20 results on '"Giaccari, Andrea"'
Search Results
2. Refinement of the diagnostic approach for the identification of children and adolescents affected by familial hypercholesterolemia: Evidence from the LIPIGEN study
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Anesi, Adriano, Arca, Marcello, Auricchio, Renata, Averna, Maurizio, Baldera, Davide, Banderali, Giuseppe, Beccuti, Guglielmo, Benso, Andrea, Berteotti, Martina, Bertolini, Stefano, Bianconi, Vanessa, Biasucci, Giacomo, Biolo, Gianni, Bonanni, Luca, Borghi, Claudio, Bossi, Antonio Carlo, Branchi, Adriana, Bruzzi, Patrizia, Bucci, Marco, Buonuomo, Paola Sabrina, Calabrò, Paolo, Calandra, Sebastiano, Carubbi, Francesca, Cavallaro, Raimondo, Cefalù, Angelo Baldassarre, Cesaro, Arturo, Cipollone, Francesco, Citroni, Nadia, Colombo, Emanuela, Coppola, Chiara, D'Addato, Sergio, Dal Pino, Beatrice, Dalla Nora, Edoardo, De Corrado, Giuseppe, Del Ben, Maria, Di Molfetta, Sergio, Di Taranto, Maria Donata, Fainelli, Giulia, Federici, Massimo, Ferri, Claudio, Fiorenza, Anna Maria, Formisano, Elena, Fortunato, Giuliana, Giaccari, Andrea, Giorgino, Francesco, Grigore, Liliana, Guardamagna, Ornella, Iannuzzi, Arcangelo, Iannuzzo, Gabriella, Iughetti, Lorenzo, Lia, Salvatore, Longo, Susanna, Lupi, Alessandro, Mandraffino, Giuseppe, Marcucci, Rossella, Maroni, Lorenzo, Massini, Giulia, Mazza, Elisa, Melchioda, Elena, Meregalli, Giancarla, Minicocci, Ilenia, Moffa, Simona, Mombelli, Giuliana, Muntoni, Sandro, Nascimbeni, Fabio, Negri, Emanuele Alberto, Notargiacomo, Serena, Panfili, Filippo Maria, Parati, Gianfranco, Passaro, Angelina, Pavanello, Chiara, Pecchioli, Valerio, Pecchioli, Lorenzo, Pellegatta, Fabio, Perla, Francesco Massimo, Pipolo, Antonio, Piro, Salvatore, Pirro, Matteo, Pisciotta, Livia, Pujia, Roberta, Putotto, Carolina, Repetti, Elena, Rinaldi, Elisabetta, Romandini, Alessandra, Sani, Elena, Sarnari, Silvia, Sarzani, Riccardo, Sbrana, Francesco, Scicali, Roberto, Scuruchi, Michele, Suppressa, Patrizia, Tarugi, Patrizia, Trenti, Chiara, Vinci, Pierandrea, Werba, José Pablo, Zambon, Sabina, Zambon, Alberto, Zenti, Maria Grazia, Casula, Manuela, Gazzotti, Marta, Capra, Maria Elena, Olmastroni, Elena, Galimberti, Federica, Catapano, Alberico L., and Pederiva, Cristina
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- 2023
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3. Effects of insulin on cardiovascular events and all-cause mortality in patients with type 2 diabetes: A meta-analysis of randomized controlled trials
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Mannucci, Edoardo, Targher, Giovanni, Nreu, Besmir, Pintaudi, Basilio, Candido, Riccardo, Giaccari, Andrea, Gallo, Marco, and Monami, Matteo
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- 2022
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4. SELF-MANAGEMENT in PATIENTS with TYPE 2 DIABETES: GROUP-BASED versus individual education. A SYSTEMATIC REVIEW with meta-analysis of RANDOMIZED TRIALS
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Mannucci, Edoardo, Giaccari, Andrea, Gallo, Marco, Bonifazi, Allegra, Belén, Ávila Del Pino, Masini, Maria Luisa, Trento, Marina, and Monami, Matteo
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- 2021
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5. Evaluation of the performance of Dutch Lipid Clinic Network score in an Italian FH population: The LIPIGEN study
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Arca, Marcello, Averna, Maurizio, Bertolini, Stefano, Calandra, Sebastiano, Catapano, Alberico Luigi, Tarugi, Patrizia, Pellegatta, Fabio, Angelico, Francesco, Bartuli, Andrea, Biasucci, Giacomo, Biolo, Gianni, Bonanni, Luca, Bonomo, Katia, Borghi, Claudio, Bossi, Antonio Carlo, Branchi, Adriana, Carubbi, Francesca, Cipollone, Francesco, Citroni, Nadia, Federici, Massimo, Ferri, Claudio, Fiorenza, Anna Maria, Giaccari, Andrea, Giorgino, Francesco, Guardamagna, Ornella, Iannuzzi, Arcangelo, Iughetti, Lorenzo, Lupattelli, Graziana, Lupi, Alessandro, Mandraffino, Giuseppe, Marcucci, Rossella, Maroni, Lorenzo, Miccoli, Roberto, Mombelli, Giuliana, Muntoni, Sandro, Pecchioli, Valerio, Pederiva, Cristina, Pipolo, Antonio, Pisciotta, Livia, Pujia, Arturo, Purrello, Francesco, Repetti, Elena, Rubba, Paolo, Sabbà, Carlo, Sampietro, Tiziana, Sarzani, Riccardo, Tagliabue, Milena Paola, Trenti, Chiara, Vigna, Giovanni Battista, Werba, Josè Pablo, Zambon, Sabina, Zenti, Maria Grazia, Minicocci, Ilenia, Noto, Davide, Fortunato, Giuliana, Banderali, Giuseppe, Benso, Andrea, Bigolin, Paola, Bonora, Enzo, Bruzzi, Patrizia, Bucci, Marco, Buonuomo, Paola Sabrina, Capra, Maria Elena, Cardolini, Iris, Cefalù, Baldassarre, Cervelli, Nazzareno, Chiariello, Giuseppe, Cocci, Guido, Colombo, Emanuela, Cremonini, Anna Laura, D'Addato, Sergio, D'Erasmo, Laura, Dal Pino, Beatrice, De Sanctis, Luisa, De Vita, Emanuele, Del Ben, Maria, Di Costanzo, Alessia, Di Taranto, Maria Donata, Fasano, Tommaso, Gentile, Luigi, Gentile, Marco, Ghirardello, Omar, Grigore, Liliana, Lussu, Milena, Meregalli, Giancarla, Moffa, Simona, Montalcini, Tiziana, Morgia, Valeria, Nascimbeni, Fabio, Pasta, Andrea, Pavanello, Chiara, Saitta, Antonino, Scicali, Roberto, Siepi, Donatella, Spagnolli, Walter, Spina, Rossella, Sticchi, Elena, Suppressa, Patrizia, Vigo, Lorenzo, Vinci, Pierandrea, Casula, Manuela, Manzato, Enzo, Olmastroni, Elena, Tragni, Elena, Zampoleri, Veronica, and Pirillo, Angela
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- 2018
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6. Italian guidelines for the treatment of type 2 diabetes.
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Mannucci, Edoardo, Candido, Riccardo, Delle Monache, Lina, Gallo, Marco, Giaccari, Andrea, Masini, Maria Luisa, Mazzone, Angela, Medea, Gerardo, Pintaudi, Basilio, Targher, Giovanni, Trento, Marina, Turchetti, Giuseppe, Lorenzoni, Valentina, Monami, Matteo, and for Società Italiana di Diabetologia (SID) and Associazione Medici Diabetologi (AMD)
- Abstract
• This guideline is intended as reference for the treatment of type 2 diabetes in adults. • Recommendations are designed as indications for healthcare professionals in charge of diabetes care. • These recommendations apply to outpatients, either in primary care or at specialist referral. • Recommendations are based on currently available evidence. [ABSTRACT FROM AUTHOR]
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- 2022
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7. SGLT-2 inhibitors for treatment of heart failure in patients with and without type 2 diabetes: A practical approach for routine clinical practice.
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Giaccari, Andrea, Pontremoli, Roberto, and Perrone Filardi, Pasquale
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HEART failure , *HEART failure patients , *TYPE 2 diabetes , *TREATMENT failure , *CHRONIC kidney failure , *MEDICAL specialties & specialists , *SODIUM-glucose cotransporters , *ACE inhibitors - Abstract
Sodium-glucose cotransporter-2 inhibitors (SGLT-2i), initially studied and approved for the treatment of diabetes, are now becoming a promising class of agents to treat heart failure (HF) and chronic kidney disease (CKD), even in patients without diabetes. While the potential benefits in several diseases (usually treated by different medical specialties) is amplifying the interest in these drugs, their use in frail patients with multiple pathologies and on polypharmacy can be complex, requiring a composite multidisciplinary approach. Following a brief overview of the evidence supporting the benefits of SGLT-2i in patients with HF or CKD, we herein provide guidance for prescribing SGLT-2i in daily practice using a multidisciplinary approach. A shared treatment algorithm is presented for initiating an SGLT-2i in patients already being treated for diabetes and HF. Tools to prevent hypoglycemia, blood pressure drop, genital infections, euglycemic diabetic ketoacidosis and eGFR dip are also provided. It is hoped that this practical, multidisciplinary guidance for initiating SGLT-2i in patients with HF and/or CKD, whatever therapy they are currently on, can help to offer SGLT-2i to the largest population of patients possible to provide the most therapeutic benefit. • SGLT-2i are a promising class of agents for heart failure and chronic kidney disease. • An algorithm is provided for prescribing SGLT-2i using a multidisciplinary approach. • Tips to prevent common adverse effects with SGLT2i are given. • Multidisciplinary guidance can help to offer SGLT-2i to more patients. [ABSTRACT FROM AUTHOR]
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- 2022
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8. Effects of pioglitazone on cardiovascular events and all-cause mortality in patients with type 2 diabetes: A meta-analysis of randomized controlled trials.
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Mannucci, Edoardo, Giaccari, Andrea, Gallo, Marco, Targher, Giovanni, Pintaudi, Basilio, Candido, Riccardo, Monami, Matteo, and SID-AMD joint panel for Italian Guidelines on Treatment of Type 2 Diabetes
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Aim: In 2019, the Italian Society of Diabetology and the Italian Association of Clinical Diabetologists nominated an expert panel to develop guidelines for drug treatment of type 2 diabetes. After identifying the effects of glucose-lowering agents on major adverse cardiovascular events (MACEs), all-cause mortality, and hospitalization for heart failure (HHF) as critical outcomes, the experts decided to perform a systematic review and meta-analysis on the effect of pioglitazone with this respect.Data Synthesis: A MEDLINE database search was performed to identify RCTs, up to June 1st, 2021, with duration≥52 weeks, in which pioglitazone was compared with either placebo or active comparators. The principal endpoints were MACE and HHF (restricted for RCT reporting MACEs within their outcomes), all-cause mortality (irrespective of the inclusion of MACEs among the pre-specified outcomes). Mantel-Haenszel odds ratio (MH-OR) with 95% Confidence Interval (95% CI) was calculated for all the endpoints considered. Eight RCTs were included in the analysis for MACEs and HF (5048 and 5117 patients in the pioglitazone and control group, respectively), and 24 in that for all-cause mortality (10,682 and 9674 patients). Pioglitazone neither significantly increased nor reduced the risk of MACE, all-cause mortality, and HHF in comparison with placebo/active comparators (MH-OR: 0.90, 95% CI 0.78-1.03, 0.91, 95% CI 0.77, 1.09, and 1.16, 95% CI 0.73, 1.83, respectively). Pioglitazone was associated with a significant reduction of MACE in patients with prior cardiovascular events (MH-OR 0.84, 95% CI 0.72-0.99).Conclusions: This meta-analysis showed no significant effects of pioglitazone on incident MACE, all-cause mortality, and HHF. [ABSTRACT FROM AUTHOR]- Published
- 2022
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9. All-cause mortality and cardiovascular events in patients with type 2 diabetes treated with alpha-glucosidase inhibitors: A meta-analysis of randomized controlled trials.
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Mannucci, Edoardo, Gallo, Marco, Pintaudi, Basilio, Targher, Giovanni, Candido, Riccardo, Giaccari, Andrea, Monami, Matteo, and SID-AMD joint panel for Italian Guidelines on Treatment of Type 2 Diabetes
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Aim: Alpha-glucosidase inhibitors are approved drugs for treating type 2 diabetes (T2DM); however, their effects on mortality and cardiovascular safety are unclear. This meta-analysis was aimed at evaluating the effects of alpha-glucosidase inhibitors on all-cause mortality and major cardiovascular events (MACE).Data Synthesis: A Medline, Embase, Cochrane database searching for alpha-glucosidase inhibitors was performed up to July 1st, 2021. All randomized controlled trials (RCT) with a duration ≥52 weeks and comparing the effects of alpha-glucosidase inhibitors with placebo or active drugs were collected. Further inclusion criteria were: RCT reporting MACE within their primary outcome, or as pre-defined secondary outcome; and RCT enrolling at least 100 patients with T2DM. Mantel-Haenszel odds ratio (MH-OR) with 95% confidence intervals were calculated for the aforementioned outcomes. A total of eight RCTs, enrolling 1124 and 908 patients on alpha-glucosidase inhibitors and comparators, respectively, were identified. No trials reported information on MACE. Treatment with alpha-glucosidase inhibitors was not associated with a significant increase of all-cause mortality compared with other therapies or no therapy/placebo (MH-OR 0.76 [0.28; 2.05]).Conclusions: The evidence of beneficial or detrimental effects of alpha-glucosidase inhibitors on all-cause mortality and cardiovascular events is not sufficient to draw any conclusions. [ABSTRACT FROM AUTHOR]- Published
- 2022
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10. Self-management in patients with type 2 diabetes: Group-based versus individual education. A systematic review with meta-analysis of randomized trails.
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Mannucci, Edoardo, Giaccari, Andrea, Gallo, Marco, Bonifazi, Allegra, Belén, Ávila D.P., Masini, Maria L., Trento, Marina, and Monami, Matteo
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Aim: Patient education is an essential component of the treatment of type 2 diabetes mellitus (T2DM). The present meta-analysis was aimed at verifying the efficacy of group-based versus individual education for self-management in patients with T2DM.Data Synthesis: A Medline and Embase search up to January 1st, 2021, was performed, including Randomized Controlled Trials (RCT) with duration>6 months, enrolling patients with T2DM and comparing individual-based with group-based educational programs. The primary outcome was endpoint HbA1c; secondary endpoints were lipid profile, body weight, blood pressure, patients' adherence/knowledge, and quality of life. The weighed difference in means (WMD) and Mantel-Haenzel Odds Ratio (MH-OR), with 95% Confidence Interval (CI), were calculated. We retrieved 14 RCT. No significant between-group difference in HbA1c (WMD -0.39[-0.89; 0.09] mmol/mol, p = 0.11) was observed. At metaregression analyses, longer trial duration, higher baseline mean age and duration of diabetes, and lower baseline HbA1c were correlated with greater efficacy of group-based programs in reducing HbA1c. When analyzed separately, trials excluding insulin-treated patients showed a significant reduction of HbA1c in favor of group education.Conclusions: In patients with T2DM, group education has similar efficacy as individual education on glucose control. Group programs are associated with an improved quality of life and patients' knowledge.Prospero and Osf Registration: ID243149. [ABSTRACT FROM AUTHOR]- Published
- 2022
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11. Cardiovascular events and all-cause mortality in patients with type 2 diabetes treated with dipeptidyl peptidase-4 inhibitors: An extensive meta-analysis of randomized controlled trials.
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Mannucci, Edoardo, Nreu, Besmir, Montereggi, Chiara, Ragghianti, Benedetta, Gallo, Marco, Giaccari, Andrea, Monami, Matteo, and SID-AMD joint panel for Italian Guidelines on Treatment of Type 2 Diabetes
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Aims: Meta-analyses of randomized trials on Dipeptidyl Peptidase-4 inhibitors (DPP4i) reported discordant results on major cardiovascular events (MACE), mortality, and heart failure. Aim of this meta-analysis of randomized trials is the assessment of the cardiovascular safety of DPP4i.Data Synthesis: A Medline, Embase, Cochrane database search for sitagliptin, vildagliptin, omarigliptin, saxagliptin, alogliptin, trelagliptin, anagliptin, linagliptin, gemigliptin, evogliptin, and teneligliptin was performed up to up January 1st, 2020. All trials with a duration ≥24 weeks and comparing the effects of DPP4i with placebo or active drugs were collected. Mantel-Haenszel odds ratio (MH-OR) with 95% Confidence Interval (95% CI) was calculated for all outcomes defined above. A total of 182 eligible trials were identified. DPP-4i were not associated with an increased risk of MACE (MH-OR 0.99 [0.93, 1.04]), all-cause mortality (MH-OR 0.99 [0.93, 1.06]), and heart failure (MH-OR 1.05 [0.96, 1.15]) with no significant differences across individual molecules, except for saxagliptin, which was associated with an increased risk of heart failure.Conclusions: As a class, DPP4i are not associated with any increase or reduction of MACE, all-cause mortality, and heart failure. Saxagliptin seems to be associated with an increased risk of hospitalization for heart failure. [ABSTRACT FROM AUTHOR]- Published
- 2021
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12. Postoperative hyperglycemia affects survival after gastrectomy for cancer: A single-center analysis using propensity score matching.
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Fiorillo, Claudio, Quero, Giuseppe, Laterza, Vito, Mascagni, Pietro, Longo, Fabio, Menghi, Roberta, Razionale, Francesco, Rosa, Fausto, Mezza, Teresa, Boskoski, Ivo, Giaccari, Andrea, and Alfieri, Sergio
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No data are present currently on the potential correlation between postoperative hyperglycemia and long-term outcomes after gastric surgery for cancer. The aim of this study was to investigate the effects of postoperative hyperglycemia on survival after curative gastrectomy for cancer. All patients who underwent gastric surgery for cancer with curative intent were reviewed retrospectively. Diabetic patients and patients who needed pancreatic resection were excluded. In all patients, a prepared intravenous infusion of NaCl and carbohydrates (Isolyte Baxter 2,000 mL/day; glucose 50.0 g/L;Ringers lactate 1,000 mL/day) was used, and the patients were kept nil by mouth until the fourth postoperative day. The glucose levels were monitored during the first 72 hours. The study population was divided into normoglycemic and hyperglycemic patients according to the blood glucose level (<140 mg/dL and ≥140 mg/dL, respectively). The 2 groups were matched for age, sex, type of operative procedure, TNM status, and lymph node status. After matching, 104 patients were included for the analysis. Perioperative morbidity accounted for 18.3% with a greater rate for hyperglycemic patients (12% vs 31%; P =.018). When compared with normoglycemic patients, hyperglycemic patients had worse overall survival (45% vs 57%; P =.05) and worse disease-free survival (46% vs 68%; P =.02). On the multivariate analysis, hyperglycemia was an independent risk factor for a worse overall and disease-free survival. Postoperative hyperglycemia owing to surgical stress conditions can affect postoperative outcomes. Additionally, hyperglycemia may be a factor that promotes gastric cancer progression. [ABSTRACT FROM AUTHOR]
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- 2020
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13. An update on pancreatic regeneration mechanisms: Searching for paths to a cure for type 2 diabetes.
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Soldovieri, Laura, Di Giuseppe, Gianfranco, Ciccarelli, Gea, Quero, Giuseppe, Cinti, Francesca, Brunetti, Michela, Nista, Enrico C., Gasbarrini, Antonio, Alfieri, Sergio, Pontecorvi, Alfredo, Giaccari, Andrea, and Mezza, Teresa
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Over the last decades, various approaches have been explored to restore sufficient β-cell mass in diabetic patients. Stem cells are certainly an attractive source of new β-cells, but an alternative option is to induce the endogenous regeneration of these cells. Since the exocrine and endocrine pancreatic glands have a common origin and a continuous crosstalk unites the two, we believe that analyzing the mechanisms that induce pancreatic regeneration in different conditions could further advance our knowledge in the field. In this review, we summarize the latest evidence on physiological and pathological conditions associated with the regulation of pancreas regeneration and proliferation, as well as the complex and coordinated signaling cascade mediating cell growth. Unraveling the mechanisms involved in intracellular signaling and regulation of pancreatic cell proliferation and regeneration may inspire future investigations to discover potential strategies to cure diabetes. [ABSTRACT FROM AUTHOR]
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- 2023
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14. Low levels of 25(OH)D and insulin-resistance: 2 unrelated features or a cause-effect in PCOS?
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Muscogiuri, Giovanna, Policola, Caterina, Prioletta, Annamaria, Sorice, GianPio, Mezza, Teresa, Lassandro, Annapia, Della Casa, Silvia, Pontecorvi, Alfredo, and Giaccari, Andrea
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Summary: Background & aims: Recent investigations have identified low vitamin D status as a hypothetical mechanism of insulin-resistance in Polycystic Ovary Syndrome (PCOS). Instead, some authors supported the hypothesis that low vitamin D levels and insulin-resistance are 2 unrelated features of body size in PCOS. Hence, we aimed to explore the association of 25-hydroxyvitamin D (25(OH)D) with anthropometric, metabolic and hormonal features in PCOS. Methods: We assessed the association of low 25(OH)D levels with endocrine parameters, insulin-sensitivity evaluated by hyperinsulinemic euglycemic clamp (HEC) and body composition measured by DEXA in 38 women affected by PCOS. Results: Low 25(OH)D (25(OH)D < 50 nmo/L) was detected in 37% of the entire cohort of patients. Body Mass Index (BMI), in particular total fat mass (p < 0.001), resulted to be the most predictor factor of 25(OH)D levels whereas Sex Hormone Binding Globulin (SHBG), Free Androgen Index (FAI), glucose uptake and fat free mass were not. Conclusions: Our data demonstrated that in PCOS low 25(OH)D levels are significantly determined by the degree of adiposity. [Copyright &y& Elsevier]
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- 2012
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15. Publish and perish.
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Giaccari, Andrea
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- 2017
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16. Welcome aboard.
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Giaccari, Andrea
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- 2015
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17. First-phase insulin secretion: can its evaluation direct therapeutic approaches?
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Di Giuseppe, Gianfranco, Ciccarelli, Gea, Soldovieri, Laura, Capece, Umberto, Cefalo, Chiara M.A., Moffa, Simona, Nista, Enrico C., Brunetti, Michela, Cinti, Francesca, Gasbarrini, Antonio, Pontecorvi, Alfredo, Giaccari, Andrea, and Mezza, Teresa
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HYPERGLYCEMIA , *SECRETION , *THERAPEUTICS , *TYPE 2 diabetes , *INSULIN , *CELL physiology - Abstract
β Cells can adapt to pathological metabolic conditions by implementing plasticity mechanisms to increase their mass and enhance insulin secretion, thus maintaining normal glucose levels at least in the early stages of type 2 diabetes mellitus (T2DM) natural history. In T2DM the first phase of insulin secretion is impaired. This defect directly affects the clinical manifestations of the disease, primarily causing postmeal hyperglycemia, and has an impact on long-term disease-related complications. Many studies have demonstrated the effectiveness of dietary and pharmacological strategies in improving postmeal hyperglycemia via enhancing β cell function and first-phase insulin secretion parameters in particular. Because only stimulation tests can accurately estimate early β cell secretory impairments, detecting them in daily clinical practice remains challenging. Our work is aimed at unraveling the role of the first-phase insulin secretion in the natural history of type 2 diabetes mellitus (T2DM) and its interrelationship with insulin resistance and with β cell function and mass. Starting from pathophysiology, we investigate the impact of impaired secretion on glucose homeostasis and explore postmeal hyperglycemia as the main clinical feature, underlining its relevance in the management of the disease. We also review dietary and pharmacological approaches aimed at improving early secretory defects and restoring residual β cell function. Furthermore, we discuss possible approaches to detect early secretory defects in clinical practice. By providing a journey through human and animal data, we attempt a unification of the recent evidence in an effort to offer a new outlook on β cell secretion. [ABSTRACT FROM AUTHOR]
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- 2023
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18. Isocratic high-performance liquid chromatographic determination of the concentration and specific radioactivity of phosphoenolpyruvate and uridine disphosphate glucose in tissue extracts
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Giaccari, Andrea and Rossetti, Luciano
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- 1989
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19. Endocrine and Metabolic Insights from Pancreatic Surgery.
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Mezza, Teresa, Cefalo, Chiara M.A., Cinti, Francesca, Quero, Giuseppe, Pontecorvi, Alfredo, Alfieri, Sergio, Holst, Jens J., and Giaccari, Andrea
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PANCREATIC surgery , *EXOCRINE pancreatic insufficiency , *PANCREATIC diseases , *TYPE 2 diabetes , *PATHOLOGY , *PANCREATECTOMY , *ENDOCRINE glands , *ACCELERATED partial breast irradiation - Abstract
Although it is well established that diabetes can also develop as a result of diseases or maneuvers on the exocrine pancreas, the complex relationship between glucose disorders and underlying pancreatic disease is still debated. There is evidence that several features linked to pancreatic diseases can modify endocrine and metabolic conditions before and after surgery. However, pancreatic surgery provides a rare opportunity to correlate in vivo endocrine and metabolic pathways with ex vivo pancreatic samples, to examine the endocrine and metabolic effects of acute islet removal, and finally to clarify the pathogenesis of diabetes. This approach could therefore represent a unique method to shed light on the molecular mechanisms, predicting factors, and metabolic consequences of insulin resistance, islet plasticity, β cell failure, and type 2 diabetes. Pancreatic disease can modify endocrine and metabolic homeostasis; however, islet characteristics play a major role in the possible appearance of diabetes. Partial pancreatectomy is an 'accelerator' of declining β cell function rather than the actual cause of diabetes. That is, diabetes appearing after partial pancreatectomy could be better classified as 'accelerated' type 2 diabetes rather than as type 3c. Pancreaticoduodenectomy requires, for anatomical reasons, the removal of 'healthy' tissue from which accurate ex vivo specimens can be obtained. Pancreatic surgery provides a rare opportunity to correlate in vivo endocrine and metabolic pathways (before surgery) with ex vivo data from pancreatic samples. Pancreatic surgery is an excellent model for examining the metabolic and hormonal effects of acute islet removal. [ABSTRACT FROM AUTHOR]
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- 2020
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20. Nuclear Export of FoxO1 Is Associated with ERK Signaling in β-Cells Lacking Insulin Receptors.
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Mezza, Teresa, Jun Shirakawa, Martinez, Rachael, Jiang Hu, Giaccari, Andrea, and Kulkarni, Rohit N.
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FORKHEAD transcription factors , *SOMATOMEDIN , *INSULIN-like growth factor receptors , *ISLANDS of Langerhans , *CELLULAR signal transduction , *EXTRACELLULAR signal-regulated kinases , *LABORATORY mice - Abstract
The insulin/insulin-like growth factor (IGF) signaling pathway plays a critical role in the regulation of islet cell biology. However, the signaling pathway(s) utilized by insulin to directly modulate β-cells is unclear. To interrogate whether insulin exerts endocrine effects in regulating proteins in the insulin/IGF-1 signaling cascade in vivo in physiological states via the insulin receptor, we designed two experimental approaches: 1) glucose gavage and 2) hyperinsulinemic intravenous infusion, for studies in either β-cell specific insulin receptor knock-out (βIRKO) or control mice. Immunostaining of sections of pancreas (collected immediately after glucose gavage or insulin infusion) from controls showed significant increases in pAKT+, p-p70S6K+, and pERK+ β-cells and a significant decrease in % nuclear FoxO1+ β-cells compared with corresponding vehicle-treated groups. In contrast, in βIRKOs, we observed no significant changes in pAKT+ or p-p70S6K+ β-cells in either experiment; however, pERK+ β-cells were significantly increased, and an attenuated decrease in % nuclear FoxO1+ β cells was evident in response to glucose gavage or insulin infusion. Treatment of control and βIRKO β-cell lines with glucose or insulin showed significantly decreased % nuclear FoxO1+ β-cells suggesting direct effects. Furthermore, blocking MAPK signaling had virtually no effect on FoxO1 nuclear export in controls, in contrast to attenuated export in βIRKO β-cells. These data suggest insulin acts on β-cells in an endocrine manner in the normal situation; and that in β-cells lacking insulin receptors, insulin and glucose minimally activate the Akt pathway, while ERK phosphorylation and FoxO1 nuclear export occur independently of insulin signaling. [ABSTRACT FROM AUTHOR]
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- 2016
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