increase of metabolic syndrome with advancing age, which appears to be not adequately treated in a large part of obese subjects. The results of the present study might be useful for public health decision-makers for programming future more extensive and aggressive non-pharmacological and pharmacological interventions in the obese population.

Risk factors, awareness of disease and use of medications in a deprived population: differences between indigent natives and undocumented migrants in Italy.

BACKGROUND: Undocumented migrants experience many health problems; a comparison with a suitable control group of natives living in the same socio-economic conditions is still lacking. METHODS: Demographic data and data on risk factors, chronic conditions and dietary habits were obtained for 6933 adults (2950 Italians and 3983 undocumented migrants) receiving medical assistance from 40 non-governmental organizations all over the country. RESULTS: Attributed to the fact that these were unselected groups, differences were found in their demographic features, the main ones being their marital status (singles: 50.5% among Italians and 42.8% among migrants; P < 0.001). Smokers were more frequent among Italians (45.3% versus 42.7% P = 0.03); the same happened with hypertension (40.5% versus 34.5% P < 0.001). Migrants were more often overweight (44.1% versus 40.5% P < 0.001) and reporting a chronic condition (20.2% versus 14.4% P < 0.001). Among those on medications (n = 1354), Italians were fewer (n = 425) and on different medications. Differences emerged also in dietary habits. CONCLUSIONS: Differences in health conditions exist between native-borns and undocumented migrants, not because of a bias related to socio-economic conditions. Further studies are needed to design sustainable health policies and tailored prevention plans.

Effects of SARS-CoV-2 pandemic on follow-up and pharmacological treatment of chronic diseases in undocumented migrants.

BACKGROUND: All over the world, the COVID-19 pandemic, not unlikely other epidemics, has hit harder people in low socioeconomic conditions.In Western countries, undocumented migrants are a growing component of this disadvantaged segment of the population.Their health conditions are frequently burdened by a number of chronic conditions, and they experience many difficulties in accessing public health services. Frequently, the only medical assistance they can get is provided by non-governmental organisations. METHODS: We studied the medical records (including pharmacological treatments) of all patients attending the outpatient clinics of Opera San Francesco (OSF; a big charity in Milano, Italy), in the first 5 months of 2020. These comprise the outbreak of the pandemic and the lockdown period. The 1914 patients (1814 undocumented migrants and 100 Italians) seen during the lockdown were compared with those seen in the same period of 2019 and with those seen in the preceding months of 2020. We especially focused on three chronic conditions: cardiovascular diseases, diabetes and psychiatric disorders. RESULTS: The number of consultations during the first 5 months of 2020 was much smaller than that of the same period of 2019. During the lockdown, we found 4048 consultations for 1914 patients, while they were 8051 in the same period of 2019 and 5681 in the first 2 months of 2020.The quantity of medicines dispensed by OSF showed a marked decrease in the period of the study and mainly during the lockdown.The decrease in consultations and dispensation of medicines was most evident for psychiatric patients and almost not existent for patients with diabetes. Female patients suffered a more pronounced reduction. CONCLUSIONS: Western countries need strategies to better assist the very poor during epidemics.Differences among different groups of disadvantaged persons should be taken into account when designing recovery plans.

Undocumented migrants during the COVID-19 pandemic: socio-economic determinants, clinical features and pharmacological treatment.

Population groups such as undocumented migrants have been almost completely forgotten during the COVID-19 pandemic, though they have been living in all European countries for decades and new arrivals have continued throughout the pandemic. The aim of this study was to investigate their health conditions during the current pandemic. We analysed the records of 272 patients with respiratory issues attending the outpatient clinic of a large charity in Milan, Italy: amongst them, 18 had COVID-19 confirmed by rhino-pharyngeal swab and 1 of them deceased. All the patients attending the clinic appeared to have several risk factors for COVID-19 and chronic conditions suspected to predispose to the disease and/or to worsen severity and outcomes: hypertension, immunosuppression and previous close contact with COVID-19 patients were the most important ones. Presenting symptoms were worse in patients with COVID-19 than in those with other respiratory issues. These results are discussed in light of the necessity to provide better healthcare to undocumented migrants.

Current Pharmacological Treatment of Type 2 Diabetes Mellitus in Undocumented Migrants: Is It Appropriate for the Phenotype of the Disease?

Type 2 diabetes is increasingly recognized as a spectrum of metabolic disorders sharing chronic hyperglycaemia. In Europe, the continually growing number of migrants from developing countries could affect diabetes phenotypes. We evaluated a population of 426 Italians and 412 undocumented migrants. Using 17 variables (with the exclusion of ethnic origin) we performed a multiple component analysis to detect potential clusters, independently from ethnicity. We also compared the two groups to evaluate potential ethnicity associated differences. We found five clusters of patients with different disease phenotypes. Comparing Italians with undocumented migrants, we noted that the first had more often cardiovascular risk factors and neurologic involvement, while the latter had a higher frequency of diabetic ulcers and renal involvement. Metformin was used in a comparable percentage of patients in all clusters, but other antidiabetic treatments showed some differences. Italians were more often on insulin, due to a larger use of long acting insulin, and received a larger number of oral antidiabetics in combination. Pharmacological treatment of comorbidities showed some differences too. We suggest that type 2 diabetes should be considered as a spectrum of diseases with different phenotypes also in heterogeneous populations, and that this is not due only to ethnic differences.

Evaluation of an Amino Acid Mix on the Secretion of Gastrointestinal Peptides, Glucometabolic Homeostasis, and Appetite in Obese Adolescents Administered with a Fixed-Dose or ad Libitum Meal.

Proteins have been demonstrated to reduce food intake in animals and humans via peripheral and central mechanisms. Supplementation of a dietetic regimen with single or mixed amino acids might represent an approach to improve the effectiveness of any body weight reduction program in obese subjects. The aim of the present study was to evaluate the effects of an amino acid mix (L-arginine + L-leucine + L-glutamine + L-tryptophan) on the secretion of some gastrointestinal peptides (i.e., ghrelin and glucagon-like peptide type 1, GLP-1), glucometabolic homeostasis (i.e., glucose, insulin, and glucagon), and appetite (hunger/satiety scored by visual analogue scale, VAS) in obese adolescents (n = 14; 10 females and 4 males; age: 16.6 ± 1.0 years; body mass index (BMI): 36.4 ± 4.6 kg/m²; fat-free mass (FFM): 54.9 ± 4.7%; fat mass (FM): 45.1 ± 4.4%) administered with a fixed-dose (lunch) or ad libitum (dinner) meal. Isocaloric maltodextrins were used as control treatment. During the lunch test, a significant increase in circulating levels of GLP-1, but not of ghrelin, was observed in the amino acid-treated group, which was congruent with significant changes in appetite, i.e., increase in satiety and decrease in hunger. A significant hyperglycemia was found in the maltodextrin-treated group during the prelunch period, without any significant changes in insulin and glucagon between the two groups. During the dinner test, there were no significant differences in appetite (hunger/satiety) and intake of calories. In conclusion, L-arginine, L-leucine, L-glutamine, and L-tryptophan, when administered to obese adolescents with a fixed-dose meal, are capable of evoking an anorexigenic response, which is, at least in part, mediated by an increase in GLP-1 released in circulation by L cells, which are capable of chemosensing specific amino acids present in the intestinal lumen. Further additional studies are requested to understand whether higher doses are necessary to inhibit ad libitum feeding.

Effects of a 3-Week In-Hospital Body Weight Reduction Program on Cardiovascular Risk Factors, Muscle Performance, and Fatigue: A Retrospective Study in a Population of Obese Adults with or without Metabolic Syndrome.

BACKGROUND: In clinical practice, there is the diffuse conviction that obese subjects with metabolic syndrome may be more difficult to treat. OBJECTIVES AND METHODS: The aim of the present study was that to investigate the effectiveness of a 3-week in-hospital body weight reduction program (BWRP) in a large population of obese subjects with and without metabolic syndrome (n = 1922; 222 men and 1700 women, age range 18-83 yr). Outcomes such as body mass index (BMI), total (TOT) and HDL cholesterol, systolic and diastolic blood pressures (SBP and DBP, respectively), coronary heart disease (CHD) score, fatigue severity score (FSS), and stair climbing test (SCT) time were evaluated before and after the intervention (Δ). A sex-, BMI-, and age-related stratification of the obese population with or without metabolic syndrome was applied. RESULTS: When compared to obese subjects without metabolic syndrome, at the basal conditions, obese subjects had a poorer cardiometabolic profile, as demonstrated by higher triglycerides, TOT-cholesterol, DBP, SBP, and CHD score, and a more compromised muscle performance (evaluated by SCT), associated with more perception of fatigue (measured by FSS). Nevertheless, obese subjects with metabolic syndrome obtained more benefits from BWRP than those without metabolic syndrome for some outcomes (i.e., ΔTOT-cholesterol, ΔSBP, and ΔCHD score). Despite these differences, the BWRP-induced weight loss was similar between the two groups (i.e., ΔBMI) as well as the gain of muscle performance (i.e., ΔSCT) and the reduction of fatigue (i.e., ΔFSS). Interestingly, the potentially deleterious fall in HDL-cholesterol levels after BWRP was less evident in obese subjects with metabolic syndrome than those without metabolic syndrome. When pooling all data, the ΔCHD score was associated with age, sex, and metabolic syndrome. The remaining outcomes, such as ΔBMI, ΔFSS, and ΔSCT time, were associated with sex and age but not with metabolic syndrome. Finally, ΔBMI was positively correlated with ΔCHD score, ΔFSS, and ΔSCT time in both obese subjects without metabolic syndrome and obese subjects with metabolic syndrome. CONCLUSIONS: When comparing obese subjects undergoing a BWRP, metabolic syndrome is not a negative predictive factor affecting the effectiveness of this intervention in terms of weight loss, muscle performance, and psychological well-being.