Nicola Bartolomeo

Possible Role of Hyperinsulinemia and Insulin Resistance in Lower Vitamin D Levels in Overweight and Obese Patients

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 (C3), and 4 (C4) serum concentrations were measured. Insulin resistance was assessed by the homeostasis model assessment (HOMAIR). 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), HOMAIR (P < 0.01), triglycerides (P < 0.01), CRP (P < 0.01), C3 (P < 0.05), and C4 (P < 0.05). Multiple regression analyses were performed with 25(OH)D as the dependent variable and BMI (or waist circumferences), fasting insulin (or HOMAIR), triglycerides, and CRP (or C3 or C4) as independent variables. Only insulin or HOMAIR maintained a significant independent association with 25(OH)D levels, whereas vitamin D did not maintain a significant independent association with CRP or C3 or C4 concentrations. 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 C3 and C4 levels, 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.

A markov model to evaluate hospital readmission

BackgroundThe analysis of non-fatal recurring events is frequently found in studies on chronic-degenerative diseases. The aim of this paper is to estimate the probability of readmission of patients with Chronic Obstructive Pulmonary Disease (COPD) or with Respiratory Failure (RF).MethodsThe Repeated hospital admissions of a patient are considered as a Markov Chain. The transitions between the states are estimated using the Nelson-Aalen estimator. The analysis was carried out using the Puglia Region hospital patient discharge database for the years 1998–2005. Patients were selected on the basis of first admission between 01/01/2001 and 31/12/2005 with ICD-9-CM code of COPD or RF as principal and/or secondary diagnosis. For those selected two possible transitions were considered in the case they had the second and third admission with an ICD-9-CM code of COPD or RF as principal diagnosis.ResultsThe probability of readmission is increased in patients with a diagnosis of RF (OR = 1.618 in the first transition and 1.279 in the second) and also in those with a diagnosis of COPD or RF as the principal diagnosis at first admission (OR = 1.615 in the first transition and 1.193 in the second). The clinical gravity and the ward from which they were discharged did not significantly influence the probability of readmission.ConclusionThe time to readmission depends on the gravity of the pathology at onset. In patients with a grave clinical picture, either COPD or Respiratory Failure, when treated and controlled after the first admission, they become minor problems and they are indicated among secondary diagnoses in any further admission.

Elevated Endothelin-1 (ET-1) Levels May Contribute to Hypoadiponectinemia in Childhood Obesity

CONTEXT Pediatric obesity is associated with endothelial dysfunction and hypoadiponectinemia, but the relationship between these two conditions remains to be fully clarified. Whether enhanced release of endothelin-1 (ET-1) may directly impair adiponectin (Ad) production in obese children is not known. OBJECTIVE The aim of the study was to explore whether and how high circulating levels of ET-1 may contribute to impair Ad production, release, and vascular activity. DESIGN AND PARTICIPANTS Sixty children were included into obese (Ob; n = 30), overweight (OW; n = 11), and lean (n = 19) groups. Total and high-molecular-weight Ad, ET-1, vascular cell adhesion molecule-1, and von Willebrand factor levels were measured in serum samples. Adipocytes were stimulated with exogenous ET-1 or with sera from lean, OW, and Ob, and Ad production and release measured in the absence or in the presence of ETA (BQ-123) and ETB (BQ-788) receptor blockers, p42/44 MAPK inhibitor PD-98059, or c-Jun NH2-terminal protein kinase inhibitor SP-600125. Vasodilation to Ad was evaluated in rat isolated arteries in the absence or in the presence of BQ-123/788. RESULTS Total and high-molecular-weight Ad was significantly decreased and ET-1 levels significantly increased in OW (P < .01) and Ob (P < .001) children. A statistically significant linear regression (P < .01) was found between Ad and ET-1. Exposure of adipocytes to exogenous ET-1 or serum from OW and Ob significantly decreased Ad mRNA and protein levels (P < 0.001). The inhibitory effect of ET-1 on Ad was reverted by BQ-123/788 or PD-98059 but not SP-600125. Ad-mediated vasodilation was further increased in arteries pretreated with BQ-123/788. CONCLUSIONS ET-1-mediated inhibition of Ad synthesis via p42/44 MAPK signaling may provide a possible explanation for hypoadiponectinemia in pediatric obesity and contribute to the development of cardiovascular complications.

Sporadic melanoma in South-Eastern Italy: the impact of melanocortin 1 receptor (MC1R) polymorphism analysis in low-risk people and report of three novel variants.

Environmental and genetic risk factors are involved in the development of melanoma. The role of the melanocortin 1 receptor (MC1R) gene has been investigated and differences according to geographic areas have been described. To evaluate the role of some clinical and genetic risk factors in melanoma development, we performed a case–control study involving 101 melanoma patients and 103 controls coming from South-Eastern Italy (Puglia), after achieving informed consent. We confirmed the role of known clinical risk factors for melanoma. Furthermore, 42 MC1R polymorphisms were observed. Three of these variants (L26V, H232L, D294Y) were not previously reported in the literature. Their predicted impact on receptor function was evaluated using bioinformatic tools. We report an overall frequency of MC1R variants in our population higher than in Northern or Central Italy. The most common polymorphism found was V60L, that has been recently reported to spread among South Mediterranean population. This variant influenced phenotypic characteristics of our population while it did not impinge on melanoma risk. An increased risk of melanoma was associated with two or more MC1R variants, when at least one was RHC, compared to people carrying the MC1R consensus sequence or a single MC1R polymorphism. Interestingly, we observed an increased risk of melanoma in subjects with darker skin and lower nevus count, usually considered at low risk, when carrying MC1R polymorphisms.

Evaluation of body composition with bioimpedence. A comparison between athletic and non-athletic children

Abstract Purpose: Conventional Bioelectrical Impedance Analysis (BIA) or Bioelectrical Impedance Vector Analysis (BIVA) can provide direct evaluations of body composition. The purpose of this study was to evaluate lean and fat mass (FM), and hydration of children involved in daily competitive sports. Methods: 190 non-athletic [8.2–10.5 years] and 29 competitive children [8.0–10.5 years] were enrolled. They were evaluated: at baseline (t0), 6 months (t1) and one year (t2). Anthropometric, BIA and BIVA, lean and FM, and hydration evaluations were performed. Results: Resistance (R/h) and reactance (Xc/h) were lower at t0 in competitive individuals when compared to controls. Xc/h (+3.28) significantly increases in competitive when compared to non-competitive individuals (+0.66, p for difference: 0.011), while phase angle (PA) was lower at t0 (5.72 vs. 6.17, p < .001) and after 6 months (p = .001). Total body water adjusted for height (TBW/h) significantly increased only in non-athletes (+0.50 ± 0.13, p < .001) between t0 and t1. At t1, extracellular water (ECW) significantly decreased (p = .026) in the two groups: −0.45 ± 0.19% in non-competitive, −1.63 ± 0.49% in competitive subjects, while intracellular water (ICW) increased. At one-year follow-up (t2), there were no statistically significant differences in R/h, Xc/h and PA in competitive individuals when compared to baseline and t1. Furthermore, we observed at t2 that hours/week of training, age, male gender and body mass index can influence FFM/h and FM/h in both competitive and non-competitive subjects. In particular, a direct correlation was for hours/week and FFM/h, inverse for hours/week and FM/h. Conclusions: Body mass index does not allow evaluating differences in lean body mass and FM between athletes and non-athletes. BIA and BIVA can give more reliable details about body composition differences in competitive adolescents and non-competitive, outlining a progressive decline in ECW and increase in ICW without affecting TBW composition of athletes.

Possible Direct Influence of Complement 3 in Decreasing Insulin Sensitvity in a Cohort of Overweight and Obese Subjects

UNLABELLED 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.

Lung cancer and COPD rates in Apulia: a multilevel multimember model for smoothing disease mapping

BackgroundIf spatial representations of hospitalization rates are used, a problem of instability arises when they are calculated on small areas, owing to the small number of expected and observed cases. Aim of this study is to assess the effect of smoothing, based on the assumption that hospitalization rates, when calculated at the municipal level, may be influenced by both the neighboring municipalities and the health service organization, as well as by environmental risk factors associated with the disease under study.MethodsTo smooth rates we hypothesize that each municipality belongs to two independent hierarchical levels; at one of these levels subjects may belong to a plurality of superior hierarchical objects. Two different models, so-called Multilevel Multimembership Models, are fitted. In the first the structure of random effects was: the municipality heterogeneity, the spatial dependence of the municipalities and the local health service organization. In the second we replaced the local health service organization effect with the environmental risk effect for each municipality area.The models were applied to spatially represent the rates of hospitalization for lung cancer and chronic obstructive pulmonary disease, determined through the hospital discharge forms recorded in Apulia for the year 2006.ResultsThe effect of smoothing was greater in smaller municipalities and in those with a more unstable Risk Adjusted Rate (RAR) due to the small number of cases and of population at risk. When a hierarchical level representing the ASL is inserted, the model fits the data better.ConclusionMaps of hospitalization rates for lung cancer and chronic obstructive pulmonary disease, shaded with the rates obtained at the end of the smoothing procedure, change the visual picture of the disease distribution over the whole territory, and if detected by the model, seem to express a geographical distribution pattern in specific areas of the region. In the case of lung cancer, the models show a clear difference between RAR and smoothed RAR. The inclusion of a random effect indicating the ASL contributed to improve the graphic representation of the results, whereas the environmental risk was not found to be a better hierarchical level than the municipality for fitting of the model.

Low 25 Hydroxyvitamin D Levels are Independently Associated with Autoimmune Thyroiditis in a Cohort of Apparently Healthy Overweight and Obese Subjects

BACKGROUND Low vitamin D levels have been associated with autoimmune disorders and, then, with the Hashimotos 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. MATERIALS AND METHODS Two hundred sixty one overweight subjects (mean age: 40.9 + 15.6 years, 200 women and 61 men) were enrolled for this study. All of them did not show any clinically evident metabolic or chronic diseases (i.e. hypertension, diabetes mellitus, renal failure, etc.) and did not use any kind of drug. Serum fasting levels of 25(OH)D, anti-thyroid peroxidase (TPO-Ab) and antithyroglobulin (TG-Ab) antibodies, free triiodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH), glucose, uric acid and lipids (triglycerides, total, HDL and LDL cholesterol) were measured. Demographic, anthropometric and clinical parameters (age, body mass index (BMI), waist circumference, blood pressure) were also assessed. RESULTS Fifty five percent of all subjects (144/261) showed vitamin D deficiency (≤ 20 ng/ml), and 17% of all individuals had AT (45/261). The percentage of subjects having vitamin D deficiency was significantly higher among those with AT (31 of 45, 69%) than in those without AT (113 of 216, 52%) (χ2= 4.1, p = 0.042). TSH levels were significantly higher in subjects with AT as compared to those without AT (M-W = 7715.5, p < 0.0001). The final logistic model of a multivariate analysis, performed with AT as the dependent variable and sex, age, BMI category, 25(OH)D category, and HDLcholesterol and TSH levels as the independent ones, showed that patients with AT were more likely to have deficiency of 25(OH)D (p = 0.031) and higher TSH (p < 0.005) levels. Seventy six percent of patients with vitamin D deficiency (110 of 144) were obese whereas 59% of patients without vitamin D deficiency were obese (69 of 117) (p=0.003). Waist circumference was different between subjects with deficiency or normal 25 (OH) D levels (p=0.016). CONCLUSION This study clearly shows that vitamin D deficiency is significantly associated to AT in overweight and obese subjects and confirms that obesity is associated to lower vitamin D circulating levels. We suggest that screening for AT should be suggested in all obese subjects with vitamin D deficiency and that vitamin D deficiency should be researched in all obese subjects with AT.

Independent Relationship of Osteocalcin Circulating Levels with Obesity, Type 2 Diabetes, Hypertension, and HDL Cholesterol.

BACKGROUND Osteocalcin, a protein synthesized by osteoblasts during the bone formation phase of bone remodeling, is used as a biomarker for the bone production process, and its serum levels are positively correlated with bone mineral density during treatment with anabolic bone drugs for osteoporosis. Higher fat mass has been shown to be a risk factor for osteoporosis and fragility fractures and body fat and bone interplay through several adipokines and bone-derived molecules, regulating bone remodeling, adipogenesis, body weight control, and glucose homeostasis. AIM The aim of this study was to evaluate the relationship between total osteocalcin levels and obesity, hypertension and type 2 diabetes. METHODS The present study was performed in a cohort of 298 patients including a) 121 overweight and obese patients, unaffected by hypertension or type 2 diabetes, b) 129 subjects affected by hypertension and not by type 2 diabetes, and c) 48 subjects affected by both hypertension and type 2 diabetes. No subject of the group of overweight and obese patients was taking any kind of drug. All patients affected by hypertension, with or without type 2 diabetes, were taking drugs for hypertension. Examining only patients affected by type 2 diabetes (n: 48), 43 (90% of all) were taking drugs to reduce blood glucose levels, 26 (54% of all) were taking drugs to reduce cholesterol levels (statins and/or ezetimide, etc), and 4 (8% of all) were taking ω-3 for hypertriglyceridemia. Each patient was evaluated for anthropometric measurements as well as for serum osteocalcin and uric acid, and plasma glucose, HbA1c, and lipid determination. RESULTS Osteocalcin levels were significantly and negatively associated with BMI, waist circumference, and HbA1c, and significantly and positively correlated with HDL-cholesterol and systolic blood pressure in the whole population. Osteocalcin levels did maintain an independent negative association with BMI, and HbA1c, and positive association with HDL cholesterol and systolic blood pressure when a multiple regression analyses was performed by considering osteocalcin levels as the dependent variable and BMI, systolic blood pressure, HbA1c, and HDL cholesterol as independent variables. When age was included in the analyses among the independent variables, osteocalcin levels maintained an independent association with BMI, systolic blood pressure, HbA1c, and HDL cholesterol, but not with age. DISCUSSION AND CONCLUSION The results of the present study seem to suggest that patients with obesity and type 2 diabetes are at higher risk of lower osteocalcin levels and bone formation, whereas higher HDLcholesterol levels and systolic blood pressure seem to be associated to higher osteocalcin production.

Detrimental effects of melanocortin‐1 receptor (MC1R) variants on the clinical outcomes of BRAF V600 metastatic melanoma patients treated with BRAF inhibitors

Melanocortin‐1 receptor (MC1R) plays a key role in skin pigmentation, and its variants are linked with a higher melanoma risk. The influence of MC1R variants on the outcomes of patients with metastatic melanoma (MM) treated with BRAF inhibitors (BRAFi) is unknown. We studied the MC1R status in a cohort of 53 consecutive BRAF‐mutated patients with MM treated with BRAFi. We also evaluated the effect of vemurafenib in four V600BRAF melanoma cell lines with/without MC1R variants.