Vitamin D deficiency is a condition that affects a high percentage of individuals of all ages. Considerable attention has been paid recently to the possible role of deficiency of this vitamin in the development of several chronic diseases, including cardiovascular and metabolic diseases. In particular, vitamin D deficiency is associated with an increase in conditions such as obesity, insulin-resistance, hypertension, diabetes, and an increased risk of death from these pathologies. There is also a significant correlation with mortality for major cardiovascular events such as heart failure, myocardial infarction, sudden cardiac death, stroke, atrial fibrillation, and peripheral vascular disease. The pathophysiological mechanisms of these correlations are yet to be determined, but hyperactivity of the renin-angiotensin-aldosterone system seems to play a leading role. The role of therapy with vitamin D supplements in improving cardiovascular outcome in patients with low levels of vitamin D remains to be determined.

Abstract BACKGROUND: Alterations of glucose metabolism represent well known risk factors for the atherosclerotic process and then for cardiovascular disease. OBJECTIVE: to investigate the association between fasting glucose and early signs of atherosclerosis, by means of carotid intima-media thickness (c-IMT) in a population of apparently healthy overweight/obese subjects. In addition, we evaluated the possible existence of a glycemic threshold above which the risk of atherosclerosis significantly increases. METHODS: 179 overweight/obese (mean BMI: 32 ± 5 kg/m2) subjects, 44 men, aged 40 ± 12.4 years, were enrolled in the study. Blood glucose, insulin, total cholesterol, high and low density lipoprotein cholesterol and triglycerides were detected in all subjects. The Homeostasis Model Assessment of insulin resistance index (HOMA-IR) was also obtained. All subjects underwent carotid echo color Doppler ultrasound to identify c-IMT. RESULTS: In our population of obese/overweight subjects with insulin resistance (HOMA-IR=3.4 ± 2), c-IMT was positively related to male gender (r = 0.23, P<0.01), age (r = 0.53, P<0.001), waist circumference (r = 0.15, P=0.04), systolic and diastolic blood pressure (r=0.27, P<0.001 and r=0.24, P<0.001 respectively), fasting glucose (r=0.29, P<0.001), triglycerides (r= 0.16 P=0.03), total and low density lipoprotein cholesterol levels (r=0.25 P<0.001 and r=0.21, P<0.01 respectively). Only male gender and fasting glycaemia were associated to c-IMT (P<0.01 and P< 0.001, respectively) at Conclusion: Blood glucose represented an independent predictor of atherosclerosis in our study population. Moreover, this seemed to be able to favor c-IMT progression for values greater than 90 mg/dl.

Objective. This study examined whether obesity is characterized by higher 24 h mean pulse pressure (24 h mean SBP-24 h mean DBP) and whether free thyroid hormones (FT3 and FT4) have a relationship with 24 h mean pulse pressure. Methods. A total of 231 euthyroid overweight and obese patients, 103 women and 128 men, aged 18–68 yrs, normotensive (n = 69) or with recently developed hypertension (n = 162), never treated with antihypertensive drugs, were investigated. Fasting insulin, TSH, FT3, FT4, glucose, and lipid serum concentrations were measured.Waist circumference was measured as an indirect parameter of central fat accumulation. Ambulatory blood pressure monitoring (ABPM) was performed. Results. 24 h mean pulse pressure (PP) showed a significant positive correlation with BMI (P < 0.001), waist circumference (P < 0.001), and FT3 (P < 0.001) and insulin serum levels (P < 0.05). When a multivariate analysis was performed, and 24 h PP was considered as the dependent variable, and waist circumference, FT3, insulin, male sex, and age as independent parameters, 24 h mean PP maintained a significant association only with waist circumference (P < 0.001) and FT3 levels (P < 0.05). Conclusion. Our results suggest that FT3 per se may contribute to higher pulse pressure in obese subjects.

The aim of this retrospective observational study was to evaluate whether adding liraglutide to lifestyle changes, metformin (Met) and testosterone replacement therapy (TRT), by means of improving weight and glycaemic control, could boost erectile function in type 2 diabetic obese men with overt hypogonadism and erectile dysfunction (ED) in a 'real-life setting'. Forty-three obese, diabetic and hypogonadal men (aged 45-59 years) were evaluated because of complaining about the recent onset of ED. They were subdivided into two groups according to whether hypogonadism occurred after puberty (G1; n = 30: 25 with dysfunctional hypogonadism and 5 with acquired hypogonadotropic hypogonadism) or before puberty (G2; n = 13: 10 with Klinefelter's syndrome and 3 with idiopathic hypogonadotropic hypogonadism). Both G1 and G2 patients were given a combination of testosterone (T) [testosterone undecanoate (TU) 1000 mg/every 12 weeks] and Met (2000-3000 mg/day) for 1 year. In the poor responders (N) to this therapy in terms of glycaemic target (G1N: n = 16; G2N: n = 10), liraglutide (L) (1.2 μg/day) was added for a second year, while the good responders (Y) to T + Met (G1Y: 14/30 and G2Y: 3/13) continued this two drugs regimen therapy for another year. All patients were asked to fill in the International Index of Erectile Function (IIEF 15) questionnaire before starting TU plus Met (T1) and after 12 months (T2) and 24 months (T3) of treatment. Patients underwent a clinical examination and a determination of serum sex hormone binding globulin (SHBG), total testosterone (T) and glycosylated haemoglobin (HbA1c) at T1, T2 and T3. At T2, each patient obtained an improvement of ED (p < 0.01) and of the metabolic parameters without reaching, however, the glycaemic goals [HbA1c = >7.5% (>58 mmol/mol)], while T turned out to be within the range of young men. L added to TU and Met regimen in G1N and G2N allowed these patients to reach not only the glycaemic target [HbA1c = <7.5% (<58 nmol/mol)] and a significant reduction in body weight (p < 0.01), but also a further increase in SHBG (p < 0.05) and T (p < 0.01) plasma levels as well as a significant increment of IIEF score (T3). Conversely, at T3 G1Y and G2Y, who received the combined therapy with TRT and Met for the second year, showed a partial failure of that treatment given that there was no improvement of the IIEF score and they showed a significant rise in serum HbA1c (p < 0.05) and weight (p < 0.04) compared with the assessments at T2. These results suggest that TRT could improve clinical and metabolic parameters in obese, type 2 diabetic men with ED and overt hypogonadism (independently of when T deficit occurred). Furthermore, in case of insufficient metabolic control the addition of L to TRT and Met regimen allows to achieve serum T levels in the range of healthy men, as well as to reach glycaemic target and to lower weight, leading to a considerable improvement of ED.

Aims: Carotid intima-media thickness (IMT) is one of the best non-invasive parameters for evaluating previous vascular lesions and could be used to identify a preclinical stage of the atherosclerotic process. The aim of our research was to develop an epidemiological study of the normal mean values of IMT of the common carotid artery, adjusted for age and sex, in the Italian population. Methods and results: In this multicenter study, a total of 1017 patients (596 males, mean age: 58.5\+13.2 years) were enrolled at four different Italian centers. Inclusion criteria were the absence of cardiovascular risk factors or presence of not more than one. Patients underwent two-dimensional echo-color Doppler scanning of the carotid arteries, adopting a high-definition vascular echographic apparatus and a 11-3 MHz linear electronic probe. The arithmetical mean of the IMT value was calculated. Data obtained from this study show the carotid IMT changes in relation to age and sex. In particular, it grows higher with increasing age, and is always higher in men than in women. Conclusion: In relation to the percentile distribution of the values in the population analyzed, the normal range of m- IMT could be established just on the basis of the patient's age and sex. In this way, the ultrasound scan operator can rely on a simple reference scheme. This will help to refine the use of carotid ultrasound as an excellent tool for detecting asymptomatic carotid alterations and patients at high risk for cerebral and cardiovascular disease.

The clinical occurrence of ectopic thyroid gland is an infrequently encountered condition, resulting from a developmental abnormality during the migration of the thyroid anlage from the floor of the primitive foregut to its final position in the neck. It can be found along the way of thyroid descent, in the midline, or laterally in the neck or even in the mediastinum or under the diaphragm. This condition is often asymptomatic, whereas symptoms could be related to ectopic thyroid size, to its relationships with surrounding organs or to diseases affecting the ectopic thyroid in the same way they involve orthotopic glands. Sometimes, a growing mass can lead to the clinical suspicion of a tumor disease. On the other hand, thyroid ectopy must be distinguished from metastasis of thyroid cancer. Scintigraphy and ultrasonography are the main diagnostic means for evaluating ectopic thyroid tissue, whereas fine needle aspiration could be useful in the presence of a nodular ectopic gland or when the coexistence of an orthotopic thyroid can arise the suspicion of a metastasis from a thyroid cancer. Surgical removal is indicated in symptomatic cases, whereas radioiodine ablation is reserved to recurrent disease. In this paper we report an emblematic case of ectopic thyroid gland and a review of the literature dealing with this condition.

Objective: To evaluate whether the addition of finasteride (a 5 <-reductase inhibitor) to conventional protocol of ovarian stimulation with gonadotropin can improve ovarian follicular growth in polycystic ovary syndrome (PCOS) women who did not respond to previous stimulation with gonadotropin alone. Design: Double-blind randomized study. Setting: Outpatient in an academic research environment. Patient(s): Thirty-six PCOS patients in whom the previous multifollicular stimulation protocols with gonadotropin failed. Intervention(s): The patients were randomly assigned to two treatment groups: group 1 underwent ovarian stimulation with recombinant FSH (rFSH) plus finasteride, and group 2 received rFSH alone. When the dominant follicle reached a mean diameter of 18 mm, hCG was administered and finasteride withdrawn. Main Outcome Measure(s): Ovulation rate in women with PCOS. Result(s): Follicular growth and ovulation occurred in eight patients in group 1, whereas no cases were detected in group 2. Conclusion(s): This study confirms that hyperandrogenism interferes with follicular growth and suggests that administration of finasteride during ovarian stimulation with rFSH improves ovulation rate in selected hyperandrogenic anovulatory women. (Fertil Steril (R) 2010; 94: 247-9. (C) 2010 by American Society for Reproductive Medicine.)

Objective: To assess the effect of olive oil, non fried fish and nuts on endothelial function in overweight/obese patients. Methods: 47 overweight/obese patients (24 men, mean age 54 ± 11 years) fed healthy diet (HD) defined according to the Nureta- PREDIMED study for 3 months; after this 3 months of HD, the patients were blindly divided into 4 groups: Controls (24: HD), Group A (8: HD+olive oil), Group B (8: HD+not-fried fish), Group C (7: HD+nuts). These four groups were also followed-up for further 15 months. All patients were evaluated at baseline, at 3 and 18 months for glucose and lipid profile, anthropometric measures and brachial artery Flow-Mediated Dilatation (FMD). Results: HD alone significantly increased FMD at 3 and 18 months follow-up as compared to baseline. Olive oil or not-fried fish or nuts significantly increased FMD as compared to HD at 18 months follow-up. Waist circumference, body mass index significantly decreased after 3 and 18 months; lipid parameters at 18 months improved in all groups as compared to baseline. Fasting glycemia did not change after 18 months (baseline: 101 ± 19 mg/dl vs 18 months: 98 ± 12 mg/dl; p=ns). Conclusions: HD is able to improve endothelial function after a short (3 months) period and olive oil, not fried fish and nuts adding seem to increase such an improvement at a longer (18 months) period. Thus, HD and some of its components can improve cardiovascular risk profile of individuals.

Abstract Introduction: The aim of the study was to assess the age-specific, sex-specific, and region-specific average sodium and potassium intake and its association with anthropometric characteristics in a sample of the Italian adult hypertensive population. Methods: A total of 1232 hypertensive patients were recruited consecutively by 47 centers recognized by the Italian Society of Hypertension. The enrolled participants were on stable antihypertensive treatment. Anthropometric indices, blood pressure, 24-h urinary sodium, and potassium excretion were measured and used as proxy for the average daily sodium and potassium intake. Results: The average sodium intake was 172 mmol (or 10.1 g of salt/day) among men and 138 (or 8.1) among women, with no difference among geographical areas. Over 90% of men and 81% of women had a consumption higher than the recommended standard dietary intake of 5 g/day. The average potassium intake was 63 and 56 mmol, respectively in men and women, again without geographical differences, nearly 92% of men and 95% of women having an intake lower than the recommended intake (100 mmol/day or 3.9 g/day). There was a significant trend to a gradual decrease in sodium intake with age in both sexes (P <0.001). There was also a direct association between BMI and sodium intake in both sexes, this association being independent of age (P < 0.001). Conclusion: In this national sample of the Italian hypertensive population, dietary sodium intake was largely higher and potassium intake much lower than the recommended intakes, and this was true for all geographical areas. Overweight and obese hypertensive patients had particularly high sodium intakes.

OBJECTIVE: To examine whether obesity, body fat distribution and insulin resistance have an independent effect on serum TSH and free thyroid hormones (FT3 and FT4) in a cohort of euthyroid women, represented by overweight and obese patients. DESIGN AND PATIENTS: A total of 201 women, aged 18-68 years, with body mass index (BMI) > or = 25.0 kg/m(2) and TSH levels < 4.0 mU/l were investigated. MEASUREMENTS: Fasting TSH, FT3, FT4, insulin, glucose, and serum lipid concentrations, and the level of insulin resistance, estimated by the homeostasis model assessment for insulin resistance (HOMA-IR). Waist circumference was measured as an indirect parameter of central fat accumulation. RESULTS: FT3 was directly associated with BMI (P < 0.01) and waist circumference (P < 0.01), and negatively correlated with age (P < 0.001). FT4 was negatively associated with HOMA-IR (P < 0.05) and fasting insulin levels (P < 0.05). TSH was positively correlated with waist circumference (P < 0.05) and negatively associated with age (P < 0.05). When multiple regression analysis was performed with FT3 as the dependent variable, and waist circumference, HOMA-IR, blood pressure levels and serum lipid concentrations as independent variables, FT3 maintained an independent association only with waist circumference (positive, P < 0.05) and age (negative, P < 0.001). When multiple regression analysis was performed with TSH as the dependent variable, and the above parameters as independent variables, TSH maintained an independent association only with waist circumference (positive, P < 0.05) and age (negative, P < 0.05). By contrast, when multiple regression analysis was performed with FT4 as the dependent variable, FT4 did not maintain an independent association with any of the independent parameters. CONCLUSIONS: Progressive central fat accumulation is associated with an increase in both FT3 and TSH serum levels, independently of insulin sensitivity, metabolic parameters and blood pressure. These results suggest that (1) progressive central fat accumulation is associated with a parallel increase in FT3 levels, possibly as an adaptive thermogenic phenomenon, and (2) the control of TSH secretion by free thyroid hormones is possibly impaired in obesity.

Hypertension is the main risk factor for cardiovascular disease (CVD) and all-cause mortality. Some studies have reported that food typical of the Mediterranean diet (MedDiet), such as whole grains, vegetables, fruits, nuts, and extra virgin olive oil, have a favorable effect on the risk of hypertension, whereas food not typical of this dietary pattern such as red meat, processed meat, and poultry has an unfavorable effect. In this review, we have summarized observational and intervention studies, meta-analyses, and systematic reviews that have evaluated the effects of the MedDiet as a pattern towards blood pressure (BP). However, the number of such studies is small. In general terms, the MedDiet has a favorable effect in reducing BP in hypertensive or healthy people but we do not have enough data to declare how strong this effect is. Many more studies are required to fully understand the BP changes induced by the MedDiet.

STUDY OBJECTIVE: Hirsutism has negative impact on adolescent psychosocial development for both cosmetic and endocrine reasons. This study evaluated the effectiveness of a new intermittent, low-dose finasteride regimen consisting of 2.5 mg of drug given every 3 days (1 day of treatment, 2 days of drug withdrawal) for 6 months in girls with hirsutism by polycystic ovarian syndrome (PCOS) or idiopathic hirsutism (IH). DESIGN AND PARTICIPANTS: Twenty-eight girls (15-19 y old) with hirsutism were randomly assigned to 2 treatment groups and treated for 6 months. Fourteen patients (7 with IH, 7 with PCOS) received finasteride; fourteen patients (7 with IH, 7 with PCOS) received placebo. Hirsutism score (HS), clinical, and hormonal effects were compared between the 2 groups. RESULTS: In patients treated with finasteride, the HS value at 6 months was 52.9% lower than that observed at baseline in girls with IH, and 52.8% lower in girls with PCOS (P < .0001 for both). Similarly, the 3α-17 β-androstenediol glucuronide serum levels were decreased by 34.8% in patients with IH, and by 47.5% in patients with PCOS (P < .0001, respectively). Finasteride treatment was well tolerated and did not alter values of BMI, serum levels of sexual hormones, metabolic parameters related to liver and kidney function as well as glycemic and lipidic asset. CONCLUSIONS: A low-dose of finasteride, given every 3 days, reduces the HS in young patients affected by PCOS or IH. Compared with conventional continuous finasteride administration, the intermittent low-dose regimen has similar efficacy with the advantage to be safer and less expensive

Low vitamin D levels have been associated with autoimmune disorders and, then, with the Hashimoto's autoimmune thyroiditis (AT), the most common autoimmune disease. Obesity is characterized by lower vitamin D levels and higher risk to develop autoimmune diseases. The aim of the study was to examine the possibility of an association between AT and decreased 25(OH) vitamin D (25(OH)D) levels in a cohort of otherwise healthy overweight and obese subjects.

Subclinical Hypothyroidism can be associated with the onset of Chronic Heart Failure (CHF), because it can favour two frequent conditions that can evolve in CHF: coronary heart disease and hypertension; it can also alter both cardiovascular morphology and function leading to CHF progression in patients already affected by CHF through mechanisms still not completely understood. Aim of this paper is to review the possible pathogenetic mechanisms explaining the influence of subclinical hypothyroidism on the onset and progression of CHF.

Bread was a staple in the traditional Mediterranean diet of the early 1960s, as well as nowadays; however, it was a stone ground sourdough bread in Nicotera and probably in the Greek cohorts of the Seven Countries Study. In the present review, the nutritional characteristics of this food are analyzed in relation to its protective effects on coronary heart disease, metabolic diseases and cancer. According to our traditions, cultural heritage and scientific evidence, we propose that only cereal foods with low glycemic index (GI) and rich in fiber have to be placed at the base of the Mediterranean diet pyramid, whereas refined grains and high GI starchy foods have to be sited at the top.

OBJECTIVE: Besides than in the control of developmental events, axonal adhesive glycoproteins may be also involved in functions requiring fine organization and connectivity of the nervous tissue. We previously demonstrated morphological alterations and functional cerebellar deficits in transgenic mice (TAG/F3 mice) ectopically expressing the F3/Contactin axonal glycoprotein under the control of a selected regulatory region from the Transient Axonal Glycoprotein (TAG-1) gene. In the present study, the hippocampal function was explored by evaluating the ability of TAG/F3 mice to encode spatial and non-spatial relationships between discrete stimuli and to analyze an anxiety-related behavior. MATERIALS AND METHODS: To the first end, mice were placed in an "open-Field" containing five objects and, after three sessions of habituation (S2-S4), their reactivity to objects displacement (S5-S4) and object substitution (S7-S6) was examined.To the second end, mice were placed in the "elevated zero maze", a standard test to explore the anxiety-related behavior, in order to study, in transgenic mice, the effects of F3 misexpression on emotional reactivity by measuring the avoidance of the unsheltered open sectors. RESULTS: Statistical evaluations of reactivity to object novelty, TAG-F3 mice showed a lower DO exploration with respect to wild-type mice and, regarding DOs, TAG/F3 mice interacted less than wild-type mice, showing an impaired spatial change response. Furthermore, the number of HDIPS in transgenic TAG/F3 mice resulted significantly lower with respect to the controls (wild type). CONCLUSIONS: These results indicate that the coordinated expression of axonal adhesive glycoproteins may be relevant for the functional maturation of the hippocampus.

: Obesity is an important risk factor for breast cancer (BC) in postmenopausal women; interlinked molecular mechanisms might be involved in the pathogenesis. Increased levels of estrogens due to aromatization of the adipose tissue, inflammatory cytokines such as tumor necrosis factor-α, interleukin-6, and prostaglandin E2, insulin resistance and hyperactivation of insulin-like growth factors pathways, adipokines, and oxidative stress are all abnormally regulated in obese women and contribute to cancerogenesis. These molecular factors interfere with intracellular signaling in the mitogen-activated protein kinase and phosphatydilinositol-3-phosphate/mammalian target of rapamycin (mTOR) pathways, which regulate the progression of the cell cycle, apoptosis, and protein synthesis. In this context, structural defects of typical genes related to both BC and obesity, such as leptin, leptin receptor, serum paraoxonase/arylesterase 1, the fat mass and obesity-associated gene and melanocortin receptor 4, have been associated with a high or low risk of BC development. The early detection of these gene alterations might be useful as risk predictors in obese women, and targeting these pathways involved in the BC pathogenesis in obese women is a potential therapeutic tool. In particular, mTOR pathway deregulation concurs in both obesity and BC, and inhibition of this might disrupt the molecular interlinks in a similar manner to that of metformin, which exerts definite anticancer activity and is currently used as an antidiabetic drug with a weight-reducing property. The identification of both genetic and pharmacological implications on the prevention and management of BC is the ultimate aim of these studies.

BACKGROUND: Renal sinus fat (RSF) has been recognized as a risk factor for arterial hypertension. This study was addressed to examine whether also para- and perirenal fat accumulation is associated to higher 24-h mean systolic (SBP) and/or diastolic blood pressure (DBP) levels in overweight and obese subjects. METHODS: A cohort of 42 overweight and obese patients, 29 women and 13 men, aged 25-55 years, not treated with any kind of drug, was examined. Body mass index (BMI), waist circumference (WC), fasting insulin and glucose serum levels, insulin resistance (assessed by using the homeostasis model assessment [HOMAIR]), and 24-h aldosterone urine levels were measured. Ambulatory blood pressure monitoring (ABPM) was measured with 15 min intervals from 7.0 a.m. to 11.0 a.m. and with 30 min intervals from 23.0 to 7.0 for consecutive 24 h, starting from 8:30 AM. Measurement of para- and perirenal fat thickness was performed by ultrasounds by a duplex Doppler apparatus. RESULTS: Para- and perirenal ultrasonographic fat thickness (PUFT) was significantly and positively correlated with WC (p < 0.01), insulin (p < 0.01), HOMAIR (p < 0.01), and 24-h mean DBP levels (p < 0.05). 24-h mean DBP was also significantly and positively correlated with 24-h aldosterone urine concentrations (p < 0.001). A multivariate analysis by multiple linear regression was performed; the final model showed that the association of 24-h mean DBP as dependent variable with PUFT (multiple R = 0.34; p = 0.026) and daily aldosterone production (multiple R = 0.59; p = 0.001) was independent of other anthropometric, hormone and metabolic parameters. DISCUSSION AND CONCLUSIONS: This study shows a positive independent association between PUFT and mean 24-h diastolic blood pressure levels in overweight and obese subjects, suggesting a possible direct role of PUFT in increasing daily diastolic blood pressure.

A group of 608 apparently healthy patients, 136 men and 472 women, either overweight or obese, aged 18-69 years, were examined. BMI, waist circumference, fasting blood glucose (FBG), insulin, and complement 3 (C3) serum levels were measured; the homeostasis model assessment (HOMAIR) was used to evaluate insulin resistance; and physical activity was quantified by a questionnaire. Results: HOMAIR showed a positive correlation with BMI (r: 0.478, p < 0.001), waist circumference (r: 0.487, p < 0.001), and C3 (r: 0.445, p < 0.001). Moreover, it was significantly associated with gender (F Fisher = 22.12, p < 0.001), and the mean HOMAIR levels were significantly different among the three groups of physical activity, with the lowest level of insulin resistance at the highest level of physical activity (F=7,31, p < 0.001). A multiple regression analysis was carried out with HOMAIR as the dependent variable and gender, age, BMI, waist circumference, C3 and the level of physical activity as independent variables (fitted model: F = 41.24, P<0.001, R2 = 0.328). HOMAIR maintained an independent association with C3 (β = 0.678, P<0.001), sex (β = 0.189, P<0.001), BMI (β = 0.637, P<0.01), and age (β = -0.004, P<0.05). Conclusions: This study of a cohort of overweight and obese subjects has shown that insulin resistance (dependent variable) is positively associated with C3 serum levels, independently of age, gender, anthropometric parameters and physical activity, suggesting that higher C3 serum levels may directly increase insulin resistance in obesity.

A cohort of 66 healthy overweight and obese patients, 53 women and 13 men were examined. Waist circumference and fasting 25(OH)D, insulin, glucose, lipid (cholesterol, HDL cholesterol, and triglyceride), C-reactive protein (CRP), and complement 3 (C, and 4 (C serum concentrations were measured. Insulin resistance was assessed by the homeostasis model assessment (HOMA. Results. 25(OH)D levels showed a significant negative correlation with BMI (P < 0.01), waist circumference (P < 0.05), fasting insulin (P < 0.01), HOMA(P < 0.01), triglycerides (P < 0.01), CRP (P < 0.01), C(P < 0.05), and C(P < 0.05). Multiple regression analyses were performed with 25(OH)D as the dependent variable and BMI (or waist circumferences), fasting insulin (or HOMA, triglycerides, and CRP (or Cor C as independent variables. Only insulin or HOMAmaintained a significant independent association with 25(OH)D levels, whereas vitamin D did not maintain a significant independent association with CRP or Cor Cconcentrations. Conclusions. The present study, performed in overweight and obese subjects, shows that 25(OH)D levels are negatively associated with inflammatory parameters such as CRP and Cand Clevels, but not independently of BMI, body fat distribution, insulin levels, or insulin resistance. Our results suggest that hyperinsulinemia and/or insulin resistance are directly responsible for decrease of 25(OH)D levels in obesity.

To evaluate the hypothesis that pretreatment with dehydroepiandrosterone(DEHA) may improve the result on in vitro fertilization (IVF) and the pregnancy outcome among infertile women with normal ovarian reserve STUDY DESIGN: Double-blind, randomized, placebo-controlled study. 52 infertile patients received the long protocol IVF. Patients in Group 1, received 75 mg of DHEA once a day , 8 weeks before starting the IVF cycle and during treatment; control group (Group 2) received placebo. The primary endpoint was pregnancy, live birth and miscarriage rates, secondary endpoint was standard IVF parameters such us stimulation duration (hCG day ), E2 on HCGday, endometrial thickness, number of retrieved oocytes, metaphase II oocytes, embryos transferred and score of leading embryos transferred. RESULT(S): Patients in the DHEA group had a significantly higher live birth rate compared with controls ( P< 0.05). Miscarriage rate was higher in control group ( P< 0.05) CONCLUSION: DHEA supplementation could have a beneficial effect on IVF outcome in infertile women with normal ovarian reserve.

Background: To verify the feasibility of ovarian stromal evaluation and correlate ovarian parameteres (echogenicity and volume) with hyperandrogenism, and both cardiovascular and metabolic risk factors in PCOS. Methods: Twenty four young PCOS patients and twelve age-matched control women were enrolled. Diagnosis of PCOS was based on the Rotterdam criteria. Ultrasound ovarian study included ovarian volume, stromal volume, stromal area and stromal area/total ovarian area ratio (S/A). Concerning hormones, insulin, LH, FSH, estradiol, androstenedione, testosterone, DHEAS, 17-hydroxy-progesterone, and SHBG were measured during the early follicular phase (days 2-5). Cardiovascular risk factors were represented by fasting plasma levels of glucose, lipids(total and HDL-cholesterol), plasminogen activator inhibitor 1 (PAI-1), von-Willebrand factor (vWF), and adiponectin. Carotid intima-media thickness (C-IMT) was measured as a parameter of cardiovascular risk. Results: A positive correlation between the S/A ratio and plasma levels of testosterone (p < 0.05) and androstenedione (p < 0.05) was found. The stromal volume, stromal area and S/A ratio were also significantly and positively correlated with PAI-1, and vWF levels, and with IMT in PCOS women (P < 0.05). Conclusions: This study shows that the ultrasound measurement of ovarian stroma is a predicting factor of hyperandrogenism degree, prothrombotic factors and cardiovascular risk in patients with PCOS.

To the Editor: Nonvalvular atrial fibrillation (NVAF) is the most common sustained arrhythmia encountered in clinical practice and is associated with a 5-fold increased risk for stroke (1). Moreover, patients with NVAF often suffer from atherosclerotic complications such as acute myocardial infarction (AMI) (2). Peripheral artery disease (PAD) is an established marker of systemic atherosclerosis but its prevalence in NVAF is still unclear. We reasoned that inclusion of ankle-brachial index (ABI), which is an established tool for diagnosis of PAD (3), in the CHA2DS2-VASc (4) score would better define the prevalence of vascular disease. Toaddress this issue, the ItalianSociety of InternalMedicine (SIMI) established an Italian registry documenting ABI inNVAF patients. The Atrial Fibrillation Registry for the ARAPACIS (Ankle- brachial Index Prevalence Assessment: Collaborative Italian Study) study is an independent research project involving all Regional Councils of SIMI. The first objective of the study was to estimate the prevalence of ABI 0.90 in NVAF patients. Consecutive patients with NVAF referred to internal medicine wards were eligible for the enrollment. Enrollment started in October 2010 and continued until October 30, 2012. Patients were enrolled if they were 18 years or older and had a diagnosis of NVAF, recording during the qualifying admission/consultation or in the preceding 12 months, and if it was possible to obtain the ABI measurement. Exclusion criteria included the following: acquired or congenital valvular AF, active cancer, disease with life expectancy <3 years, hyperthyroidism and pregnancy. We initially planned to include 3,000 patients. The Data and Safety Monitoring Board (Online Appendix) decided to perform an interim analysis to assess the prevalence of ABI in the enrolled populationsdas a higher than expected prevalence of low ABI was detecteddand decided to interrupt the patients’ enrollment. The sample size was amended as follows: a sample of 2,027 patients leads to the expected prevalence of 21% with a 95% confidence interval width of 3.5% (StataCorp LP, College Station, Texas). Among the 2,027 NVAF patients included in the study, hyper- tension was detected in 83%, diabetes mellitus in 23%, dyslipidemia in 39%, metabolic syndrome in 29%, and smoking in 15%. At least 1 atherosclerotic risk factor was detected in 90% of patients. The NVAF population was at high risk for stroke, with only 18% having a CHA2DS2-VASc score of 0 to 1, while 82% had a risk 2. Despite this, 16% were untreated with any antith- rombotic drug, 19% were treated with antiplatelet drugs (APs), and 61% with oral anticoagulants (OAC); 4% of patients were treated with both APs and OAC. Among the AF population, 428 patients (21%) had ABI 0.90 (69%); 204 patients (10%) had ABI 1.40 (Fig. 1). ABI recorded only in 1 leg was excluded from the analysis (n ¼ 14). ABI 0.90 progressively increased from paroxysmal to permanent NVAF (18%, tensive (88% vs. 82%; p ¼ 0.032), diabetic (34% vs. 20%; p < 0.0001), or smokers (20% vs. 14%; p ¼ 0.0008), or to have experi- enced transient ischemic attack or stroke (17% vs. 10%; p < 0.001). 21%, 24%; p ¼ 0.0315). NVAF patients with ABI 0.90 were more likely to be hyper- NVAF patients with ABI 0.90 had a higher percentage of CHA2DS2-VASc score 2 compared with those with ABI >0.90 (93% vs. 82%; p < 0.0001). significantly associated with a smoking habit (odds ratio [OR]: 1.99; 95% confidence interval [CI]: 1.48 to 2.66; p < 0.0001), diabetes (OR: 1.93; 95% CI: 1.51 to 2.46; p < 0.0001), age class 65 to 74 years (OR: 2.05; 95% CI: 1.40 to 3.07; p < 0.0001), age Logistic regression analysis demonstrated that ABI 0.90 was class 75 years (OR: 3.12; 95% CI: 2.16 to 4.61; p < 0.0001), and history of previous transient ischemic attack/stroke (OR: 1.64; 95% CI: 1.20 to 2.24; p ¼ 0.002). Vascul

Objective: The study aim was to compare C3 levels with the common carotid artery intima-media thickness (CCAIMT) in subjects of both genders, with a wide range of BMI, independently of age, gender, and abdominal obesity. Method: 140 euthyroid, mainly overweight/obese subjects (age 18-30 years) were examined. BMI, waist circumference, blood pressure, fasting insulin, glucose, lipids, C3 and C-reactive protein serum concentrations, and insulin resistance degree (estimated by homeostasis model assessment for insulin resistance (HOMAIR)) were measured. Results: CCA-IMT was positively (p < 0.001) correlated with BMI, waist circumference, systolic and diastolic blood pressures, HOMAIR, and insulin, CRP, and C3 serum levels. The multiple linear regression analysis showed that only male gender and waist circumference maintained an independent relation with the CCA-IMT. Conclusion: This study suggests that central fat accumulation and male gender independently increase the thickness of the arterial wall, whereas inflammation and inflammatory markers do not have an independent effect on this parameter.

Monocyte chemoattractant protein 1 (MCP-1) has been implicated in the recruitment of monocytes to atheroma and of monocytes and macrophages to adipose tissue. The aim of the study was to examine whether MCP-1 levels are associated independently with the main thermo-genetic hormones (serum TSH and thyroid hormones and 24-h urinary catecholamines) and insulin resistance in a population mainly represented by overweight and obese women. A cohort of 100 consecutive euthyroid women, aged 18–65 years, and with a wide range of BMI, was examined. Central fat accumulation (indirectly measured by waist circumference), fasting MCP-1 plasma levels, and TSH,FT3, FT4, insulin, glucose, and lipid(cholesterol, HDL- cholesterol and triglyceride) serum concentrations, and 24-h urinary catecholamines were measured. Insulin resistance was estimated by homeostasis model assessment forinsulin resistance (HOMAIR). MCP-1 levels were directly associated with BMI (<0.001), waist circumference (p<0.001), insulin (p< 0.001), HOMAIR (p< 0.001), diastolic blood pressure (DBP) (p< 0.001), systolic blood pressure (SBP) (p< 0.001), triglycerides (TG) (p<0.05), and 24-h urinary noradrenaline (p<0.05), and negatively correlated with HDL-cholesterol (p<0.01). When a multiple regression analysis was performed with MCP-1 as the dependent variable, and only parameters showing a significant univariate association with MCP-1 were considered as the independent variables, MCP-1 maintained an independent positive association with insulin (p<0.01), and DBP (p<0.05). When insulin was replaced by HOMAIR in the regression analysis, MCP-1 maintained an independent positive association with HOMAIR (p<0.05), DBP (p<0.05), and BMI (p<0.05). In conclusion, this study suggests that insulin, BMI, and diastolic blood pressure cooperate independently in increasing MCP-1 levels, whereas thyroid hormones and catecholamines have no apparent influence on this chemokine.

CONTEXT AND OBJECTIVE: High-mobility group box-1 (HMGB1) is a pro-inflammatory cytokine that may contribute to the pathogenesis of micro- and macrovascular complications commonly observed in diabetes. We investigated whether HMGB1 is associated with: i) markers of low-grade inflammation (LGI) and endothelial dysfunction (ED) and pulse pressure (PP, a marker of arterial stiffness); ii) prevalent nephropathy, retinopathy and cardiovascular disease (CVD) in type 1 diabetes; and iii) the potential mediating roles of LGI, ED and PP therein. DESIGN AND METHODS: This was a cross-sectional nested case-control study of 463 patients (226 women; mean age 40±10 years) with type 1 diabetes from the EURODIAB Prospective Complications Study. We used linear and binary or multinomial logistic regression analyses adjusted for traditional risk factors. RESULTS: Serum Ln-HMGB1 levels were positively associated with LGI and ED (standardised β=0.07 (95% confidence interval (CI): 0.02-0.12) and β=0.08 (95% CI: 0.02-0.14) respectively), but not with PP. Higher Ln-HMGB1 (per unit) was associated with greater odds of micro- and macroalbuminuria: odds ratio (OR)=1.24 (95% CI: 0.90-1.71) and OR=1.61 (95% CI: 1.15-2.25) respectively, P for trend=0.004. Further adjustments for LGI or ED did not attenuate these associations. No such associations were found between Ln-HMGB1 and estimated glomerular filtration rate (eGFR), retinopathy or CVD, however. CONCLUSIONS: In type 1 diabetes, higher serum HMGB1 levels are associated with greater prevalence and severity of albuminuria, though not with eGFR, retinopathy and CVD. Prospective studies are needed to clarify the causal role of HMGB1, if any, in the pathogenesis of vascular complications in type 1 diabetes.

Rates of depression are significantly increased in diabetic patients, and even more in the elderly. About 20–30 % of patients with diabetes suffer from clinically relevant depressive disorders, 10 % of which being affected by the major depression disorder. Moreover, people with depression seem to be more prone to develop an associated diabetes mellitus, and depression can worsen glycemic control in diabetes, with higher risk to develop complications and adverse outcomes, whereas improving depressive symptoms is generally associated with a better glycemic control. Thus, the coexistence of depression and diabetes has a negative impact on both lifestyle and quality of life, with a reduction of physical activity and an increase in the request for medical care and prescriptions, possibly increasing the healthcare costs and the susceptibility to further diseases. These negative aspects are particularly evident in the elderly, with further decrease in the mobility, worsening of disability, frailty, geriatric syndromes and increased mortality. Healthcare providers should be aware of the possible coexistence of depression and diabetes and of the related consequences, to better manage the patients affected by these two pathological conditions.

Although the neurohypophyseal hormones vasopressin and oxytocin are mostly known for their role respectively in antiduresis the former and in labour, lactation and maternal behavior the latter, both might exert widespread influences either on emotion and cognition in healthy subjects, showing some gender-related differences. They interact one each other facilitating shifts between positive socially- oriented and defensive states. In fact, vasopressin amplifies the reactivity to stressors showing also beneficial effects on attention, verbal learning as well as memory, whereas oxytocin reduces the amplitude of the stress response, improves emotion processing, and can play a negative effect on memory and verbal learning in healthy individuals. Several data indicate the possible involvement of this neuropeptides in the pathophysiology of psychiatric conditions involving social interactions, such as autism, as well as in schizophrenia and depression. Aim of this paper is to review the literature dealing with the role played by neurohypophyseal hormones in neuropsychiatric disorders.

Leptin plays a key role in obstructive sleep apnea syndrome (OSAS). Leptin production in human airways has been previously evaluated by measuring leptin concentration in the exhaled breath condensate and in the induced sputum. The aim was to study leptin expression in the cells of induced sputum and in exhaled breath condensate of subjects with OSAS. Moreover, leptin concentrations in the blood were measured in the same groups of subjects. We enrolled four groups of patients: (1) obese patients with OSAS (OO); (2) non-obese patients with OSAS (NOO); (3) obese patients without OSAS (ONO); and (4) non-obese subjects without OSAS (C). Leptin expression was evaluated by immunocytochemistry in the sputum cells of the enrolled subjects. The concentrations of leptin in the exhaled breath condensate and plasma were measured by using a specific enzyme immunoassay. Leptin protein expression and the percentage of macrophages and neutrophils expressing leptin were higher in the induced sputum of OO, NOO and ONO patients than in C. Leptin concentrations in the exhaled breath condensate were significantly higher in OO patients (5.12 (3.8-6.6) ng ml(-1)) than in NOO (4.1 (3.9-5.2) ng ml(-1)) and ONO (4.2 (3.6-5.0) ng ml(-1)) patients. The concentration of leptin in plasma was significantly more elevated in OO (36 (24-65.9) ng ml(-1)) than in NOO (30.2 (12.4-51.4) ng ml(-1)), whereas it was not significantly different in ONO patients. This study showed that leptin in sputum and in the exhaled breath condensate is higher in obese patients with OSAS than in obese subjects without OSAS. Moreover, different mechanisms for determining leptin concentrations in the exhaled breath condensate and the blood are suggested.

A great debate in literature exists nowadays on the role of uric acid as a marker of cardiovascular and metabolic organ damage or a risk factor for cardiovascular and metabolic disease.

The nonapeptide hormone vasopressin (VP), synthesized by the hypothalamic supraoptic and paraventricular nuclei, exerts important effects on cardiovascular system via its receptors V1, V2 and V3. Patients with congestive heart failure (CHF) present elevated plasma VP levels that induce vasoconstriction, left ventricular hypertrophy, and free water reabsorption that leads to edema and hyponatremia, markers of advanced CHF. Vaptans, antagonists of VP receptors, are able to increase urine output and plasma sodium levels without the increased risk of arrhythmic death induced by diuretics, even though, further studies are needed to establish a possible role of these drugs in the treatment of CHF. Aim of this paper is to review the role of vasopressin in CHF.

Bakground and objective: The sleep-wake cycle is characterized by a circadian rhythm involving neurotransmitters and neurohormones that are released from brainstem nuclei and hypothalamus. Aim of this review is to analyze the role played by central neural pathways, neurotrasmitters and neurohormones in the regulation of vigilance states.

Vitamin D deficiency is on the increase all over the world. The clinical role of vitamin D in calcium and bone metabolism is well known, but lower levels of the vitamin are also linked to obesity and an increased risk of developing cardiovascular disease, type 2 diabetes, and cancer. The molecular mechanisms of these associations are only partially understood, but it is known that vitamin D stimulates lipolysis and inhibits adipogenesis in human adipocytes, and lower vitamin D may induce body fat accumulation. Vitamin D receptors are expressed in pancreatic beta cells and skeletal muscle cells, and their activation results in increased insulin release and responsiveness to insulin for glucose transport. Vitamin D has recently been found to have potent antiproliferative, prodifferentiative, and immunomodulatory effects in many tissues. Vitamin D deficiency is often missed clinically even though its measurement is a simple laboratory test and its treatment is inexpensive and usually well tolerated. Nevertheless, physicians are not sufficiently informed about the effects of vitamin D other than those on the skeletal metabolism, and they rarely ask for plasma vitamin D measurement. The purpose of this review is to examine the association between vitamin D deficiency, obesity, and the risk of type 2 diabetes.