Rare melanocortin-3 receptor mutations with in vitro functional consequences are associated with human obesity.

In contrast to the melanocortin 4 receptor, the possible role of the melanocortin 3 receptor (MC3R) in regulating body weight is still debated. We have previously reported three mutations in the MC3R gene showing association with human obesity, but these results were not confirmed in a study of severe obese North American adults. In this study, we evaluated the entire coding region of MC3R in 839 severely obese subjects and 967 lean controls of Italian and French origin. In vitro functional analysis of the mutations detected was also performed. The total prevalence of rare MC3R variants was not significantly different in obese subjects when compared with controls (P= 0.18). However, the prevalence of mutations with functional alterations was significantly higher in the obese group (P= 0.022). In conclusions, the results of this large study demonstrate that in the populations studied functionally significant MC3R variants are associated with obesity supporting the current hypothesis that rare variants might have a stronger impact on the individual susceptibility to gain weight. They also underline the importance of detailed in vitro functional studies in order to prove the pathogenic effect of such variants. Further investigations in larger cohorts will be needed in order to define the specific phenotypic characteristics potentially correlated with reduced MC3R signalling.

TECNOB Study: Ad Interim Results of a Randomized Controlled Trial of a Multidisciplinary Telecare Intervention for Obese Patients with Type-2 Diabetes.

BACKGROUND: Obesity increases the risk of many health complications such as hypertension, coronary heart disease and type 2 diabetes, needs long-lasting treatment for effective results and involves high public and private care-costs. Therefore, it is imperative that enduring and low-cost clinical programs for obesity and related co-morbidities are developed and evaluated. Information and communication technologies (ICT) can help clinicians to deliver treatment in a cost-effective and time-saving manner to a large number of obese individuals with co-morbidities. OBJECTIVE: To examine ad interim effectiveness of a 12-month multidisciplinary telecare intervention for weight loss provided to obese patients with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS: A single-center randomized controlled trial (TECNOB study) started in December 2008. At present, 72 obese patients with type 2 diabetes have been recruited and randomly allocated to the TECNOB program (n=37) or to a control condition (n=39). However, only 34 participants have completed at least the 3-month follow-up and have been included in this ad interim analysis. 21 out of them have reached also the 6-month follow-up and 13 have achieved the end of the program. Study is still on-going. INTERVENTION: All participants attended 1-month inpatient intensive program that involved individualized medical care, diet therapy, physical training and brief psychological counseling. At discharge, participants allocated to the TECNOB program were instructed to use a weight-loss web-site, a web-based videoconference tool, a dietary software installed into their cellular phones and an electronic armband measuring daily steps and energy expenditure. MAIN OUTCOME MEASURES: Weight and disordered eating-related behaviors and cognitions (EDI-2) at entry to hospital, at discharge from hospital, at 3,6 and 12 months. RESULTS: Ad interim analysis of data from 34 participants showed no statistically significant difference between groups in weight change at any time-point. However, within-group analysis revealed significant reductions of initial weight at discharge from hospital, at 3 months, at 6 months but not at 12 months. Control group had higher scores in Interpersonal distrust at 12 months. CONCLUSION: This ad interim findings revealed that the effect of the inpatient treatment was high and probably overwhelmed the effect of the TECNOB intervention. Much statistical power and long-term follow-up may enhance the probability to detect the TECNOB effect over and above the great one exerted by the inpatient program.

TECNOB: study design of a randomized controlled trial of a multidisciplinary telecare intervention for obese patients with type-2 diabetes.

BACKGROUND: Obesity is one of the most important medical and public health problems of our time: it increases the risk of many health complications such as hypertension, coronary heart disease and type 2 diabetes, needs long-lasting treatment for effective results and involves high public and private costs. Therefore, it is imperative that enduring and low-cost clinical programs for obesity and related co-morbidities are developed and evaluated. METHODS/DESIGN: TECNOB (TEChnology for OBesity) is a comprehensive two-phase stepped down program enhanced by telemedicine for the long-term treatment of obese people with type 2 diabetes seeking intervention for weight loss. Its core features are the hospital-based intensive treatment (1-month), that consists of diet therapy, physical training and psychological counseling, and the continuity of care at home using new information and communication technologies (ICT) such as internet and mobile phones. The effectiveness of the TECNOB program compared with usual care (hospital-based treatment only) will be evaluated in a randomized controlled trial (RCT) with a 12-month follow-up. The primary outcome is weight in kilograms. Secondary outcome measures are energy expenditure measured using an electronic armband, glycated hemoglobin, binge eating, self-efficacy in eating and weight control, body satisfaction, healthy habit formation, disordered eating-related behaviors and cognitions, psychopathological symptoms and weight-related quality of life. Furthermore, the study will explore what behavioral and psychological variables are predictive of treatment success among those we have considered. DISCUSSION: The TECNOB study aims to inform the evidence-based knowledge of how telemedicine may enhance the effectiveness of clinical interventions for weight loss and related type-2 diabetes, and which type of obese patients may benefit the most from such interventions. Broadly, the study aims also to have a effect on the theoretical model behind the traditional health care service, in favor of a change towards a new "health care everywhere" approach.

Use of the ICF to describe functioning and disability in obese patients.

PURPOSE: To describe the functioning and disability in adult patients with severe obesity through an implementation of ICF-based tools in a clinical inpatient setting, and to highlight the most relevant domains of functioning. METHODS: Adult obese inpatients with BMI > or = 35 kg/m(2) were enrolled and underwent a clinical evaluation following a standardized diagnostic protocol. ICF categories were filled according to established coding rules, on the basis of an extended list composed by ICF Core Set for obesity, the ICF checklist and other categories linked to the diagnostic protocol. Categories reported as a problem by at least 20% of patients were considered relevant for describing functional profiles of obese patients. RESULTS: Fifty-one patients were enrolled and 43 ICF categories were selected: 11 body functions (26% out of the total selected categories), 3 body structures (7%), 15 activities and participation (35%) and 14 environmental factors (32%). Six ICF categories were not included in the Core-Set for obesity. CONCLUSIONS: Our study shows the applicability of an extended list of ICF categories to describe functioning and disability of obese patients, and provide a preliminary indication to expanding the ICF Core Set for obesity.

Sporadic mutations in melanocortin receptor 3 in morbid obese individuals.

Several mutations in the melanocortin receptor 4 gene have been identified in humans and account for 3-6% of morbid obesity. In contrast, strong evidence of a causative role for melanocortin receptor 3 (MC3R) mutations are still lacking. In MC3R knockout mice, high feed efficiency rather than hyperphagia seems to contribute to increased fat mass. On the basis of this evidence, the objective of the present study was to investigate the presence of MC3R mutations in a group of 290 obese subjects (mean BMI 44.2+/-5.9 kg/m2). As a control, a group of 215 normal-weight subjects (mean BMI 22.4+/-2.7 kg/m2) was also screened. Three novel mutations in the MC3R gene (A293T, I335S and X361S) were identified among the obese patients. The mutations segregated with obesity in the members of the families studied. In vitro expression studies of each mutation demonstrated a loss of function of the I335S-mutated receptor. These findings suggest that, in humans, MC3R mutations may be a cause of a dominantly inherited form of obesity. However, this association as well as the specific phenotypic characteristics resulting from these mutations need to be further evaluated in larger series of obese subjects.

Evaluation of rosiglitazone administration on cardiovascular function in severe obesity.

BACKGROUND: Obese patients have myocardial structural and functional alterations related to insulin resistance. HYPOTHESIS: The purpose of the study was to analyze the effects of rosiglitazone, an insulin sensitizer agent, on cardiac morphometry and functioning. METHODS: In 2 groups of sex- and age-matched, nondiabetic, obese patients (5 men and 7 women, age 19-51 y; group A: body mass index [BMI] 40.6 +/- 3.4 kg/m(2); group B: BMI 42.6 +/- 2.7 kg/m(2)), we evaluated the basal insulin sensitivity index (HOMA[IS]), body composition by bioelectrical impedance analysis and 24-h blood pressure monitoring. Furthermore, all patients underwent conventional 2-Dimensional and color Doppler echocardiography, and pulsed-wave tissue Doppler imaging (TDI). After the baseline evaluation, all patients were put on a hypocaloric diet (70% basal metabolic rate) plus placebo if they were in group A, or plus rosiglitazone (4 mg twice daily; Avandia [GlaxoSmithKline plc., Brentford, Middlesex, United Kingdom]) if they were in group B, for 6 mo. RESULTS: Significant decreases in body weight, total fat mass, BMI, and systolic blood pressure were registered in both groups. Rosiglitazone administration appeared more efficient in improving HOMA(IS) (mean difference: 0.30 +/- 0.19 versus 0.11 +/- 0.21, p < 0.05). Left ventricular (LV) diastolic diameter (49.4 +/- 7.7 versus 52.3 +/- 5.4 mm, p < 0.05) and E wave (0.89 +/- 0.18 versus 0.99 +/- 0.20 m/sec, p < 0.05) increased in the rosiglitazone group due to a rise in preload and water content without peripheral edema. The increase in systolic (Sa) wave velocity in both groups was probably a result of the general improvement in insulin metabolism and the decrease in blood pressure. CONCLUSIONS: We confirmed the positive effect of rosiglitazone on glucose metabolism in obese, nondiabetic patients, but changes in insulin sensitivity did not explain the cardiac effects produced by further mechanisms.

Short-term effects of a hypocaloric diet and a physical activity programme on weight loss and exercise capacity in obese subjects with chronic ischaemic heart disease: a study in everyday practice.

OBJECTIVE: The objective of this paper is to describe the effects of a rehabilitation programme in obese patients affected with chronic ischaemic heart disease; to identify the factors that influence weight loss and improvement in exercise capacity in everyday practice. METHODS AND RESULTS: We studied 562 white patients (381 men) who followed a 23.3 +/- 3.9 days in-hospital programme. They attended daily sessions of aerobic activity (cycloergometer, walking, and strength exercise); a low-calorie diet was set at approximately 80% of resting energy expenditure. By the end of the programme BMI decreased from 38.0 +/- 4.9 to 36.7 +/- 4.8 kg/m2 (P < 0.001 ). Attained metabolic equivalents (METs) increased from 6.2 +/- 2.5 METs to 7.3 +/- 2.7 (P < 0.001). Age, sex, presence of diabetes and education level were significantly related to the outcomes. Patients who took beta-blockers and statins had less BMI improvement: -1.2 +/- 0.7 kg/m2 vs. -1.4 +/- 0.6 (P = 0.013) and -1.3 +/- 0.6 vs. -1.4 +/- 0.7 (P = 0.023), respectively. Patients that took diuretics and angiotensin receptor blockers (ARB) had less improvement in exercise capacity: 0.9 +/- 1.0 METS vs. 1.3 +/- 1.3 (P < 0.001) and 0.8 +/- 1.3 vs. 1.2 +/- 1.3 (P = 0.011 ), respectively. After a median interval of 358 days, 152 patients were seen at a follow-up visit: their BMI increased by 1.0 +/- 2.4 kg/m2 and only 21% of patients lost weight. CONCLUSIONS: Rehabilitation improves exercise capacity and induces significant weight loss in obese patients with stable IHD, but women, diabetic, elderly and poorly educated subjects obtained unsatisfactory results. Use of diuretics and ARB seem to worsen the results. At follow-up only a small percentage of patients further improves BMI.

Conditional cardiovascular response to growth hormone therapy in adult patients with Prader-Willi syndrome.

CONTEXT: In Prader-Willi syndrome (PWS), an altered GH secretion has been related to reduced cardiac mass and systolic function when compared with controls. OBJECTIVES: The objective of the study was to evaluate the cardiovascular response to GH therapy in adult PWS patients. STUDY PARTICIPANTS: Thirteen obese PWS adults (seven males and six females, aged 26.9+/-1.2 yr, body mass index 46.3+/-1.6 kg/m2) participated in the study. METHODS: Determination of IGF-I, metabolic parameters, echocardiography, and cardioscintigraphy with dobutamine stimulation was made during 12 months GH therapy, with results analyzed by repeated-measures ANOVA. RESULTS: GH therapy increased IGF-I (P<0.0001); decreased C-reactive protein levels (P<0.05); and improved lean mass (P<0.001), fat mass (P<0.05), and visceral fat (P<0.001). Echocardiography showed that 6- and 12-month GH therapy increased left ventricle mass in 76 and in 61% of patients, respectively (P<0.05), did not change diastolic function, and slightly decreased the left ventricle ejection fraction (LVEF) (P=0.054). Cardioscintigraphy documented stable values of LVEF throughout the study, whereas right ventricle ejection fraction decreased significantly (P<0.05) being normally responsive to dobutamine infusion. A positive association between IGF-I z-scores and LVEF occurred at the 6- and 12-month follow-up (P<0.05). CONCLUSIONS: In PWS, GH therapy increased cardiac mass devoid of diastolic consequences. The observation of a slight deterioration of right heart function as well as the association between IGF-I and left ventricular function during GH therapy suggest the need for appropriate cardiac and hormonal monitoring in the therapeutic strategy for Prader-Willi syndrome.

The impact of growth hormone/insulin-like growth factor-I axis and nocturnal breathing disorders on cardiovascular features of adult patients with Prader-Willi syndrome.

CONTEXT: Adult patients with Prader-Willi syndrome (PWS) are prone to develop obesity, GH deficiency (GHD), and their related complications, with cardiopulmonary failure explaining more than half of PWS fatalities. OBJECTIVE AND STUDY PARTICIPANTS: This study was undertaken to examine the effect of GHD and sleep breathing disorders on cardiovascular risk factors and heart features of 13 PWS (age 26.9 +/- 1.2 yr) and 13 age-, gender-, and body mass index-matched obese individuals (age 26.2 +/- 0.8 yr). RESULTS: Compared with controls, PWS patients had lower GH response to arginine+GHRH, IGF-I levels, triglycerides, total and LDL-cholesterol, insulin, and insulin resistance measured by a homeostatic model approach. Dual-energy x-ray absorptiometry, abdominal computed tomography scans, and polysomnography revealed a greater fat mass, similar abdominal fat, but greater sleep breathing disorders in PWS than obese subjects. Echocardiography showed no systolic or diastolic alteration, although PWS had lower left ventricle (LV) mass (135.7 +/- 7.7 vs. 163.5 +/- 8.4 g, P < 0.05) and near significantly lower values of LV end-diastole diameter (P = 0.08), compared with obese controls. Baseline radionuclide angiography documented comparable values of systolic and diastolic values between groups. However, adrenergic stimulation with dobutamine caused a lower increase of LV ejection fraction (71.9 +/- 1.9 vs. 76.3 +/- 1.2%, P < 0.05) and heart rate (103 +/- 6.9 vs. 128 +/- 2.8 beats/min, P < 0.05) in PWS than obese individuals. By multivariate analysis, nocturnal oxygen desaturation and IGF-I levels were main significant predictors of LV mass and heart rate in PWS patients. CONCLUSIONS: PWS differs from simple obesity by a healthier metabolic profile, impaired nocturnal breathing, decreased heart geometry, and systolic and chronotropic performance. GHD and the predictive role of IGF-I on structural and functional heart parameters suggest a GH/IGF-I-mediated control of cardiac risk in PWS.

Safety and efficacy of therapy with botulinum toxin in obesity: a pilot study.

BACKGROUND: Botulin toxin (BTX) has been proposed as a potential obesity treatment. METHODS: In a pilot study, the short-term efficacy and safety of BTX was assessed in eight subjects (four men, four women; median age, 46 years; range, 35-57 years) with severe obesity (median body mass index [BMI], 47.1 kg/m(2); range 38.2-56.7 kg/m(2)) and multiple dietary treatment failures. In a single endoscopic session, 500 UI of BTX-A was injected in the gastric antral region. RESULTS: No clinically significant side effects were observed. In all patients, despite their not being on a specific diet, a reduction of body weight was observed at 1 month (median baseline weight, 124.4 kg vs 121.8 kg at 1 month; P < 0.05). Two treatment-unrelated dropouts were observed. At 4 months, three of the six patients had a further weight loss. The treatment effect was apparently independent of changes in hunger or satiety, or of changes in fasting and postprandial plasma ghrelin and serum leptin, thus suggesting a different pharmacological mechanism. CONCLUSIONS: BTX-A treatment appears to be safe and well tolerated by obese patients, while its short-term efficacy varied widely.

The relationship between active ghrelin levels and human obesity involves alterations in resting energy expenditure.

Ghrelin is a gastric hormone that exerts a stimulatory effect on appetite and fat accumulation. Ser(3) octanoylation is regarded as a prerequisite for ghrelin biological activity, although des-octanoylated forms may retain biological functions in vitro. Circulating ghrelin levels are usually low in obesity and in states of positive energy balance. Hence, the aim of our study was to analyze plasma active and serum total ghrelin levels in 20 obese (ages, 22-42 yr; body mass index, 41.3 +/- 1.1 kg/m(2)) and 20 lean subjects (ages, 22-43 yr; body mass index, 22.4 +/- 0.6 kg/m(2)) as well as their relationship to measures of glucose homeostasis, body fat, and resting energy expenditure (REE). The measured/predicted REE percentage ratio was calculated to subdivide groups into those with positive (> or = 100% ) and negative (<100%) ratio values. In obese patients, plasma active (180 +/- 18 vs. 411 +/- 57 pg/ml; P < 0.001) and serum total ghrelin levels (3650 +/- 408 vs. 5263 +/- 643 pg/ml; P < 0.05) were significantly lower when compared with lean subjects. Hence, ghrelin activity, defined as the proportion of active over total ghrelin levels, was similarly reduced in the obese state (6.1 +/- 0.9% vs. 8.4 +/- 1%; P < 0.05). There was a significant correlation between active and total ghrelin (r = 0.62; P < 0.001), and between total ghrelin and insulin (r = -0.53; P < 0.001) or insulin resistance using the homeostatis model of assessment-insulin resistance (r = -0.49; P < 0.001) approach. Significantly higher active ghrelin levels (214 +/- 22 vs. 159 +/- 30 pg/ml; P < 0.05) and ghrelin activity (8 +/- 1.7% vs. 4.9 +/- 0.9%; P < 0.05) were observed in patients with positive compared with negative measured/predicted REE ratio values. Our study shows that obesity is associated with an impairment of the entire ghrelin system. The observation that ghrelin is further decreased in cases of abnormal energy profit adds new evidence to the relationship between ghrelin activity and energy balance in obesity.

Lymphocytes and immunoglobulin patterns across the threshold of severe obesity.

The proinflammatory state of metabolic disorders encompasses the alterations in leukocyte counts and acute-phase reactants, and thus, predisposes to acute and chronic cardiovascular events linked to fat accumulation. Leptin is a marker of adiposity and also yields regulatory effects on innate and adaptive immunity; however, its role on the immune function of obese subjects remains to be elucidated. The aim of this study is to determine the influence of obesity and the role of leptin concentrations on lymphocyte counts and immunoglobulin levels as broad markers of immune function. Cross-sectional analysis in 147 obese (64 M, BMI 43 ± 8.1 kg/m(2)) and 111 age- and sex-matched controls (36 M, BMI 22.5 ± 2.6 kg/m(2)) by assessment of peripheral leukocyte counts, immunoglobulin (Ig) A, G, M levels, leptin, glucose and lipid homeostasis, and acute-phase reactants. Compared to controls, all the leukocyte components were significantly increased in obesity (p < 0.0001 for all) except for basophils and eosinophils. While IgA and IgG levels were similar between groups, IgM levels were lower (p < 0.001) in obese individuals. A significant relationship was evident between leptin and leukocyte counts (p < 0.001), with this latter being correlated to insulin resistance, adiposity, and lipid profile. At the stepwise multiple regression analysis, leukocytes were best predicted by leptin (ß = 0.43, p < 0.0001) and male gender (ß = 0.15, p < 0.05), yet when obesity entered the equation, it acted as an independent predictor of leukocytes (ß = 0.51, p < 0.0001). Leptin also acted as a predictor of IgA levels (ß = 0.20, p < 0.01). Current results show that IgM levels are significantly decreased in patients with obesity in association to significant increments in leukocyte counts. These latter are markedly correlated to leptin levels, insulin resistance, lipid profile, and adiposity. This circumstance, and the significant correlation seen between leptin and IgA levels, may suggest an indirect intervention of leptin in the immunologic alterations consequent to obesity and related to its cardiovascular risk.

Cocaine abuse and sleep apnea in severe obesity.

Obesity is a cause of sleep breathing disorders that result in excessive daytime sleepiness. We describe the adaptive strategy used by an obese person who started to snort cocaine to remedy incoercible drowsiness affecting his working financial skills. Clinical workup documented severe sleep apnea, which was treated by noninvasive ventilation and resulted in withdrawing cocaine abuse. Undiagnosed sleep disorders may trigger surreptitious psychostimulant abuse in vulnerable individuals.

Molecular and morphologic characterization of superficial- and deep-subcutaneous adipose tissue subdivisions in human obesity.

OBJECTIVE: Human abdominal subcutaneous white adipose tissue (SAT) is composed of two different subcompartments: a "superficial" SAT (SSAT), located between the skin and a fibrous-fascia plane; and a deeper SAT, located under this fibrous fascia plane, indicated as "deep" SAT (DSAT). DESIGN AND METHODS: In order to investigate whether SSAT and DSAT have different molecular and morphological features, paired SSAT/DSAT biopsies were collected from 10 female obese patients and used for microarray and morphologic analysis. The stroma-vascular fraction cells were also isolated from both depots and cultured in vitro to assess the lipid accumulation rate. RESULTS: SSAT and DSAT displayed different patterns of gene expression, mainly for metabolic and inflammatory genes, respectively. Detailed gene expression analysis indicated that several metabolic genes, including adiponectin, are preferentially expressed in SSAT, whereas inflammatory genes are over-expressed in DSAT. Despite a similar lipid accumulation rate in vitro, in vivo SSAT showed a significant adipocyte hypertrophy together with a significantly lower inflammatory infiltration and vascular vessel lumen mean size, when compared to DSAT. CONCLUSIONS: These data show that, SSAT and DSAT are functionally and morphologically different and emphasize the importance of considering independent these two adipose depots when investigating SAT biology and obesity complications.

Quality of life, disability, and body mass index are related in obese patients.

The aim of this study is to analyze the relationship between health-related quality of life (QoL), disability, and degree of obesity. Adult obese patients (BMI>30) were consecutively enrolled in this cross-sectional observational study. The WHO Disability Assessment Schedule (WHO-DAS II) and the short version of the impact of weight on QoL (IWQoL-Lite) were administered. Spearman's rank correlation analysis was performed. A P value of less than 0.01 was used to set the statistical significance. A total of 117 patients (mean age: 47.4 years, mean BMI: 43.7) were enrolled. Correlations between WHO-DAS II and IWQoL-Lite were between 0.21 and 0.78. BMI between 0.19 and 0.26 correlated with WHO-DAS II and BMI between 0.23 and 0.49 correlated with IWQoL-Lite. In conclusion, low/moderate correlations between BMI index, disability, and health-related QoL measures, and a low association between the two outcome measures are reported, supporting the idea that they underline different and not transposable dimensions.

Serum adiponectin levels in advanced-stage Parkinson's disease patients.

Patients with advanced Parkinson's disease (PD) experience body weight loss and reductions in the most common cardiovascular risk factors. At present, the pathogenetic mechanisms involved have not been elucidated. Increased serum concentrations of adiponectin, which possesses antiatherogenic and anti-inflammatory properties, are associated with a reduction in cardiovascular risk. The objective of this study was to determine adiponectin serum concentrations in PD patients. Thirty PD patients underwent a full nutritional status assessment, including the determination of adiponectin serum concentrations. Mean ± SD adiponectin concentrations were 9.59 ± 5.9 µg/mL (interquartile range: 5.92-12.9 µg/mL). In PD patients, adiponectin serum levels were similar to those in normal-weight, healthy, young subjects and significantly higher than that in an aged-matched group of morbidly obese subjects. Further studies are warranted to establish the role of adiponectin in the management of PD patients.

Obesity-related disability: key factors identified by the International Classification of Functioning, Disability and Health.

PURPOSE: To identify obese patients' disability features considering the level of body impairments, activity limitations and participation restrictions in relation to environmental factors' effect. METHOD: Adult obese inpatients (BMI > 35) were enrolled and were administered a set of 166 ICF categories. Count-based indexes were developed for each ICF component: correlations and regression on performance and capacity indexes were performed. RESULTS: Fifty-one patients (62.7% females, mean age 38.1) entered in the study. Description of ICF-based disability components is reported. Capacity is better correlated with body functions (r = 0.619, P < 0.01) and body structures (r = 0.375, P < 0.01) than performance; on the contrary, environmental barriers are correlated better with performance (r = 0.531, P < 0.01) than with capacity. Impairments in body functions and environmental barriers are the best predictors of limitations both in capacity and in performance. CONCLUSIONS: Through this multidisciplinary approach, supported by ICFs biopsychosocial model, we described functioning and disability in obese patients, highlighting the strong effect of body functions' impairments and the limited one of environmental factors. This approach can guide rehabilitation programmes, the promotion of positive health outcomes and the modification of patients' lifestyle, not only intended as an issue of barriers' elimination, but as the activation and maintenance of environmental facilitators.

Investigations of thyroid hormones and antibodies in obesity: leptin levels are associated with thyroid autoimmunity independent of bioanthropometric, hormonal, and weight-related determinants.

OBJECTIVES: Obesity can alter the thyroid hormone status as a result of a dysregulated endocrine loop between the hypothalamo-pituitary unit and adipose tissue. The adipocytokine leptin has been shown to promote autoimmunity; hence, we aimed to clarify whether leptin excess of obesity could increase the susceptibility to develop autoimmune thyroid disease (AITD). STUDY DESIGN: This cross-sectional study was performed in a tertiary care center. METHODS: Free thyroid hormones, TSH, thyroglobulin, and antithyroid antibodies levels were tested in 165 obese and 118 lean subjects. Results were plotted against variables related to body composition, leptin levels, glucose homeostasis, energy expenditure, and pattern of weight accrual. RESULTS: Compared with controls, obese patients had lower free T3 levels and free T4 levels (P<0.01), greater prevalence of hypothyroidism (P<0.05), and higher commonness of antithyroid antibodies (P<0.05). As a marker of AITD, thyroid peroxidase antibodies were more frequent in the obese group (P<0.01). Correlation analysis showed that leptin levels were associated with AITD (P<0.01) independent of bioanthropometric variables. Multiple logistic regression analysis in pooled groups identified female sex and leptin as significant predictors of AITD. CONCLUSIONS: Obesity increases the susceptibility to harbor AITD with an emerging role for leptin as a peripheral determinant, which needs to be confirmed in future investigations.