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Costanzo P.,University of Naples Federico II | Costanzo P.,University of Hull | Cleland J.G.,University of Hull | Atkin S.L.,Unit of Endocrinology and Metabolism | And 2 more authors.
Current Treatment Options in Cardiovascular Medicine | Year: 2012

Opinion statement: Although carotid intima-media thickness (IMT) has been broadly used as a tool to evaluate cardiovascular risk, its role as a surrogate endpoint is still debated. The main issue is the fact that no study has ever been powered to show a relationship between changes in carotid IMT during follow-up and cardiovascular events. A meta-analysis of existing clinical studies was performed to investigate this relationship but it failed to demonstrate a predictive role of regression in carotid IMT for cardiovascular events. The reasons for the lack of a clear evidence for a predictive role of IMT progression are unknown but are likely multifactorial. Firstly, it may depend on the fact that this index is not a pure atherosclerosis index. Second, carotid atherosclerosis does not always reflect coronary atherosclerosis. Furthermore, methodologic problems related to intra- and interobserver variability make this index not adequately reproducible when tracking the progression of carotid atherosclerosis. A further meta-analysis based on individual patient data, instead of published data, has been planned to better address the predictive role of IMT. Lastly, in the future, the variability of ultrasound measurements of carotid IMT are likely to be reduced by further development of automatic calculation of this index by magnetic resonance imaging. © 2011 Springer Science+Business Media, LLC. Source

Bacchi E.,University of Verona | Negri C.,Unit of Endocrinology and Metabolism | Tarperi C.,University of Verona | Baraldo A.,University of Verona | And 8 more authors.
Acta Diabetologica | Year: 2014

Factors contributing to the reduced cardiorespiratory fitness typical of sedentary subjects with type 2 diabetes are still largely unknown. In this study, we assessed the relationships between cardiorespiratory fitness and abdominal and skeletal muscle fat content in 39 untrained type 2 diabetes subjects, 27 males and 12 females (mean ± SD age 56.5 ± 7.3 year, BMI 29.4 ± 4.7 kg/m2). Peak oxygen uptake (VO2peak) and ventilatory threshold (VO2VT) were assessed by maximal cycle ergometer exercise test, insulin sensitivity by euglycemic-hyperinsulinemic clamp, and body composition by dual-energy X-ray absorptiometry. Magnetic resonance imaging was used to evaluate visceral, total subcutaneous (SAT), superficial (SSAT) and deep sub-depots of subcutaneous abdominal adipose tissue, and sagittal abdominal diameter (SAD), as well as femoral quadriceps skeletal muscle fat content. In univariate analysis, both VO2peak and VO 2VT were inversely associated with BMI, total fat mass, SAT, SSAT, and sagittal abdominal diameter. VO2peak was also inversely associated with skeletal muscle fat content. A significant direct association was observed between VO2VT and insulin sensitivity. No associations between cardiorespiratory fitness parameters and metabolic profile data were found. In multivariable regression analysis, after adjusting for age and gender, VO2peak was independently predicted by higher HDL cholesterol, and lower SAD and skeletal muscle fat content (R2 = 0.64, p < 0.001), whereas VO2VT was predicted only by sagittal abdominal diameter (R2 = 0.48, p = 0.025). In conclusion, in untrained type 2 diabetes subjects, peak oxygen uptake is associated with sagittal abdominal diameter, skeletal muscle fat content, and HDL cholesterol levels. Future research should target these features in prospective intervention studies. © Springer-Verlag 2013. Source

Cicero A.F.G.,University of Bologna | Magni P.,University of Milan | More M.,Unit of Endocrinology and Metabolism | Ruscica M.,University of Milan | And 4 more authors.
International Journal of Endocrinology | Year: 2011

We evaluated the association of the sex hormone pattern and the serum level of the main adipokines to metabolic syndrome (MS) and its components in 199 pharmacologically untreated subjects. Men and women included in the age-class subgroups were matched for body mass index, waist circumference, blood pressure, heart rate, fasting plasma glucose, and plasma lipids. Men without MS had significantly lower leptin/adiponectin ratio than men with MS. Women without MS had lower leptin and leptin/adiponectin ratio than women with MS but had significantly higher adiponectin, estrone, and dehydroepiandrosterone levels. In men, the leptin/adiponectin ratio is the main factor associated to MS diagnosis (OR: 3.36, 95 CI 1.40-8.08), while in women adiponectin alone appears to be a protective factor (OR: 0.87, 95 CI 0.79-0.95). In conclusion, in a sample of pharmacologically untreated subjects, leptin/adiponectin ratio seems to be the factor more strongly associated to MS and its components. Copyright © 2011 Arrigo F. G. Cicero et al. Source

Fabris M.,Institute of Clinical Pathology | Tonutti E.,Laboratory of Immunopathology and Allergy | Panighel C.,Unit of Endocrinology and Metabolism | Blasone N.,Laboratory of Immunopathology and Allergy | And 7 more authors.
Immunology, Endocrine and Metabolic Agents in Medicinal Chemistry | Year: 2011

Aim of the study: B-Lymphocyte Stimulator (BLyS), a key regulator of B-cell homeostasis, was recently involved in the regulation of malignant cell survival in both hematological and non-hematological cancers. In this study we analyzed the possible role of BLyS in neuroendocrine tumors (NET). Methods: Sixty-two consecutive unselected patients with a diagnosis of NET were enrolled in the study. According to the clinical course, patients were classified in 3 subgroups: patients with evidence of persistent but stable disease (n = 19), patients in remission (n = 13) and patients with evidence of recurrent disease (progressive patients, n = 30). Patients were compared to 77 sex-matched blood donors (HBDs). BLyS and Chromogranin A (CgA) serum levels were analyzed by ELISA. Results: Overall, NET patients presented more elevated BLyS levels than HBDs (1195± 568 pg/ml vs 666±240 pg/ml; p <0.0001) and BLyS levels correlated with tumor differentiation. Patients with stable disease or in remission presented with significant lower BLyS levels than patients with disease progression (906±273 pg/ml versus 1503±637 pg/ml; p <0.0001). Patients with metastases displayed higher BLyS levels than patients without metastases (1391±724 pg/ml versus 1079±422 pg/ml; p=0.022). Of note, BLyS levels during the follow-up (after 6.6±2.8 months) demonstrated a significant increase in progressive patients (from 1576±927 pg/ml to 2003±1268 pg/ml; p=0.0107), while remained substantially unchanged in stable/remission cases (from 1103±427 pg/ml to 1060±400 pg/ml; p=0.52). In contrast, CgA in the same series showed contradictory changes. Conclusions: Elevated BLyS levels characterized patients with NET and BLyS appears as a new potential marker in the management of these neoplastic diseases. © 2011 Bentham Science Publishers. Source

Nenquin M.,Unit of Endocrinology and Metabolism | Henquin J.-C.,Unit of Endocrinology and Metabolism
Diabetes, Obesity and Metabolism | Year: 2016

Amplification of insulin secretion by cyclic AMP involves activation of protein kinase A (PKA) and Epac2 in pancreatic β cells. Recent hypotheses suggest that sulphonylurea receptor-1 (SUR1), the regulatory subunit of ATP-sensitive potassium channels, is implicated in Epac2 effects and that direct activation of Epac2 by hypoglycaemic sulphonylureas contributes to the stimulation of insulin secretion by these drugs. In the present experiments, using islets from Sur1KO mice, we show that dibutyryl-cAMP and membrane-permeant selective activators of Epac or PKA normally amplify insulin secretion in β cells lacking SUR1. In contrast to Epac activator, sulphonylureas (glibenclamide and tolbutamide) did not increase insulin secretion in Sur1KO islets, as would be expected if they were activating Epac2 directly. Furthermore, glibenclamide and tolbutamide did not augment the amplification of insulin secretion produced by Epac activator or dibutyryl-cAMP. Collectively, the results show that SUR1 is dispensable for amplification of insulin secretion by Epac2 activation and that direct activation of Epac2 is unimportant for the action of therapeutic concentrations of sulphonylureas in β cells. © 2015 John Wiley & Sons Ltd. Source

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