Genoveffa Pizza

Bisphenol A in polycystic ovary syndrome and its association with liver-spleen axis.

Bisphenol A, one of the highest‐volume chemicals currently available, is known to act as endocrine disruptor and alters several metabolic functions, including inflammatory pathways. Elevated serum levels of bisphenol A have been found in women with polycystic ovary syndrome (PCOS) and a role of low‐grade chronic inflammation has been recently reported in the pathogenesis of this syndrome. Increased spleen volume, a reliable and stable index of chronic inflammation, was strictly associated with the severity of hepatic steatosis (HS) in obese subjects, determining the so‐called liver–spleen axis.

Liver-spleen axis, insulin-like growth factor-(IGF)-I axis and fat mass in overweight/obese females

BackgroundFat mass (FM) in overweight/obese subjects has a primary role in determining low-grade chronic inflammation and, in turn, insulin resistance (IR) and ectopic lipid storage within the liver. Obesity, aging, and FM influence the growth hormone/insulin-like growth factor (IGF)-I axis, and chronic inflammation might reduce IGF-I signaling. Altered IGF-I axis is frequently observed in patients with Hepatic steatosis (HS). We tested the hypothesis that FM, or spleen volume and C-reactive protein (CRP)--all indexes of chronic inflammation--could affect the IGF-I axis status in overweight/obese, independently of HS.MethodsThe study population included 48 overweight/obese women (age 41 ± 13 years; BMI: 35.8 ± 5.8 kg/m2; range: 25.3-53.7), who underwent assessment of fasting plasma glucose and insulin, homeostasis model assessment of insulin resistance (HOMA), cholesterol and triglycerides, HDL-cholesterol, transaminases, high-sensitive CRP, uric acid, IGF-I, IGF binding protein (BP)-1, IGFBP-3, and IGF-I/IGFBP-3 ratio. Standard deviation score of IGF-I according to age (zSDS) were also calculated. FM was determined by bioelectrical impedance analysis. HS severity grading (score 0-4 according liver hyperechogenicity) and spleen longitudinal diameter (SLD) were evaluated by ultrasound.ResultsMetabolic syndrome (MS) and HS were present in 33% and 85% of subjects, respectively. MS prevalence was 43% in subjects with increased SLD. IGF-I values, but not IGF-I zSDS, and IGF-I/IGFBP-3 ratio were significantly lower, while FM%, FPI, HOMA, ALT, CRP, were significantly higher in patients with severe HS than in those with mild HS. IGF-I zSDS (r = -0.42, r = -0.54, respectively; p < 0.05), and IGFBP-1 (r = -0.38, r = -0.42, respectively; p < 0.05) correlated negatively with HS severity and FM%. IGF-I/IGFBP-3 ratio correlated negatively with CRP, HS severity, and SLD (r = -0.30, r = -0.33, r = -0.43, respectively; p < 0.05). At multivariate analysis the best determinants of IGF-I were FM% (β = -0.49; p = 0.001) and IGFBP-1 (β = -0.32; p = 0.05), while SLD was in the IGF-I/IGFBP-3 ratio (β = -0.43; p = 0.004).ConclusionsThe present study suggests that lower IGF-I status in our study population is associated with higher FM, SLD, CRP and more severe HS.

Prevalence of the metabolic syndrome in moderately-severely obese subjects with and without growth hormone deficiency

Background and aim: There is a considerable heterogeneity in metabolic phenotype among equally obese subjects. Impaired GH secretion is frequent in obese patients, with GH secretion reduced up to levels that are comparable to those found in adult patients with organic GH deficiency (GHD). Low GH status exerts detrimental effects on metabolic abnormalities in organic GHD patients. The aim of this observational, retrospective study was to investigate the prevalence of the metabolic syndrome (MetS) in moderately-severely obese subjects who met criteria for GDH (GHD) and in those with normal GH status (GH sufficient: GHS). Methods and results: One-hundred and ninety-five moderately-severely obese individuals partecipated, 149 women and 46 males [body mass index (BMI) 43.0±4.4 kg/m2 aged 34.3±11.8 yr]. Main outcome measures were: GH peak after GHRH plus arginine test, IGF-I, MetS parameters according to National Cholesterol Education Program criteria. Fifty-five subjects (27.3%) were GHD (49 females and 6 males). The prevalence of MetS parameters was 70.9% in GHD subgroup vs 52.9% in GHS (χ2=5.281; p=0.02) and the likelihood of MetS was highest in GHD subgroup (odds ratio: 2.174; 95% confidence interval 1.113 to 4.248). At the multiple regression analysis either GH peak or IGF-I were the major determinants of waist circumference (β=-0.380, t=−6.110 and β=-0.326, t=−4.704, respectively; p<0.001), while age and IGF-I were the major determinants of MetS (β=0.255, t= 3.342, and β=−0.282, t=−3.270; p=0.02, respectively). Conclusions: Among moderately-severely obese individuals the prevalence of the MetS was higher in GHD than in GHS subjects. Thus, in obese subjects, GH status investigation might be considered in the clinical evaluation of their metabolic risk profile.

The treatment of hyperinsulinemic hypoglycaemia in adults: an update

BackgroundTreatment of hyperinsulinemic hypoglycaemia (HH) is challenging due to the rarity of this condition and the difficulty of differential diagnosis. The aim of this article is to give an overview of the recent literature on the management of adult HH.MethodsA search for reviews, original articles, original case reports between 1995 and 2016 in PubMed using the following keywords: hyperinsulinemic hypoglycaemia, insulinoma, nesidioblastosis, gastric bypass, autoimmune hypoglycaemia, hyperinsulinism, treatment was performed.ResultsOne hundred and forty articles were selected and analysed focusing on the most recent treatments of HH.ConclusionsNew approaches to treatment of HH are available including mini-invasive surgical techniques and alternative local–regional ablative therapy for benign insulinoma and everolimus for malignant insulinoma. A correct differential diagnosis is of paramount importance to avoid unnecessary surgical operations and to implement the appropriate treatment mainly in the uncommon forms of HH, such as nesidioblastosis and autoimmune hypoglycaemia.

Effects of short-term treatment with orlistat on growth hormone/insulin-like growth factor-I axis in obese post-menopausal women

Aim: Obesity is associated with an altered GH/IGF-I axis status, accounting for the increased cardiovascular risk in obese subjects with GH deficiency. Aim of this randomized, simple-blind, cross-over study was to verify the effectiveness of a short-term treatment with orlistat in reducing non-esterified fatty acid (NEFA) and influencing the endogenous activity of GH/IGF-I axis in obese subjects. Outcome measures: The primary outcome measures were post-prandial lipemia; GH peak after GHRH+arginine; IGF-I; IGF-binding protein (BP)-3, IGF-I/IGFBP-3 ratio. Secondary outcome measures were insulin resistance (IR) indexes (homeostasis model assessment of insulin resistance and Insulin Sensitivity Index). Study design: Twenty obese post-menopausal women (age: 53.6±6.2; body mass index: 34.1 ±4.0) were randomized to receive normo-caloric diet plus + orlistat (Roche, UK; 120 mg tid) or normo-caloric diet without the additional treatment. The duration of follow-up was 10 days for each treatment period. Results: Orlistat induced a weight-independent reduction in post-prandial NEFA levels compared with diet alone, with higher GH peak, IGF-I, and IGF-I/IGFBP3 ratio. GH peak was correlated negatively with postprandial NEFA and positively with IGF-I and IGF-I/IGFBP-3 ratio. Conclusions: Orlistat is effective in inducing a weight-independent higher reduction in post-prandial NEFA levels than dietary treatment alone along with increase in GH peak, IGF-I levels, and IGF-I/IGFBP-3 ratio. These results might add a new potential benefit of orlistat in the management of obese subjects.

The safety of available treatments options for neuroendocrine tumors

ABSTRACT Introduction: Neuroendocrine neoplasms (NEN) represent a heterogeneous group of malignancies generally characterized by low proliferation and indolent course. However, about half of the newly diagnosed cases are metastatic and require long-term systemic therapies. Areas covered: This review revises the literature to summarize the current knowledge upon safety of all systemic treatment options available. Thirty three different clinical studies have been considered, including 4 on somatostatin analogues (SSA), 5 on targeted therapies, 10 on peptide receptor radionuclide therapy (PRRT), and 14 on chemotherapy. Expert opinion: SSA are safe and well tolerated without any relevant severe adverse event and very low treatment discontinuation rate. Targeted therapies show a satisfying safety profile. Most adverse events are grade 1–2 and easy manageable with dose reduction or temporary interruption. PRRT is manageable and safe with a low rate of grade 3–4 adverse events. However, severe renal and hematologic toxicity may occur. Chemotherapy is usually considered after previous therapeutic lines. Therefore, these subjects are more susceptible to experience adverse events due to cumulative toxicities or poor performance status. The available systemic treatment options are generally well tolerated and suitable for long-term administration. Cumulative toxicity should be taken in account for the definition of therapeutic sequence.

The management of neuroendocrine tumours: A nutritional viewpoint

ABSTRACT Nutritional status in patients with neuroendocrine tumours (NETs), especially of gastroenteropancreatic origin, can be deeply affected by excessive production of gastrointestinal hormones, peptides, and amines, which can lead to malabsorption, diarrhoea, steatorrhea, and altered gastrointestinal motility. Besides, the surgical and/or medical management of NETs can lead to alteration of gastrointestinal secretory, motor, and absorptive functions, with both dietary and nutritional consequences. Indeed, disease-related malnutrition is a frequently encountered yet both underrecognized and understudied clinical phenomenon in patients with NETs, with substantial prognostic and socioeconomic consequences. Most of these conditions can be alleviated by a tailored nutritional approach, also with the aim of improving the efficacy of cancer treatments. In this setting, skilled nutritionists can play a fundamental role in the multidisciplinary health care team in NETs management and their presence should be recommended. The aim of this review is to provide dietary advices for each specific condition in patients with NETs, underlining the importance of a nutritional approach to treat malnutrition in this setting. Further, we will provide preliminary evidence coming from our data on the assessment of nutritional status in a single cohort of patients with NETs.

Preliminary data on effects of metformin on PED/PEA-15 cellular levels in obese women with polycystic ovary syndrome

Background: The cellular abundance of the phosphoprotein enriched in diabetes (PED/PEA-15), a 15 kDa protein related to insulin resistance (IR), is increased in women with polycystic ovary syndrome (PCOS). Aim: To investigate whether metformin (MET) has additive effects on PED/PEA-15 protein levels. Material/subjects and methods: This is an open label, prospective clinical study over 6 months. Ten hyperandrogenic obese PCOS women [age: 24.6±1.6 yr; body mass index (BMI): 30.7±1.2 kg/m2] were treated with MET (1250 mg/day). Ten age- and BMI-matched normo-androgenic women were used as controls. Outcome measures are: PED/PEA-15 protein levels, fasting plasma glucose and insulin (FPI), reciprocal index of homeostasis model assessment of insulin resistance (1/HOMA-IR); quantitative insulin sensitivity check index (QUICKI); whole-body insulin sensitivity index (ISI); SHBG; total testosterone; free androgen index (FAI). Results: At baseline FPI and PED/PEA-15 protein levels were higher, while 1/HOMA-IR, QUICKI, and ISI were lower (p<0.001) in MET group than in controls. After treatment, independently of body weight and hyperandrogenism, FPI, and PED/PEA-15 protein levels decreased (p=0.001 and 0.004, respectively), while, 1/HOMA-IR, QUICKI, and ISI increased (p<0.001). PED/PEA-15 protein levels correlated significantly with ISI either before (r=0.636; p=0.048), and after treatment (r=0.758; p=0.011). Conclusions: PED/PEA-15 protein levels reduced after a short course of treatment with MET in a group hyperandrogenic obese PCOS women. This effect was independent of body weight and hyperandrogenism, and correlated with ISI, thus adding a further benefit to obese PCOS women.

Polycystic Ovary Syndrome and Hepatic Steatosis: Could Low-Grade Chronic Inflammation Be Mediated by the Spleen?

Polycystic Ovary Syndrome (PCOS) is characterized by an extreme variety of phenotypes and controversial metabolic implications. Hepatic Steatosis (HS) and low-grade chronic inflammation (LGCI) might be common findings in PCOS. We conducted a cross-sectional study to evaluate the LGCI and HS in young women with PCOS according to their Body Mass index (BMI), Insulin Resistance (IR), and PCOS phenotypes. Sixty young premenopausal PCOS women and 20 age-matched controls participated. Primary outcome measures were the presence/severity of HS; LGCI index evaluated as spleen longitudinal diameter (SLD) by UltraSound, C-Reactive Protein (CRP) and Interleukin (IL)-6 levels; BMI and the Homeostasis Model Assessment (HoMA) of IR. The second outcome measures were testosterone, Sex Hormone-Binding Globulin (SHBG) levels, and Free Androgen Index (FAI). The presence of HS and LGCI was not significantly different between NW and O/O patients, while there were significant differences particularly when the PCOS-women were grouped according to IR or to PCOS phenotypes. At multiple regression adjusted for BMI, HoMA-IR and the spleen size were the major determinants of the severity of HS (β= 0.36, p=0.007, and β= 0.28, p=0.034, respectively). At multiple regression SLD represented the unique predictor of FAI (β=0.32; p=0.018). In young women with PCOS, HS was detected independently from obesity and was well predicted not only by IR but also by spleen size, with variable expression of the liver-spleen axis across the different PCOS subtypes. A possible role of the spleen in determining LGCI also in women with PCOS is emphasized.

Beyond waist circumference in an adult male population of Southern Italy: Is there any role for subscapular skinfold thickness in the relationship between insulin-like growth factor-I system and metabolic parameters?

Background: Apart from waist circumference, other adiposity measures, such as subscapular skin fold (SST), arouse growing interest due to their relationship to metabolic complications and cardiovascular risk. The IGF-I system is deregulated in obese subjects in proportion to their degree of visceral adiposity. Aim: To examine the association among IGF-I, IGF-binding protein (BP)-1 and -3 levels and different measures of adiposity in a sample of adult male population in Southern Italy. Materials and methods: A complete database for this analysis was available for 229 (age range 50–82 yr) participating at 2002–2004 Olivetti Heart Study follow-up. Results: After adjustment for age, IGF-I was inversely associated with body mass index (BMI) and waist circumference (p<0.05). IGFBP-1 was inversely associated with BMI, waist circumference, SST, homeostasis model assessment (HOMA) index, fat mass. HOMA index, age, and SST significantly predicted the IGFBP-1 plasma levels, with 24% of IGFBP-1 variability explained at a linear regression analysis. Conclusions: IGFBP-1 inversely correlated to adiposity and HOMA index. Among adiposity indexes, SST was the best predictor of IGFBP-1 levels. The evaluation of some components of the IGF system, and simple measures of body adiposity, such as SST, may represent a further tool to better evidence phenotype profiles associated to the pathogenetic mechanism of cardiovascular risk factor clustering in male adults.