Insulin resistance and cardiometabolic indexes: comparison of concordance in working-age subjects with overweight and obesity.

PURPOSE: The aim of the study was to evaluate indexes of insulin resistance and cardiometabolic risk in a large population of workers with overweight or obesity, in order to identify a possible efficient, cheap and simple strategy to apply in workers' health surveillance. METHODS: The evaluation of IR and cardiometabolic risk indexes (HOMA, QUICKI, Ty/HDLC, TyG, insuTAG, Castelli risk indexes 1 and 2, non-HDLC, TRL-C, AIP, and VAI) was performed in a population of 1195 working-age subjects with overweight or obesity (322 males, mean age 49 ± 11 years). RESULTS: The prevalence of IR and cardiometabolic risk was higher among males for all indexes. Aging, waist circumference, BMI, blood pressure, glucose, CRP, fibrinogen and uric acid were correlated more frequently with IR/cardiometabolic indexes in women, homocysteine in men. The percentage of the workers identified as insulin resistant (IR+) or at higher cardiometabolic risk greatly vary according to the different index used. CONCLUSION: With a small group of biomarkers and anthropometric measures (fasting glucose and insulin, lipid profile, BMI and waist circumference) is possible to calculate a number of IR/cardiometabolic indexes, which, likely reflecting different pathophysiological aspects also related to gender, might help in a personalized evaluation of IR and cardiometabolic risk. Graphical abstract.

Fibromyalgia and Nutrition: An Updated Review.

Due to the lack of specific and standardized treatments for the management of fibromyalgia (FM), available evidence suggests a multidisciplinary approach, and nutrition represents an important therapeutic strategy. This work aims to update the relationship between FM and nutrition, through a review of more recent scientific evidence based on a systematic research on PubMed. Of 66 records initially identified, 26 studies were selected and included in the present work. Although there is not sufficient evidence for the efficacy of specific nutritional protocols, the examined papers indicate a potential role of selected nutrients, micronutrients and food components in managing FM symptoms. However, several concerns persist as nutritional status and/or nutritional integration can improve FM symptoms, without expecting to lead to a remission of the disease. The use of targeted nutritional supplements may be of some relevance for the management of FM, but the up to date evidence remains weak. It is advisable, thus, to perform further studies of higher quality.KEY TEACHING POINTSFibromyalgia (FM) is characterized by chronic and diffuse musculoskeletal pain, often associated with a large set of symptoms.The therapeutic approach of FM include pharmacological and non-pharmacological interventions. Among them, an important role is played by nutrition.Of 66 record screened, 12 studies were included in the present review and five of them were randomized controlled trials. Nevertheless, the overall quality of those trials was scarce.Literature concerning FM and nutritions is growing. However, little evidence suggests that nutrition and/or nutritional intervention play a significant role on FM severity.The results of this review underline the need to carry out clinical studies of higher quality and rigor, possibly RCTs, focused on the role of nutrition in the symptoms and/or severity of FM.

Low concordance between HbA1c and OGTT to diagnose prediabetes and diabetes in overweight or obesity.

BACKGROUND: Glycated haemoglobin (HbA1c) test, introduced for diagnosing prediabetes and diabetes by the American Diabetes Association for some years, is currently under extensive discussion for contradictory data on the concordance between this test and the oral glucose tolerance test (OGTT). HYPOTHESIS: To assess concordance between HbA1c and OGTT to diagnose prediabetes and diabetes in subjects with overweight or obesity, focusing on possible gender-related differences. METHODS: A total of 949 outpatients with overweight or obesity at risk for diabetes (mean age 50 ± 15 years; 660 F) were enrolled and underwent HbA1c test and OGTT. RESULTS: In both genders, HbA1c test identified more patients with prediabetes than OGTT (42% vs 22% in males, 40% vs 18% in females, respectively): a slight concordance between HbA1c and OGTT (60% of total tests in both genders). In subjects diagnosed by OGTT, post-OGTT insulin levels and HOMA INDEX were significantly higher than those found in HbA1c(+) cases. Instead, those diagnosed with HbA1c were significantly older and showed higher uric acid than those with both tests (-). CONCLUSIONS: HbA1c test and OGTT did not reach full concordance for the diagnosis of diabetes and prediabetes in both genders. The two tests likely reflect different physiopathological aspects of dysglycaemia, suggesting that the 'diagnostic thresholds' could be reconsidered in light of the discordance observed.

Gender-related association between uric acid, homocysteine, γ-glutamyltransferase, inflammatory biomarkers and metabolic syndrome in subjects affected by obesity.

AIM: Evaluation of gender-related differences in uric acid (UA), homocysteine and inflammatory biomarkers as metabolic syndrome (MetS) determinants. PATIENTS & METHODS: Anthropometric and routine data were obtained from 825 obese subjects (591 F, mean age 54 ± 14 years). RESULTS: Hyperuricemia was 24% in both genders. Waist circumference, creatinine, triglycerides, C-reactive protein and γ-glutamyltransferase were identified as UA-independent determinants in females and creatinine and insulin in males. Hyperuricemia increased MetS risk in both genders (2.8-fold and 1.5-fold in males and females). CONCLUSION: UA and γ-glutamyltransferase positively relate to MetS in both genders, although inflammatory abnormalities are closer related to UA and MetS in females. These differences in gender physiology may account for epidemiologic gender disparities and help to develop gender-targeted clinical strategies.

Oxidative status in treatment-naïve essential thrombocythemia: a pilot study in a single center.

Oxidative stress (OS), due to pro-oxidant species [reactive oxygen species (ROS)] excess not counterbalanced by endogenous antioxidant molecules [e.g., reduced glutathione (GSH)], is involved in the pathogenesis of human cancers, but few data are available on essential thrombocythemia (ET). This study aims to investigate OS in ET off-therapy patients. Thirty ET treatment-naïve patients were compared with 26 age-matched and gender-matched controls. Serum ROS, urinary 8-hydroxydeoxyguanosine, full blood GSH levels, and reduced/oxidized GSH ratio (GSH/GSSG) were measured. Data were adjusted for gender, age, JAK2 mutational status, smoking, dyslipidemia, or hypercholesterolemia requiring drug therapy, antiplatelet therapy, treatment with acetylsalicylic acid, high-sensitive C-reactive protein levels, and absolute monocyte count. ROS and GSH levels were increased in both patients and controls. Patients showed increased GSSG (p = 0.05), reduced GSH/GSSG ratio (p = 0.08), and similar 8-hydroxydeoxyguanosine levels when compared with controls. No differences in OS parameters were found between JAK2-positive and JAK2-negative patients. Confounding factors did not modify the results. Our study suggests an OS condition in a cohort of treatment-naïve ET patients, not associated with JAK2 mutational status or with chronic inflammation situation. GSH/GSSG ratio, altered in ET patients because of increased GSSG levels, showed the presence of higher GSH levels in ET than controls as a possible compensatory mechanism of an excess of pro-oxidant production. Copyright © 2015 John Wiley & Sons, Ltd.

Homocysteine metabolism in children and adolescents with epidermolysis bullosa.

BACKGROUND: Epidermolysis bullosa (EB) belongs to a family of rare heterogeneous, genetic disorders characterized by blistering of the skin and mucous membranes in response to minor mechanical trauma. The involvement of the oral mucosa and oesophagus stenosis is suggested to be responsible for severe nutritional deficiencies, but few studies have till now considered this aspect. This observational study aimed to evaluate homocysteine status in children and adolescents with EB by assessing total plasma homocysteine (tHcy) and metabolically related vitamins (B6, B12, folate) concentrations. METHODS: Twenty EB patients (12 M; age range 0.5-19 years) were evaluated for: plasma tHcy, serum B12 and holotranscobalamin (HoloTC, the active fraction of B12), serum and erythrocyte folate (s-F and Ery-F, respectively), plasma B6 and serum high sensitive C-reactive-protein (hsCRP) levels. Clinical severity was also evaluated through the Birmingham Epidermolysis Bullosa Severity (BEBS) score. A sex and age well-matched population was also enrolled. RESULTS: EB patients showed tHcy levels higher (p = 0.04) and B6 levels lower (p = 0.03) than controls. B12, HoloTC, s-F and ery-F concentrations did not differ between patients and controls. Multiple linear regression analysis showed that tHcy levels were independent of the metabolically related vitamins levels. In addition, serum hsCRP levels were higher in EB patients than in controls (p = 0.003) and correlated negatively with B6 concentrations (r = -0.6; p = 0.009). BEBS score correlated negatively with HoloTC (p = 0.022) and B6 (p = 0.005) levels and positively with age (p = 0.031) and hsCRP levels (p < 0.001). CONCLUSIONS: The assessment of tHcy and metabolically related vitamin levels describes an important aspect of EB patients' nutritional status which can result essential for their long term care. Monitoring B6 levels in EB patients could be particularly important in order to prevent several complications associated with B6 deficiency and to avoid a B6 excess which sustains an inflammatory condition.

Efficacy of chelation therapy to remove aluminium intoxication.

There is a distinct correlation between aluminium (Al) intoxication and neurodegenerative diseases (ND). We demonstrated how patients affected by ND showing Al intoxication benefit from short-term treatment with calcium disodium ethylene diamine tetraacetic acid (EDTA) (chelation therapy). Such therapy further improved through daily treatment with the antioxidant Cellfood. In the present study we examined the efficacy of long-term treatment, using both EDTA and Cellfood. Slow intravenous treatment with the chelating agent EDTA (2 g/10 mL diluted in 500 mL physiological saline administered in 2 h) (chelation test) removed Al, which was detected (using inductively coupled plasma mass spectrometry) in urine samples collected from patients over 12 h. Patients that revealed Al intoxication (expressed in µg per g creatinine) underwent EDTA chelation therapy once a week for ten weeks, then once every two weeks for a further six or twelve months. At the end of treatment (a total of 22 or 34 chelation therapies, respectively), associated with daily assumption of Cellfood, Al levels in the urine samples were analysed. In addition, the following blood parameters were determined: homocysteine, vitamin B12, and folate, as well as the oxidative status e.g. reactive oxygen species (ROS), total antioxidant capacity (TAC), oxidized LDL (oxLDL), and glutathione. Our results showed that Al intoxication reduced significantly following EDTA and Cellfood treatment, and clinical symptoms improved. After treatment, ROS, oxLDL, and homocysteine decreased significantly, whereas vitamin B12, folate and TAC improved significantly. In conclusion, our data show the efficacy of chelation therapy associated with Cellfood in subjects affected by Al intoxication who have developed ND.

Oxidative status in different settings and with different methodological approaches compared by Receiver Operating Characteristic curve analysis.

OBJECTIVES: To test the performance of different analytical approaches in highlighting the occurrence of deregulated redox status in various physio-pathological situations. DESIGN AND METHODS: 35 light and 61 heavy smokers, 19 chronic renal failure, 59 kidney transplanted patients, and 87 healthy controls were retrospectively considered for the study. Serum oxidative stress and antioxidant status, assessed by spectrophotometric Reactive Oxygen Metabolites (d-ROMs) and Total Antioxidant Capacity (TAC) tests, respectively, were compared with plasma free (F-MDA) and total (T-MDA) malondialdehyde, both quantified by isotope-dilution-gas chromatography-mass spectrometry (ID-GC-MS). Sensitivity, specificity and cut-off points of T-MDA, F-MDA, d-ROMs and TAC were evaluated by both Receiver Operating Characteristic (ROC) analyses and area under the ROC curve (AUC). RESULTS: Only T-MDA assay showed a clear absence of oxidative stress in controls and significant increase in all patients (AUC 1.00, sensitivity and specificity 100%). Accuracy was good for d-ROMs (AUC 0.87, sensitivity 72.8%, specificity 100%) and F-MDA (AUC 0.82, sensitivity 74.7%, specificity 83.9%), but not high enough for TAC to show in patients impaired antioxidant defense (AUC 0.66, sensitivity 52.0%, specificity 92.9%). CONCLUSIONS: This study reveals T-MDA as the best marker to detect oxidative stress, shows the ability of d-ROMs to identify modified oxidative status particularly in the presence of high damages, and evidences the poor TAC performance. d-ROMs and TAC assays could be useful for routine purposes; however, for an accurate clinical data evaluation, their comparison versus a "gold standard method" is required.

Improvement of oxidative and metabolic parameters by cellfood administration in patients affected by neurodegenerative diseases on chelation treatment.

OBJECTIVE: This prospective pilot study aimed at evaluating the effects of therapy with antioxidant compounds (Cellfood, and other antioxidants) on patients affected by neurodegenerative diseases (ND), who displayed toxic metal burden and were subjected to chelation treatment with the chelating agent calcium disodium ethylenediaminetetraacetic acid (CaNa2EDTA or EDTA). METHODS: Two groups of subjects were studied: (a) 39 patients affected by ND and (b) 11 subjects unaffected by ND (controls). The following blood parameters were analyzed before and after three months' treatment with chelation+Cellfood or chelation+other antioxidants: oxidative status (reactive oxygen species, ROS; total antioxidant capacity, TAC; oxidized LDL, oxLDL; glutathione), homocysteine, vitamin B12, and folate. RESULTS: After 3-months' chelation+Cellfood administration oxLDL decreased, ROS levels were significantly lower, and TAC and glutathione levels were significantly higher than after chelation+other antioxidants treatment, both in ND patients and in controls. Moreover, homocysteine metabolism had also improved in both groups. CONCLUSIONS: Chelation+Cellfood treatment was more efficient than chelation+other antioxidants improving oxidative status and homocysteine metabolism significantly in ND patients and controls. Although limited to a small number of cases, this study showed how helpful antioxidant treatment with Cellfood was in improving the subjects' metabolic conditions.

Thrombin generation in patients with idiopathic sudden sensorineural hearing loss.

INTRODUCTION: The pathogenesis of idiopathic sudden sensorineural hearing loss (ISSNHL) is still unknown. Systemic hemostasis derangement causing local vascular occlusion might be one of the pathogenetic mechanisms. MATERIAL AND METHODS: Forty-one patients with ISSNHL and 48 healthy subjects were investigated. We measured thrombin generation in the presence or absence of thrombomodulin in platelet-poor or platelet-rich plasma by means of a home-made method based on calibrated automated thrombin generation, which should mimic much more closely than any other conventional coagulation test the balance of coagulation operating in vivo. DNA analyses for the most common prothrombotic genotypes such as factor V Leiden, prothrombin G20210A, MTHFR or platelet GPIIIa A1/A2 were also carried out in patients and controls. RESULTS: Patients generated as much thrombin as controls both in platelet-rich and platelet-poor plasma and the frequency of the most common prothrombotic genotypes were similar in patients and controls. CONCLUSIONS: The results suggest that the pathogenesis of ISSNHL is not due to systemic blood hypercoagulability. Other culprits such as local vascular abnormalities, viral infections, immune-mediated mechanisms or abnormalities of inner ear and central nervous system should be advocated to explain ISSNHL.

An encapsulated juice powder concentrate improves markers of pulmonary function and cardiovascular risk factors in heavy smokers.

OBJECTIVE: Cigarette smoking is associated with reduced pulmonary function and increased risk factors for cardiovascular disease. This randomized placebo-controlled double-blind study evaluated the effects of two different combinations of mixed fruit and vegetable juice powder concentrate (Juice Plus+, NSA, Collierville, TN) on heavy smokers. METHODS: At baseline (T 0) and after 3 months' supplementation (T 1), pulmonary function parameters and cardiovascular risk factors-that is, plasma total homocysteine (tHcy) with related B vitamins and cysteine (tCys) concentrations-were assessed in 75 apparently healthy smokers (aged 49.2 ± 10.6 years, >20 cigarettes/d, duration ≥10 years) randomized into 3 groups: placebo (P), fruit/vegetable (FV) and fruit/vegetable/berry (FVB). RESULTS: T 0: most smokers showed abnormalities in tHcy and tCys concentrations. T 1: respiratory function was unchanged in P and slightly, but not significantly, improved in FV, whereas FVB showed a significant improvement in forced expiratory flow at 25% (FEF25; p < 0.0001 vs P and FV) and significant improvement in CO diffusion lung/alveolar volume (DLCO/VA). FV and FVB (50%) showed significant reduction in tHcy and tCys compared to T 0 ( p < 0.0001) and P ( p < 0.0001). CONCLUSIONS: At T 1, both supplemented groups, but to a greater extent the FVB group, showed improvements in some pulmonary parameters, cardiovascular risk factors, and folate status. The beneficial effects of Juice Plus+ supplementation could potentially help smokers, even if smoking cessation is advisable.

A biomarker of oxidative stress as a nontraditional risk factor in obese subjects.

BACKGROUND: Oxidative stress has been postulated as an additive factor linking obesity to cardiovascular disease. MATERIALS & METHODS: Derivatives of reactive oxygen species metabolites (d-ROMs) were measured in 136 obese (42 males, 94 females; mean age: 47 ± 12 years; BMI: 36 ± 5 kg/m(2)) and in 306 over- and normal-weight subjects (112 males, 194 females; age: 47 ± 12 years; BMI: 24 ± 3 kg/m(2)). RESULTS: d-ROMs levels were higher in obese than in over- and normal-weight subjects (395 ± 104 vs 362 ± 102 and 351 ± 84 arbitrary units (AU); p < 0.001), in women than males (390 ± 104 vs 327 ± 68 AU; p < 0.001), in subjects with than those without hypertension (390 ± 103 vs 360 ± 95 AU; p < 0.01) and in smokers than former and nonsmokers (380 ± 97 vs 358 ± 97 AU; p < 0.05). A positive correlation was found between d-ROMs and BMI (r = 0.25; p < 0.001) and age (r = 0.13; p < 0.01). Levels of d-ROM (>75th percentile: 420 AU) remained as an independent obesity predictor (odds ratio: 2.5; p < 0.001) in women. Continuous variables are reported as mean ± standard deviation. CONCLUSION: d-ROMs are a powerful obesity predictor, and could represent a reliable tool in obesity and cardiovascular risk evaluation, especially in women.

Unbalanced oxidative status in idiopathic sudden sensorineural hearing loss.

An impaired cochlear perfusion seems to be an important etiopathogenetic event in idiopathic sudden sensorineural hearing loss (ISSNHL). Recently, oxidative stress has been proposed as risk factors of microvascular damage. This observational study aimed to evaluate the possible role of oxidative stress in ISSNHL. In thirty-nine ISSNHL patients and seventy healthy subjects serum reactive oxygen species concentrations (ROS) and total antioxidant capacity (TAC) were measured by spectrophotometric methods on F.R.E.E. analyzer (Diacron International, Italy). Moreover, a global oxidative stress index (Oxidative-INDEX), reflecting both oxidative and antioxidant counterparts, was also calculated. 25/39 patients showed oxidative stress due to ROS levels significantly higher than controls (348.2 ± 84.8 vs. 306.75 ± 46.7 UCarr; p = 0.001). The Oxidative-INDEX was significantly higher in patients than in controls (0.75 ± 2.4 vs. -0.0007 ± 1.28 AU, p = 0.03). As oxidative stress is a key determinant in endothelial dysfunction, our findings could suggest vascular impairment involvement in ISSNHL etiopathogenesis.

Metal chelation therapy in rheumathoid arthritis: a case report. Successful management of rheumathoid arthritis by metal chelation therapy.

Toxic metals are involved in the pathogenesis of some neurodegenerative and vascular diseases and are known to impair the immune system functions. We report here the case of a patient affected by heavy metal intoxication, who had developed an autoimmune disease. There was evidence of aluminium, cadmium and lead intoxication in a 63-year old Italian woman affected by rheumatoid arthritis (RA). We treated the patient with calcium disodium edetate (EDTA) once a week for a year in order to remove traces of heavy metal intoxication. Oxidative status profile was carried out at the beginning and after 6 months' EDTA chelation. At the end of the treatment, the patient did not show any signs of metal intoxication, RA symptoms and oxidative status improved.

Determinants of oxidative stress related to gender: relevance of age and smoking habit.

BACKGROUND: Magnitude and major causes of oxidative stress may be different between sexes, although limitedly addressed in clinical studies with controversial results. The present study aimed to determine whether any gender-related difference exists concerning oxidative stress in a population of 332 subjects of both sexes, in a wide age range, with and without cigarette smoking habit. METHODS: The Oxidative-INDEX was calculated after evaluation of serum hydroperoxides (ROMs) and total antioxidant capacity (OXY) by means of commercial kits (d-ROMs and Oxy-adsorbent Tests, Diacron, Italy) subtracting the OXY standardized variable from the ROMs standardized variable. RESULTS: The Oxidative-INDEX resulted higher in women with respect to men (p<0.001), in smokers (p<0.01) than in non-smokers, and correlated with cigarette number (p<0.01), age (p<0.001), and post-menopausal status (p<0.001). The multivariate analysis identified age, high blood pressure, and smoking habit as factors independently associated with the Oxidative-INDEX in men, whereas cigarette smoking and age represented the independent risk factors for an elevated oxidative stress status in women. CONCLUSIONS: Gender-based differences in oxidative stress levels may provide a biochemical basis for the epidemiologic differences in the disease susceptibility between sexes, and suggest different strategies for risk assessment, diagnosis, and treatment specifically targeted to men and women.

Effects of encapsulated fruit and vegetable juice powder concentrates on oxidative status in heavy smokers.

OBJECTIVE: Long-term cigarette smoking has negative effects on oxidative status, promoting low-density lipoprotein (LDL) oxidation and formation of lipid peroxides. We evaluated the effects of 2 different encapsulated formulas, consisting primarily of mixed juice powder concentrate, on oxidative status compared with placebo. METHODS: This randomized, double-blind, placebo-controlled study was performed on 101 apparently healthy heavy smokers (>20 cigarettes/d, duration >10 years; median age 47 years, range 41-57 years; 54 M) before and after 3 months' supplementation. Subjects were randomized into 3 groups, well matched for sex and age: (1) placebo; (2) fruit/vegetable (FV); and (3) fruit/vegetable/berry (FVB). Analysis of oxidative status was performed on 75 (46 M) compliant subjects (>95% of assigned capsules). Changes in lipid panel parameters, oxidative-INDEX (Oxy-I, calculated on the basis of serum hydroperoxides and total antioxidant capacity measured by spectrophotometric methods), oxidized-LDL (ox-LDL; enzyme-linked immunosorbent assay [ELISA] method), and malondialdehyde (MDA; gas chromatography-mass spectrometry method) in free (fMDA), bound (bMDA), and total (tMDA = fMDA + bMDA) forms are reported. Statistical analysis was performed with R statistical software. RESULTS: After supplementation, compared with placebo, both FV and FVB groups showed a significant decrease in total cholesterol (p < 0.05), ox-LDL (p = 0.03), and fMDA levels (p = 0.004) accompanied by a slight increase in bMDA concentrations, possibly as the result of fMDA conjugation. Moreover, a significant decrease in Oxy-I was found in both active groups compared with placebo (p < 0.001). CONCLUSION: Intervention with both nutraceutical formulations resulted in improvement in some oxidative alterations attributed to long-term cigarette smoking.