Differences in spinal posture and mobility between children/adolescents with obesity and age-matched normal-weight individuals.

The aim of this study was to cross-sectionally explore the association of obesity with spinal posture and mobility, commonly associated with musculoskeletal problems, by comparing the spinal parameters between 90 obese and 109 normal-weight children and adolescents. A non-invasive electromechanical device, the Idiag M360 (Idiag, Fehraltorf, Switzerland), was used to measure the spinal parameters. An age-and-sex-adjusted two-way analysis of variance (ANOVA) was used to determine postural and mobility differences between the two groups. Children and adolescents with obesity had significantly greater thoracic kyphosis [difference between groups (Δ) = 13.00, 95% CI 10.10-15.80, p < 0.0001] and thoracic extension (Δ = 6.50, 95% CI 2.90-11.60, p = 0.005), as well as smaller mobility in thoracic flexion (Δ = 5.00, 95% CI 1.20-8.80, p = 0.01), thoracic lateral flexion (Δ = 17.70, 95% CI 11.60-23.80, p < 0.0001), lumbar flexion (Δ = 12.10, 95% CI 8.70-15.50, p < 0.0001), lumbar extension (Δ = 7.10, 95% CI 3.10-12.20, p = 0.003) and lumbar lateral flexion (Δ = 9.10, 95% CI 5.50-12.80, p < 0.0001) compared to the normal-weight children and adolescents. These findings provide important information about the characteristics of the spine in children and adolescents with obesity and unique insights into obesity-related mechanical challenges that the spine has to withstand and strategies designed to improve spinal mobility in this young population.

Stimulated GH levels during the transition phase in Prader-Willi syndrome.

PURPOSE: Early institution of GH therapy in children with Prader-Willi syndrome (PWS) yields beneficial effects on their phenotype and is associated with a persistent improvement of body composition, both in the transition age and in adulthood. Reports from GH stimulation testing in PWS adults, however, suggest that GH deficiency (GHD) is not a universal feature of the syndrome, and the current Consensus Guidelines suggest to perform a reassessment of persistent GHD so as to continue GH therapy after reaching adult height. Few data about GH responsiveness to stimulation testing throughout the transitional period in PWS are available to date. Thus, we investigated the prevalence of GHD in a large cohort of patients with PWS during the transition phase. PATIENTS AND METHODS: One hundred forty-one PWS patients, 72 females and 69 males, aged 15.4-24.9 years, were evaluated by dynamic testing with growth hormone-releasing hormone (GHRH) plus arginine (GHRH + ARG). To define GHD, both BMI-dependent and BMI-independent diagnostic cut-off limits were considered. RESULTS: According to BMI-dependent criteria, 10.7% of normal weight (NW), 18.5% of overweight and 22.1% of obese PWS maintained a status of GHD. Similar results were obtained by adopting a cut-off limit specific for the adult age (26.2%), as well as criteria for the transition phase in NW subjects (25%). CONCLUSION: Our study shows that about 20% of patients with PWS fulfilled the criteria for GHD during the transitional age, suggesting the need of an integrated analysis of GH/IGF-I axis, in the context of the general clinical picture and other endocrine abnormalities, in all subjects after attainment of final stature.

Acute and Cumulative Effects With Whole-Body Vibration Exercises Using 2 Biomechanical Conditions on the Flexibility and Rating of Perceived Exertion in Individuals With Metabolic Syndrome: A Randomized Clinical Trial Pilot Study.

This study evaluated the effects of 6 weeks of whole-body vibration (WBV) exercise on flexibility and the rating of perceived exertion (RPE) in metabolic syndrome (MetS) individuals using 2 biomechanical conditions (fixed frequency [FF] and variable frequency [VF]). Nineteen MetS individuals were randomly allocated in FF-WBV (n = 9, 7 women and 2 men) and VF-WBV (n = 10, 8 women and 2 men) groups. Anterior trunk flexion (ATF) and RPE were determined before and after each session. The acute cumulative exposure effects were analyzed. The FF-WBV group was exposed to 5 Hz on a side alternating vibrating platform (SAVP), exposed to 10 and 50 seconds with the SAVP turned off. The VF-WBV group individuals were intermittently exposed (1 minute WBV exercise/1 minute rest) to 5 to 16 Hz, increased by 1 Hz per session and the peak-to-peak displacement (PPD) were 2.5, 5.0, and 7.5 mm. Regarding to ATF, significant improvements (P < .05) were observed in the in the acute (VF group) and cumulative intervention (FF and VF-WBV groups). The RPE significantly (P < .05) improved only in VF-WBV (cumulative intervention). In conclusion, WBV exercise improved the flexibility and decreased the RPE in MetS individuals. These findings suggest that WBV exercise can be incorporated into physical activities for MetS individuals.

Obese adolescents exhibit a constant ratio of GH isoforms after whole body vibration and maximal voluntary contractions.

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.

GH responses to whole body vibration alone or in combination with maximal voluntary contractions in obese male adolescents.

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 ±â€¯SD: 17.1 ±â€¯3.3 yrs.; weight: 107.4 ±â€¯17.8 kg; body mass index (BMI): 36.5 ±â€¯6.6 kg/m2; BMI standard deviation score (SDS): 3.1 ±â€¯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.

The relationship between hyperthyrotropinemia and metabolic and cardiovascular risk factors in a large group of overweight and obese children and adolescents.

PURPOSE: Mild TSH elevations are frequently observed in obese patients, in the absence of any detectable thyroid disease. Our objective is to evaluate the relationship between the raised TSH levels and the biochemical and clinical consequences of obesity. METHODS: This is a retrospective cross-sectional study of a large population of obese children and adolescents. We evaluated 833 subjects (340 m, 493 f), aged 14.4 ± 2.5 (range 5.2-18.5) years, height SDS 0.27 ± 1.04 (-3.49-4.35), and BMI SDS 2.94 ± 0.59 (1.60-4.68). Body composition, free T4, TSH, anti-TPO antibodies, anti-TG antibodies, inflammation markers (total WBC and the subtypes, ultrasensitive C-reactive protein), and metabolic parameters [AST, ALT, γGT, ALP, glycaemia, insulin, total cholesterol (TC), HDL-cholesterol (HDL-C), and LDL-cholesterol (LDL-C), triglycerides (TG)] were measured, and oral disposition index (ODI) and cardiovascular risk factors (TC/HDL-C and TG/HDL-C) were calculated. After exclusion of the subjects showing anti-thyroid antibodies, the remaining 779 (325 m, 454 f) were then subdivided into two subgroups according to a TSH value below (group A) or above (group B) 4.5 mU/L. RESULTS: Clinical characteristics and hematological markers of patients with and without positive anti-thyroid antibodies were similar, with the exception of higher TSH levels in the latter group. Using analysis of covariance, the subjects of group B had significantly higher values of TC (170.3 ± 28.7 vs 163.3 ± 32.9 mg/dL; p < 0.05), systolic (125.8 ± 13.5 vs 124.5 ± 13.1 mm/Hg), and diastolic blood pressure (79.2 ± 8.0 vs 77.9 ± 8.2 mm/Hg) than subjects of group A. No difference was observed in body composition, ODI, and the cardiovascular risk factors between these two groups. CONCLUSION: TSH elevation in overweight and obese children and adolescents, being associated with a higher TC and blood pressure, might negatively influence the cardiac status. Longitudinal studies are requested, however, to confirm this hypothesis and, therefore, to conclude whether a substitutive treatment with l-thyroxine is really needed in these patients.

Hedonic eating in Prader-Willi syndrome is associated with blunted PYY secretion.

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.

Short-term, supra-physiological rhGH administration induces transient DNA damage in peripheral lymphocytes of healthy women.

PURPOSE: While a good safety for recombinant human growth hormone (rhGH) therapy at replacement doses is recognized, a possible link between high concentration of the GH-IGF-I axis hormones and side negative effect has been reported. The aim of this pilot study was to assess whether a short-term exposure to supra-physiological doses of rhGH may affect DNA integrity in human lymphocytes (PBL). METHODS: Eighteen healthy Caucasian female (24.2 ± 3.5 years) were randomly included in a Control (n = 9) and rhGH administration group (n = 9, 3-week treatment). DNA damage (comet assay), chromosomal breaks, and mitotic index in phytohemagglutinin-stimulated PBL were evaluated before (PRE), immediately (POST), and 30 days (POST30) after the last rhGH administration (0.029 mg kg- 1 BW; 6 days/week), together with serum IGF-1 and IGFBP-3 concentrations. RESULTS: rhGH administration increased IGF-I, without evidence of persisting IGF-I and IGFBP-3 changes 30 days after withdrawal. Total DNA breakage (% DNA in tails) was not significantly different in subjects treated with rhGH in comparison with controls, although the rhGH-treated subjects showed an higher percentage of heavily damaged nuclei immediately after the treatment (POST30 vs. PRE: p = 0.003), with a lower mitogenic potential of lymphocytes, detectable up to the POST30 (PRE vs. POST: p = 0.02; PRE vs. POST30: p = 0.007). CONCLUSIONS: This pilot study showed that 3 weeks of short-term supra-physiological rhGH administration in healthy women induce a transient DNA damage and mitogenic impairment in PBL. The analysis of DNA damage should be explored as useful tool in monitoring the mid to long-term effects of high rhGH treatment or abuse.

Effects of high-intensity interval training on physical capacities and substrate oxidation rate in obese adolescents.

PURPOSE: To investigate the effects of a 3-week weight-management program entailing moderate energy restriction, nutritional education, psychological counseling and three different exercise training (a: low intensity, LI: 40 % V'O2max; b: high intensity, HI: 70 % V'O2max; c: high-intensity interval training, HIIT), on body composition, energy expenditure and fat oxidation rate in obese adolescents. METHODS: Thirty obese adolescents (age: 15-17 years, BMI: 37.5 kg m-2) participated in this study. Before starting (week 0, W0) and at the end of the weight-management program (week 3, W3), body composition was assessed by an impedancemeter; basal metabolic rate (BMR), energy expenditure and substrate oxidation rate were measured during exercise and post-exercise recovery by indirect calorimetry. RESULTS: At W3, body mass (BM) and fat mass (FM) decreased significantly in all groups, the decreases being significantly greater in the LI than in the HI and HIIT subgroups (BM: -8.4 ± 1.5 vs -6.3 ± 1.9 vs -4.9 ± 1.3 kg and FM: -4.2 ± 1.9 vs -2.8 ± 1.2 vs -2.3 ± 1.4 kg, p < 0.05, respectively). V'O2peak, expressed in relative values, changed significantly only in the HI and HIIT groups by 0.009 ± 0.005 and 0.007 ± 0.004 L kg FFM-1 min-1 (p < 0.05). Furthermore, the HI and HIIT subgroups exhibited a greater absolute rate of fat oxidation between 50 and 70 % V'O2peak at W3. No significant changes were observed at W3 in BMR, energy expenditure during exercise and post-exercise recovery. CONCLUSION: A 3-week weight-management program induced a greater decrease in BM and FM in the LI than in the HI and HIIT subgroups, and greater increase in V'O2peak and fat oxidation rate in the HI and HIIT than in the LI subgroup.

Drugs Delivery by Charities: A Possible Epidemiologic Indicator in Children of Undocumented Migrants.

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.

The burden of chronic noncommunicable diseases in undocumented migrants: a 1-year survey of drugs dispensation by a non-governmental organization in Italy.

OBJECTIVES: This study was carried out with two objectives. The first one was to have an insight into the prevalence of chronic noncommunicable diseases (CNCD) in undocumented migrants, and the second one was to evaluate if differences existed among different ethnic groups. STUDY DESIGN: The study is based on the collection of data on drug dispensation by a non-governmental organization (NGO) providing free medical assistance to undocumented migrants in Milan, Italy. All the prescriptions to adult subjects from January 1 to December 31 2014 (total 8438) were recorded and analyzed. All the data available for the patients receiving prescriptions (age, gender and country of birth) were also collected in anonymous form. Ethical approval for the study was given by the Ethics Committee of the NGO. METHODS: Drugs were grouped according to the anatomical therapeutic chemical (ATC) classification and their quantities expressed as daily defined doses (DDDs)/1000 patients/day. The 56 ATC levels were divided into three groups according to their use for acute, chronic, or both acute and chronic diseases. The statistical analysis of drug dispensation was performed for the whole population and for the five ethnic groups into which it had been divided. RESULTS: Prescription of medicines for chronic conditions was significantly greater than for acute (154.2 ± 45.9 vs 51.3 ± 18.4 DDD/1000 patients/day, P < 0.02) and for both acute and chronic conditions (57.9 ± 12.8 DDD/1000 patients/day, P < 0.02). Five ATC classes accounted for 60% of all chronic prescriptions. They were differently distributed among the five ethnic groups (e.g., Asians required more antihypertensives and antidiabetics, East Europeans required more lipid modifying drugs, antihypertensives and antithrombotics). CONCLUSIONS: Our data show an important use of medicines for chronic diseases in a population of undocumented migrants. Though with some limitations, this could be an indicator of a high prevalence of CNCD in this population, with significant differences among different ethnic groups. This situation should be considered when planning health interventions, also in consideration of the fact that it could have an impact on European Health Services in a short time.

Supra-physiological rhGH administration induces gender-related differences in the hypothalamus-pituitary-thyroid (HPT) axis in healthy individuals.

PURPOSE: The use of recombinant human growth hormone (rhGH) is a common habit among athletes. While the effects of rhGH administration have been described with contrasting results in males, no data exist in females to date. The aim of the present study was to evaluate the effects of rhGH administration on TSH, FT4 and FT3 levels and the time requested to return to baseline values after treatment withdrawal. METHODS: Twenty-one healthy trained male and female athletes were treated with 0.03 mg rhGH/kg body mass 6 days/week for 3 weeks. We collected blood samples immediately before the first daily rhGH administration, at 3, 4, 8, 15 and 21 days of treatment and at 3 and 9 days after rhGH withdrawal. RESULTS: In males, rhGH administration induced a significant (p < 0.01) early and stable TSH decrease and IGF-I increase, and a delayed FT4 reduction without FT3 modification, suggesting a central regulatory mechanism. In females, rhGH administration induced a significant (p < 0.01) early and transient TSH decrease and IGF-I increase, and a transient reduction in FT4 without any changes in FT3 concentrations. rhGH withdrawal was associated with a prompt normalization of TSH and FT4 levels in males, while in females the effects of rhGH treatment had already disappeared during the last period of treatment. CONCLUSION: We suggest that rhGH inhibits TSH at central level both in males and females. The pattern of normalization was different in the two genders probably due to gonadal steroids modulation on GH-IGF-I axis.

Prediction of basal metabolic rate in patients with Prader-Willi syndrome.

BACKGROUND/OBJECTIVES: The objective of this study was to develop new equations for predicting basal metabolic rate (BMR) in Prader-Willi syndrome (PWS) subjects and to compare their accuracy with commonly used equations developed by Lazzer (2007), Livingston (2005), Huang (2004), Nelson (1992), Mifflin (1990), Owen (1987), WHO (1985), Bernstein (1983) and Harris-Benedict (1919), using the Bland-Altman method. SUBJECTS/METHODS: BMR was measured by indirect calorimetry and fat-free mass (FFM) and fat mass (FM) by a tetrapolar impedancemeter in 80 Caucasian PWS patients (mean body mass index: 39.1 kg/m(2); 17-50 years). Equations were derived by stepwise multiple regression analysis using a calibration group (n:50) and tested against the validation group (n:30). RESULTS: Two new equations, based on anthropometric (BMR=body mass × 0.052+sex × 0.778-age × 0.033+2.839 (R(2)adj=0.61, s.e.=0.89 MJ per day)) or body composition (BMR=FFMx0.074+FMx0.042+sexx0.636-agex0.037+2.515 (R(2)adj=0.69, s.e.=0.82 MJ per day)), were generated. Predicted BMR (PBMR) was not significantly different from the measured BMR (<3.3%), and was accurate in 59% and 62% of patients, respectively. Nevertheless, significant magnitude bias was found for both equations (P<0.001, R(2)=0.36). The Owen (1987), Mifflin (1990), Huang (2004) and Lazzer (2007) equations showed mean differences <5% and PBMR was accurate in ~50% of patients. The Livingston (2005), WHO (1985) and Harris-Benedict (1919) equations showed a PBMR overestimation >7% and were accurate in <50% of patients. The Nelson (1992) and Bernstein (1983) equations showed a greater PBMR underestimation in >60% of subjects. CONCLUSIONS: The new prediction equations showed significantly higher accuracy compared with equations tested, with exception of Lazzer (2007) and Livingston (2005) equations, and result in lower mean differences and lower limits of agreement compared with the equations tested.

Unaltered ratio of circulating levels of growth hormone/GH isoforms in adults with Prader-Willi syndrome after GHRH plus arginine administration.

Human growth hormone (GH) is a heterogeneous protein hormone consisting of several isoforms, the most abundant being 22 kDa- and 20 kDa-GH. The availability of analytical methods to measure these GH isoforms might represent a valuable diagnostic tool to investigate GH hyposecretory states, including Prader-Willi syndrome (PWS), one of the most common causes of syndromic obesity. The aim of the present study was to measure circulating levels of 22 kDa- and 20 kDa-GH in PWS adults (n=14; M/F: 5/9; genotype DEL15/UPD15: 12/2; age: 19.0±3.7 years; BMI: 29.9±8.7 kg/m2) after combined GH releasing hormone (GHRH) plus arginine (ARG) administration. The results were analysed subdividing the study population in obese vs. nonobese (6/8) and GH deficient vs. nonGH deficient (GHD) (6/8) subjects, according to appropriate BMI-related diagnostic cut-off limits of GH peak response to the provocative test. Circulating levels of 22 kDa-GH were measured by a chemiluminescent method based on a detection monoclonal antibody targeting an epitope in the loop connecting helix 1 and 2 of GH, which is missing in 20 kDa-GH; the 20 kDa-GH was measured using a time resolved fluorescence assay based on two monoclonal antibodies with no cross-reactivity to 22-kDa GH. GHRH plus ARG significantly stimulated the secretions of 22 kDa- and 20 kDa-GH in nonobese (at 30, 45, 60 and 90 min and at 45, 60, 90 and 120 min vs. 0 min, p<0.05, with GH peaks of 15.8±10.3 ng/ml and 2.7±1.2 ng/ml, respectively) and in nonGHD PWS (at 30, 45 and 60 min and at 45, 60 and 90 min vs 0 min, p<0.05, with GH peaks of 12.5±9.0 ng/ml and 2.0±1.8 ng/ml, respectively). No significant GHRH plus ARG-induced changes in 22 kDa- and 20 kDa-GH were observed in obese or GHD PWS patients, the only exception being the increase of 22 kDa-GH (p<0.05) 60 min after the stimulus administration in GHD group (with GH peaks of 6.9±4.7 ng/ml and 0.8±0.6 ng/ml in obese subjects and 8.5±6.0 ng/ml and 1.2±1.0 ng/ml in GHD subjects for 22 kDa- and 20 kDa-GH, respectively). The GH responses for both isoforms were significantly higher in nonobese than in obese PWS patients (at 45 and 60 min for 22 kDa-GH and at 45, 60, 90 and 120 min for 20 kDa-GH, p<0.05), while no differences were detected between GHD vs. nonGHD groups. As previously reported in healthy subjects, the ratios of circulating levels of 22 kDa- to 20 kDa-GH remained constant after GHRH plus ARG both in obese/non-obese and GHD/non-GHD groups, thus suggesting the preservation of a normal balance in GH isoforms in PWS.

Does segmental body composition differ in women with Prader-Willi syndrome compared to women with essential obesity?

BACKGROUND: Subjects with Prader-Willi syndrome (PWS) have a higher fat mass and a lower fat-free mass compared to subjects with essential obesity. However, few data are presently available on the segmental body composition (BC) of PWS subjects. AIM: To evaluate whether women with PWS and women with essential obesity, matched for age and percent body fat, differ in segmental fat distribution and surrogate markers of cardiometabolic disease (CMD). SUBJECTS AND METHODS: 35 women with PWS and 50 women with essential obesity were matched for age and percent body fat using coarsened exact matching. BC was measured by dual-energy X-ray absorptiometry. Oral glucose tolerance testing and measurements of cholesterol, triglycerides, C-reactive protein, and blood pressure were performed. Comparisons between PWS and obese women were performed using generalized linear models. RESULTS: Trunk fat was lower in PWS than in obese women on both absolute [-7.3 (95% confidence interval -9.4 to -5.2) kg] and relative [-4.1 (-6.9 to -1.4)% of body fat] grounds. PWS and obese women had similar surrogate markers of CMD, with the exception of HDL-cholesterol, which was higher in PWS women. CONCLUSION: Trunk fat is lower in obese women with PWS than in those with essential obesity. Surrogate markers of CMD are, however, mostly similar in the two groups.

Prediction of basal metabolic rate in obese children and adolescents considering pubertal stages and anthropometric characteristics or body composition.

BACKGROUND/OBJECTIVES: To develop and crossvalidate new equations for predicting basal metabolic rate (BMR) in obese children and adolescents in relation to pubertal stages, anthropometric characteristics or body composition. SUBJECTS/METHODS: A total of 1696 obese Caucasian children and adolescents (mean body mass index z-score: 3.5±0.8) participated in this study. BMR was determined by indirect calorimetry and fat-free mass (FFM) and fat mass (FM) by bioelectrical impedance analysis. Equations were derived by stepwise multiple regression analysis using a calibration cohort of 848 subjects, and the equations were crossvalidated with a Bland and Altman method in the remaining 848 subjects. RESULTS: Two new specific equations based on gender (1: males; 0: females), pubertal stages (from 1 to 5, assessed according Marshall & Tanner methods) and body weight (BW, kg), stature (m) or body composition (kg) were generated as follows: (1) BMR=(BW × 0.044)+(stature × 2.836)-(pubertal stage × 0.148)+(gender × 0.781)-0.551 (adjusted coefficient of determination (R(2)adj)= 0.69 and root mean squared error (RMSE)=0.954 MJ); (2) BMR=(FFM × 0.082)+(FM × 0.037)-(pubertal stage × 0.125)+(gender × 0.706)+2.528 (R(2)adj= 0.70 and RMSE=0.943 MJ). In the crossvalidation group, mean-predicted BMR was not significantly different from the mean-measured BMR (MBMR) for all children and adolescents, as well as for boys and girls (difference<2 %), and the limits of agreement (±2 s.d.) were +1.95 and -1.98 MJ/d, (P=NS). BMR was predicted accurately (90-110% of MBMR) in 67% of subjects. CONCLUSION: The new prediction equations considering the pubertal stages allow an accurate and more appropriate (vs equations using chronological age) estimation of BMR in obese children and adolescents.

Concurrent comparison of the measurement properties of generic and disease-specific questionnaires in obese inpatients.

BACKGROUND: The concurrent comparison of questionnaires assessing health-related quality of life in the same population is necessary for better appreciating their performance and to select the best instrument for a given purpose (e.g. clinical trials and observational studies). AIM: The aim of this study was to compare the measurement properties of two disease-specific and generic questionnaires: the Obesity-related Well-Being (ORWELL97), the Obesity-Related Disability test (TSD-OC), the EuroQoL, and the World Health Organization Quality of Life questionnaire. MATERIALS/SUBJECTS: Two-hundreds and forty-nine obese inpatients [age 47 (standard deviation, SD 15) years, body mass index 44.4 (SD 5.2) kg/m(2), 69 % female] completed the four questionnaires before and after a 3-week multidisciplinary weight reduction program. Standard measurement properties were calculated and compared. RESULTS: Intra-class correlation coefficient ranged from 0.73 to 0.90 for most of the instruments and subscales. The standard error of measurement ranged from 9 to 21 % for the generic instruments, and from 9 to 44 % for the specific questionnaires. Missing data and ceiling effects were found for TSD-OC. Responsiveness was similar for all the instruments. The correlations between the change scores of the instruments were small (<0.37). CONCLUSIONS: It was not possible to identify a "best" instrument, but overall the ORWELL97 seems to show better measurement properties. The two specific instruments measured different constructs and they did not show a clear superior performance compared to the generic questionnaires.

GH responsiveness before and after a 3-week multidisciplinary body weight reduction program associated with an incremental respiratory muscle endurance training in obese adolescents.

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 (p<0.05). The administration of the second bout of RMET resulted in a significantly lower (p<0.05) 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, p<0.05) and FM (from 43.1±5.7 kg to 41.9±5.3 kg, p<0.05), 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.

Unexpectedly increased anorexigenic postprandial responses of PYY and GLP-1 to fast ice cream consumption in adult patients with Prader-Willi syndrome.

OBJECTIVE: The effect of eating rate on the release of anorexigenic gut peptides in Prader-Willi syndrome (PWS), a neurogenetic disorder clinically characterized by hyperphagia and excessive obesity, has not been investigated so far. DESIGN AND PATIENTS: Postprandial PYY and GLP-1 levels to fast (5 min) and slow (30 min) ice cream consumption were measured in PWS adult patients and age-matched patients with simple obesity and normal-weighted subjects. Visual analog scales (VASs) were used to evaluate the subjective feelings of hunger and satiety. RESULTS: Fast ice cream consumption stimulated GLP-1 release in normal subjects, a greater increase being observed with slow feeding. Fast or slow feeding did not change circulating levels of GLP-1 in obese patients, while, unexpectedly, fast feeding (but not slow feeding) stimulated GLP-1 release in PWS patients. Plasma PYY concentrations increased in all groups, irrespective of the eating rate. Slow feeding was more effective in stimulating PYY release in normal subjects, while fast feeding was more effective in PWS patients. Slow feeding evoked a lower hunger and higher satiety compared with fast feeding in normal subjects, this finding being not evident in obese patients. Unexpectedly, fast feeding evoked a lower hunger and higher satiety in PWS patients in comparison with slow feeding. CONCLUSIONS: Fast feeding leads to higher concentrations of anorexigenic gut peptides and favours satiety in PWS adult patients, this pattern being not evident in age-matched patients with simple obesity, thus suggesting the existence of a different pathophysiological substrate in these two clinical conditions.

The GHRH + arginine stimulated pituitary GH secretion in children and adults with Prader-Willi syndrome shows age- and BMI-dependent and genotype-related differences.

OBJECTIVE: The quantitative and qualitative aspects of the pituitary response in children and adults with Prader-Willi syndrome (PWS) are compared in order to verify the possible age-dependent and genotype-related differences in terms of GH secretion. DESIGN: 29 young subjects (21 males and 8 females) and 65 adults (24 males and 41 females) with PWS were studied. All subjects underwent a standard GH Releasing Hormone (GHRH 1-29, 1 µg/kg as i.v. bolus at 0 minutes)+arginine (0.5 g/kg) test. Peak GH values, standard GH area under the curve (AUC), AUC of the instantaneous secretion rate (ISR), and secretion response analysis (i.e. half-secretion time) were evaluated. A regression analysis was performed to investigate which are the patient characteristics that affect the amplitude and shape of the GH secretion response. RESULTS: Peak GH values and AUCGH were significantly higher in PWS children than in PWS adults, these differences being also significant both in PWS DEL15 (only peak GH value) and PWS UPD15. Moreover, PWS children showed significantly lower half secretion time than PWS adults, this delayed response being present both in PWS DEL15 and PWS UPD15. Significant negative correlations between AUCGH and BMISDS were observed in the two groups (adults and children), as well as in adults and children DEL15, but not in adults and children PWS UPD15. A regression analysis performed on the whole dataset showed that for PWS DEL15 the statistically significant variable explaining GH responsiveness was BMISDS (p<0.0001), while for UPD15 no statistically significant covariate was found. Conversely, when the delay of the secretion response was considered, the regression model yielding the best performances was the one with only age as a regressor (p<0.001). CONCLUSIONS: The quantitative and qualitative analyses of GH responsiveness to GHRH+arginine highlight relevant differences between PWS children and PWS adults and genotype-related traits. The negative influence of BMISDS on GH secretion reinforces the need for an early start of life-long weight management in PWS subjects.