A new index to simplify the screening of hypertension in overweight or obese youth.

BACKGROUND AND AIMS: Hypertension (HTH) is a frequent complication in pediatric obesity. To simplify the screening of HTH in overweight/obese (Ow/Ob) youth, we compared the performance of a new index (High Blood Pressure index, HBPi) with respect to the standard criteria of the IV Report [systolic BP (SBP) and/or diastolic BP (DBP) ≥95th percentile for age, gender and height]. We also compared the performance of HBPi with other simplified indices such as the BP/height ratio and the absolute height-specific BP thresholds. Ten pediatrics' outpatient centers participating in the "CARdiometabolic risk factors in ITALY study" provided medical records of 4225 Ow/Ob children and adolescents (age 6-16 years). METHODS AND RESULTS: Centers were divided into two groups: training set (TS) (n = 2204 participants) and validation set (VS) (n = 2021 participants). The simplified HBPi (mmHg) was: (SBP/2 + DBP/10) - age + (1 × female gender). In the TS, a HBPi value ≥57 mmHg in both children and adolescents had high sensitivity (0.89), specificity (0.97), positive (0.89) and negative (0.97) predictive values in classifying youth at high risk of HTN compared with the IV Report. In the VS, the HBPi showed a better performance than high levels of BP/height ratio and height-specific BP thresholds in classifying individuals at risk of HTN: area under curves 0.95 (0.93-0.96), 0.80 (0.78-0.82), 0.76 (0.74-0.79), respectively; specificities 0.95 (0.94-0.96), 0.69 (0.67-0.72), 0.60 (0.57-0.62), respectively. CONCLUSIONS: HBPi, combining SBP and DBP, gender and age, may help pediatricians to implement HTN screening in Ow/Ob youth.

Impaired fasting glucose and impaired glucose tolerance in children and adolescents with overweight/obesity.

OBJECTIVE: To investigate in a large sample of overweight/obese (OW/OB) children and adolescents the prevalence of prediabetic phenotypes such as impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), and to assess their association with cardiometabolic risk (CMR) factors including hepatic steatosis (HS). METHODS: Population data were obtained from the CARdiometabolic risk factors in children and adolescents in ITALY study. Between 2003 and 2013, 3088 youths (972 children and 2116 adolescents) received oral glucose tolerance test (OGTT) and were included in the study. In 798 individuals, abdominal ultrasound for identification of HS was available. RESULTS: The prevalence of IFG (3.2 vs. 3.3%) and IGT (4.6 vs. 5.0%) was similar between children and adolescents. Children with isolated IGT had a 2-11 fold increased risk of high LDL-C, non-HDL-C, Tg/HDL-C ratio, and low insulin sensitivity, when compared to those with normal glucose tolerance (NGT). No significant association of IFG with any CMR factor was found in children. Among adolescents, IGT subjects, and to a lesser extent those with IFG, showed a worse CMR profile compared to NGT subgroup. In the overall sample, IGT phenotype showed a twofold increased risk of HS compared to NGT subgroup. CONCLUSIONS: Our study shows an unexpected similar prevalence of IFG and IGT between children and adolescents with overweight/obesity. The IGT phenotype was associated with a worse CMR profile in both children and adolescents. Phenotyping prediabetes conditions by OGTT should be done as part of prediction and prevention of cardiometabolic diseases in OW/OB youth since early childhood.

Adipose tissue microbiota in humans: an open issue.

BACKGROUND: A specific 'adipose tissue' microbiota has been recently identified in mice and hypothesized in humans. The purpose of this study was to verify the presence of microbiota of human whole adipose tissue and isolated adipocytes by combining culture-dependent and independent methods. METHODS: Standard microbiological cultural techniques and 16S ribosomal RNA (16S rRNA) gene sequencing (Illumina technology) on DNA and RNA were employed to study (a) whole abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) from 14 obese and five normal-weight subjects and (b) mature adipocytes isolated from SAT and VAT after collagenase digestion or mechanical separation. To optimize the 16S rRNA gene detection, we used different DNA extraction methods (lysis with proteinase K, proteinase K+lysozyme and microbeads) and amplification procedures (semi-quantitative standard PCR and real-time quantitative PCR). RESULTS: Microbiological cultures were negative in all analyzed samples. In enzymatically isolated adipocytes, 90% of the sequenced bacterial DNA belonged to Clostridium histolyticum, the bacterium from which the collagenase enzyme was isolated. Bacterial 16S rRNA gene was not detected from DNA and RNA of whole SAT and VAT, as well as of mechanically isolated mature adipocytes, even after blocking with a specific primer the nonspecific amplification of human mitochondrial 12S rRNA. CONCLUSIONS: Our results do not support the presence of a human adipose tissue microbiota. In addition, they emphasized the technical problems encountered when applying metagenomic studies to human tissues with very low or absent bacterial load.

White blood cell count may identify abnormal cardiometabolic phenotype and preclinical organ damage in overweight/obese children.

BACKGROUND AND AIMS: Subclinical inflammation is a central component of cardiometabolic disease risk in obese subjects. The aim of the study was to evaluate whether the white blood cell count (WBCc) may help to identify an abnormal cardiometabolic phenotype in overweight (Ow) or obese (Ob) children. METHODS AND RESULTS: A cross-sectional sample of 2835 Ow/Ob children and adolescents (age 6-18 years) was recruited from 10 Italian centers for the care of obesity. Anthropometric and biochemical variables were assessed in the overall sample. Waist to height ratio (WhtR), alanine aminotransferase (ALT), lipids, 2 h post-load plasma glucose (2hPG), left ventricular (LV) geometry and carotid intima-media thickness (cIMT) were assessed in 2128, 2300, 1834, 535 and 315 children, respectively. Insulin resistance and whole body insulin sensitivity index (WBISI) were analyzed using homeostatic model assessment (HOMA-IR) and Matsuda's test. Groups divided in quartiles of WBCc significantly differed for body mass index, WhtR, 2hPG, HOMA-IR, WBISI, lipids, ALT, cIMT, LV mass and relative wall thickness. Children with high WBCc (≥8700 cell/mm(3)) showed a 1.3-2.5 fold increased probability of having high normal 2hPG, high ALT, high cIMT, or LV remodeling/concentric LV hypertrophy, after adjustment for age, gender, pubertal status, BMI and centers. CONCLUSIONS: This study shows that WBCc is associated with early derangements of glucose metabolism and preclinical signs of liver, vascular and cardiac damage. The WBCc may be an effective and low-cost tool for identifying Ow and Ob children at the greatest risk of potential complications.

Stage of change and motivation to healthy diet and habitual physical activity in type 2 diabetes.

Lifestyle changes to healthy diet (HD) and habitual physical activity (HPA) are recommended in type 2 diabetes mellitus (T2DM). Yet, for most people with diabetes, it may be difficult to start changing. We investigated the stage of change toward healthier lifestyles according to Prochaska's model, and the associated psychological factors in T2DM patients, as a prerequisite to improve strategies to implement behavior changes in the population. A total of 1,353 consecutive outpatients with T2DM attending 14 tertiary centers for diabetes treatment completed the validated EMME-3 questionnaire, consisting of two parallel sets of instruments to define the stage of change for HD and HPA, respectively. Logistic regression was used to determine the factors associated with stages that may hinder behavioral changes. A stage of change favoring progress to healthier behaviors was more common in the area of HD than in HPA, with higher scores in action and maintenance. Differences were observed in relation to gender, age and duration of disease. After adjustment for confounders, resistance to change toward HD was associated with higher body mass index (BMI) (odds ratio (OR) 1.05; 95 % confidence interval (CI) 1.02-1.08). Resistance to improve HPA also increased with BMI (OR 1.06; 95 % CI 1.03-1.10) and decreased with education level (OR 0.74; 95 % CI 0.64-0.92). Changing lifestyle, particularly in the area of HPA, is not perceived as an essential part of treatment by many subjects with T2DM. This evidence must be considered when planning behavioral programs, and specific interventions are needed to promote adherence to HPA.

Permanence of molecular features of obesity in subcutaneous adipose tissue of ex-obese subjects.

OBJECTIVE: 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. DESIGN: 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: 30 > or = BMI < or = 34.9, OB2-SAT: 35 > or = BMI < or = 39.9, OB3-SAT: BMI > or = 40). SUBJECTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The nicotinic acetylcholine receptor α7 in subcutaneous mature adipocytes: downregulation in human obesity and modulation by diet-induced weight loss.

BACKGROUND: 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. OBJECTIVE: To investigate the expression and protein content of α7nAChR in human subcutaneous adipose tissue (SAT) and in isolated mature adipocytes. DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.

Percutaneous transluminal angioplasty improves glucose control and quality of life in patients with critical limb ischemia.

AIM: To evaluate the benefit of endovascular peripheral revascularization on glucose control in patients with chronic limb ischemia. METHODS AND RESULTS: Over a 12 month period, 61 patients (41 male, range 49-88 years of age) presenting with critical limb ischemia (CLI) were treated according to the Trans Atlantic Inter Society Consensus (TASC II) guidelines. After discharge, all patients were asked to measure their glucose level three times daily, and glycated hemoglobin was checked monthly up to 12 months, as well as to fill a questionnaire to assess their Quality of Life (QoL). The revascularization procedure was successful in 90% of cases. Glycemic control and glycated hemoglobin in 22 diabetic patients subgroup were significantly improved after the treatment and remained stable over the follow-up period. There was a significant improvement in QoL that increased steadily from the operation and to reach a plateau after six months. CONCLUSIONS: Peripheral percutaneous angioplasty in subjects with CLI significantly improves glycemic control and ameliorates QoL. Revascularization positively effects also long-term diabetes control as well as QoL.

[Management of high blood pressure in children and adolescents: Recommendations of the European Society of hypertension]. / Manejo de la hipertensión arterial en niños y adolescentes: recomendaciones de la Sociedad Europea de Hipertensión.

Hypertension in children and adolescents has been gaining ground in cardiovascular medicine, mainly due to the advances made in several areas of pathophysiological and clinical research. These guidelines arose from the consensus reached by specialists in the detection and control of hypertension in children and adolescents. Furthermore, these guidelines are a compendium of scientific data and the extensive clinical experience it contains represents the most complete information that doctors, nurses and families should take into account when making decisions. These guidelines, which stress the importance of hypertension in children and adolescents, and its contribution to the current epidemic of cardiovascular disease, should act as a stimulus for governments to develop a global effort for the early detection and suitable treatment of high pressure in children and adolescents. J Hypertens 27:1719-1742 Q 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Manejo de la hipertensión arterial en niños y adolescentes: recomendaciones de la Sociedad Europea de Hipertensión / Management of high blood pressure in children and adolescents: Recommendations of the European Society of hypertension

La hipertensión en niños y adolescentes ha ido ganando terreno en la medicina cardiovascular, gracias a los avances producidos en distintas áreas de la investigación fisiopatológica y clínica. Estas guías nacen del consenso al que han llegado los especialistas en la detección y control de la hipertensión en niños y adolescentes. Por otra parte, dichas guías son un compendio de los datos científicos y la extensa experiencia clínica con la que se cuenta, y constituyen la información clínica más completa que los médicos, enfermeras y familiares deberían tener en cuenta a la hora de tomar decisiones. Estas guías, que hacen hincapié en la importancia de la hipertensión en niños y adolescentes, así como en el papel que desempeña en la actual epidemia de enfermedades cardiovasculares, deberían constituir un estímulo para que los gobiernos desarrollaran un esfuerzo global para una detección precoz y un tratamiento adecuado de la hipertensión arterial en niños y adolescentes. J Hypertens 27:1719-1742 Q 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins(AU)

Hypertension in children and adolescents has been gaining ground in cardiovascular medicine, mainly due to the advances made in several areas of pathophysiological and clinical research. These guidelines arose from the consensus reached by specialists in the detection and control of hypertension in children and adolescents. Furthermore, these guidelines are a compendium of scientific data and the extensive clinical experience it contains represents the most complete information that doctors, nurses and families should take into account when making decisions. These guidelines, which stress the importance of hypertension in children and adolescents, and its contribution to the current epidemic of cardiovascular disease, should act as a stimulus for governments to develop a global effort for the early detection and suitable treatment of high pressure in children and adolescents. J Hypertens 27:1719-1742 Q 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins(AU)

Predictors of the early impairment of renal disease in human obesity.

OBJECTIVE: The mechanisms underlying the association of the increased albumin excretion rate (AER) with adiposity have yet to be clarified. We therefore investigated (1) the predictors of AER after 3 months of lifestyle intervention in a large cohort of nondiabetic obese women and (2) the relationships between AER and the adipose tissue gene expression of adipokines linked to inflammation and insulin resistance. SUBJECTS: A total of 269 obese nondiabetic women (age 49.9+/-13.1 years, body mass index (BMI) 36.8+/-4.6 kg m(-2)) participated in this program. Measurements used were anthropometrics parameters, blood pressure, oral glucose tolerance test, lipids, creatinine, AER, homeostasis model assessment of insulin resistance (HOMA-IR) and glomerular filtration rate at baseline and after 3 months of lifestyle intervention. At baseline, in a subgroup of 34 women, subcutaneous adipose tissue biopsy was carried out for the analysis of mRNA expression levels of adiponectin, suppressor of cytokine signaling 3 (SOCS-3), tumor necrosis factor alpha (TNF-alpha), pentraxine 3 (PTX-3), angiotensinogen and angiotensin-converting enzyme, and a blood sample was also taken from this group for the measurement of circulating adiponectin, interleukin-6, TNF-alpha and PTX-3. Microalbuminuria was defined as albumin/creatinine ratio >or=3.5 mg mmol(-1). Real-time PCR was used to quantify mRNA. RESULTS: Six percent of obese women had microalbuminuria. When dividing the whole cohort into three groups according to AER changes (decrease, stability and increase), we noted that 2 h glucose, insulin and HOMA-IR significantly decreased (P<0.05 for all) only in women who had a decrease in AER, whereas BMI and waist circumference significantly decreased in all the three groups (P<0.05). At baseline, higher AER was associated to significantly higher adipose tissue mRNA expression levels of SOCS-3 and PTX-3 (P<0.05) and to higher TNF-alpha and angiotensinogen expression. CONCLUSIONS: In obese women, weight loss alone is not sufficient to induce the AER decrease that occurs only with a concomitant improvement in glucose homeostasis. The adipose tissue gene expression profile seems to favor the early renal impairment often seen in obese subjects.

Expression of long pentraxin PTX3 in human adipose tissue and its relation with cardiovascular risk factors.

UNLABELLED: Pentraxin 3 (PTX3) is an acute phase protein strongly expressed by advanced atherosclerotic lesions. We investigated (a) PTX3 expression and secretion in subcutaneous adipose tissue (SAT) and omental visceral adipose tissue (VAT) obtained from 21 obese (37.4+/-8.15 yr) and 10 normal weight subjects (43.7+/-11.07 yr) and (b) the relationships of adipose PTX3 with tumour necrosis factor alpha (TNFalpha) and adiponectin expression and with cardiometabolic risk factors. Real-time PCR was used to quantify specific mRNA for PTX3, CD68 (macrophage marker), TNFalpha and adiponectin. Fresh adipose tissue was cultured and PTX3 measured in the medium. Serum insulin, glucose, HDL and LDL cholesterol, triglycerides, C-reactive protein (CRP), fibrinogen, adiponectin, TNFalpha and PTX3 were measured. PTX3 expression was similar in the two fat compartments and tended to be higher in obese than in normal weight subjects in VAT only (p=0.05). CD68 and PTX3 expressions were correlated with each other in SAT but not in VAT. After adjustment for age and sex, VAT-PTX3 expression and release were correlated with VAT-TNFalpha expression (p<0.01 for both) and with LDL/HDL ratio (p<0.01 and p<0.001). VAT-PTX3 expression was also correlated with BMI, triglycerides, CRP, fibrinogen and adiponectin (p<0.05 for all). In the multivariate analysis with VAT-PTX3 RNA levels as dependent variable, LDL/HDL ratio and fibrinogen remained independently associated with VAT-PTX3 expression (p<0.01 for both). These associations were not seen within SAT. CONCLUSIONS: Human adipose tissue expresses and releases PTX3 likely under TNFalpha control. VAT production of PTX3 seems to contribute to the mechanisms underlying the development of atherosclerosis.

Sympathoadrenergic and metabolic factors are involved in ambulatory blood pressure rise in childhood obesity.

We investigated in a young Italian obese population, the relationship between ambulatory BP (ABP) and several pathophysiological factors linking obesity to hypertension. A total of 89 obese children and adolescents underwent a 24-h ambulatory BP monitoring (ABPM) and an oral glucose tolerance test. The circulating levels of insulin, lipids, uric acid, C-reactive protein, interleukin-6, renin and aldosterone and the 24-h urinary levels of epinephrine, norepinephrine and albumin excretion rate were measured. Nine percent of subjects had daytime sustained hypertension (SH), 26% night-time hypertension and 11% a non-dipping pattern. SH subjects compared to those with sustained normotension (SN) were more obese (P<0.05), with a more frequent family history of hypertension (P<0.05), higher urinary catecholamine (P<0.05) and heart rate values (P<0.05) after adjustment for standard deviation score (SDS) of body mass index (BMI) and sex. Subjects with night-time hypertension compared to those with night-time normotension were more obese (P<0.0001), with a higher prevalence of impaired glucose tolerance (P<0.05) and metabolic syndrome (P<0.05) and higher 2-h glucose (P<0.05), uric acid (P<0.05) and triglycerides (P<0.05). In multivariate regression analysis, daytime systolic BP (SBP) remained independently correlated with urinary norepinephrine and SDS-BMI (P<0.05 for both), daytime diastolic BP (DBP) with waist circumference (P<0.05) and night-time SBP and DBP with SDS-BMI (P<0.01 for both). The risk of having systolic and diastolic hypertension increased with the increase in SDS-BMI and waist circumference, respectively. In conclusion, in our cohort of obese children and adolescents, daytime and night-time hypertension were associated with activation of the sympathoadrenal system and worst metabolic conditions, respectively.

Type 2 diabetes and metabolic syndrome are associated with increased expression of 11beta-hydroxysteroid dehydrogenase 1 in obese subjects.

OBJECTIVE: The role of glucocorticoids production in adipose tissue in the development of metabolic disorders in humans has not been fully characterized. We investigated whether in obese subjects, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) expression in subcutaneous (SAT) and visceral (VAT) adipose tissue is associated with the occurrence of metabolic disorders and the expression of adiponectin and tumor necrosis factor alpha (TNFalpha) and two glucocorticoid-regulated adipokines able to influence the metabolic control. DESIGN AND SUBJECTS: Sixty-two obese patients were enrolled in the study. SAT and VAT samples were obtained from 13 patients undergoing bariatric surgery (body mass index (BMI) 39.1+/-5.3 kg/m(2)). SAT samples were obtained from 49 patients who underwent periumbilical biopsy (BMI 36.9+/-5.1 kg/m(2)). MEASUREMENTS: Oral glucose tolerance tests in subjects without known diabetes. Circulating glucose, lipid, insulin, adiponectin, TNFalpha and urinary-free cortisol levels. Real-time PCR to quantify mRNA levels of 11beta-HSD1, hexose-6-phosphate dehydrogenase (H6PDH), adiponectin and TNFalpha. Western blot analysis to evaluate 11beta-HSD1 protein expression. RESULTS: In the majority of the obese subjects, VAT expresses more 11beta-HSD1 than SAT. VAT 11beta-HSD1 expression was not associated with metabolic disorders. SAT 11beta-HSD1 mRNA levels were higher in subjects with than in those without metabolic syndrome (P<0.05) and in patients with type 2 diabetes compared to patients with impaired or normal glucose tolerance (P<0.0001). SAT 11beta-HSD1 expression was independently related to fasting glucose (P<0.0001) and urinary-free cortisol levels (P<0.01), and increased expression of 11beta-HSD1 was associated with increased adiponectin and TNFalpha expression and decreased serum adiponectin levels (all P's <0.05). CONCLUSIONS: In obese subjects, increased 11beta-HSD1 expression in SAT, but not in VAT, is associated with the worsening of metabolic conditions. We hypothesize that higher glucocorticoid production in adipose tissue would favor the development of metabolic disorders through a decrease in adiponectin release.

Adiponectin receptors gene expression in lymphocytes of obese and anorexic patients.

AIM: Two adiponectin receptors (ADIPORs), ADIPOR1 and ADIPOR2, are widely expressed in tissues. Whether changes in the expression of ADIPORs are associated with obesity and insulin resistance in humans is still unclear. The aim of this study was to explore whether lymphocyte ADIPOR1 and ADIPOR2 mRNA expression is associated with obesity, insulin resistance, first-phase insulin secretion and serum adiponectin levels. METHODS: Using reverse transcription-polymerase chain reaction, we measured ADIPOR1 and ADIPOR2 mRNA levels in the lymphocytes of 59 obese patients, of whom 39 had normal glucose tolerance, 8 had impaired glucose tolerance or impaired fasting glucose, and 12 had type 2 diabetes, and of 21 women with restrictive anorexia nervosa. RESULTS: In all subjects, ADIPOR1 expression was 2.2-fold higher than that of ADIPOR2 (p < 0.0001). The mRNA expression level of both receptors correlated with each other (p < 0.0001). After adjustment for age and sex, lymphocyte ADIPORs mRNA expression (ADIPOR1, p < 0.005; ADIPOR2, p < 0.05) and serum adiponectin (p < 0.0001) were significantly lower in obese patients than in anorexic subjects. In a multivariate analysis with ADIPOR1 as the dependent variable and body mass index (BMI), blood pressure and adiponectin as the independent variables, only serum adiponectin remained positively and independently correlated with ADIPOR1 (p < 0.05). Adiponectin was independently and negatively related to BMI and sex. CONCLUSIONS: We have demonstrated in this study that lymphocytes express ADIPORs and that, similar to serum adiponectin, ADIPORs expression is markedly reduced in obese subjects. ADIPORs expression is not independently related to BMI, insulin resistance and beta-cell function.

Metabolic syndrome in obese Caucasian children: prevalence using WHO-derived criteria and association with nontraditional cardiovascular risk factors.

OBJECTIVE: Studies on the prevalence of metabolic syndrome (MS) in European obese children using child-based criteria are scanty. Moreover, it is unknown if nontraditional cardiovascular disease (CVD) risk factors are associated with the MS at this early age in these subjects. DESIGN AND SUBJECTS: We studied the prevalence of the MS in 588 Caucasian obese children and adolescents by devising a World Health Organization derived definition and child-specific criteria, whose deviation from normalcy was based on an age, sex, and ethnically comparable control group of 1363 subjects. In a subgroup of 206 obese children, we investigated the association of the MS with nontraditional CVD risk factors. MEASUREMENTS: Fasting blood samples for glucose and lipids measurements were taken in both control and obese children. In addition, the obese children underwent an oral glucose tolerance test. In the subgroup of 206 obese children, albumin excretion rate , plasma uric acid, fibrinogen, plasminogen activator inhibitor type 1(PAI-1), C-reactive protein, interleukin 6 and white blood cells were also measured. RESULTS: The prevalence of MS was 23.3%. A similar prevalence of 23% of MS was recorded in the subgroup of 206 obese children in whom measurements of nontraditional CVD risk factors were available. After adjustment for the degree of obesity, subjects with MS had significantly higher uric acid (6.6+/-0.23 vs 6.1+/-0.12 mg/dl, P<0.0001) and PAI-1 plasma concentrations (231.4+/-25.50 vs 214.3+/-12.96 ng/ml, P<0.05) and a higher frequency of microalbuminuria (37 vs 20%, P<0.05) than those without MS. Microalbuminuria, uric acid and PAI-1 explained 10.6% of the variance of MS. CONCLUSION: Approximately, a quarter of Caucasian obese children have the MS. The association of MS with several nontraditional risk factors for CVD early in life suggests a heightened CVD risk in these individuals.

[Obesity and low-grade systemic inflammation]. / Obesità ed infiammazione sistemica cronica.

The aim of this review is to deal with the significance of obesity as a promotor of a chronic low-grade inflammatory reaction favouring the development of atherosclerosis and cardiovascular diseases. Adipose tissue synthetizes and releases inflammatory cytokines involved in various atherothrombotic mechanisms and in glucose and lipid metabolism. A local renin-angiotensin system may partially support the obesity related hypertension. Most obese subjects had elevated plasma levels of inflammatory markers which correlate with the degree of obesity and insulin resistance and decrease after weight reduction and exercise. Some evidences suggest that long-chain polyunsaturated fatty acids and thiazolidinediones may be useful in preventing atherosclerosis. Obesity, by itself, has been considered an independent risk factor for cardiovascular diseases. The hypothesis that it is linked to the associated low-grade chronic inflammation is supported by the existence of altered indexes of chronic inflammation also in obese children who are free of other pathological conditions. Further research will be required to determine the pathophysiological meaning of the chronic inflammation associated to obesity.

Salivary cortisol measurement in normal-weight, obese and anorexic women: comparison with plasma cortisol.

OBJECTIVE: To compare salivary, plasma and urinary free cortisol (UFC) measurements in patients with anorexia nervosa, in whom an overdrive of the hypothalamic-pituitary-adrenal (HPA) axis is well established but information on salivary cortisol is lacking, in viscerally obese patients in whom subtle abnormalities of cortisol secretion and metabolism are postulated, and in normal-weight healthy women. PARTICIPANTS AND EXPERIMENTAL DESIGN: Measurement of salivary cortisol offers a convenient way to assess the concentrations of free, biologically active cortisol in plasma in different physiopathological settings. Forty-seven drug-free, newly diagnosed women with active restrictive anorexia nervosa, 30 restrictive anorexic women undergoing chronic psychopharmacological treatment, 47 women with mild-to-moderate visceral obesity, 103 women with severe central obesity and 63 normal-weight healthy women entered the study. Salivary and blood samples were collected at 0800 h, 1700 h and 2400 h, together with three consecutive 24-h urine specimens for UFC determination. In controls and patients with anorexia nervosa (n=83), salivary and plasma cortisol were also measured after a 1-mg overnight dexamethasone suppression test (DST). In patients with anorexia nervosa, mood was rated by the Hamilton scale for anxiety and depression. RESULTS: Untreated patients with anorexia nervosa showed increased plasma and salivary cortisol and UFC concentrations (all P<0.001 compared with controls), and decreased cortisol suppression after DST in plasma and saliva (P<0.0001 and P<0.005 respectively compared with controls). These alterations were less pronounced, although still statistically significant, in treated patients with anorexia nervosa. Salivary cortisol was highly correlated with paired plasma cortisol in the whole population and after splitting the participants by group (P<0.0001). However, for plasma cortisol values greater than 500 nmol/l (the corticosteroid-binding globulin saturation point), this parallelism was lost. Taking plasma cortisol as a reference, the level of agreement for post-dexamethasone salivary and plasma cortisol was 58.9% among suppressors and 77.8% among non-suppressors (chi2 test: P<0.01). Decreased 0800 h/2400 h cortisol ratios were observed in plasma and saliva in drug-free patients with anorexia nervosa (P<0.005 and P<0.05 respectively compared with controls), and in saliva in severely obese patients (P<0.05 compared with controls). Depression and anxiety scores were unrelated to cortisol concentrations in any compartment. CONCLUSIONS: Salivary cortisol measurement is a valuable and convenient alternative to plasma cortisol measurement. It enables demonstration of the overdrive of the HPA axis in anorexia nervosa and subtle perturbations of the cortisol diurnal rhythm in women with visceral obesity. With the establishment of more specific and widely acceptable cut-off values for dynamic testing, measurement of salivary cortisol could largely replace plasma cortisol measurement.