Search

Context: Gut hormones seem to play an important role in postprandial bone turnover, which also may be affected by postprandial plasma glucose excursions and insulin secretion., Objective: To investigate the effect of an oral glucose tolerance test (OGTT) and an isoglycemic intravenous glucose infusion (IIGI) on bone resorption and formation markers in individuals with type 1 diabetes and healthy controls., Methods: This observational case-control study, conducted at the Center for Clinical Metabolic Research, Gentofte Hospital, Hellerup, Denmark, included 9 individuals with C-peptide negative type 1 diabetes and 8 healthy controls matched for gender, age, and body mass index. Subjects underwent an OGTT and a subsequent IIGI. We analyzed changes in bone resorption assessed by measurements of carboxy-terminal type I collagen crosslinks (CTX) and in bone formation as assessed by procollagen type I N-terminal propeptide (PINP) concentrations., Results: Baseline CTX and PINP levels were similar in the 2 groups. Both groups exhibited significantly greater suppression of CTX during OGTT than IIGI. PINP levels were unaffected by OGTT and IIGI, respectively, in healthy controls. Participants with type 1 diabetes displayed impaired suppression of CTX-assessed bone resorption and inappropriate suppression of PINP-assessed bone formation during OGTT., Conclusion: Our data suggest the existence of a gut-bone axis reducing bone resorption in response to oral glucose independently of plasma glucose excursions and insulin secretion. Subjects with type 1 diabetes showed impaired suppression of bone resorption and reduced bone formation during OGTT, which may allude to the reduced bone mineral density and increased fracture risk characterizing these individuals., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context: Endothelial progenitor cells (EPCs), which are involved in the mechanisms of vascular repair and sexual function, are decreased in diabetic women compared with general population., Objective: This work aimed to investigate the circulating levels of EPCs and the change in sexual function during the menstrual cycle in women with type 1 diabetes (T1DM) compared with healthy women., Methods: This case-control observational study was conducted at the Unit of Endocrinology and Metabolic Diseases at University Hospital "Luigi Vanvitelli'' of Naples. Participants included 36 women with T1DM and 64 age-matched healthy controls. EPCs were quantified by flow cytometry and sexual function was assessed using the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale. All assessments were made at the follicular, ovulatory, and luteal phases of the same menstrual cycle. Main outcome measures included differences in EPCs levels and sexual function between patients and controls., Results: Compared with controls, women with T1DM showed significantly lower levels of both CD34 + (P < .001) and CD34 + CD133 + cells (P < .001) in the ovulatory phase, and CD34 + KDR + cells both in the ovulatory phase and in the luteal phase (P < .001 for both). Diabetic women showed significantly lower total FSFI scores and higher FSDS score than control women in all phases of the menstrual cycle. FSFI total score was predicted by both CD34 + CD133 + and CD34 + KDR + cells in the follicular phase, CD34 + and CD34 + KDR + CD133 + cells in the ovulatory phase, and CD34 + KDR + and CD34 + KDR + CD133 + cells in the luteal phase., Conclusion: Women with T1DM show lower levels of EPCs during the menstrual cycle compared with controls. EPCs count predicts sexual function in this selected population., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.)

Context: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe chronic illness that reduces the quality of life. A potential role of neuroendocrine autoimmune dysfunction has been hypothesized., Objective: This work aims to investigate the occurrence of antipituitary (APA) and antihypothalamic (AHA) antibodies and possible related hypothalamic/pituitary dysfunctions in ME/CSF patients., Methods: This is a case-control study conducted in a university hospital setting (Stanford, California, USA; and Naples, Italy). Thirty women with ME/CSF (group 1) diagnosed according to Fukuda, Canadian, and Institute of Medicine criteria, at Stanford University, were enrolled and compared with 25 age-matched healthy controls. APA and AHA were detected by immunofluorescence; moreover, we investigated hormonal secretions of anterior pituitary and respective target glands. APA and AHA titers both were assessed and the prevalence of pituitary hormone deficiencies was also investigated., Results: Patients in group 1 showed a high prevalence of AHA (33%) and APA (56%) and significantly lower levels of adrenocorticotropin (ACTH)/cortisol, and growth hormone (GH) peak/insulin-like growth factor-1 (IGF-1) vs controls (all AHA/APA negative). Patients in group 1A (13 patients positive at high titers, ≥ 1:32) showed ACTH/cortisol and GH peak/IGF-1 levels significantly lower and more severe forms of ME/CFS with respect to patients in group 1B (7 positive at middle/low titers, 1:16-1:8) and 1C (10 antibody-negative patients)., Conclusion: Both AHA and/or APA at high titers were associated with hypothalamic/pituitary dysfunction, suggesting that hypothalamic/pituitary autoimmunity may play an important role in the manifestations of ME/CFS, especially in its more severe forms., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context: An improvement of some autoimmune diseases associated with celiac disease (CD) has been observed after a gluten-free diet (GFD)., Objective: The aim of this longitudinal study was to evaluate the effect of a GFD on autoimmune pituitary impairment in patients with CD and potential/subclinical lymphocytic hypophysitis (LYH)., Design: Five-year longitudinal observational study., Setting: Tertiary referral center for immunoendocrinology at the University of Campania "Luigi Vanvitelli"., Patients: Ninety-three newly diagnosed LYH patients (high titer of antipituitary antibodies [APA] and normal or subclinically impaired pituitary function) were enrolled from 2000 to 2013 and grouped as follows: group 1, consisting of 43 patients with LYH + CD, and group 2, consisting of 50 patients with isolated LYH only., Intervention: A GFD was started in patients in group 1 after the diagnosis of CD., Main Outcome Measures: APA titers and pituitary function were evaluated at the beginning of the study and then yearly for 5 years in both groups. Patients progressing to a clinically overt LYH were excluded from the follow-up., Results: Complete remission of LYH (disappearance of APA and recovery of pituitary function in patients with previous subclinical hypopituitarism) occurred in 15 patients in group 1 after a GFD (34%) and spontaneously in only 1 patient in group 2 (2%) (P < .001). Two patients in group 1 and 25 in group 2 progressed to a clinically overt hypopituitarism and dropped out from the study to receive an appropriate replacement therapy. The presence of CD was the only independent predictor of pituitary function recovery (hazard ratio [HR] 0.059, 95% confidence interval [CI] 0.01-0.54, P = .012)., Conclusion: In patients with LYH and CD, a GFD may be able to induce remission of subclinical LYH, or prevent the progression to clinical stage of this disease., (Published by Oxford University Press on behalf of the Endocrine Society 2020.)

Context: Women with autoimmune Addison's disease with normal ovulatory cycles but positive for steroid cell antibodies (StCA) have been considered at risk of premature ovarian insufficiency (POI)., Design: Thirty-three women younger than 40 years, with subclinical-clinical autoimmune Addison's disease but with normally ovulatory menses, were followed up for 10 years to evaluate the long-term time-related variations of StCA, ovarian function and follicular reserve. All patients and 27 control women were investigated at the start and every year for the presence and titre of StCA (by indirect immunofluorescence), serum concentrations of anti-Mullerian hormone (AMH) and ovarian function at four consecutive menses every year., Results: At the start of the study StCA were present in 16 women (group 1), at low/middle titres (≤1:32) in seven of them (43.8%, group 1A), at high titres (>1:32) in the remaining nine patients (group 1B, 56.2%), while they were absent from 17 patients (group 2). During the follow-up period, all women in group 1A remained StCA-positive at low/middle titres with normal ovulatory menses and normal gonadotrophin and AMH levels, while all patients in group 1B showed a further increase of StCA titres (1:128-1:256) and progressed through three stages of ovarian function. None of the patients in group 2 and controls showed the appearance of StCA or ovarian dysfunction during the follow-up., Conclusions: The presence of StCA at high titres can be considered a good predictive marker of subsequent development of autoimmune POI. To single out the stages of autoimmune POI may allow a timely therapeutic choice in the subclinical and early clinical stages., (© 2017 European Society of Endocrinology.)

The importance of metabolic syndrome (MetS) lies in its associated risk of cardiovascular disease and type 2 diabetes, as well as other harmful conditions such as nonalcoholic fatty liver disease. In this report, the available scientific evidence on the associations between lifestyle changes and MetS and its components is reviewed to derive recommendations for MetS prevention and management. Weight loss through an energy-restricted diet together with increased energy expenditure through physical activity contribute to the prevention and treatment of MetS. A Mediterranean-type diet, with or without energy restriction, is an effective treatment component. This dietary pattern should be built upon an increased intake of unsaturated fat, primarily from olive oil, and emphasize the consumption of legumes, cereals (whole grains), fruits, vegetables, nuts, fish, and low-fat dairy products, as well as moderate consumption of alcohol. Other dietary patterns (Dietary Approaches to Stop Hypertension, new Nordic, and vegetarian diets) have also been proposed as alternatives for preventing MetS. Quitting smoking and reducing intake of sugar-sweetened beverages and meat and meat products are mandatory. Nevertheless, there are inconsistencies and gaps in the evidence, and additional research is needed to define the most appropriate therapies for MetS. In conclusion, a healthy lifestyle is critical to prevent or delay the onset of MetS in susceptible individuals and to prevent cardiovascular disease and type 2 diabetes in those with existing MetS. The recommendations provided in this article should help patients and clinicians understand and implement the most effective approaches for lifestyle change to prevent MetS and improve cardiometabolic health., (© The Author(s) 2017. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background We assessed the long-term effects of a Mediterranean diet on circulating levels of endothelial progenitor cells (EPCs) and the carotid intima-media thickness (CIMT) in patients with type 2 diabetes. Design This was a parallel, two-arm, single-centre trial. Methods Two hundred and fifteen men and women with newly diagnosed type 2 diabetes were randomized to a Mediterranean diet ( n = 108) or a low-fat diet ( n = 107). The primary outcome measures were changes in the EPC count and the CIMT of the common carotid artery after the treatment period defined as the end of trial (EOT). Results At the EOT, both the CD34 + KDR + and CD34 + KDR + CD133 + counts had increased with the Mediterranean diet compared with the low-fat diet ( p < 0.05 for both). At the EOT evaluation, there was a significant ( p = 0.024) difference of -0.025 mm in the CIMT favouring the Mediterranean diet. Compared with the low-fat diet, the rate of regression in the CIMT was higher in the Mediterranean diet group (51 vs. 26%), whereas the rate of progression was lower (25 vs. 50%) ( p = 0.032 for both). Changes in the CIMT were inversely correlated with the changes in EPC levels (CD34 + KDR + , r = -0.24, p = 0.020; CD34 + KDR + CD133 + , r = -0.28, p = 0.014). At the EOT, changes in levels of HbA1c, HOMA, total cholesterol, high-density lipoprotein cholesterol and systolic blood pressure were significantly greater with the Mediterranean diet than with the low-fat diet. Conclusion Compared with a low-fat diet, a long-term trial with Mediterranean diet was associated with an increase in circulating EPCs levels and prevention of the progression of subclinical atherosclerosis in patients with newly diagnosed type 2 diabetes.

Background: Some cases of apparently idiopathic GH deficiency (GHD) may be caused by pituitary autoimmunity., Objective: To study the variations in pituitary function and antipituitary antibodies (APA) from childhood to transition age in patients with apparently idiopathic GHD., Design: We conducted a longitudinal study., Patients and Methods: Pituitary function and APA detection by immunofluorescence were investigated in 24 childhood patients with isolated GHD before starting recombinant GH therapy and after the stopping of this therapy in transition age. Sera of patients positive for APA were processed by double immunofluorescence to identify their pituitary target., Results: At diagnosis, 16 out of 24 patients were APA positive targeting only somatotrophs (group 1), while the remaining eight were APA negative (group 2). When retested off therapy, 12 out of 16 patients in group 1 persisted being APA positive, while the remaining four became negative with recovery of pituitary function. All patients in group 2 persisted being APA negative but still showing GHD. Of the 12 patients persistently APA positive, eight with confirmed GHD showed APA still targeting somatotrophs, whereas four showed APA targeting only gonadotrophs associated with isolated hypogonadotropic hypogonadism (HH)., Conclusion: Patients with APA at middle but not at high titer in childhood may show a remission of autoimmune GHD in childhood after GH replacement therapy. As APA may shift their target in transition period, an early characterization of APA by double immunofluorescence is advisable in APA positive GHD patients showing delayed puberty, to allow an early diagnosis and an appropriate therapy, thus preventing the progression toward HH., (© 2016 European Society of Endocrinology.)

Recently, an increased incidence of central diabetes insipidus (CDI) in pregnancy, and less frequently in the post partum period, has been reported, most probably favoured by some conditions occurring in pregnancy. This study was aimed at investigating the influence of pregnancy on a pre-existing potential/subclinical hypothalamic autoimmunity. We studied the longitudinal behaviour of arginine-vasopressin cell antibodies (AVPcAbs) and post-pituitary function in two young women with a positive history of autoimmune disease and presence of AVPcAbs, but without clinical CDI, and who became pregnant 5 and 7 months after our first observation. The behaviour of post-pituitary function and AVPcAbs (by immunofluorescence) was evaluated at baseline, during pregnancy and for 2 years after delivery. AVPcAbs, present at low/middle titres at baseline in both patients, showed a titre increase during pregnancy in one patient and after delivery in the other patient, with development of clinically overt CDI. Therapy with 1-deamino-8-d-arginine vasopressin (DDAVP) caused a prompt clinical remission. After a first unsuccessful attempt of withdrawal, the therapy was definitively stopped at the 6th and the 7th month of post partum period respectively, when AVPcAbs disappeared, accompanied by post-pituitary function recovery, persisting until the end of the follow-up. The determination of AVPcAbs is advisable in patients with autoimmune diseases planning their pregnancy, because they could be considered good predictive markers of gestational or post partum autoimmune CDI. The monitoring of AVPcAb titres and post-pituitary function during pregnancy in these patients may allow for an early diagnosis and an early replacement therapy, which could induce the disappearance of these antibodies with consequent complete remission of CDI., (© 2015 European Society of Endocrinology.)

Introduction: Premature ejaculation (PE) is the most common male sexual dysfunction. Its prevalence in Type 1 diabetes is unknown., Aim: The aim of this study was to assess the prevalence of PE in Type 1 diabetes and the influence of glycemic control on ejaculatory function., Methods: One hundred Type 1 diabetic male patients (age < 40 years) and 51 age-matched nondiabetic control subjects were evaluated for PE. A subgroup of 30 diabetic patients (20 with PE and 10 without) were also evaluated for blood glucose variability., Main Outcome Measures: The presence of PE was assessed with the premature ejaculation diagnostic tool (PEDT) and the self-estimated intravaginal ejaculatory latency time (IELT). Glucose variability was evaluated by continuous glucose monitoring for a 7-day period with a DexCom G4 CGM system: the mean amplitude of glycemic excursions (MAGEs), low (LBGI) and high (HBGI) blood glucose indices, and the standard deviation of blood glucose (BGSD) were calculated., Results: PE prevalence did not differ significantly between the two groups: pathological values of the PEDT score (>8) and IELT score (<1 minute) were recorded in 24 out of 100 diabetic patients (24%) and in 12 out of 51 controls (23.5%). There were significant associations between hemoglobin A1c and the PEDT score (r = 0.27; P = 0.006) and IELT (r = -0.3; P = 0.01). In the subgroup assessed for glucose variability, the PEDT score was associated with LBGI (r = 0.43; P = 0.01), but not with BGSD (r = 0.1, P = 0.6), MAGE (r = -0.1; P = 0.4), or HBGI (r = 0.1; P = 0.6)., Conclusions: Our results show a similar prevalence of PE in young male patients with Type 1 diabetes and in the age-matched control population; in diabetic patients with PE, a higher glycemic variability in the hypoglycemic domain is significantly associated with the PEDT score., (© 2014 International Society for Sexual Medicine.)

Context: Obesity in children/adolescents has been associated with subtle cardiac abnormalities, including myocardial dysfunction and cardiac autonomic dysregulation at rest, both likely responsible for a higher mortality in adulthood. Food intake induces remarkable adjustments of cardiovascular autonomic activity in healthy subjects., Objective: The objective of the study was to evaluate in obese children/adolescents meal-induced cardiac autonomic response and the role played by insulin resistance., Design and Setting: Sixty-eight obese and 30 matched normal-weight children/adolescents underwent blood sampling and cardiovascular autonomic analysis while recumbent and 20 minutes after a mixed meal ingestion. Spectrum analysis of the R-R interval and systolic blood pressure (SBP) variability provided the indices of sympathetic [low frequency (LFRR)] and vagal [high frequency (HFRR)] modulation of the sinoatrial node and the low frequency component of SBP. The homeostasis model assessment of insulin resistance served to separate insulin resistant (n = 35) from non insulin resistant (n = 33) obese children/adolescents., Results: At baseline, C-reactive protein, the LFRR to HFRR ratio, SBP, and low frequency oscillatory component of SBP variability in obese children/adolescents were significantly (P < .05) greater than in referent subjects, whereas high-density lipoprotein cholesterol and HFRR were lower; meal-induced increase in the LFRR to HFRR ratio was significantly less than in controls and exaggeratedly scanty (or opposite) among insulin resistant subjects. The homeostasis model assessment of insulin resistance index strongly and inversely correlated (r = -0.871; P < .001) with meal-induced changes in the LFRR to HFRR ratio among obese subjects., Conclusions: Autonomic modulation of the heart was impaired after eating in obese children/adolescents. This abnormality was exaggerated among insulin resistant subjects and strongly correlated with the degree of insulin resistance.

Introduction: Penile rigidity depends on maximizing inflow while minimizing outflow., Aim: The aim of this review is to describe the principal factors and mechanisms involved., Main Outcome Measure: Erectile quality is the main outcome measure., Methods: Data from the pertinent literature were examined to inform our conclusions., Results: Nitric oxide (NO) is the principal factor increasing blood flow into the penis. Penile engorgement and the pelvic floor muscles maintain an adequate erection by impeding outflow of blood by exerting pressure on the penile veins from within and from outside of the penile tunica. Extrinsic pressure by the pelvic floor muscles further raises intracavernosal pressure above maximum inflow pressure to achieve full penile rigidity. Aging and poor lifestyle choices are associated with metabolic impediments to NO production. Aging is also associated with fewer smooth muscle cells and increased fibrosis within the corpora cavernosa, preventing adequate penile engorgement and pressure on the penile veins. Those same penile structural changes occur rapidly following the penile nerve injury that accompanies even "nerve-sparing" radical prostatectomy and are largely prevented in animal models by early chronic use of a phosphodiesterase type 5 (PDE5) inhibitor. Pelvic floor muscles may also decrease in tone and bulk with age, and pelvic floor muscle exercises have been shown to improve erectile function to a similar degree compared with a PDE5 inhibitor in men with erectile dysfunction (ED)., Conclusions: Because NO is critical for vascular health and ED is strongly associated with cardiovascular disease, maximal attention should be focused on measures known to increase vascular NO production, including the use of PDE5 inhibitors. Attention should also be paid to early, regular use of PDE5 inhibition to reduce the incidence of ED following penile nerve injury and to assuring normal function of the pelvic floor muscles. These approaches to maximizing erectile function are complementary rather than competitive, as they operate on entirely different aspects of erectile hydraulics., (© 2014 International Society for Sexual Medicine.)

Introduction: Both type 2 diabetes and secondary hypogonadism may be associated with low vitamin D levels., Aim: The aim of this study was to evaluate 25-hydroxyvitamin D (25(OH)D) concentrations in type 2 diabetic males with and without hypogonadism., Methods: We performed a case-control study among 122 male adults with type 2 diabetes, 51 with associated hypogonadism (Group 1) and 71 with normal gonadal function (Group 2). One hundred age-matched nondiabetic males with normal gonadal function served as a control group., Main Outcome Measures: Levels of 25(OH)D were assessed by a chemiluminescent immunoassay in all patients. Morning testosterone, pituitary, thyroid, parathyroid hormones, fasting glucose, and hemoglobin A1c were also evaluated., Results: The overall diabetic population showed a mean 25(OH)D concentration (22.3 ± 6.09 ng/mL) significantly lower than the control group (34.3 ± 7.2, P < 0.001), with 81% of diabetic patients presenting 25(OH)D deficiency (<20 ng/mL) or insufficiency (20-29.9 ng/mL). The lowest 25(OH)D concentration was found in Group 1 (20.1 ± 6.58 ng/mL). Concentration of 25(OH)D was significantly lower in the 42 patients with hypogonadotropic hypogonadism as compared with the 9 patients with hypergonadotropic hypogonadism (19.4 ± 7.06 vs. 23.8 ± 6.11 ng/mL, P < 0.001). No difference in erectile dysfunction (ED) prevalence between Group 1 and Group 2 was found, nor was there a correlation between the severity of ED and vitamin D levels (r = -0.10, P = 0.39)., Conclusions: These results show that type 2 diabetic patients with hypogonadism present lower 25(OH)D concentration and higher prevalence of vitamin D deficiency, compared with patients without hypogonadism. The finding that 25(OH)D concentrations were similar between type 2 diabetic patients with hypergonadotropic hypogonadism and those with normal gonadal function deserves further study., (© 2013 International Society for Sexual Medicine.)

Background: The risk of bone fractures in subjects with the metabolic syndrome is unknown. We did a meta-analysis to assess the association between metabolic syndrome, risk of fractures, and bone mineral density (BMD)., Materials and Methods: We did searches on electronic databases (Medline, Scopus, and ISI Web of Knowledge) until December 2012 and searched reports to identify studies in humans on bone fractures and BMD at different sites. Two independent reviewers collected the relevant reports. We did random-effects meta-analyses to determine the risk of fractures and BMD values associated with metabolic syndrome., Results: A total of 17 studies, with 35 datasets, were included. In 10 articles (14 datasets) including 1350 incident and 1628 prevalent fractures, metabolic syndrome was associated with a reduced fracture risk (risk ratio = 0.85, 95% confidence interval, 0.71-1.00; high heterogeneity: I(2) = 55%, P = .006). Omission of 2 outlier studies resulted in a significant negative association (risk ratio = 0.85, P = .012; I(2) = 34%, P = .130). Most of the reduced fracture risk was seen in cohort studies (18% reduced risk), suggesting a direction of causality; sex, site of fracture, and definition of the syndrome did not affect the estimates. In 16 articles, including 29 341 subjects, there was no difference in spine, femoral neck, or calcaneus BMD values between subjects with or without metabolic syndrome; mean differences ranged from 0.001 to 0.012 g/cm(2) (P > .10)., Conclusions: This article shows a reduced risk of bone fractures associated with metabolic syndrome, without modification of BMD. The clinical significance of these findings remains uncertain and should be addressed in future prospective studies.

Introduction: Female sexual function is dependent, in part, upon normal endothelial function within the genital arterial (hypogastric-cavernosal) vascular bed. The first two Princeton Consensus Conferences were focused on relationships between male sexual function and cardiovascular health, and development of contemporary clinical guidelines for dysfunction management., Aim: The third Princeton Consensus Conference updated recommendations and assessed, for the first time, the association between female sexual dysfunction (FSD) and presence of systemic vascular endothelial dysfunction and its consequences in women. This report focuses on the association between cardiometabolic risk factors and female sexual health., Methods: A panel of experts reviewed multinational data concerning associations between several cardiometabolic risks in women (hypertension, dyslipidemia and/or hyperlipemia, cigarette smoking, diabetes mellitus, and metabolic syndrome/obesity) and sexual health. Literature was reviewed concerning associations between FSD and presence or absence of cardiovascular disease, predictive association of FSD with cardiovascular events, and the possibility of vascular risk factor treatment modifying FSD., Main Outcome Measure: Main outcome measures used were cardiometabolic risk factors and female sexual health, specifically genital arousal., Results: Women treated for hypertension have more FSD than normotensives. Women with hyperlipidemia but without cardiovascular disease have more FSD than women without hyperlipidemia. Women with metabolic syndrome/obesity have more FSD than those without. Cardiometabolic risk factors, diabetes, and coronary heart disease are associated with more FSD. Data support that treatment of metabolic syndrome/obesity is associated with less FSD. Currently, there are no data to support that FSD is a predictor of future cardiovascular events., Conclusion: Female sexual health is complex: there is relative independence between subjective and objective aspects of arousal and desire, with numerous contributing factors (hormonal, psychological, interpersonal, and social). Based on limited current data, there appears to be an association between female sexual health and vascular risk factors (hypertension, hyperlipidemia, metabolic syndrome/obesity, diabetes, and coronary heart disease). More research is needed., (© 2012 International Society for Sexual Medicine.)

Introduction: Although epidemiological evidence seems to support a role for lifestyle factors in the pathogenesis of erectile dysfunction (ED), limited data are available suggesting that dietary changes may improve ED., Aim: To provide an update on clinical evidence regarding the role of dietary factors in ED., Methods: A systematic literature search was performed using MEDLINE and other database (EMBASE, SCOPUS) with MeSH terms and keywords for "erectile dysfunction", "diet", "dietary patterns", "Mediterranean diet", and "lifestyle"., Main Outcome Measures: To examine the data relating to erectile dysfunction with dietary factors, its relationship and the impact of dietary treatment., Results: Only few studies assessed the role or the effect of diet on ED. A dietary pattern which is high in fruit, vegetables, nuts, whole grains, and fish but low in red and processed meat and refined grains is more represented in subjects without ED. Mediterranean diet has been proposed as a healthy dietary pattern based on evidence that greater adherence to this diet is associated with lower all-cause and disease-specific survival. In type 2 diabetic men, those with the highest adherence to the Mediterranean diet had the lowest prevalence of ED and were more likely to be sexually active. In clinical trials, Mediterranean diet was more effective than a control diet in ameliorating ED or restoring absent ED in people with obesity or metabolic syndrome., Conclusion: The adoption of a Mediterranean diet may be associated with an improvement of erectile dysfunction.

Introduction: There are no reported studies assessing the relation between diet and erectile dysfunction (ED) in men with diabetes., Aim: In the present study, we explored the relation between consumption of a Mediterranean-type diet and ED in a population of type 2 diabetic men., Methods: Patients with type 2 diabetes were enrolled if they had a diagnosis of type 2 diabetes for at least six months but less than 10 years, age 35-70 years, body mass index (BMI) of 24 or higher, HbA1c of 6.5% or higher, treatment with diet or oral drugs. All diabetic patients were invited to complete a food-frequency questionnaire and self-report measures of sexual function. A total of 555 (90.8%) of the 611 diabetic men completed both questionnaires and were analyzed in the present study., Main Outcome Measures: Adherence to a Mediterranean diet was assessed by a 9-point scale that incorporated the salient characteristics of this diet (range of scores, 0-9, with higher scores indicating greater adherence). ED was assessed with the International Index of Erectile Function-5., Results: Diabetic men with the highest scores (6-9) had lower BMI, waist circumference, and waist-to-hip ratio, a lower prevalence of obesity and metabolic syndrome, a higher level of physical activity, and better glucose and lipid profiles than the diabetic men who scored <3 points on the scale. The proportion of sexually active men showed a significant increase across tertiles of adherence to Mediterranean diet (from 65.1% to 74.4%, P = 0.01). Moreover, men with the highest score of adherence were more likely to have a lower prevalence of global ED (51.9% vs. 62%, P = 0.01) and severe ED (16.5% vs. 26.4%, P = 0.01) as compared with low adherers., Conclusions: In men with type 2 diabetes, greater adherence to Mediterranean diet is associated with a lower prevalence of ED.

Introduction: There are no reported studies assessing the relation between diet and sexual function in women with diabetes., Aim: In the present study, we explored the relation between consumption of a Mediterranean-type diet and sexual function in a population of type 2 diabetic women., Methods: Patients with type 2 diabetes were enrolled if they had a diagnosis of type 2 diabetes for at least six months but less than 10 years, age 35-70 years, body mass index (BMI) of 24 or higher, HbA1c of 6.5% or higher, treatment with diet or oral drugs. All diabetic patients were invited to complete a food-frequency questionnaire and self-report measures of sexual function. A total of 595 (90.2%) of the 659 women completed both questionnaires and were analyzed in the present study., Main Outcome Measures: Adherence to a Mediterranean diet was assessed by a 9-point scale that incorporated the salient characteristics of this diet (range of scores, 0-9, with higher scores indicating greater adherence). The Female Sexual Function Index (FSFI) was used for assessing the key dimensions of female sexual function., Results: Diabetic women with the highest scores (6-9) had lower BMI, waist circumference, and waist-to-hip ratio, a lower prevalence of depression, obesity and metabolic syndrome, a higher level of physical activity, and better glucose and lipid profiles than the diabetic women who scored <3 points on the scale. The proportion of sexually active women showed a significant increase across tertiles of adherence to Mediterranean diet (from 54.2% to 65.1%, P = 0.01). Based on the FSFI cutoff score for female sexual dysfunction (FSD) of 23, women with the highest score of adherence had a lower prevalence of sexual dysfunction as compared with women of lower tertiles (47.6%, 53.9%, and 57.8%, higher, middle, and lower tertile, respectively, P = 0.01). These associations remained significant after adjustment for many potential confounders., Conclusions: In women with type 2 diabetes, greater adherence to Mediterranean diet is associated with a lower prevalence of FSD.

Introduction: A limiting step in the evaluation of female sexual dysfunction (FSD) is the availability of a rapid screening procedure. Often, practitioners avoid investigating sexual symptoms due to concerns of insufficient time or lack of proper tools to address FSD., Aim: The purpose of this study was to prepare and validate an abridged form of the most popular psychometric diagnostic test (Female Sexual Function Index, FSFI-19) to provide a fast screener of FSD for easy use in outpatient visits, epidemiological studies, and assessment of treatment response., Methods: We interviewed and administered the FSFI-19 to 200 women attending outpatient clinics for sexual and reproductive medicine. Forty women were excluded because they had no sexual activity or failed to attend the retest visit. Patients were evaluated on two subsequent visits to validate the abridged form of the questionnaire. Overall, 105 were found to suffer from a FSD., Main Outcome Measure: We assessed, individually, the sensibility and sensitivity of all questions of the full-length FSFI. We then estimated the performance of each item with respect to the specific sexual domain they address. By selecting the best combination of performing items in each domain, we built an abridged, 6-item form of the FSFI., Results: The Receiver Operating Characteristic curves of the FSFI-6 showed that women who scored

Objective: The objective of the study was to investigate the effect of different periods of hyperglycemia on the reversal of endothelial dysfunction by glucose normalization and antioxidant therapy., Research Design and Methods: Ten healthy subjects and three subgroups of 10 type 1 diabetic subjects were enrolled as follows: 1) patients within 1 month of diagnosis; 2) patients between 4.5 and 5.2 yr from diagnosis and with glycosylated hemoglobin levels 7% or greater since diagnosis; 3) patients between 4.8 and 5.4 yr from diagnosis and with glycosylated hemoglobin levels greater than 7% since diagnosis. Each patient participated in three experiments: 1) 24-h insulin treatment, achieving a near normalization of glycemia, together with the addition of the antioxidant vitamin C during the last 12 h; 2) 24-h vitamin C treatment with insulin treatment for the last 12 h; and 3) treatment with both vitamin C and insulin for 24 h., Results: Endothelial function, as measured by flow-mediated vasodilation of the brachial artery and levels of nitrotyrosine, an oxidative stress marker, were normalized by each treatment in subgroups 1 and 2. In the third subgroup, neither glucose normalization nor vitamin C treatment alone was able to normalize endothelial dysfunction or oxidative stress. Combining insulin and vitamin C, however, normalized endothelial dysfunction and nitrotyrosine., Conclusions: This study suggests that long-lasting hyperglycemia in type 1 diabetic patients induces long-term alterations in endothelial cells, which may contribute to endothelial dysfunction and is interrupted only by both glucose and oxidative stress normalization.

Introduction: No reported studies exist assessing the relationship between sexual function and hyperlipidemia in women., Aim: In this study, we assessed the domains of sexual function in a representative sample of sexually active premenopausal women with hyperlipidemia, but without cardiovascular disease, as compared with an age-matched female population without hyperlipidemia., Methods: To be enrolled in the study, women had to meet at least one of the following criteria for the diagnosis of hyperlipidemia: low-density lipoprotein (LDL) cholesterol levels >160 mg/dL; high-density lipoprotein (HDL) cholesterol levels <50 mg/dL; or triglyceride levels >150 mg/dL. Lipid parameters were assessed and verified on blood taken at least twice in the hospital during the screening phase. Four hundred forty-one premenopausal women with hyperlipidemia were compared with 115 age-matched premenopausal women without hyperlipidemia., Main Outcome Measures: We used the Female Sexual Function Index (FSFI) for assessing the key dimensions of female sexual function., Results: The two groups were well matched for age and smoking prevalence. Compared with women of the control group, women with hyperlipidemia had reduced mean global FSFI score (22.8 +/- 6.8 vs. 29.4 +/- 4.9, P < 0.001). Individual analysis of the different domains showed that women with hyperlipidemia reported significantly lower arousal, orgasm, lubrication, and satisfaction scores than control women. Based on the total FSFI score, 51% of women with hyperlipidemia had scores of 26 or less, indicating sexual dysfunction, as compared with 21% of women without hyperlipidemia (P < 0.001). Based on a more conservative analysis including women under the lower quartile of the distribution of FSFI score, 32% of women with hyperlipidemia had scores of 23 or less, as compared with 9% of women without hyperlipidemia (P < 0.001). Multiple regression analysis identified age, body mass index, HDL-cholesterol and triglycerides as independent predictors of FSFI score., Conclusions: Women with hyperlipidemia have significantly lower FSFI-domain scores as compared with age-matched women without hyperlipidemia. HDL cholesterol and triglyceride levels were independently associated with the FSFI score.

Introduction: Bone marrow-derived endothelial progenitor cells (EPCs) circulate in the peripheral blood and are involved in endothelial homeostasis and repair., Aim: The aim of this study was to assess the circulating levels of different EPC phenotypes in overweight men with or without erectile dysfunction (ED). As endothelial dysfunction is considered a necessary link with ED, endothelium-dependent vasodilation and its relation with EPCs were also investigated., Methods: We studied 30, otherwise healthy, overweight subjects with symptomatic ED for at least 6 months, and 30 age- and weight-matched subjects without ED. Erectile function was assessed by completing the International Index of Erectile Function (IIEF-5), which consists of items 5, 15, 4, 2, and 7 from the full-scale IIEF-15., Main Outcome Measures: Seven subpopulations of EPCs were determined by flow cytometry on the basis of the surface expression of CD34, CD133, and KDR antigens: CD34(+), CD133(+), KDR(+), CD34(+)CD133(+), CD34(+)KDR(+), CD133(+)KDR(+), and CD34(+)CD133(+)KDR(+). Endothelium-dependent flow-mediated dilation (FMD) was evaluated in the right brachial artery with a high-resolution ultrasound machine following reactive hyperemia., Results: CD34(+)KDR(+) cell count was significantly lower in men with ED as compared with men without ED (63.1 +/- 4 vs. 92.4 +/- 6 cells/10(6) events, mean +/- standard error, P < 0.01). There was a significant direct correlation between circulating CD34(+)KDR(+) cells and the IIEF score (r = 0.44; P = 0.01): men with the severe form of ED presented the lowest level of circulating EPC CD34(+)KDR(+) cells. No significant correlation was found between the circulating levels of the other EPC phenotypes and the IIEF score. There was a significant correlation between CD34(+)KDR(+) cell count and FMD (r = 0.45; P = 0.01), but not between FMD and the other phenotypes., Conclusions: Circulating levels of CD34(+)KDR(+) EPC are reduced in overweight subjects with ED and correlate with the severity of ED. Other EPC phenotypes are not related to ED, suggesting that the CD34(+)KDR(+) phenotype of EPCs may be preferred in future studies.

Introduction: Limited data are available supporting the notion that treatment of lifestyle risk factors may improve erectile dysfunction (ED)., Aim: In the present study, we analyzed the effect of a program of changing in lifestyle designed to improve erectile function in subjects with ED or at increasing risk for ED., Methods: Men were identified in our database of subjects participating in randomized controlled trials evaluating the effect of lifestyle changes. A total of 209 subjects were randomly assigned to one of the two treatment groups. The 104 men randomly assigned to the intervention program received detailed advice about how to reduce body weight, improve quality of diet, and increase physical activity. The 105 subjects in the control group were given general information about healthy food choices and general guidance on increasing their level of physical activity., Main Outcome Measures: Changes in erectile function score (International Index of Erectile Function-5 [IIEF-5]; items 5, 15, 4, 2, and 7 from the full-scale IIEF-15) and dependence of the restoration of erectile function on the changes in lifestyle that were achieved., Results: Erectile function score improved in the intervention group. At baseline, 35 subjects in the intervention group and 38 subjects in the control group had normal erectile function (34% and 36%, respectively). After 2 years, these figures were 58 subjects in the intervention group and 40 subjects in the control group, respectively (56% and 38%, P = 0.015). There was a strong correlation between the success score and restoration of erectile function., Conclusions: It is possible to achieve an improvement of erectile function in men at risk by means of nonpharmacological intervention aiming at weight loss and increasing physical activity.

Introduction: Endothelial microparticles (EMPs) may play a role as biomarkers of vascular injury. EMPs are higher in men with diabetes diabetic men with erectile dysfunction (ED) than in nondiabetic potent men., Aim: The aim of this study was to quantize different phenotypic circulating EMP levels among diabetic and nondiabetic patients with ED, and to determine whether EMPs are released as a result of activation or apoptosis., Methods: We studied 30 type 2 diabetic and 24 nondiabetic subjects with symptomatic ED from at least 6 months, and 20 nondiabetic men without ED matched for age and weight with diabetic and nondiabetic subjects. Erectile function was assessed by completing the International Index of Erectile Function (IEEF)-5, which consists of Items 5, 15, 4, 2, and 7 from the full-scale IIEF-15. A score of 21 or less indicates the presence of ED., Main Outcome Measures: EMP levels in plasma were quantified by flow cytometry. Markers for apoptosis (platelet/endothelial cell adhesion molecule 1/CD31 antigen) and activation (E-selectin/CD62E antigen) were compared. Endothelium-dependent flow-mediated dilation (FMD) was evaluated in the right brachial artery with a high-resolution ultrasound machine following reactive hyperemia., Results: Diabetic patients were found to have the highest levels of EMP31+; diabetic and nondiabetic men with ED were found to have significantly higher levels of EMP62+ than nondiabetic men without ED. The EMP62/EMP31 ratio, an index of endothelial activation (high ratio) or apoptosis (low ratio), was lowest in diabetic men with ED (0.20). In the whole group of 54 men with ED (diabetic and nondiabetic), there was an inverse correlation between FMD and the number of circulating EMPs (P < 0.05)., Conclusions: The presence of diabetes in subjects with ED is associated with a different pattern of endothelial cell injury. The phenotypic assessment of EMPs in diabetic patients with ED is consistent with increased apoptotic activity.

Context: Two-hour postprandial hyperglycemia is related to chronic complications of diabetes and is currently used in the international guidelines to drive the therapy., Objective: Our objective was to assess the size and timing of post-meal glucose peaks in the everyday life of type 2 diabetic patients and the relationship with carotid atherosclerosis., Design, Setting, and Patients: This was an observational study performed in 644 outpatients with type 2 diabetes attending diabetes clinics located in the area of the Campania County, South Italy, who provided complete home blood glucose profiles and centralized carotid intima-media thickness (CIMT) assessment. The study was conducted from 2001-2005., Main Outcome Measures: Incremental glucose peak (IGP) was the maximal incremental increase in blood glucose obtained at any point after the meal. CIMT was assessed by carotid sonography., Results: The level of glycosylated hemoglobin and CIMT progressively increased across quintiles of IGP (P for trend = 0.01 for both). In univariate analysis, all examined glycemic parameters were significantly correlated with CIMT. IGP (r = 0.40; P = 0.006) showed the strongest correlation with CIMT, which remained significant in multiple linear regression analysis (R(2) = 0.26; P = 0.01). IGP was associated with a significant increase of CIMT in tertiles of glycosylated hemoglobin. IGP occurred within 1 h from the start of the meal in 95% of the entire diabetic population., Conclusion: IGPs are frequent in the everyday life of patients with type 2 diabetes, occur for most (95%) within 1 h after meal, timing of IGPs is not influenced by treatment (diet or drugs), and IGPs correlate with CIMT.

Introduction: Female sexual dysfunction (FSD) is a significant public health problem. There are no reported studies assessing the relation between sexual function and neuropathy in women, except for diabetes mellitus., Aim: The aim of this study was to explore the correlations between peripheral and autonomic neuropathy, and Female Sexual Function Index (FSFI) among nondiabetic women with or without FSD., Methods: During a 6-month period, women were screened among outpatients seeking routine weight loss help. Cases were women, either pre- or postmenopausal, with abnormal values of FSFI score; controls were women from the same population with normal values of FSFI score, matched with cases for age and menopausal status. The total score range was 2-36; a score of 23 or lower indicated sexual dysfunction. The tool was administered during the follicular (days 5-8) phase of the menstrual cycle., Main Outcome Measures: The assessment of peripheral neuropathy was based on the quantitative sensory examination using the vibratory, thermal, and pain sensory thresholds. The assessment of autonomic neuropathy was based on cardiovascular reflex tests (deep breathing and squatting)., Results: The results of the quantitative sensory testing examination showed pathological changes in about 20% of women with FSD; the tests were abnormal in about 5% of women in the group without FSD. The percentage of women with abnormalities of autonomic cardiovascular tests was higher in the group with FSD compared with the group without FSD., Conclusions: Our results suggest an involvement of both somatic and autonomic nerve fibers in nondiabetic women with FSD.

Context: Cell-derived microparticles are supposed to be involved in atherogenesis., Objective: This study aimed to evaluate circulating microparticles in obese women and their relation with anthropometric measures and endothelial dysfunction., Design, Setting, and Participants: Forty-one obese [body mass index (BMI) > 30 kg/m(2)] women and 40 normal weight (BMI < 25 kg/m(2)) age-matched women were studied. Flow cytometry was used to assess microparticles by quantification of circulating endothelial microparticles (EMP, CD31+/CD42b-) and platelet microparticles (PMP, CD31+/CD42b+) in peripheral blood; endothelium-dependent flow-mediated vasodilation (FMD) was evaluated in the right brachial artery after reactive hyperemia., Results: Compared with lean women, obese women presented significantly higher numbers of EMP and PMP, and reduced FMD. BMI did not correlate with either EMP (r = 0.02, P = 0.9) or PMP (r = -0.07, P = 0.645), whereas waist-to-hip ratio (WHR) showed significant correlation with both microparticles (r = 0.699, P < 0.001; r = 0.373, P = 0.016, respectively). Both EMP and PMP counts positively correlated with impairment of FMD in obese women. Multivariate analysis correcting for age, anthropometric indices, lipid parameters, and PMP identified EMP as the only independent predictor for impaired endothelial-dependent vasodilation (P = 0.003)., Conclusions: EMP are elevated in obese women and independently involved in the pathogenesis of endothelial dysfunction. WHR is the anthropometric measure more closely related to EMP and endothelial dysfunction.

Autism is a neurodevelopmental disorder characterized by impairment in three core symptom domains: socialization, communication, and repetitive/stereotyped behaviours. Other associated symptom domains are also affected including impulsivity/aggression, self-injury, anxiety, and mood lability. Divalproex has been shown to have efficacy in treating epilepsy, bipolar disorder, mood lability, and impulsive aggression. The present study evaluated the use of divalproex in the treatment of repetitive, compulsive-like symptoms of autism spectrum disorder (ASD). Thirteen individuals with ASD participated in an 8-wk, double-blind, placebo-controlled trial of divalproex sodium vs. placebo. There was a significant group difference on improvement in repetitive behaviours as measured by the Children's Yale-Brown Obsessive Compulsive Scale (C-YBOCS) (p=0.037) and a large effect size (d=1.616). This study provides preliminary support for the use of divalproex in treating repetitive behaviours in ASD. Further research is needed to evaluate the specificity and mechanism of action of these findings.

Both epidemiological studies and intervention trials support an important role of diet in reducing the risk of a variety of chronic diseases, including cardiovascular disease, and overall mortality. We discuss available evidence indicating that the generation of a pro-inflammatory milieu might be one mechanism through which unhealthy diets are linked to metabolic and cardiovascular diseases. In practical terms, fully understanding the link between diet and inflammation holds the premise to elucidate the mechanisms by which dietary patterns improve cardiovascular health.

Aims: We designed this study in order to determine the effect of insulin on cardiac function in overweight and obese subjects during exercise., Methods and Results: The cardiac function of 62 normal glucose tolerant subjects, aged 30-40 and divided into normal weight (group 1, n=22, BMI 20-24.9 kg/m(2)), overweight (group 2, n=20, BMI 25-29.9 kg/m(2)), and obesity (group 3, n=20, BMI 30-35 kg/m(2)) was evaluated at rest and during dynamic exercise through angiocardioscintigraphy, when on hyperinsulinaemic euglycaemic clamp (test A) and when on normal saline infusion (test B). Left ventricular function at rest was statistically greater (P<0.05) in both tests in overweight and obese subjects compared with normal weight controls, with no statistical difference (P=0.057) within groups between insulin and normal saline infusion. During exercise, cardiac function improved in all the subjects in both tests. The increase was lower in overweight and obese patients, even if statistically significant only in obese vs. control subjects in both tests (P<0.05). Insulin sensitivity showed a significant correlation (P< or =0.001) with left ventricular ejection fraction (LVEF) at rest and with change in LVEF during clamp., Conclusion: Our findings suggest a metabolic pathogenesis for the impaired LV function in obesity.

Background: Atherosclerosis is a major cause of death in elderly individuals. Endothelial dysfunction is recognized as a key early event in atherogenesis. In the present study, we evaluated the possible beneficial effect of amino acid administration on endothelial regulation in elderly subjects., Methods: A total of 25 healthy elderly subjects were administered essential amino acids (EAA) for 4 months. Before and after EAA administration, each subject underwent brachial reactivity investigation with and without an intra-arterial infusion of 4 micromol/min of N(G)-monomethyl-l-arginine (L-NMMA), an inhibitor of nitric oxide (NO) synthase., Results: At baseline, age correlated with free plasma insulin growth factor-1 IGF-1 (r = -0.48; P < .01), plasma Trolox equivalent antioxidant capacity (TEAC) (r = -0.40; P < .04), and thiobarbituric acid-reactive substances (TBARS) (r = 0.42, P < .04), and homeostasis model assessment (HOMA) index (r = 0.45, P < .03), as well as with changes in diameter (r = -0.49, P < .01) and flow (r = -0.43, P < .03). Administration of EAA was associated with a significant increase in plasma TEAC (P < .001) and decline in plasma TBARS (P < .001) and with improvement in changes in diameter (7.15 +/-1.10 v 8.98 +/-1.80, P < .001) and flow (5.6 +/-1.2 v 6.4 +/- 1.2, P < .03). These latter two associations were independent of changes in HOMA index (P < .04 for both correlations). The beneficial effects of EAA administration on brachial reactivity were partly attenuated by L-NMMA., Conclusions: Administration of EAA may improve brachial reactivity in elderly persons and may also protect against the development of atherosclerosis via the rise in plasma-free IGF-1 levels.

Background: Morning blood pressure (BP) peak may be a risk factor for cardiovascular disease. Whether morning BP should be a target of hypertension treatment is not known. We investigated the relationship between morning BP variations, carotid internal-medial thickness (CIMT), circulating inflammatory markers, and sympathetic activity in hypertensive patients with different patterns of morning BP increase at baseline and after antihypertensive treatment., Methods: One hundred twenty-eight hypertensive patients with morning BP peak (MP+) were compared with 196 hypertensive patients without morning BP peak (MP-). All patients performed 24-h ambulatory BP monitoring, assessment of CIMT, circulating concentration of C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-18 (IL-18), and urinary catecholamines., Results: Compared with MP- patients, MP+ patients had higher CIMT and urinary catecholamine output (P < .001), as well as CRP, IL-6, and IL-18 (P < .001). We randomly assigned 128 drug-naive MP+ patients to either metoprolol or carvedilol, two antihypertensive drugs with different effects on sympathetic activity. The primary outcome was change in CIMT and circulating inflammatory markers at 12 months. Morning BP decreased more among patients in the carvedilol group (P < .001), whereas clinic BP showed a similar decrease in both groups. The CIMT (P < .001), IL-6 (P < .001), IL-18 (P < .001), and CRP (P < .001) decreased more in the carvedilol group than in the metoprolol group. The CIMT regression was observed in 49% of patients in the carvedilol group and 18% of patients in the metoprolol group (P < .01). Reduction in CIMT was directly associated with changes in morning BP., Conclusions: Higher CIMT and circulating inflammatory markers coexist in hypertensive patients with morning BP peak, and might contribute to their increased cardiovascular risk. Carotid atherosclerosis can be prevented by control of morning BP.

Significant changes in body composition, body fat distribution, and resting metabolic rate (RMR) occur with aging. Interestingly, studies on human longevity pointed out that long-lived subjects are less prone to the anthropometrics and metabolic derangement normally observed in the elderly. Indeed, the relationship between energy expenditure and longevity has been poorly investigated. Thus, energy expenditure parameters of 28 long-lived subjects were assessed and compared with those of 26 adults and 27 younger elderly. All subjects enrolled were female. In the whole population, RMR was negatively correlated with age (P < 0.05), waist to hip ratio (WHR) (P < 0.001), fat mass (P < 0.001), and percent body fat (P < 0.03); respiratory quotient (Rq) displayed an age-related decrease (P < 0.001) and was negatively correlated with WHR (P < 0.001) and fat-free mass (FFM) (P < 0.006). In multivariate analysis, both RMR and Rq had FFM, WHR, but not body mass index as significant and independent determinants. Splitting the whole study group into subgroups according to age, long-lived subjects had oxygen volume, carbon dioxide volume, and Rq significantly higher than aged subjects but lower than adult subjects. In addition, long-lived subjects had total volume of expired air and RMR greater than aged subjects but not different from ones found in adults. In long-lived subjects, Rq was negatively correlated with percent body fat (P < 0.02), plasma glucose (P < 0.05), free fatty acid (P < 0.05), and WHR (P < 0.05), whereas RMR was negatively correlated with WHR (P < 0.05). No significant associations of RMR and Rq with FFM were found. In conclusion, our data demonstrate that human longevity seems protected toward an age-related decline. It is likely that the lack of the anthropometrics derangement may preserve long-lived subjects from the age-related decrease in energy metabolism.

Background: Hyperinsulinemia/insulin resistance and elevated plasma free fatty acids (FFA) levels are involved in the hypertension and cardiac sympathetic overactivity. Metformin improves insulin action and lower plasma FFA concentrations. We investigate the possible effect of metformin on arterial blood pressure (BP) and cardiac sympathetic nervous system., Methods: One hundred twenty overweight type 2 diabetic patients were treated by placebo (n = 60) + diet or metformin (850 mg twice daily) (n = 60) + diet for 4 months, to evaluate the effect of metformin treatment on the cardiac autonomic nervous system. Insulin resistance was measured by the Homeostasis Model Assessment (HOMA) index. Heart rate variability (HRV) assessed cardiac sympathovagal balance., Results: Metformin treatment, but not placebo treatment, was associated with a decrease in fasting plasma glucose (P <.05), insulin (P <.05), triglyceride (P <.05), and FFA (P <.03) concentrations and HOMA index (P <.03). Metformin treatment was also associated with a significant improvement in cardiac sympathovagal balance but not in mean arterial BP. Furthermore, in a multivariate analysis, delta change in sympathovagal balance index (LF/HF ratio) were associated with delta change in plasma FFA concentrations and HOMA index independently of gender and delta change in plasma triglyceride and HbA1c concentrations., Conclusions: Our study demonstrated that metformin treatment might be useful for improving cardiac sympathovagal balance in obese type 2 diabetic patients.

Background: Endothelial dysfunction and inflammation are present in both type 2 diabetes mellitus (T2DM) and obesity. In this paper we compared the role of weight loss and of glycaemic control in determining circulating levels of ICAM-1, endothelin-1 (ET-1), and E-selectin in patients with morbid (grade 3) obesity., Methods and Results: ICAM-1, E-selectin, and ET-1 were higher in obese patients (n=96) than in lean controls (n=30); among obese patients, the three molecules were higher in T2DM patients (n=26) than in patients with normal (NGT, n=43) or impaired (IGT, n=27) glucose tolerance. Sixty-eight obese patients had a significant weight loss induced by bariatric surgery, and showed a significant decrease in blood glucose, HbA1c and all molecules, so that ICAM-1, E-selectin, and ET-1 were not different in NGT, IGT and T2DM patients, and in lean controls; in 13 patients with a small weight loss induced by diet, changes were not significant, in spite of a significant reduction in blood glucose and HbA1c. At stepwise regression, changes in ICAM-1, ET-1, and E-selectin significantly correlated only with change in body mass index., Conclusions: These data indicate that weight loss is more important than glycaemic control in regulating circulating levels of ICAM-1, ET-1, E-selectin in morbidly obese subjects.

The potential role of anti-inflammatory cytokines in human obesity is unknown. We tested the hypothesis that low serum IL-10 concentrations associate with the metabolic syndrome in obese women. Compared with 50 matched nonobese women, the prevalence of the metabolic syndrome (>/=3 of the following abnormalities: waist circumference, >88 cm; triglycerides, >1.69 mmol/liter; high density lipoprotein cholesterol, <1.29 mmol/liter; blood pressure, >130/85 mm Hg; glucose, >6.1 mmol/liter) was higher in 50 obese women (52% vs. 16%; P < 0.01). As a group, obese women had higher circulating levels of IL-6, C-reactive protein, and IL-10 than nonobese women. In both obese and nonobese women, IL-10 levels were lower in those with than in women without the metabolic syndrome: obese, 1.3 (0.7/2.1) pg/ml vs. 4.5 (4.3/7.4) pg/ml (median and quartiles; P < 0.01); and nonobese, 0.9 (0.7/1.3) pg/ml vs. 1.3 (0.9/3.3) pg/ml (P < 0.05). After 12 months of a lifestyle program, body weight decreased by 10.9 +/- 1.7 kg and was associated with a significant decrement of IL-6, C-reactive protein, and IL-10 levels; the decrease in IL-10 levels was confined to obese women without the metabolic syndrome. These results show that circulating levels of the anti-inflammatory cytokine IL-10 are elevated in obese women and that low IL-10 levels are associated with the metabolic syndrome.

Obesity is associated with an increased risk of developing atherosclerosis, which may be mediated, at least in part, by increased secretion of proinflammatory cytokines by adipose tissue. We examined the hypothesis that circulating levels of IL-18 were elevated in obese women and would be reduced by weight loss. In a sample of 40 obese (body mass index, 36.4 +/- 3.1 kg/m(2)) women we found that plasma IL-18 levels were higher than in 40 normal weight control women (P < 0.01) and were positively associated with body weight (r = 0.46; P < 0.01) and visceral fat (waist to hip ratio; r = 0.39; P < 0.01). Caloric restriction-induced weight loss (> or = 10% of original weight) over 1 yr reduced IL-18 levels from 247 (204/309) to 147 (111/210) pg/ml (medians and 25%/75%; P < 0.01), positively associated with changes in body mass index and waist to hip ratio. In obese women, IL-18 levels are associated with body weight and abdominal fat deposition; weight loss is an important intervention to reduce IL-18 levels. IL-18 may be a novel cytokine operating in human obesity.

We evaluated 66 obese patients grouped by waist-to-hip ratio (WHR) into group A (WHR > 0.85, n = 30) and group B (WHR < or = 0.85, n = 36), before and after 1 yr of diet-induced weight loss compared with 25 nonobese women. Before diet, the longest values of QT intervals and the highest levels of FFA and catecholamines were in group A (P < 0.01). In obese women (both groups), the corrected QT (QTc); interval correlated with plasma FFA (P < 0.01) and catecholamine (P < 0.02) concentrations. After 1 yr of diet, at the same levels of body weight reduction, the decrement of the QTc interval (P < 0.02), FFA (P < 0.01) and catecholamine (P < 0.02) levels were significantly greater in-group A than group B. In multivariate analysis, the decline of the QTc interval after weight loss was associated with changes in plasma FFA independently of changes in WHR and plasma catecholamines. Our data suggest that the QTc interval is tightly correlated with plasma FFA levels; shortening of cardiac repolarization times in the course of long-lasting weight reduction may reduce the risk of ventricular electrical instability, especially in women with abdominal adiposity.