Marco Calogero Amato

Visceral Adiposity Index: A reliable indicator of visceral fat function associated with cardiometabolic risk

OBJECTIVE To individuate a novel sex-specific index, based on waist circumference, BMI, triglycerides, and HDL cholesterol, indirectly expressing visceral fat function. RESEARCH DESIGN AND METHODS Visceral adiposity index (VAI) was first modeled on 315 nonobese healthy subjects. Using two multiple logistic regression models, VAI was retrospectively validated in 1,498 primary care patients in comparison to classical cardio- and cerebrovascular risk factors. RESULTS All components of metabolic syndrome increased significantly across VAI quintiles. VAI was independently associated with both cardiovascular (odd ratio [OR] 2.45; 95% CI 1.52–3.95; P < 0.001) and cerebrovascular (1.63; 1.06–2.50; P = 0.025) events. VAI also showed significant inverse correlation with insulin sensitivity during euglycemic-hyperinsulinemic clamp in a subgroup of patients (Rs = −0.721; P < 0.001). By contrast, no correlations were found for waist circumference and BMI. CONCLUSIONS Our study suggests VAI is a valuable indicator of “visceral adipose function” and insulin sensitivity, and its increase is strongly associated with cardiometabolic risk.

In vitro identification and characterization of CD133pos cancer stem-like cells in anaplastic thyroid carcinoma cell lines

Background Recent publications suggest that neoplastic initiation and growth are dependent on a small subset of cells, termed cancer stem cells (CSCs). Anaplastic Thyroid Carcinoma (ATC) is a very aggressive solid tumor with poor prognosis, characterized by high dedifferentiation. The existence of CSCs might account for the heterogeneity of ATC lesions. CD133 has been identified as a stem cell marker for normal and cancerous tissues, although its biological function remains unknown. Methodology/Principal Findings ATC cell lines ARO, KAT-4, KAT-18 and FRO were analyzed for CD133 expression. Flow cytometry showed CD133pos cells only in ARO and KAT-4 (64±9% and 57±12%, respectively). These data were confirmed by qRT-PCR and immunocytochemistry. ARO and KAT-4 were also positive for fetal marker oncofetal fibronectin and negative for thyrocyte-specific differentiating markers thyroglobulin, thyroperoxidase and sodium/iodide symporter. Sorted ARO/CD133pos cells exhibited higher proliferation, self-renewal, colony-forming ability in comparison with ARO/CD133neg. Furthermore, ARO/CD133pos showed levels of thyroid transcription factor TTF-1 similar to the fetal thyroid cell line TAD-2, while the expression in ARO/CD133neg was negligible. The expression of the stem cell marker OCT-4 detected by RT-PCR and flow cytometry was markedly higher in ARO/CD133pos in comparison to ARO/CD133neg cells. The stem cell markers c-KIT and THY-1 were negative. Sensitivity to chemotherapy agents was investigated, showing remarkable resistance to chemotherapy-induced apoptosis in ARO/CD133pos when compared with ARO/CD133neg cells. Conclusions/Significance We describe CD133pos cells in ATC cell lines. ARO/CD133pos cells exhibit stem cell-like features - such as high proliferation, self-renewal ability, expression of OCT-4 - and are characterized by higher resistance to chemotherapy. The simultaneous positivity for thyroid specific factor TTF-1 and onfFN suggest they might represent putative thyroid cancer stem-like cells. Our in vitro findings might provide new insights for novel therapeutic approaches.

Visceral adiposity index is associated with histological findings and high viral load in patients with chronic hepatitis C due to genotype 1.

Metabolic factors have been associated with liver damage in patients with genotype 1 chronic hepatitis C (G1 CHC). We tested visceral adiposity index (VAI), a new marker of adipose dysfunction in G1 CHC, patients to assess its association with host and viral factors and its link to both histological findings and sustained virological response (SVR). Two hundred thirty‐six consecutive G1 CHC patients were evaluated by way of liver biopsy and anthropometric and metabolic measurements, including insulin resistance (IR), homeostasis model assessment (HOMA), and VAI using waist circumference, body mass index, triglycerides, and high‐density lipoprotein cholesterol. All biopsies were scored by one pathologist for staging and grading and graded for steatosis, which was considered moderate to severe if ≥30%. Multiple linear regression analysis revealed that VAI score was independently associated with higher HOMA score (P = 0.009), log10 hepatitis C virus RNA levels (P = 0.01), necroinflammatory activity (P = 0.04), and steatosis (P = 0.04). Multiple logistic regression analysis revealed that IR (OR 3.879, 95% CI 1.727‐8.713, P = 0.001), higher VAI score (OR 1.472, 95% CI 1.051‐2.062, P = 0.02), and fibrosis (OR 2.255, 95% CI 1.349‐3.768, P = 0.002) were linked to steatosis ≥30%. Logistic regression analysis revealed that older age (OR 1.030, 95% CI 1.002‐1.059, P = 0.03), higher VAI score (OR 1.618, 95% CI 1.001‐2.617, P = 0.04), and fibrosis (OR 2.608, 95% CI 1.565‐4.345, P < 0.001) were independently associated with moderate to severe necroinflammatory activity. No independent associations were found between VAI score and both fibrosis and SVR. Conclusion: In G1 CHC patients, higher VAI score is independently associated with both steatosis and necroinflammatory activity and has a direct correlation with viral load. (HEPATOLOGY 2010.)

Insulin resistance and polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in humans, affecting approximately 7-8% of women of reproductive age. Despite the criteria adopted, PCOS is considered to be a predominantly hyperandrogenetic syndrome and the evaluation of metabolic parameters and insulin sensitivity is not mandatory. Most women with PCOS also exhibit features of the metabolic syndrome, including insulin resistance, obesity and dyslipidaemia. While the association with type 2 diabetes is well established, whether the incidence of cardiovascular disease is increased in women with PCOS remains unclear. Acknowledging the strong impact of insulin-resistance in the genesis of PCOS could be helpful not only to make the diagnosis more robust, but also for conferring better cardiovascular risk prevention. Several current studies support a strong recommendation that women with PCOS should undergo comprehensive evaluation for the metabolic syndrome and recognized cardiovascular risk factors, and receive appropriate treatment as needed. Lifestyle modifications remain the first-line therapy for all obese women with PCOS. However, many of these women do not lose weight easily. Insulin-sensitizing drugs are discussed as a promising and unique therapeutic option for the chronic treatment of PCOS.

BRAFV600E mutation and p27kip1 expression in papillary carcinomas of the thyroid ≤1 cm and their paired lymph node metastases

BRAFV600E mutation and p27kip1 expression have been introduced as novel indicators that may predict prognosis in different tumors, as well as in papillary thyroid carcinomas.

The oligomenorrhoic phenotypes of polycystic ovary syndrome are characterized by a high visceral adiposity index: a likely condition of cardiometabolic risk

BACKGROUND Women with polycystic ovary syndrome (PCOS) frequently exhibit central obesity, glucose intolerance, atherogenic dyslipidemia and hypertension, which are characteristic features of a condition of cardiometabolic risk. Our objective was to investigate the relationship between visceral adiposity index (VAI) and phenotypic characteristics in women with PCOS. METHODS We conducted a cross-sectional case-control study in our Endocrinology Outpatients Clinic. A total of 220 women with PCOS (Rotterdam definition) and 144 age- and BMI-matched healthy women were studied. We evaluated hyperandrogenemia and clinical hyperandrogenism, ovarian morphology, hypothalamic-hypophyseal axis and metabolic syndrome parameters. An oral glucose tolerance test (75 g glucose) measured areas under the curve (AUC) for insulin (AUC(2h-insulin)) and for glucose (AUC(2h-glucose)). Homeostasis model assessment of insulin resistance, the Matsuda index of insulin resistance and VAI were determined. RESULTS Of all the variables examined, at multivariate analysis, only AUC(2h-insulin) [odds ratio (OR): 1.00; 95% confidence interval (CI): 1.00-1.00; P = 0.003] and VAI score (OR: 1.81; 95% CI: 1.20-2.73; P = 0.005) showed an independent association with PCOS. All phenotypes with oligomenorrhea showed a higher VAI score than the control group (oligomenorrhea + hyperandrogenism: 2.49 ± 1.46 versus 1.62 ± 0.84, P < 0.001; oligomenorrhea + polycystic ovary morphology: 2.25 ± 1.4 versus 1.62 ± 0.84, P = 0.001; complete phenotype: 2.45 ± 1.63 versus 1.62 ± 0.84, P < 0.001). CONCLUSIONS Our data suggest that VAI could be an easy and useful tool in daily clinical practice and in population studies for the assessment of cardiometabolic risk associated with PCOS.

The impact of insulin resistance, serum adipocytokines and visceral obesity on steatosis and fibrosis in patients with chronic hepatitis C

Aims  To assess whether host metabolic factors influence the degree of hepatic steatosis and fibrosis in patients infected with hepatitis C virus, and to evaluate the impact of anti‐viral therapy on insulin resistance and serum levels of adipocytokines.

Cut-off points of the visceral adiposity index (VAI) identifying a visceral adipose dysfunction associated with cardiometabolic risk in a Caucasian Sicilian population

BackgroundThe Visceral Adiposity Index (VAI) is a sex-specific mathematical index, based on Waist Circumference (WC), Body Mass Index (BMI), triglycerides (TG) and HDL cholesterol (HDL) levels, indirectly expressing visceral adipose function and insulin sensitivity. Our aim was to find the optimal cut-off points of VAI identifying a visceral adipose dysfunction (VAD) associated with cardiometabolic risk in a Caucasian Sicilian population.MethodsMedical check-up data of 1,764 Primary Care patients (PC patients) were retrospectively and cross-sectionally examined using a receiver-operating characteristic (ROC) curve to determine appropriate stratified-for-age cut-off of VAI, for the identification of PC patients with Metabolic Syndrome (MetS) according to the NCEP-ATP III criteria. The PC patients with higher VAI scores were subdivided into three groups according to VAI tertiles (i.e. PC patients with mild VAD, moderate VAD or severe VAD). Finally, VAD classes were compared to classical cardio- and cerebrovascular risk factors as independent predictors of coronary heart disease and/or myocardial infarction, transient ischemic attack and/or ischemic stroke.ResultsModerate and severe VADs proved to be independently associated with cardiovascular events [(OR: 5.35; 95% CI: 1.92-14.87; p = 0.001) and (OR: 7.46; 95% CI: 2.64-21.05; p < 0.001) respectively]. Mild, moderate and severe VADs were found to be independently associated with cerebrovascular events [(OR: 2.73; 95% CI: 1.12-6.65; p = 0.027), (OR: 4.20; 95% CI: 1.86-9.45; p = 0.001) and (OR: 5.10; 95% CI: 2.14-12.17; p < 0.001) respectively].ConclusionsOur study suggests that among Caucasian Sicilian subjects there are clear cut-off points of VAI able to identify a VAD strongly associated with cardiometabolic risk.

Visceral adiposity index: an indicator of adipose tissue dysfunction.

The Visceral Adiposity Index (VAI) has recently proven to be an indicator of adipose distribution and function that indirectly expresses cardiometabolic risk. In addition, VAI has been proposed as a useful tool for early detection of a condition of cardiometabolic risk before it develops into an overt metabolic syndrome. The application of the VAI in particular populations of patients (women with polycystic ovary syndrome, patients with acromegaly, patients with NAFLD/NASH, patients with HCV hepatitis, patients with type 2 diabetes, and general population) has produced interesting results, which have led to the hypothesis that the VAI could be considered a marker of adipose tissue dysfunction. Unfortunately, in some cases, on the same patient population, there is conflicting evidence. We think that this could be mainly due to a lack of knowledge of the application limits of the index, on the part of various authors, and to having applied the VAI in non-Caucasian populations. Future prospective studies could certainly better define the possible usefulness of the VAI as a predictor of cardiometabolic risk.

Visceral adiposity index is associated with significant fibrosis in patients with non‐alcoholic fatty liver disease

Aliment Pharmacol Ther 2012; 35: 238–247