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The use of wood in timber bridges is increased over the past 20 years, mainly since wood is a renewable and sustainable resource. Nevertheless wood is a natural engineering material that is prone to deterioration caused by fungi decay, insect attack and temperature. For wood and wooden bridges there is in fact a strong correlation between durability of the material and bearing capacity. Deformations in a timber structure are often a good indicator of the structural condition. Within this context, in this study some structural issues dealing with the design of a timber bridge for pedestrians are investigated. In a first step, the bridge shape is designed taking into account various aspects: timber as a bridge material; properties of structural wood products; rain systems for preservation and protection; wearing surfaces for timber decks in order to ensure durability; static and dynamic loads; static scheme. In a second step, the bridge shape is optimized by a procedure based on the calibration of natural modes of vibration.

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.

To evaluate a multidisciplinary clinical protocol for obesity treatment by mapping it against the International Classification of Functioning, Disability and Health (ICF) and to determine the areas, defined by the ICF, in which no standardized assessment tools are available.Assessment instruments used by a multidisciplinary team were linked to ICF categories and compared with a list of ICF categories composed by the ICF checklist and the comprehensive ICF core-set for obesity. Other relevant ICF categories were added, and not relevant ones were deleted when appropriate.Five ICF categories were deleted and 11 were added, and 166 ICF categories were linked to assessment tools and to semi-structured interviews. The majority were linked to assessment tools, but within the domain of the environmental factors all ICF categories were mapped using semi-structured interviews.Our results show that an extended list of ICF categories is adequate to cover a wide spectrum of clinical and functional information, and it could be employed to describe, disability profiles of obese patients, to develop preventive measures and to identify what factors in the environment need to be changed to improve rehabilitation's outcomes.

To compare the predictive role of abdominal fat distribution by computed tomography (CT) with that of total abdominal fat by sagittal abdominal diameter (SAD) on cardiovascular risk in severe obesity.A cross-sectional, clinical study.64 males and 64 females, aged 42+/-15 years (mean+/-s.d.; range 18-75 years), BMI (kg/m(2)) 41.7+/-5.3 (30.2-57.6).Blood glucose, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides (TGLs), insulin (IRI), insulin resistance (HOMA-IR), slice areas (cm(2)) of total (tSAT), superficial (sSAT) and deep subcutaneous adipose tissue (dSAT), visceral adipose tissue (VAT) and SAD (mm) by CT.The sSAT depot was negatively associated with blood glucose, HOMA-IR, LDL cholesterol and TGLs, whereas dSAT was negatively associated with HDL cholesterol. VAT was associated with blood glucose and HOMA-IR, whereas SAD was associated with all variables evaluated. In males, VAT was associated with blood glucose (r(2)=0.12, P0.01), SAD was associated with blood glucose (r(2)=0.67, P0.01), IRI (r(2)=0.65, P0.05), and HOMA-IR (r(2)=0.67, P0.01). In females, sSAT was negatively associated with blood glucose (r(2)=0.63, P0.05), whereas VAT was associated positively with blood glucose (r(2)=0.21, P0.001), total cholesterol (r(2)=0.16, P0.01), LDL cholesterol (r(2)=0.20, P0.001) and TGLs (r(2)=0.12, P0.01). SAD was associated positively with IRI (r(2)=0.52, P0.05), HOMA-IR (r(2)=0.53, P0.05), total cholesterol (r(2)=0.52, P0.05), LDL cholesterol (r(2)=0.54, P0.01), TGLs (r(2)=0.52, P0.05) and negatively to HDL cholesterol (r(2)=0.51, P0.001).When compared with CT-based measures of abdominal fat compartments, SAD is a more predictive indicator of cardiovascular risk in severe obesity.

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.Adult obese inpatients with BMIor = 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.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.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.

AIM In obese patients, the diet-induced weight loss markedly improves glucose tolerance with an increase in insulin sensitivity and a partial reduction of insulin secretion. The association with metformin treatment might potentiate the effect of diet alone. METHODS From patients admitted to our Nutritional Division for diet programme, we selected obese, non-diabetic, uncomplicated patients with age 18-65 years and body mass index 35-50 kg/m(2) and studied the effects of a 6-month pharmacological treatment with either metformin (850 mg twice daily) or rosiglitazone (4 mg twice daily) on possible changes in body weight, fat mass, glucose and lipids metabolism. RESULTS A significant weight loss and reduction of fat mass was demonstrated with metformin (-9.7 +/- 1.8 kg and -6.6 +/- 1.1 kg) and also with rosiglitazone (-11.0 +/- 1.9 kg and -7.2 +/- 1.8 kg), without fluid retention in either treatment group. Rosiglitazone administration induced a significant decrease in glucose concentration (4.7 +/- 0.1 vs. 4.4 +/- 0.1 mmol/l, p < 0.005) and insulin-circulating level (13.6 +/- 1.5 vs. 8.0 +/- 0.,7 microU/ml, p < 0.005), an increase in insulin sensitivity as measured by homeostatic model assessment (HOMA) of insulin sensitivity (68.9 +/- 8.8 vs. 109.9 +/- 10.3, p < 0.005) with a concomitant decrease in beta-cell function as measured by HOMA of beta-cell function (163.2 +/- 16.1 vs. 127.4 +/- 8.4, p < 0.005). In contrast, metformin did not produce any significant effect on blood glucose concentration, insulin level and HOMA2 indexes. No adverse events were registered with pharmacological treatments. CONCLUSION Our study shows that in severely obese, non-diabetic, hyperinsulinaemic patients undergoing a nutritional programme, rosiglitazone is more effective than metformin in producing favourable changes in fasting-based indexes of glucose metabolism, with a reduction of both insulin resistance and hyperinsulinaemia. In spite of previous studies reporting rosiglitazone-induced body weight gain, in our study the joint treatment with diet and rosiglitazone was accompanied by weight loss and fat mass reduction.

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.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 (P0.001 ). Attained metabolic equivalents (METs) increased from 6.2 +/- 2.5 METs to 7.3 +/- 2.7 (P0.001). 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 (P0.001) 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.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.

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/m(2)). As a control, a group of 215 normal-weight subjects ( mean BMI 22.4 +/- 2.7 kg/m(2)) 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 1335S- 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.

Objective: Abdominal visceral (VAT) and subcutaneous adipose tissue (SAT) display significant metabolic differences, with VAT showing a functional association to metabolic/cardiovascular disorders. A third abdominal adipose layer, derived by the division of SAT and identified as deep subcutaneous adipose tissue (dSAT), may play a significant and independent metabolic role. The aim of this study was to evaluate depot-specific differences in the expression of proteins key to adipocyte metabolism in a lean population to establish a potential physiologic role for dSAT. Research Methods and Procedures: Adipocytes and preadipocytes were isolated from whole biopsies taken from superficial SAT (sSAT), dSAT, and VAT samples obtained from 10 healthy normal weight patients (7 women and 3 men), with a mean age of 56.4 ± 4.04 years and a mean BMI of 23.1 ± 0.5 kg/m2. Samples were evaluated for depot-specific differences in insulin sensitivity using adiponectin, glucose transport protein 4 (GLUT4), and resistin mRNA and protein expression, glucocorticoid metabolism by 11β-hydroxysteroid dehydrogenase type-1 (11β-HSD1) expression, and alterations in the adipokines leptin and tumor necrosis factor-α (TNF-α). Results: Although no regional differences in expression were observed for adiponectin or TNF-α, dSAT whole biopsies and adipocytes, while intermediary to both sSAT and VAT, reflected more of the VAT expression profile of 11β-HSD1, leptin, and resistin. Only in the case of the intracellular pool of GLUT4 proteins in whole biopsies was an independent pattern of expression observed for dSAT. In an evaluation of the homeostatic model, dSAT 11β-HSD1 protein (r = 0.9573, p = 0.0002) and TNF-α mRNA (r = 0.8210, p = 0.0236) correlated positively to the homeostatic model. Discussion: Overall, dSAT seems to be a distinct abdominal adipose depot supporting an independent metabolic function that may have a potential role in the development of obesity-associated complications.

To examine the reliability and validity of the SenseWear Pro 2 Armband (SWA; Body Media, Pittsburgh, PA) during rest and exercise compared with indirect calorimetry (IC) in obese individuals.Energy expenditure was assessed during rest with the SWA and IC in 142 obese adults (37 men and 105 women, BMI = 42.3 +/- 7.0) and in 25 lean and overweight adults (BMI = 25.3 +/- 3.2) who were used as a comparison group. Twenty-nine of the obese adults also participated in three separate short exercise sessions including cycle ergometry, stair stepping, and treadmill walking.The repeatability of SWA estimates in obese subjects was high (r = 0.88, p0.001). The SWA generally underestimated the resting energy expenditure (REE) (1811 +/- 346 vs. 1880 +/- 382 kcal/d) and highly overestimated the energy expenditure during the exercise sessions in obese individuals. REE estimations by SWA were significantly correlated with fat-free mass (r = 0.88, p0.001). Bland-Altman plots based statistical analysis for the estimated REE, and measured IC showed a low agreement (Total Error20% but Systematic Error5%) between the two methods in obese subjects, although they showed a high correlation and a very good agreement in lean and overweight patients.The SWA is an easy to handle, practical, new portable device for measuring energy expenditure. The accuracy of the SWA appeared to be poor in the obese subjects we examined, especially those with high REE both in rest and exercise. We believe that it is necessary to incorporate new, obesity-specific algorithms in the relative software.

OBJECTIVE It is unclear if poor health outcomes of adult patients with Prader-Willi syndrome (PWS) are influenced by GH deficiency (GHD). Few studies have been focused on PWS adults, but further information on the concomitant role of obesity on GH/IGF-I axis function is needed. The aim of our study was to investigate the prevalence of GHD in a large group of adult subjects with genetically confirmed PWS. DESIGN AND SUBJECTS We studied the GH response to a combined administration of GHRH (1 microg/kg i.v. at 0 minutes) and arginine (ARG) (30 g i.v., infused from 0 to 30 minutes) as well as the baseline IGF-I levels, in a group of 44 PWS adults (18 males, 26 females) aged 18-41.1 years. The same protocol was carried out in a control group of 17 obese subjects (7 males, 10 females) aged 21.8-45.8 years. MEASUREMENTS Blood samples were taken at -15 and 0 minutes and then 30, 45, 60, 90 and 120 minutes after GHRH administration. Serum GH and total IGF-I concentrations were measured by chemioluminescence. Statistical analysis was performed by Student's t-test for unpaired data, and using analysis of variance for parametric and nonparametric (Mann-Whitney test) data, where appropriate. The relationship between pairs of variables was assessed by Pearson's correlation. Independent variables influencing GH secretion were tested by multiple linear regression analysis. RESULTS The GH response to GHRH + ARG was significantly lower in PWS patients (GH peak (mean +/- SE) 8.4 +/- 1.2 microg/l; AUC: 471.4 +/- 77.8 microg/l/h) than obese subjects (GH peak 15.7 +/- 2.9 microg/l, P < 0.02; AUC 956 +/- 182.9 microg/l/h, P < 0.005). When considered individually, 17 of 44 PWS individuals (38.6%) were severely GHD, according to the cut-off limit of 4.1 microg/l for obese individuals, and low IGF-I-values were present in 33 PWS patients. Moreover, impaired GH response was combined with subnormal IGF-I levels in all PWS patients with GHD. CONCLUSIONS Adult subjects with PWS had a reduced responsiveness to GHRH + ARG administration associated with reduced IGF-I levels. In addition, a severe GHD for age was demonstrated in a significant percentage of PWS subjects. These findings are in agreement with the hypothesis that a complex derangement of hypothalamus-pituitary axis occurred in PWS, and suggested that impaired GH secretion is not an artefact of obesity.

Context: Release of ghrelin, a gastrointestinal hormone regulating feeding and energy balance, is blunted in obesity, a condition associated with insulin resistance. Objective: The objective was to identify anthropometric and metabolic predictors of postabsorptive ghrelin secretion. Design: We evaluated ghrelin, insulin, glucose, and leptin secretion overnight and after intake of different macronutrients. Subjects: Ten obese subjects (age, 31.8 ± 2.5 yr; body mass index, 43.4 ± 0.8 kg/m2) and six lean subjects (age, 33.5 ± 2.4 yr; body mass index, 21.8 ± 1.4 kg/m2) participated in the study. Main Outcome Measures: The main outcome measures were resting energy expenditure (REE); fat mass; nighttime approximate entropy (ApEn) and synchronicity (cross-ApEn) of ghrelin, insulin, and leptin; insulin sensitivity by homeostatic model approach insulin-sensitivity (HOMA-S%); postabsorptive area under the curve (AUC); and Δ of ghrelin, insulin, glucose, and leptin after carbohydrate-, lipid-, and protein-rich test meals. Results: Nighttime ApEn scores were higher in obese than lean subjects (P < 0.01). Cross-ApEn revealed a synchronicity between ghrelin-insulin, ghrelin-leptin, and insulin-leptin in both groups. Compared with baseline, ghrelin decreased significantly (P < 0.01) in lean and obese subjects after carbohydrates (42.2 vs. 28.5%; P < 0.05), lipids (40.2 vs. 26.2%; P < 0.01), and proteins (42.2 vs. 26.3%; P < 0.01) devoid of between-meal ghrelin differences. Significant associations occurred between nocturnal ghrelin ApEn and insulin (r = 0.53; P < 0.05), postmeal ghrelin AUCs and REE (r = −0.57; P < 0.05), and HOMA-S% (r = 0.52; P < 0.05), postmeal ghrelin Δ and HOMA-S% (r = 0.60; P < 0.05). REE (β = −0.57; P = 0.02) and ghrelin ApEn (β = −0.62; P = 0.01) were predictors of postmeal ghrelin AUC and Δ, respectively. Conclusions: Obesity determined a decreased orderliness of ghrelin secretion and a relative loss of ghrelin-insulin synchrony. Postabsorptive ghrelin secretion decreased significantly both in obese and lean subjects, was related to insulin sensitivity, and was predicted by energy expenditure and hormone pulsatility.

Objective: To define an equation that predicts exercise capacity taking into account body mass index (BMI). Design: Retrospective analysis and validation study of a multidisciplinary programme aimed at weight loss and physical rehabilitation. Setting: Tertiary referral hospital. Patients and methods: 372 consecutive obese participants (249 men) with stable ischaemic heart disease, aged mean 60.1 (SD 8.7) years, underwent a treadmill exercise test. BMI was 37.8 (4.5) kg/m 2 . In the validation study the model was tested in 87 patients with similar characteristics. Results: Mean exercise intensity was 6.6 (SD 2.4) metabolic equivalents (METs). Multivariate linear regression analysis defined two simple models that considered exercise intensity as the dependent variable and a set of independent variables such as anthropometric measures, age and sex in the first one, plus associated clinical conditions and drug treatment in the second one. The correlation coefficients of the two models were R = 0.630 and R = 0.677, respectively. Age, BMI and sex were the strongest predictors of exercise capacity. The first derived equation efficiently predicted exercise capacity: in the validation study predicted exercise intensity was 6.3 (1.6) METs and attained exercise intensity was 6.3 (2.4) METs (p = 0.903) with a highly significant correlation ( R = 0.534, p Conclusion: BMI is an important determinant of exercise capacity of obese people with ischaemic heart disease. The use of a simple equation may help in predicting exercise capacity, in individualising exercise protocol and in setting up rehabilitation programs for obese patients.

To evaluate by ultrasound the ratio between preperitoneal (P) and subcutaneous (S) fat (AFI), in quantifying the cardiovascular risk in 258 obese patients (BMI 41.2+/-6.3 kg/m2; age 45.1 +/- 13.6 years).Glucose, insulin, lipid profile, uric acid and fibrinogen were measured. HOMA-IR, waist girth, AFI and quartiles of BMI were calculated.AFI lowered with increasing BMI and showed a positive correlation with TGL (r=0.37, P0.01) and uric acid (r=0.40, P0.001) in the 1st quartile of BMI (30.2-36.4) and a negative correlation with HDL (r=- 0.32, P0.001) in the 3rd quartile (40.6-45.1). When BMI exceeded the value of 45.2 kg/m2 these correlations were no longer significant. In all subjects S correlated positively with uric acid (r=0.64, P0.001), and negatively with HOMA-IR (r=- 0.41, P0.001) and TGL (r=- 0.35, P=0.02); P correlated positively with CHOL (r=0.48, P=0.04) and TGL (r=0.33, P=0.03), and negatively with HDL (r=- 0.46, P=0.03). Waist girth showed more significant correlations than AFI in the lower quartiles of BMI, but not at the highest one.AFI, P and S, as waist girth do not seem to quantify the metabolic risk factors of cardiovascular disease in severe obese subjects, but AFI is probably useful in obese populations with BMI45 kg/m2, even though not as strong as waist girth.

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 (

Summary objective Acromegaly is a syndrome with a high risk of impaired glucose tolerance (IGT) and diabetes mellitus (DM). Somatostatin analogues, which are used for medical treatment of acromegaly, may exert different hormonal effects on glucose homeostasis. Twenty-four active acromegalic patients were studied in order to determine the long-term effects of octreotide-LAR and SR-lanreotide on insulin sensitivity and carbohydrate metabolism. design Prospective study. patients We studied 24 patients with active acromegaly, 11 males and 13 females, aged 50·7 ± 12·7 years, body mass index (BMI) 30·1 ± 4·8 (kg/m2). measurements All patients underwent an oral glucose tolerance test (OGTT) and 12 also had an euglycaemic hyperinsulinaemic clamp. All patients were evaluated at baseline and after 6 months of somatostatin analogues therapy. results Acromegalic patients showed low M-values in respect to the control group at baseline (P

Summary OBJECTIVE We have recently reported that, in healthy elderly Dutch individuals, a N363S polymorphism in the glucocorticoid receptor (GR) gene is associated with higher sensitivity to low-dose dexamethasone (0·25 mg), evaluated as both cortisol suppression and insulin response, and with an increased body mass index (BMI). In the present study we investigated the role of the N363S polymorphism, and a Bcl I restriction site polymorphism in a group of Italian patients with severe obesity. DESIGN Two hundred and seventy-nine patients (mean BMI 45·9 ± 0·9 kg/m 2 ) were genotyped using both PCR-restriction fragment length polymorphism analysis and Taqman Sequence Detection System. Determination of several metabolic and antropometric parameters was also performed in order to correlate them to the genotype. RESULTS In this group of obese patients, 13 subjects (eight female, five males) were heterozygous for the N363S variant (allelic frequency 2·3%) and had significantly higher BMI ( P < 0·04), resting energy expenditure ( P < 0·03) and food intake ( P < 0·01) when compared to wild-type homozygotes. When the data were analysed according to sex, female heterozygotes for the N363S allele had significantly higher BMI ( P = 0·04), resting energy expenditure ( P = 0·03) and food intake ( P = 0·008) than obese women with the wild-type 363 GR gene. Male carriers of this variant also had higher values for these variables although the differences did not reach statistical significance. A case‐control study with homozygous wild-type obese subjects which were age-, sex- and BMI-matched, revealed no difference in resting energy expenditure and food intake. The allele frequency of the Bcl I variant was 27% (89 females and 41 males out of 269 subjects). No differences in anthropometric and metabolic parameters were found between subjects heterozygous or homozygous for this variant GR in this obese population. However, when we studied the effect of the presence of the Bcl I polymorphism and the N363S variant in the same individual, we found that the subjects who carried both polymorphisms had a tendency towards higher systolic and diastolic blood pressure and significantly higher total and LDLcholesterol levels ( P = 0·005 and P = 0·05, respectively). DISCUSSION Taking the results of this study and those obtained in the Dutch population, we speculate that heterozygous carriers of the N363S variant who develop obesity, may become even more obese, possibly because they have a hypersensitive insulin response and thus, via activation of lipogenesis, store fat more efficiently. Furthermore, these data suggest that N363S carriers who carry the Bcl I polymorphism as well, tend to have a slightly unfavourable cardiovascular profile.

Acromegaly is frequently associated with the presence of thyroid disorders, however the exact prevalence is still controversial. An Italian multicenter study was performed on 258 patients with active acromegaly (high levels of IGF-I and lack of suppression of serum GH levels below 2 microg/l after an OGTT). The control group was represented by 150 patients affected by non-functioning and PRL-secreting pituitary adenomas. Two hundred and two out of 258 acromegalic patients (78%) were affected by thyroid disorders with a significantly higher prevalence with respect to the control group (27%, p

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.

BACKGROUND Hypertension represents a well-known risk factor for cardiovascular diseases. The pathogenesis of hypertension in acromegaly is commonly viewed as multifactorial, but the possible influence of metabolic disorders on blood pressure (BP) in affected patients is largely unknown. OBJECTIVE The aim of the present study was to evaluate the impact of glucose metabolism abnormalities on BP values in a series of patients with active acromegaly. DESIGN An open multicentre prospective study. PATIENTS Sixty-eight patients with active disease, aged 47·5 ± 11·7 years, have been studied. Thirty-nine had normal glucose tolerance (NGT), 16 impaired glucose tolerance (IGT) and 13 suffered from diabetes mellitus (DM). MEASUREMENTS Mean clinical BP values were calculated as the mean of BP values obtained by sphygmomanometric measurement in three separate occasions and mean 24-h, diurnal and nocturnal systolic (SBP) and diastolic (DBP) values were obtained by 24-h ambulatory blood pressure monitoring (ABPM). RESULTS Patient's age and the degree of glucose tolerance abnormalities were found to significantly and independently influence BP values. All clinical and ABPM SBP and DBP values significantly increased with age by linear regression (P

Surgery is generally recommended for large thyroid toxic nodules (TTNs). When surgery is not applicable, both radioactive iodine (RAI) and percutaneous ethanol injection (PEI) are alternative treatments. In this retrospective study, the long-term efficacy of nonsurgical treatments was evaluated in 43 patients with TTN, selected on the basis of presence of hyperthyroidism and a fairly large nodule (3- and 4-cm in diameter) completely inhibiting controlateral lobe captation during scintigraphy. Twenty-one patients were treated by RAI (administered dose 670+/-160 MBq; range 555-925) and twenty-two were treated by PEI (6+/-1 sessions; range 5-9). FT4, FT3, thyrotropin (TSH), and nodule volume were assessed before and at fixed intervals after treatment. Median follow-up was 36 months (range, 12-84). Compared to baseline values, with both therapies, serum FT4, FT3, and nodule volume were decreased (p < 0.01) and serum TSH was increased (p < 0.01), after 3 months and during the entire follow-up. Nodule volume reduction percentage was 66.8+/-22.0 and 78.4+/-18.0, in the RAI- and PEI-treated groups, respectively. At the end of follow-up, 34 patients were euthyroid (16 RAI- and 18 PEI-treated). Four RAI-treated patients (19%) showed slightly high TSH levels (4.2-5.3 mU/L), whereas three PEI-treated patients (13.6%) still had suppressed TSH levels, although being clinically asymptomatic. One RAI-treated patient (4.8%) showed overt hypothyroidism during the follow-up period and was then treated with L-thyroxin. One patient (4.6%), who was initially cured by PEI, became newly hyperthyroid during the follow-up period. Both treatments were well-tolerated. In conclusion, both of these nonsurgical treatments are effective and may be chosen also for relatively large TTNs. Specifically, RAI seems to be more effective for treating hyperthyroidism but has minimal sequelae of subclinical or clinical hypothyroidism, while, after PEI treatment the possibility of stable subclinical hyperthyroidism or hyperthyroidism relapse should be taken into account.

Increased mortality from cardiovascular diseases has been reported in acromegaly. Our objective was to evaluate the impact of glucose tolerance abnormalities and/or systemic hypertension in further worsening the acromegalic cardiomyopathy. The study design was open transversal. The subjects studied were 130 consecutive naive acromegalic patients (74 women and 56 men; age, 17-80 yr). Interventricular septum (IST) and left ventricular (LV) posterior wall thickness (PWT), LV mass index (LVMi), maximal early to late diastolic flow velocity ratio (E/A), isovolumic relaxation time (IRT), and LV ejection fraction (EF) were measured by echocardiography. The results were analyzed in line with the presence of glucose tolerance abnormalities (normal in 60, impaired in 38, diabetes mellitus in 32) and the presence (in 46) or absence (in 84) of hypertension. Patients with impaired glucose tolerance and diabetes mellitus had significantly higher age (P = 0.01), and systolic (P = 0.01) and diastolic (P = 0.01) blood pressures and lower E/A (P = 0.01) and EF (P = 0.01) than those with normal glucose tolerance. Disease duration, circulating GH and insulin-like growth factor I (IGF-I) levels, IST, LVPWT, LVMi, and IRT were similar in the 3 groups. Normotensive patients had significantly lower age (P

To study clinical, anthropometric and metabolic determinants of serum leptin concentrations in a series of patients with a wide range of obesity.400 patients, 116 males and 284 females, aged 44+/-12.3 years with body mass index (BMI) ranging from 31 to 82 kg/m2 (mean 41.4+/-7.1).Energy intake by 7-day recall, resting energy expenditure (REE) by indirect calorimetry, body composition determined by bioelectrical impedance; C index, an anthropometric index of abdominal fat distribution, and waist-hip ratio (WHR), blood glucose serum leptin concentrations, total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, uric acid, and insulin concentrations HOMA IRI (homeostastis model assessment of insulin resistance index).Leptin concentrations were higher in obese than in normal subjects and in females than in males without differences between diabetic and non-diabetic patients; leptin concentrations were not related to age and showed a strong negative association with energy intake only in the group of women with BMI less than 40. Leptin concentrations showed a direct correlation with BMI and body fat values (expressed either as percentage of total body mass or absolute fat mass) independent of age and sex. After adjustment for fat mass, leptin values higher than predicted were found in women whereas concentrations lower than predicted were found predominantly in men. Leptin showed an inverse correlation with WHR and C-index, the latter persisting also after correction for gender and fat mass. REE, but not REE/kg fat-free mass (FFM) was inversely related to leptin also after correction for sex and absolute fat mass. Leptin concentrations were directly associated with HOMA IRI, insulin and HDL cholesterol and inversely associated with triglycerides and uric acid. The relationship of leptin with HOMA IRI was still evident after adjusting for sex but was lost when absolute fat mass was added to the model; HDL cholesterol and triglycerides appeared to be variables independent of leptin concentrations even when both sex and fat mass were added to the model.In a large group of obese patients (half of whom had severe obesity, gender, BMI and fat mass accounted for the largest proportion of serum leptin concentrations variability. We found that in obese subjects there is an effect of fat distribution on leptin concentrations and that, after excluding variability due to absolute fat mass, patients with a greater amount of abdominal fat have relatively low leptin concentrations which in turn relates to a metabolic profile compatible with an increased cardiovascular risk. Women with milder obesity may retain some degree of control of food intake by leptin.

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.

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/m2) and 111 age- and sex-matched controls (36 M, BMI 22.5 ± 2.6 kg/m2) 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 (β = 0.43, p < 0.0001) and male gender (β = 0.15, p < 0.05), yet when obesity entered the equation, it acted as an independent predictor of leukocytes (β = 0.51, p < 0.0001). Leptin also acted as a predictor of IgA levels (β = 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.

Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups. © 2013 Nature America, Inc. All rights reserved.

Obesity is a pathological condition characterized by an excess of body fat. Both environmental and biological factors have been considered to explain the worldwide diffusion of the obese phenotype. Most likely, the abnormal accumulation of body fat can be seen as a complex interaction between the two factors. In particular, several studies have focused on the hypothalamic mechanisms controlling food intake and energy expenditure; extensive genetic investigations have demonstrated a low but appreciable percentage of obese patients bearing a single gene mutation underlying the clinical picture. Moreover, Genome-wide association studies have shown a relevant number of loci bearing Single Nucleotide Polymorphisms that increase obesity susceptibility by interacting with environmental conditions. Obesity is now considered as a social health problem since excess of fat per se or through complex metabolic activities of adipocytes may allow the development of several chronic comorbidities such as type 2 diabetes, cardiovascular disease, liver steatosis potentially evolving to cirrhosis and sleep apnea. As a consequence, obesity must be considered a serious disease leading to poor quality of life and, potentially, severe disability.

Bariatric surgery represents a powerful tool for morbid obesity treatment. However, after stabilization of weight loss that follows surgical interventions, ex-obese patients face the problem of residual tissues removal. Actually, it is unknown whether the characteristics of this residual subcutaneous adipose tissue (SAT) are 'restored' with regard to molecular and morphological features.To clarify this issue, we compared the SAT gene expression profile of ex-obese patients (ExOB-SAT, mean body mass index (BMI): 27.2±1.3 kg m(-2)) with that of lean (normal weight, NW-SAT, mean BMI: 22.6±1.1 kg m(-2)), overweight (OW-SAT, BMI: 27.65±0.2 kg m(-2)) and obese patients, according to BMI classes (OB1-SAT: 30or = BMIor = 34.9, OB2-SAT: 35or = BMIor = 39.9, OB3-SAT: BMIor = 40).A total of 58 samples of SAT were collected during surgical interventions. Gene expression levels were assessed by microarrays and significant genes were validated by RT-qPCR. Adipocyte hypertrophy, inflammatory infiltration and fibrosis were assessed by morphological techniques.Global gene expression in ExOB-SAT was closely related to gene expression of OB3-SAT by hierarchical clustering procedures, in spite of different BMI. Metallothioneins (MT1A and MT2A) were the key over-expressed genes in both groups. At morphologic level, adipocyte hypertrophy and inflammatory infiltration improved after weight loss in ExOB-SAT, despite a persistence of fibrosis.Taken together, these results demonstrate that SAT gene expression is not fully restored, even after an extensive and stable weight loss. The persistence of 'obesity molecular features' in ExOB-SAT suggests that the molecular signature of adipose tissue is not solely dependent on weight loss and may need longer time period to completely disappear.

Autoimmune thyroid diseases (AITDs) are clustered in families, but the nature of this clustering is still poorly understood. One possible approach to the identification of genetic factors interacting with the AITDs is the study of the association between polymorphic markers and AITDs themselves. In the present study we have shown an association between an allele of a HindIII restriction fragment length polymorphism (EAβH) intragenic to c-erbAβ, which codes for the thyroid hormone β receptor, and Graves’ disease. This polymorphism can be detected by PCR followed by digestion with the restriction enzyme HindIII. The allelic frequencies were analysed in a panel of DNAs extracted from a population of individuals affected by thyroid disease and originating from southern Italy. A control group (n=120) from the same area was also analysed. The distribution of EAβH alleles was significantly different (Pn=94) but not in autoimmune thyroiditis (n=60), as compared with controls. Also the distribution of the EAβH genotypes was significantly different in Graves’ patients (P=0·003), as compared with controls, the homozygous state EAβH+/EAβH+ being more frequent in Graves’ patients than in all the other groups. We did not find any association between EAβH genotypes and clinical parameters in Graves’ patients, including eye signs, thyroid volume and level of TSH-binding inhibiting immunoglobulins. Our data support the idea that Graves’ disease is a genetically distinct group within the AITDs.

Attanasio R, Cozzi R, Oppizzi G, Dallabonzana D, Chiodini I, Benini Z, Orlandi P, Liuzzi A, Chiodini PG. Persistence of somatostatinergic tone in acromegaly. Eur J Endocrinol 1995;132:27–31. ISSN 0804–4643 It is a matter of debate whether hypothalamic somatostatin (SRIH) secretion in acromegaly is preserved and still regulated by the physiological feedback mechanisms of growth hormone (GH) and insulin-like growth factor I. To gather further information on this, the reproducibility of plasma GH changes induced by growth hormone-releasing hormone (GHRH) administration was evaluated in 15 acromegalic patients. There was a highly significant correlation between the peak/basal ratio (P/B) GH response in the 15 patients administered GHRH on two separate occasions (r = 0.99, p sd of within-subject GHRH variability was observed in response to GHRH plus pyridostigmine when compared to GHRH alone. An inverse correlation (r = −0.37, p Roberto Attanasio, Divisione di Endocrinologia, Ospedale Niguarda, Piazza Ospedale Maggiore 3, 1-20162 Milano, Italy

It is known that cholinergic anti-inflammatory reflex regulates inflammation in peripheral tissues. Nicotinic acetylcholine receptors (nAChRs) are mediators of this anti-inflammatory pathway and also non-neuronal cells express functional nAChrs. A role for α7-subtype acetylcholine cholinergic receptor (α7nAChR) in insulin sensitivity improvement has already been shown in rodents both in vivo and in vitro. However, no data are available on α7nAChR expression in human adipocytes. To investigate the expression and protein content of α7nAChR in human subcutaneous adipose tissue (SAT) and in isolated mature adipocytes. A total of 39 SAT biopsy specimens obtained from obese and normal-weight subjects were used to assess α7nAChR messenger RNA levels and to stimulate α7nAChR with a specific agonist and antagonist in vitro. Additional SATs from eight non-diabetic obese subjects were also studied, before and after a 3-month lifestyle intervention. α7nAChR expression was significantly lower in the SAT of obese subjects compared with that of normal-weight subjects. In mature adipocytes isolated from morbidly obese subjects (body mass index>40 kg m−2), α7nAChR expression was 75% lower compared with adipocytes from normal-weight subjects. In adipocytes of obese subjects, α7nAChR was downregulated also at protein level. In eight non-diabetic obese subjects, a lifestyle intervention (3 months of diet and physical activity) induced a significant weight loss and an increase in α7nAChR SAT expression. In vitro stimulation of adipocytes with the specific α7nAChR agonist PNU282987 induced a significant anti-inflammatory effect. Furthermore, a similar downregulation of the inflammatory profile, associated with a significant increase in α7nAChR protein level, was observed after genistein stimulation. These results provide evidence that α7nAChR expression levels are significantly decreased in obese subjects, and that this receptor modulates inflammatory gene expression in human adipocytes. The upregulation of α7nAChR by genistein stimulation opens new insights for the management of low-grade inflammation linked to human obesity.

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.

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. © Castelnuovo et al.

International audience; 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

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).This cross-sectional study was performed in a tertiary care center.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.Compared with controls, obese patients had lower free T3 levels and free T4 levels (P0.01), greater prevalence of hypothyroidism (P0.05), and higher commonness of antithyroid antibodies (P0.05). As a marker of AITD, thyroid peroxidase antibodies were more frequent in the obese group (P0.01). Correlation analysis showed that leptin levels were associated with AITD (P0.01) independent of bioanthropometric variables. Multiple logistic regression analysis in pooled groups identified female sex and leptin as significant predictors of AITD.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.

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. Trial registration Current Controlled Trials ISRCTN07265661

Recently, the presence of different polymorphisms in the regulatory region of the ob gene has been associated with variations in leptin levels. However, the results of these studies are still contradictory. The aim of the present investigation was to evaluate the presence of the A19G polymorphism in an Italian population of obese patients and to verify its association with leptin levels and anthropometric, metabolic, and clinical parameters. Two hundred five obese patients [body mass index (BMI) > 36 kg/m2; 135 women and 70 men; mean age, 46.9 ± 14.23 yr] were screened for presence of the polymorphism; 61 normal-weight controls (mean BMI, 21.05 kg/m2; 53 women, 8 men) were also screened to compare polymorphism frequency. For obese patients, BMI, waist-to-hip ratio, resting energy expenditure, body composition, fasting leptin, total cholesterol, high-density lipoproteins, triglycerides, and caloric intake were determined. Genotype frequencies in obese and control subjects were compared using the contingency table chi-square test; in obese subjects an ANOVA was performed to evaluate association between the polymorphism and several clinical parameters. No significant differences in genotype distribution between control and obese subjects were found. No significant correlations were found between this polymorphism and serum leptin levels and the other parameters considered. These findings confirm the results obtained in both a Finnish and a French population; taken together, these observations might rule out a significant role for the A19->G polymorphism in the regulation of leptin levels and other clinical, anthropometric, and metabolic parameters.

Abdominal visceral tissue (VAT) and subcutaneous adipose tissue (SAT), comprised of superficial-SAT (sSAT) and deep-SAT (dSAT), are metabolically distinct. The antidiabetic agents thiazolidinediones (TZDs), in addition to their insulin-sensitizing effects, redistribute SAT suggesting that TZD action involves adipose tissue depot-specific regulation. We investigated the expression of proteins key to adipocyte metabolism on differentiated first passage (P1) preadipocytes treated with rosiglitazone, to establish a role for the diverse depots of abdominal adipose tissue in the insulin-sensitizing effects of TZDs. Adipocytes and preadipocytes were isolated from sSAT, dSAT, and VAT samples obtained from eight normal subjects. Preadipocytes (P1) left untreated (U) or treated with a classic differentiation cocktail (DI) including rosiglitazone (DIR) for 9 days were evaluated for strata-specific differences in differentiation including peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and lipoprotein lipase (LPL) expression, insulin sensitivity via adiponectin and glucose transport-4 (GLUT4), glucocorticoid metabolism with 11 beta-hydroxysteroid dehydrogenase type-1 (11 beta HSD1), and alterations in the adipokine leptin. While depot-specific differences were absent with the classic differentiation cocktail, with rosiglitazone sSAT had the most potent response followed by dSAT, whereas VAT was resistant to differentiation. With rosiglitazone, universal strata effects were observed for PPAR-gamma, LPL, and leptin, with VAT in all cases expressing significantly lower basal expression levels. Clear dSAT-specific changes were observed with decreased intracellular GLUT4. Specific sSAT alterations included decreased 11 beta HSD1 whereas secreted adiponectin was potently upregulated in sSAT with respect to dSAT and VAT. Overall, the subcompartments of SAT, sSAT, and dSAT, appear to participate in the metabolic changes that arise with rosiglitazone administration.

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. Copyright © 2008 Wiley Periodicals, Inc.

Background: Prader-Willi syndrome (PWS) is associated with an inappropriate proportion of fat mass (FM) to non-FM compared to simple obesity. Altered body composition in PWS resembles that seen in subjects with GH deficiency, in which a reduction of lean body mass (LBM) is observed. The low LBM may contribute to the reduced motor skills seen in PWS patients. Aim: The objective of the study was to investigate the effects of GH therapy on exercise capacity and body composition in a group of adult subjects with PWS. Subjects and methods: Twelve PWS adults (7 males and 5 females, aged 26.4±4.4 yr, body mass index 44.3±4.6 kg/m2) participated in the study. Body composition analysis and exercise stress test were carried out throughout the 12 months GH therapy. Body composition was measured by Dual Energy X-ray Absorptiometry. Physical performance was evaluated using treadmill exercise test. Exercise intensity was expressed as metabolic equivalents (MET, 1 MET= 3.5 ml O2 kg−1min−1). Statistical analysis was performed by repeated-measures analysis of variance followed by post-hoc analysis with t test for paired data for comparisons among the different follow ups. Results: Compared to baseline GH therapy increased LBM at 6 (p

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/m 2 ) 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. (J Clin Endocrinol Metab 92: 1364–1371, 2007)

Summary Objective The adipose-borne hormone leptin circulates in free and protein-bound forms but little information is available about their biological significance. Free leptin (FL) levels are related to changes in fat mass, whereas bound leptin (BL) appears to be associated with resting energy expenditure (REE). Our aim was to assess FL and BL levels in normal weight and obese subjects and correlate them with metabolic and nutritional variables. Design and Patients The partitioning of plasma leptin between FL and BL was evaluated in a population (n = 44) including both genders and different degrees of adiposity [body mass index (BMI) range 18·6–79·6 kg/m2]. Measurements Total leptin and FL and BL concentrations were measured by fast protein liquid chromatography (FPLC) followed by radioimmunoassay (RIA). Body composition, REE, insulin sensitivity, lipid parameters associated with cardiovascular risk and macronutrient preference were also assessed. Results The BL/FL ratio was significantly reduced in obese subjects due to a major increase in FL compared with BL. Consequently, the gender difference of the %BL/%FL ratio present in lean subjects (35/65 in women; 65/35 in men) was lost in obese subjects. REE was negatively correlated with total leptin (P