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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.

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. &nbsp

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.

Circadian rhythms are generated by a series of genes, collectively named

Background: Comorbidities are a growing problem in older patients in many clinical settings, but electronic records may give an unsatisfactory picture of this complexity. Analysis of drug prescriptions can add further diagnostic information to that gathered from billing diagnostic codes, but the risk exhists that potentially inappropriate prescriptions may lead to over-estimating comorbidities. Methods: We analysed the administrative records and drug prescriptions of the 304 patients discharged during 2016 from a neurological rehabilitation unit. International Classification of Diseases – 9th revision diagnostic codes were matched with prescriptions at discharge, coded according to the Anatomical Therapeutic Chemical classification. The codes of the prescriptions not explained by the diagnostic codes were recorded, grouped, corrected for potential inappropriate prescribing, and analysed. Results: Of the 304 patients, 295 had at least one prescribed drug not inferable from their diagnostic codes. The mean number of these prescriptions was 3.5 ± 1.9 per patient, and that of prescriptions remaining after correction for potentially inappropriate prescribing was 2.0 ± 1.5. The more frequent groups of potentially inappropriate medications were anti-acids, psychotropic drugs, laxatives, potassium supplements, cardiovascular drugs and lipid modifying agents. Administrative databases underestimate the complexity of older patients in neurological rehabilitation wards. More reliable data can be obtained by adding the analysis of drug prescriptions, but correction for potentially inappropriate prescription seems necessary to avoid an over-estimation of comorbidities.

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.

Aims Migrants from countries in which health and social conditions are unsatisfactory, and their offspring, are becoming a growing component of the western population. Available health data show that their morbidity is at least comparable to that of the host country population, with a significant contribution of chronic diseases as diabetes. The possibility that diabetes shows different features in undocumented migrants is the hypothesis that we tried to investigate in this study. Methods We retrospectively analysed the data of 413 patients with type 2 diabetes mellitus (T2DM): 222 patients followed in a diabetes clinic at a University Hospital and 191 undocumented migrants cared for by a Charity in Milan, Italy. Results We found that the onset of the disease was earlier in migrants; they showed a significant lower body mass index (BMI) and had lower socioeconomic conditions. They had a worse glycaemic control. The pattern of complications was also different between the two groups, with cardiovascular complications more frequent in Italians. Finally, also pharmacologic treatment differed significantly. Conclusions Age of onset, clinical manifestations and complications of T2DM in undocumented migrants and natives may show significant differences. This is important for both epidemiological and clinical reasons. If these preliminary observations are confirmed by larger studies, we can conclude that undocumented migrants should be screened for T2DM earlier than natives, and that therapies should be tailored to the specific features of their disease.

Exposure to air pollution - and particularly to particulate matter (PM) - is strongly associated with higher risk of neurodevelopmental disorders, poor mental health and cognitive defects. In animal models, disruption of CNS development and disturbances of adult neurogenesis contribute to PM neurotoxicity. Recent studies show that gestational PM exposure not only affects embryonic neurodevelopment, but also disturbs postnatal brain growth and maturation, by interfering with neurogenic/gliogenic events, myelination and synaptogenesis. Similarly, adult neurogenesis is affected at many levels, from neural stem cell amplification up to the maturation and integration of novel neurons in the adult brain parenchyma. The underlying mechanisms are still by and large unknown. Beyond microglia activation and neuroinflammation, recent studies propose a role for novel epigenetic mechanisms, including DNA methylation and extracellular vesicles-associated microRNAs.

BackgroundAll 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.MethodsWe 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.ResultsThe 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.ConclusionsWestern 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.

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), 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. &nbsp

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 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.

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&ndash, 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 (&Delta, ). 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., &Delta, TOT-cholesterol, &Delta, SBP, and &Delta, CHD score). Despite these differences, the BWRP-induced weight loss was similar between the two groups (i.e., &Delta, BMI) as well as the gain of muscle performance (i.e., &Delta, SCT) and the reduction of fatigue (i.e., &Delta, FSS). 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 &Delta, CHD score was associated with age, sex, and metabolic syndrome. The remaining outcomes, such as &Delta, BMI, &Delta, FSS, and &Delta, SCT time, were associated with sex and age but not with metabolic syndrome. Finally, &Delta, BMI was positively correlated with &Delta, CHD score, &Delta, SCT 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.

The satiating effect of whey proteins depends upon their unique amino acid composition because there is no difference when comparing whey proteins or a mix of amino acids mimicking the amino acid composition of whey proteins. The specific amino acids underlying the satiating effect of whey proteins have not been investigated to date. Aims and Methods. The aim of the present study was to evaluate the appetite-suppressant effect of an isocaloric drink containing whey proteins or maltodextrins on appetite (satiety/hunger measured by a visual analogue scale or VAS), anorexigenic gastrointestinal peptides (circulating levels of glucagon-like peptide 1 (GLP-1) and peptide tyrosine tyrosine (PYY)) and amino acids (circulating levels of single, total [TAA] and branched-chain amino acids [BCAA]) in a cohort of obese female subjects (n = 8, age: 18.4 &plusmn, 3.1 years, body mass index, BMI: 39.2 &plusmn, 4.6 kg/m2). Results. Each drink significantly increased satiety and decreased hunger, the effects being more evident with whey proteins than maltodextrins. Similarly, circulating levels of GLP-1, PYY and amino acids (TAA, BCAA and alanine, arginine, asparagine, citrulline, glutamine, hydroxyproline, isoleucine, histidine, leucine, lysine, methionine, ornithine, phenylalanine, proline, serine, threonine, tyrosine, and valine) were significantly higher with whey proteins than maltodextrins. In subjects administered whey proteins (but not maltodextrins), isoleucine, leucine, lysine, methionine, phenylalanine, proline, tyrosine, and valine were significantly correlated with hunger (negatively), satiety, and GLP-1 (positively). Conclusions. Eight specific amino acids (isoleucine, leucine, lysine, methionine, phenylalanine, proline, tyrosine, and valine) were implicated in the appetite-suppressant and GLP-1-stimulating effects of whey proteins, which may be mediated by their binding with nutrient-sensing receptors expressed by L cells within the gastrointestinal wall. The long-term satiating effect of whey proteins and the effectiveness of a supplementation with these amino acids (i.e., as a nutraceutical intervention) administered during body weight reduction programs need to be further investigated.

Iodine deficiency still remains a significant health issue worldwide. Pregnant and lactating women are at risk for iodine deficiency when living in mild iodine-deficient areas such as Italy. This study aims at evaluating the consumption of iodized salt, iodine-rich-foods and maternal micronutrient supplements in a group of women with limited access to the Italian National Health System. A cross-sectional survey was conducted among immigrant and Italian women living in poverty and referring to 40 Non-Governmental Organization throughout Italy for their health needs. 3483 women answered the ad hoc questionnaire between January 2017 and February 2018. The consumption of iodized salt was very low, and even lower among immigrant women. Determinants of iodized salt consumption were the period spent in Italy for immigrant women and living in a family-type setting, parity and, particularly, the degree of education for Italian ones. 17.5% of immigrant women and 8.6% of the Italian ones reported a diagnosis of thyroid disease. 521 women, 75.4% of whom were immigrants, were pregnant or breast-feeding. The majority (57.3%) had no specific maternal supplementation. Both Italian and immigrating women with a low income or without access to the public health system have a poor adherence both to the salt iodization policy and to folic acid and iodine supplements in preconception and pregnancy. They also referred a low-frequency intake of iodine-rich-foods. The identification of barriers to health care access could be useful to promote specific health interventions in this target population.

Purpose The purpose of this paper is to evaluate gender-related differences in the use of drugs for chronic diseases in undocumented migrants. Design/methodology/approach The authors analyzed the databases of two charitable organizations providing medical help and medicines to undocumented migrants. Data were available for 9,822 patients in the period 2014–2016. The authors grouped medicines according to the Anatomical Therapeutic Chemical (ATC) classification. We considered the ATC group as an indicator of a group of diseases. Findings Both males and females needed medicines for chronic diseases in a comparable manner. When we analyzed the age distribution, The authors noticed that males showed a tendency to begin to be affected at an earlier age; however, this cumulative difference was not statistically significant. But when we looked at six groups of drugs separately (cardiovascular, respiratory, anti-thrombotic, neurologic, psychiatric, anti-diabetic), the authors found that females always needed drugs for chronic diseases at a later age, always with a significant difference (ppp Research limitations/implications This is a retrospective study based on the analysis of existing databases, but the peculiar features of this population (undocumented migrants) do not allow at the moment controlled studies. Practical implications Our observations could be important when planning public health strategies, especially in the field of prevention. Originality/value This is the first report of gender differences in the use of medicines for chronic diseases within a large sample of undocumented migrants.

Although capsaicin has been reported to reduce energy intake and increase energy expenditure in an adult (normal weight or overweight) population, thus resulting in a net negative energy balance and weight loss, these beneficial effects have not been investigated in young obese subjects. We hypothesize that capsaicin acutely administered in young obese subjects exerts the same effects on energy balance and that these effects are mediated by changes in gastrointestinal peptides regulating appetite. Thus, the aim of the present study was to evaluate the acute effects of capsaicin (2 mg) or placebo on energy intake, hunger, and satiety in obese adolescents and young adults (female-male ratio: 4:6, age: 21.0 ± 5.8 years; body mass index: 41.5 ± 4.3 kg/m2) provided an ad libitum dinner. Furthermore, circulating levels of some orexigenic (ghrelin) and anorexigenic (glucagon-like peptide 1 and peptide YY) peptides were measured after a meal completely consumed (lunch), together with the evaluation of hunger and satiety and assessment of resting energy expenditure (REE) through indirect computerized calorimetry. When compared to placebo, capsaicin did not significantly change either energy intake or hunger/satiety 6 hours after its administration (dinner). No differences in circulating levels of ghrelin, glucagon-like peptide 1, and peptide YY and in hunger/satiety were found in the 3 hours immediately after food ingestion among obese subjects treated with capsaicin or placebo (lunch). By contrast, the meal significantly increased REE in the capsaicin- but not placebo-treated group (capsaicin: from 1957.2 ± 455.1 kcal/d up to 2342.3 ± 562.1 kcal/d, P < .05; placebo: from 2060.1 ± 483.4 kcal/d up to 2296.0 ± 484.5 kcal/d). The pre-post meal difference in REE after capsaicin administration was significantly higher than that observed after placebo (385.1 ± 164.4 kcal/d vs 235.9 ± 166.1 kcal/d, P < .05). In conclusion, although capsaicin does not exert hypophagic effects, these preliminary data demonstrate its ability as a metabolic activator in young obese subjects.

Human GH is present in pituitary and circulation as several isoforms, the prevalent being 22 kDa- and 20 kDa-GH. Recently, we have demonstrated the preservation of a normal balance in GH isoforms after GH releasing hormone (GHRH) plus arginine (ARG) administration in adult patients with Prader-Willi syndrome (PWS), one of the most common causes of syndromic obesity, often associated with GH deficiency (GHD). Aim of the present study was to measure circulating levels of 22 kDa- and 20 kDa-GH in young PWS patients (n = 24; F/M: 10/14; genotype UPD/DEL/met +: 11/11/2; age: 10.8 ± 5.3 years; BMI SDS: 2.0 ± 2.0; GHD: 16/24; obesity: 12/24) after combined GHRH + ARG or ARG administration. The results were analysed subdividing the GHRH + ARG and ARG groups on the basis of PWS genotype, GHD status and obesity. Circulating levels of 22 kDa- and 20 kDa-GH were measured by a chemiluminescent or fluorescent method based on specific pairs of monoclonal antibodies. GHRH + ARG or ARG significantly stimulated the secretion of 22 kDa-GH but not that of 20 kDa-GH in all PWS patients. No significant GHRH + ARG- vs. ARG-induced changes in the ratios of 22 kDa- to 20 kDa-GH peaks were observed in all PWS patients, although 22 kDa- or 20 kDa-GH peaks were significantly higher in the GHRH + ARG than ARG group. When subdividing PWS patients in UPD vs. DEL, obese vs. non obese and GHD vs. non GHD subgroups, GH peaks were significantly higher in nonobese than obese patients and in non GHD than GHD patients administered with either GHRH + ARG or ARG test, apart from the comparisons in the DEL/UPD subgroups. Anyway, the ratios of peak levels of 22 kDa- to 20 kDa-GH were similar after GHRH + ARG vs. ARG in all subgroups investigated. In conclusion, this study shows that administration of two different pharmacological tests, i.e. ARG, capable of reducing hypothalamic somatostatinergic tone, and GHRH (+ ARG), that directly acts at pituitary level on the somatotropic cell, evokes the same ratios of GH isoforms in young PWS patients, suggesting that the hypothalamic dysfunction in this genetic disorder does not alter the qualitative and quantitative composition of GH isoforms present in circulation.

Metabolic syndrome is a combination of cardiometabolic risk factors, frequently detected in obese children and adolescents. To date, few clinical studies have evaluated the effectiveness of multidisciplinary body weight reduction programs on body mass index, body composition, muscle performance and fatigue in pediatric obese subjects suffering from metabolic syndrome, which might represent a sub-population that is more difficult to be treated and worthy of more intensive interventions than a population less metabolically complicated. The aim of the present study was to compare the impact of a three-week in-hospital multidisciplinary integrated body weight reduction program (BWRP) on body mass index (BMI), body composition (particularly, fat mass (FM) and fat-free mass (FFM)), motor control (evaluated by one-leg standing balance (OLSB) test), muscle performance (evaluated by the stair climbing test (SCT)) and fatigue (evaluated by fatigue severity scale (FSS)) in a pediatric obese population with or without metabolic syndrome. A pediatric population of 548 obese subjects without metabolic syndrome (F/M = 312/236, age range: 8&ndash, 18 years, BMI: 36.3 &plusmn, 6.7 kg/m2) and 96 obese subjects with metabolic syndrome (F/M = 53/43, age range: 9&ndash, BMI: 38.3 &plusmn, 6.9 kg/m2) was recruited. The BWRP significantly reduced BMI, FM (expressed as %), SCT time and FSS score, and increased OLSB time in all subgroups of obese subjects, independent of sex and metabolic syndrome, with preservation of FFM. No significant differences in |&Delta, BMI|, |&Delta, FM|, |&Delta, OLSB| or |&Delta, SCT| times and |&Delta, FSS| score were found when comparing subjects (males and females) with or without metabolic syndrome, apart from obese females without metabolic syndrome, who exhibited a lower weight loss and FM (expressed as %) reduction when compared to the corresponding male counterpart. In conclusion, the beneficial effects of a three-week BWRP on BMI, body composition, muscle performance and fatigue in a pediatric obese population were not found to be different in patients with or without metabolic syndrome, thus indicating that the more metabolically compromised patient is as responsive to a short-term BWRP as the patient without metabolic syndrome. More prolonged follow-up studies are, however, necessary in order to verify whether the adherence to the multidisciplinary recommendations at home and the long-term maintenance of the positive effects in the two subgroups of patients will remain similar or not.

Background: Obesity is a widespread problem in the elderly, being associated with severe comorbidities negatively influencing life expectancy. Integrated multidisciplinary metabolic rehabilitation aimed to reduce body weight (BW) and fatigue, increase physical autonomy and introduce healthy life style changes has been proposed as a useful intervention to improve the general health status and quality of life of the obese geriatric population. Methods: Six hundred-eighty four severely obese subjects (F/M = 592/92, age range: 61&ndash, 83 years, mean body mass index, BMI &plusmn, SD: 42.6 &plusmn, 5.6 kg/m2) were admitted to take part in a three-week in-hospital BW reduction program (BWRP), entailing energy restricted diet, psychological counselling, physical rehabilitation and nutritional education. Biochemical parameters, cardiovascular risk factors (throughout the Coronary Heart Disease Risk, CHD-R), fatigue (throughout the Fatigue Severity Scale, FSS) and lower limb muscle performance (throughout the Stair Climbing Test, SCT) were evaluated before and at the end of the BWRP. Results: A 4% BW reduction was achieved at the end of the BWRP. This finding was associated with a significant improvement of the metabolic homeostasis (i.e., decrease in total cholesterol and glucose) and a reduction of systolic blood pressure in both females and males, thus resulting in a reduction of CHD-R in the male group. Total FSS score and SCT time decreased in female and male obese patients. The effects of BWPR were comparable among all age-related subgroups (&gt, 60, 60&ndash, 69 and &gt, 70 years), apart from &Delta, CHD-R, which was higher in male subgroups. Finally, age was negatively correlated with &Delta, BMI and &Delta, FSS. Conclusions: Though only a relatively limited number of outcomes were investigated, the present study shows that a 4% BW reduction in severely elderly obese patients is associated with positive multisystemic effects, particularly, muscle-skeletal and cardiometabolic benefits, which can favorably influence their general well-being and improve the autonomy level in performing more common daily activities. The maintenance of a healthy life style, including controlled food intake and regular physical activity, after a BWRP is obviously recommended in all elderly obese patients to further improve their clinical condition.

Exercise is recognized to evoke multisystemic adaptations that, particularly in obese subjects, reduce body weight, improve glucometabolic control, counteract sarcopenia, and lower the risk of cardiometabolic diseases. Understanding the molecular and cellular mechanisms of exercise-induced benefits is of great interest due to the therapeutic implications against obesity. The aim of the present study was to evaluate time-related changes in size distribution and cell origin of extracellular vesicles (EVs) in obese and normal-weight subjects who underwent a moderate-intensity exercise on a treadmill (at 60% of their VO2max). Blood samples were drawn before, immediately at the end of the exercise and during the postexercise recovery period (3 and 24 h). Circulating EVs were analyzed by a nanoparticle tracking analysis and flow cytometry after labeling with the following cell-specific markers: CD14 (monocyte/macrophage), CD61 (platelet), CD62E (activated endothelium), CD105 (total endothelium), SCGA (skeletal muscle), and FABP (adipose tissue). In all subjects, acute exercise reduced the release of total (i.e., 30–700 nm) EVs in circulation, predominantly EVs in the microvesicle size range (i.e., 130–700 nm EVs). The postexercise release of microvesicles was higher in normal-weight than obese subjects; after exercise, circulating levels of exosomes (i.e., 30–130 nm EVs) and microvesicles were, respectively, lower and higher in females than males. In all experimental subgroups (males vs. females and obese vs. normal-weight subjects), acute exercise reduced and increased, respectively, CD61 + and SCGA + EVs, being the effect on CD61 + EVs prolonged up to 24 h after the end of the test with subjects in resting conditions. Total EVs, exosomes, and CD61 + EVs were associated with HOMA-IR. Though preliminary, the results of the present study show that a single bout of acute exercise modulates the release of EVs in circulation, which are tissue-, sex-, and BMI specific, suggesting that the exercise-related benefits might depend upon a complex interaction of tissue, endocrine, and metabolic factors.

Describing the health status of a population is difficult, especially in the case of irregular migrants who are now a growing population in western Countries. Data for children of these families are almost inexistent. In the absence of databases on this peculiar pediatric population, we analyzed drugs dispensation by a major Charity to have an insight into their health needs. This observational retrospective study was carried out during the entire 2015 and enrolled 628 undocumented children. A cohort of 8438 adult patients belonging to the same ethnic groups was used for comparison. Respiratory drugs were those most commonly prescribed, followed by those for skin and ocular diseases and by those for gastrointestinal disorders. Also in adults respiratory medications were the most dispensed, but almost in equal measure than cardiovascular drugs.To our knowledge this is the first study on the health needs of undocumented children residing in a western Country. The method we used seems to be a useful method for epidemiological analysis. As could be expected, respiratory and skin diseases ranked first, possibly owing to environmental factors.

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.

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 &plusmn, 1.0 years, body mass index (BMI): 36.4 &plusmn, 4.6 kg/m&sup2, fat-free mass (FFM): 54.9 &plusmn, 4.7%, fat mass (FM): 45.1 &plusmn, 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.

Background Growth hormone (GH) is a heterogeneous protein composed of several molecular isoforms, the most abundant ones being the 22 kDa- and 20 kDa-GH. Exercise-induced secretion of GH isoforms has been extensively investigated in normal-weight individuals due to antidoping purposes, particularly recombinant human GH (rhGH) abuse. On the other hand, the evaluation of exercise-induced responses in GH isoforms has never been performed in obese subjects. Methods The acute effects of whole body vibration (WBV) or maximal voluntary contraction (MVC) alone and the combination of MVC with WBV (MVC + WBV) on circulating levels of 22 kDa- and 20 kDa-GH were evaluated in 8 obese male adolescents [mean age ± SD: 17.1 ± 3.3 yrs.; weight: 107.4 ± 17.8 kg; body mass index (BMI): 36.5 ± 6.6 kg/m2; BMI standard deviation score (SDS): 3.1 ± 0.6]. Results MVC (alone or combined with WBV) significantly stimulated 22 kDa- and 20 kDa-GH secretion, while WBV alone was ineffective. In particular, 22 kDa- and 20 kDa-GH peaks were significantly higher after MVC + WBV and MVC than WBV. In addition, 22 kDa-GH (but not 20 kDa-GH) peak was significantly higher after MVC + WBV than MVC. Importantly, the ratio of circulating levels of 22 kDa- to 20 kDa-GH was constant throughout the time window of evaluation after exercise and similar among the three different protocols of exercise. Conclusions The results of the present study confirm the ability of MVC, alone and in combination with WBV, to stimulate both 22 kDa- and 20 kDa-GH secretion in obese patients, these responses being related to the exercise workload. Since the ratio of 22 kDa- to 20 kDa-GH is constant after exercise and independent from the protocols of exercise as in normal-weight subjects, hyposomatotropism in obesity does not seem to depend on an unbalance of circulating GH isoforms. Since the present study was carried out in a small cohort of obese sedentary adolescents, these preliminary results should be confirmed in further future studies enrolling overweight/obese subjects with a wider age range.

Background The anabolic, lipolytic and anti-inflammatory effects of exercise-stimulated GH secretion could be usefully exploited in the multidisciplinary rehabilitative programs of obese patients, who are reported to suffer from hyposomatotropism. To date, evaluation of GH responses to whole body vibration (WBV) in combination with maximal voluntary contractions (MVC) has been performed in normal-weight subjects, but not obese patients. Thus, aim of the present study was to investigate the effects of WBV and MVC, alone and combined, on GH responsiveness in obese subjects. Methods The acute effects of WBV or MVC alone and the combination of MVC with WBV (MVC + WBV) on serum GH, cortisol and IGF-I and blood lactate (LA) levels were evaluated in 8 obese male adolescents [mean age ± SD: 17.1 ± 3.3 yrs.; weight: 107.4 ± 17.8 kg; body mass index (BMI): 36.5 ± 6.6 kg/m2; BMI standard deviation score (SDS): 3.1 ± 0.6]. Results WBV and MVC (alone or combined) significantly stimulated GH secretion. In particular, GH peaks and net areas under the curve (nAUCs) were significantly higher after MVC + WBV and MVC than WBV, without any difference between MVC + WBV and MVC groups; anyway, an additive effect on GH levels immediately after the execution of MVC + WBV test was found in comparison with MVC test. LA peaks significantly increased after each exercise (vs. basal condition), being significantly higher after MVC + WBV and MVC than WBV, without any difference between MVC + WBV and MVC groups. Peak LA values were significantly correlated with GH peaks and nAUCs. In contrast to the unchanged IGF-I levels, MVC + WBV and MVC (but not WBV) significantly stimulated cortisol secretion. Conclusions The results of the present study confirm the ability of MVC and WBV to stimulate GH secretion in obese patients. Rehabilitative programs combining different types of exercise eliciting a potent GH response seem to be important to counteract the hyposomatotropism of obese patients. Due to its limited stress upon joints without provoking an excessive fatigue, WBV could be usefully employed in the initial stages of a weight loss program alone or in combination with more potent GH releasing stimuli, such as MVC.

An algorithm to identify patients with type 2 diabetes among undocumented migrants using data on drug dispensation by charities. Gianfrancesco Fiorini, Cesare Cerri, Antonello E Rigamonti, Silvia Bini, Nicoletta Marazzi, Alessandro Sartorio, Silvano G. Cella Abstract Background. Electronic databases of chronic diseases are available in many countries. Health data of residents, natives and documented migrants, are thus easily accessible. This does not happen for the growing population of undocumented migrants. Methods. We analysed the databases of two Italian non-governmental organisations (NGOs) containing the records of all drug dispensations to 12,386 undocumented migrants from January 1st, 2013 to December 31st, 2016, with the aim to identify treated for type 2 diabetes (T2D) on the basis of demographic data and dispensed medicines. Medications were identified according to the Anatomical Chemical Therapeutic (ATC) classification. All the patients with at least one dispensation per year of any A10 (antidiabetic) drug were selected. An algorithm to match this observation with the diagnosis of type 2 diabetes mellitus (T2D), on the basis of demographic data and use or not of insulin, was developed. The algorithm was validated in 400 diabetic and 400 non-diabetic patients randomly selected. Results. The algorithm correctly identified all patients (N=660) with T2D. When our patients were grouped according to ethnicity, we found that all ethnic groups contributed a comparable percentage of patients with T2D. Also, no difference was seen between the group of EU citizens living in poverty cared for by the NGOs and any of the ethnic groups. Conclusions. This algorithm can be used to identify patients treated for T2D when no diagnostic codes are available, as is frequently the case with undocumented migrants. Therefore it can be useful for many aspects of public health.

Several studies have demonstrated that the obesity-related hyposomatropism is usually reversible after a consistent weight loss induced by diet and/or bariatric surgery. Recently, a single bout of respiratory muscle endurance training (RMET) by means of a specific commercially available device (Spiro Tiger®) has been reported to induce a marked GH response in obese adults, its GH-releasing effect being significantly lower in obese adolescents. The GH response disappeared in both obese adults and adolescents when RMET was repeated at 2-h intervals in-between. The aim of the present study was to evaluate GH responses to repeated bouts of RMET administered before and after a 3-week in-hospital multidisciplinary body weight reduction program (entailing energy-restricted diet, 90 min/daily aerobic physical activity, psychological counseling, and nutritional education) combined with a progressively increasing RMET (15 daily sessions, 5 sessions per week) in 7 obese male adolescents [age: 12-17 years; body mass index (BMI): 38.5±3.1 kg/m2; percent fat mass (FM): 37.0±2.0%]. Blood samplings for GH determinations were collected during the 1st and 15th sessions, which were composed of 2 consecutive bouts of RMET (of identical intensity and duration) at 2-h interval in-between. At the beginning of the study, baseline GH levels significantly increased after the first bout of RMET in all subjects (p0.05). The administration of the second bout of RMET resulted in a significantly lower (p0.05) GH increase in comparison with the first one. Three weeks of the integrated intervention significantly reduced both body weight (from 115.3±9.2 kg to 111.5±8.7 kg, p0.05) and FM (from 43.1±5.7 kg to 41.9±5.3 kg, p0.05), these combined effects being, however, not sufficient to influence GH responsiveness to the 2 repeated bouts of RMET (GH peaks to the first bout: 4.8±1.6 ng/ml vs. 4.8±1.6 ng/ml; GH peaks to the second bout: 0.9±0.2 ng/ml vs. 1.1±0.1 ng/ml, before and after 3 weeks of the treatment, respectively, p=NS). In conclusion, a 3-week incremental RMET combined with a body weight reduction intervention does not seem useful to positively influence the reduced GH responsiveness to 2 repeated RMET bouts in obese adolescents. More intensive and/or long-term RMET protocols, associated with energy-restricted diets, determining more consistent changes in body composition, are likely needed to restore the impaired GH-IGF-1 function of obese adolescents.

Repeated bouts of GH-releasing stimuli (both pharmacological and physiological, such as aerobic exercise) at 2-h intervals are associated with a blunting of somatotropic responsiveness in normal adults, while a persistent GH responsiveness to consecutive stimuli is reported to occur in children and adolescents. Recently, a single bout of respiratory muscle endurance training (RMET) by means of a specific commercially available device (Spiro Tiger®) has been shown to induce relevant GH responses in both normal-weighted and obese adult subjects. The aim of the present study was to evaluate GH responses to repeated bouts of RMET in obese adolescents and adults. Seven obese male adolescents (age: 15.7±0.4 years; body mass index, BMI: 38.0±3.3 kg/m2) and 10 obese adults (age: 22.2±1.4 years; BMI: 39.9±1.0 kg/m2) underwent an incremental progressive RMET protocol of 11 daily sessions. Blood samplings for GH determinations were collected during the 12th session, which was composed of 2 consecutive bouts of RMET (of identical intensity and duration: 1 min at a respiration rate of 28 acts/min, 5 min at 32 acts/min, 5 min at 34 acts/min, 4 min at 36 acts/min) at a 2-h interval in-between. Baseline GH levels significantly increased after the first bout of RMET in all subjects, higher GH peaks being found in obese adults than in obese adolescents (peaks: 14.3±2.1 ng/ml vs. 4.8±1.6 ng/ml, respectively, p

In recent years, whole body vibration (WBV) has become an efficient complement or alternative to resistance training. Very limited data on the effects of different WBV protocols on anabolic hormones are available. In this study, we compared the growth hormone (GH), blood lactate (LA), and cortisol responses to different protocols involving WBV. Six healthy women recreationally active performed 10 sets of 12 dynamic squats in the following conditions: squatting alone (S), squatting+vibration (SV), squatting+external load (SE), and squatting+external load+vibration (SEV). All responses at the different stimuli determined acute increases in GH, cortisol, and LA. In particular, GH secretion significantly increased in all 4 conditions immediately after the exercise session compared to other time points. Furthermore, a significantly larger increase was identified following SEV as compared to the other conditions. Cortisol concentrations significantly decreased after S, SV and SE whereas they increased significantly following SEV. LA peaks occurred immediately at the end of each condition. However it reached statistical significance only following SEV. The results of our study demonstrate that the combination of squatting+external load+vibration (SEV) could represent the most suitable modality to potentiate the somatotropic function and, indirectly, to obtain an increase in muscle strength and positive changes in the body composition. Further studies are necessary in order to determine the chronic effects of this exercise modality on the hormonal profile.

ObjectiveEating slowly increases the postprandial responses of some anorexigenic gut hormones in healthy lean subjects. As the rate of food intake is positively associated with obesity, the aim of the study was to determine whether eating the same meal at different rates evokes different postprandial anorexigenic responses in obese adolescent and adult subjects.Design and methodsEighteen obese adolescents and adults were enrolled. A test meal was consumed on two different sessions by each subject, meal duration taking either 5 min (fast feeding) or 30 min (slow feeding). Circulating levels of glucagon-like peptide 1 (GLP1), peptide YY (PYY), glucose, insulin, and triglycerides were measured over 210 min. Visual analog scales were used to evaluate the subjective feelings of hunger and satiety.ResultsFast feeding did not stimulate GLP1 release in obese adolescent and adults, whereas slow feeding increased circulating levels of GLP1 only in obese adolescents. Plasma PYY concentrations increased both in obese adolescents and in adults, irrespective of the eating rate, but slow feeding was more effective in stimulating PYY release in obese adolescents than in adults. Simultaneously, slow feeding evoked a higher satiety only in obese adolescents compared with fast feeding but not in obese adults. In obese adolescents, slow feeding decreased hunger (only at 210 min). Irrespective of the eating rate, postprandial responses of insulin and triglycerides were higher in obese adults than in obese adolescents. Conclusion: Slow feeding leads to higher concentrations of anorexigenic gut peptides and favors satiety in obese adolescents, but this physiological control of food intake is lost in obese adults.

Although different hypotheses have been proposed, the underlying mechanism(s) of the weight loss induced by laparoscopic sleeve gastrectomy (LSG) is still unknown. The aim of this study was to determine whether eating the same meal at different rates (fast vs. slow feeding) evokes different post-prandial anorexigenic gut peptide responses in ten obese patients undergoing LSG. Circulating levels of GLP-1, PYY, glucose, insulin and triglycerides were measured before and 3 months after LSG. Visual analogue scales were used to evaluate the subjective feelings of hunger and satiety. Irrespective of the operative state, either fast or slow feeding did not stimulate GLP-1 release (vs. 0 min); plasma levels of PYY were increased (vs. 0 min) by fast and slow feeding only after LSG. There were no differences in post-prandial levels of GLP-1 when comparing fast to slow feeding or pre-to-post-operative state. Plasma levels of PYY after fast or slow feeding were higher in post, rather than pre-operative state, with no differences when comparing PYY release after fast and slow feeding. Hunger and satiety were decreased and increased, respectively, (vs. 0 min) by food intake. Fast feeding evoked a higher satiety than slow feeding in both pre- and post-operative states, with no differences in hunger. In both pre- and post-operative states, there were similar responses for hunger and satiety after food intake. Finally, LSG improved insulin resistance after either fast or slow feeding. These (negative) findings would suggest a negligible contribution of the anorexigenic gut peptide responses in LSG-induced weight loss.

Hedonic and homeostatic hunger represent two different forms of eating: just for pleasure or following energy deprivation, respectively. Consumption of food for pleasure was reported to be associated with increased circulating levels of both the orexigenic peptide ghrelin and some specific endocannabinoids in normal-weight subjects and patients with morbid obesity. To date, the effects of palatable food on these mediators in Prader–Willi syndrome (PWS) are still unknown. To explore the role of some gastrointestinal orexigenic and anorexigenic peptides and endocannabinoids (and some related congeners) in chocolate consumption, we measured changes in circulating levels of ghrelin, cholecystokinin (CCK), peptide YY (PYY), anandamide (AEA), 2-arachidonoyl-glycerol (2-AG), palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) in eight satiated adult PWS patients after consumption of chocolate and, on a separate day, of a non-palatable isocaloric food with the same macronutrient composition. Evaluation of hunger and satiety was also performed by visual analogic scale. The anticipatory phase and the consumption of food for pleasure were associated with decreased circulating levels of PYY. An increase in PEA levels was also observed. By contrast, circulating levels of ghrelin, CCK, AEA, 2-AG and OEA did not differ before and after the exposure/ingestion of either chocolate or non-palatable foods. Hunger and satiety were similar in the hedonic and non-palatable sessions. In conclusion, when motivation to eat is promoted by highly palatable foods, a depressed post-prandial PYY secretion is observed in PWS. Although preliminary, these findings seem to hypothesize a possible role of PYY agonists in the management of PWS patients. Abbreviations: AEA, Anandamide; 2-AG, 2-arachidonoyl-glycerol; CB1, cannabinoid receptor type 1; OEA, oleoylethanolamide; PEA, palmitoylethanolamide; PWS: Prader-Willi syndrome; VAS, visual analog scales

Reportedly, fibromyalgia (FM) is frequently associated with reduced IGF-1 levels and GH hyporesponsiveness to different GH stimulation tests. Since there is a high prevalence of obesity in FM, and obesity itself is characterized by hyposomatotropism, the aim of this study was to assess IGF-1 levels and GH responsiveness in sixteen severely obese women suffering from FM, who, subdivided into two subgroups on the basis of their age-dependent IGF-1 values (> or

To evaluate psychotropic drug use in undocumented migrants and natives in the same conditions of poverty. We studied drug dispensation by a nongovernmental organization during the year 2014. Drugs were identified according to the Anatomical Chemical Therapeutic classification and their quantity was measured in defined daily doses (DDD). We determined the percentage of patients taking at least one medicine with psychotropic activity in relation to the total number of patients receiving medicines of any class. We also calculated the individual DDD for psychoactive drugs. The percentage of natives receiving this type of medicine is significantly higher than that of undocumented migrants. Individual DDDs for each class of psychotropic drug are comparable in Italians and undocumented migrants and, among the latter, no difference was found in relation to ethnicity. Our findings describe for the first time the use of psychotropic medicines by undocumented migrants. On this basis, we hypothesize that poverty is more important than migration and ethnicity in generating the need for this type of pharmacological treatment. Both natives and undocumented migrants show poor adherence to treatment. This situation should be considered when programming health interventions in this field for the very poor and undocumented migrants.

Background: Whole body vibration (WBV) has been reported to exert growth hormone(GH)-releasing effects in healthy subjects. Despite the potential of WBV to positively affect body composition changes via lipolytic effects, few studies have been performed in obese subjects to date. Methods: This study evaluated the acute effects of WBV alone or in combination with squatting plus external load (WBV+S) on serum GH levels and blood lactate concentrations in 7 severely obese women (age 22 ± 5 years; BMI 39.9 ± 2.9 kg/m2). Results: WBV and WBV+S determined a significant GH increase (mean GH peaks 5.1 ± 1.9 ng/ml, p < 0.001 vs. basal, and 6.5 ± 3.7 ng/ml, p < 0.001 vs. basal, respectively), GH peaks occurring immediately after both exercise sessions. No significant differences were observed between GH peaks and GH net incremental area under the curve (nAUC) after both conditions (p = 0.39 and p = 0.53, respectively), the whole pattern of GH responsiveness being comparable among all the subjects. Lactate concentrations increased after both conditions (mean lactate peaks 2.0 ± 0.5 mmol/l, p < 0.05 vs. basal, and 4.5 ± 2.0 mmol/l, p < 0.001 vs. basal, respectively). The lactate response was significantly higher after WBV+S than after WBV (p < 0.05). Baseline GH and GH peak values positively correlated to baseline lactate and lactate peak concentrations in both conditions (R2 = 0.64, p < 0.001, and R2 = 0.52, p < 0.05, respectively). Conclusions: WBV alone stimulates GH release and lactate production in severely obese female subjects, with no additive effect when combined with squatting plus external load. Further additional studies are required to verify the chronic effects of WBV exercise on the GH/IGF-1 system, which could represent a potentially effective approach for weight management in obese subjects.

To investigate in severely obese adolescents the effects of a 3-week multidisciplinary weight-reduction intervention involving moderate energy restriction, individualised physical activity and behavior therapy on the response of somehormonal and metabolic parameters to meals and exercise. DESIGN: Clinical longitudinal study on in-patients in a specialised institution. SUBJECTS: A total of 20 obese adolescents (10 boys and 10 girls) aged 12-17 yr [body mass index (BMI): 37.7±6.1 kg/m2; fat mass (FM): 44.8±13.2 kg]. MEASUREMENTS: The changes in plasma concentration of leptin, ghrelin, growth hormone (GH), insulin-like growth factor 1 (IGF-1), insulin, glucose and non esterified fatty acids (NEFA) in response to standardised meals and exercise bouts were measured before and after the weight-reduction intervention. At the same times, body composition was assessed by bioelectrical impedance as well as appetite sensations using a visual analog scale. RESULTS: At the end of the intervention, the adolescents had lost body weight and FM (expressed both in kg and %) (P < 0.05), without any significant fat-free mass (FFM) loss (in % terms). In response to both meals and exercise, after the 3-week intervention, plasma leptin concentration decreased significantly (P < 0.05), whereas the other hormones (insulin, ghrelin, GH and IGF-1) and metabolic parameters (glucose and NEFA) did not change. Interestingly, appetite was not affected by the intervention. CONCLUSION: This 3-week multidisciplinary intervention in obese adolescents induced a significant body weight loss with beneficial changes in body composition. However, despite there being no change in metabolic parameters and ghrelin in response to meals and exercise after the intervention, plasma concentrations of leptin were decreased. The failure of ghrelin levels to increase by this approach might explain the good control of appetite observed at the end of the study.

Background and aimsGhrelin is an orexigenic 28-amino acid peptide produced by the stomach. Circulating ghrelin levels rise shortly before and fall shortly after every meal. Peptide YY (PYY), an anorexigenic 36-amino acid peptide, is secreted primarily from the intestinal mucosa of the ileum and large intestine. Plasma PYY levels begin to rise within 15 min after starting to eat and plateau within ∼90 min, remaining elevated for up to 6 h. Recently, some studies have tried to evaluate the potential role of ghrelin and PYY in the hyperphagia of patients with Prader–Willi syndrome (PWS). While hyperghrelinemia is well characterized in PWS, conflicting results have been reported for PYY. The aim of the study was to investigate ghrelin and PYY responses to a standard liquid high-fat meal in children with PWS.Patients and methodsCirculating levels of total ghrelin and PYY levels were assayed by RIA after overnight fasting and 45, 60, 90, and 180 min following a standard meal (Ensure 6 ml/kg) in 16 patients with PWS (11 boys and five girls, aged 4.6–10.7 years, including ten receiving 0.02 mg/kg per day rhGH for 2–18 months; body mass index (BMI) z-score: 0.6±0.2 and 1.6±0.5 for children treated or not treated with rhGH respectively), ten obese (eight boys and two girls, aged 9.2–15.6 years; BMI z-score: 2.4±0.2, i.e. BMI >97th centile for chronological age and sex) subjects, and 16 normal-weight controls (five boys and 11 girls, aged 5.8–17.3 years; BMI z-score: 0.6±0.2).ResultsPWS children showed higher fasting levels of ghrelin than obese and lean controls. Postprandial ghrelin drop was more pronounced in PWS than in the other study groups. No significant difference on fasting levels of PYY was found among groups. PWS showed a higher postprandial PYY rise than obese and lean controls. PWS patients treated and not treated with GH showed similar fasting and postprandial levels of ghrelin and PYY. Fasting PYY levels correlated negatively (Pr=−0.68) with those of ghrelin only in PWS. ConclusionsThe results of this study confirm fasting hyperghrelinemia in PWS. Since in PWS adults an impaired postprandial suppression of plasma ghrelin was previously reported to be associated with a blunted postprandial PYY response, the finding of a meal-induced decrease and increase in ghrelin and PYY levels respectively in PWS children would imply that the regulation of appetite/satiety of these peptides is operative during childhood, and it progressively deteriorates and vanishes in adulthood when hyperphagia and obesity worsen.

Myostatin and mechano-growth factor (MGF), an isoform of insulin-like growth factor-I (IGF-I), are two important regulators of muscle hypertrophy. The aim of the present study was to investigate the effects of recombinant human growth hormone (rhGH) and/or testosterone on muscle MGF/IGF-IEa/myostatin expression in intact and hypophysectomized rats treated for 15 d with 1) saline or rhGH, 2) sesame oil or testosterone, 3) saline+sesame oil, or rhGH+testosterone (first experiment) or for 7 d with saline or rhGH (second experiment). Animals were killed by decapitation 24 h or 4 d after the last injection (first or second experiment, respectively). Muscle expressions of MGF, IGF-IEa, and myostatin were determined by RT-PCR. A significant increase in the weight of gastrocnemius muscle was observed only in hypophysectomized rats treated with rhGH alone or in combination with testosterone. Administration of rhGH to hypophysectomized rats caused a marked increase in both MGF and IGF-IEa muscle mRNA levels (without any change in the muscle expression of myostatin), an effect that was abolished when testosterone was combined with rhGH. Conversely, in intact rats rhGH increased myostatin muscle mRNA levels without affecting those of MGF and IGF-IEa. Testosterone, alone or combined with rhGH, induced an inhibition of myostatin expression in the muscle of intact rats, but did not change muscle paradigms of hypophysectomized rats. In conclusion, rhGH and/or testosterone anabolic effects in the muscle are mediated by a different expression of MGF/IGF-IEa/myostatin, which is related to the pituitary function.