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3. Predictors of early discontinuation of dapagliflozin versus other glucose-lowering medications: a retrospective multicenter real-world study

Author

Fadini, G. P., Li Volsi, P., Devangelio, E., Poli, M., Cazzetta, G., Felace, G., Avogaro, A., Consoli, A., Formoso, G., Grossi, G., Pucci, A., Sesti, G., Andreozzi, F., Capobianco, G., Gatti, A., Bonadonna, R., Zavaroni, I., Cas, A. D., Buzzetti, R., Leto, G., Sorice, G. P., D'Angelo, P., Morano, S., Bossi, A. C., Duratorre, E., Franzetti, I., Morpurgo, P. S., Orsi, E., Querci, F., Boemi, M., D'Angelo, F., Petrelli, M., Aimaretti, G., Karamouzis, I., Cavalot, F., Saglietti, G., Cervone, S., Lamacchia, O., Arena, S., Di Benedetto, A., Frittitta, L., Giordano, C., Piro, S., Rizzo, M., Chianetta, R., Mannina, C., Anichini, R., Penno, G., Solini, A., Fattor, B., Bonora, E., Cigolini, M., Lapolla, A., Chilelli, N. C., Simioni, N., Frison, V., Vinci, C., Fadini G.P., Li Volsi P., Devangelio E., Poli M., Cazzetta G., Felace G., Avogaro A., Consoli A., Formoso G., Grossi G., Pucci A., Sesti G., Andreozzi F., Capobianco G., Gatti A., Bonadonna R., Zavaroni I., Cas A.D., Buzzetti R., Leto G., Sorice G.P., D'Angelo P., Morano S., Bossi A.C., Duratorre E., Franzetti I., Morpurgo P.S., Orsi E., Querci F., Boemi M., D'Angelo F., Petrelli M., Aimaretti G., Karamouzis I., Cavalot F., Saglietti G., Cervone S., Lamacchia O., Arena S., Di Benedetto A., Frittitta L., Giordano C., Piro S., Rizzo M., Chianetta R., Mannina C., Anichini R., Penno G., Solini A., Fattor B., Bonora E., Cigolini M., Lapolla A., Chilelli N.C., Simioni N., Frison V., and Vinci C.

Subjects
Blood Glucose, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Type 2 diabetes, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Glucosides, Diabetes mellitus, Internal medicine, Adherence, Observational, Pharmacotherapy, Real-world, Aged, Benzhydryl Compounds, Diabetes Mellitus, Type 2, Dipeptidyl-Peptidase IV Inhibitors, Female, Humans, Hypoglycemic Agents, Middle Aged, Retrospective Studies, Withholding Treatment, Diabetes Mellitus, medicine, Outpatient clinic, Dapagliflozin, business.industry, Retrospective cohort study, medicine.disease, Metformin, Discontinuation, chemistry, Tolerability, 030220 oncology & carcinogenesis, business, Type 2, medicine.drug
Abstract

Background and aims: In routine clinical practice, early discontinuation of newly initiated glucose-lowering medications (GLM) is relatively common. We herein evaluated if the clinical characteristics associated with early discontinuation of dapagliflozin were different from those associated with early discontinuation of other GLM. Methods: The DARWIN-T2D was a multicenter retrospective study conducted at diabetes specialist outpatient clinics in Italy. We included 2484 patients who were initiated on dapagliflozin in 2015–2016 and 14,801 patients who were initiated on other GLM (DPP-4 inhibitors, GLP-1 receptor agonists, or gliclazide) in the same period. After excluding patients who had not (yet) returned to follow-up, we compared the characteristics of patients who persisted on drug versus those who were no longer on drug at the first available follow-up after at least 3months. Results: As compared to those who persisted on drug, patients who discontinued dapagliflozin (51.7%) were more often female, had higher baseline fasting plasma glucose (FPG), HbA1c, and eGFR, and less common use of metformin. Upon multiple regression, higher HbA1c, higher eGFR, and lower metformin use remained independently associated with early discontinuation. Among patients who had been initiated on other GLM, 41.7% discontinued. Variables independently associated with discontinuation were older age, longer diabetes duration, higher HbA1c, eGFR, and albumin excretion, more common use of insulin and less metformin. Conclusion: In routine clinical practice, all variables associated with dapagliflozin discontinuation were also associated with discontinuation of other GLM. Thus, despite a distinctive mechanism of action and a peculiar tolerability profile, no specific predictor of dapagliflozin discontinuation was detected.

Published
2019

4. Similar effectiveness of dapagliflozin and GLP-1 receptor agonists concerning combined endpoints in routine clinical practice: A multicentre retrospective study

Author

Fadini, G. P., Sciannameo, V., Franzetti, I., Bottigliengo, D., D'Angelo, P., Vinci, C., Berchialla, P., Arena, S., Buzzetti, R., Avogaro, A., Consoli, A., Formoso, G., Grossi, G., Pucci, A., Sesti, G., Andreozzi, F., Capobianco, G., Gatti, A., Bonadonna, R., Zavaroni, I., Cas, A. D., Felace, G., Volsi, P. L., Leto, G., Sorice, G. P., Morano, S., Bossi, A. C., Duratorre, E., Morpurgo, P. S., Orsi, E., Querci, F., Boemi, M., D'Angelo, F., Petrelli, M., Aimaretti, G., Karamouzis, I., Cavalot, F., Saglietti, G., Cazzetta, G., Cervone, S., Devangelio, E., Lamacchia, O., Di Benedetto, A., Frittitta, L., Giordano, C., Piro, S., Rizzo, M., Chianetta, R., Mannina, C., Anichini, R., Penno, G., Solini, A., Fattor, B., Bonora, E., Cigolini, M., Lapolla, A., Chilelli, N. C., Poli, M., Simioni, N., Frison, V., Fadini G.P., Sciannameo V., Franzetti I., Bottigliengo D., D'Angelo P., Vinci C., Berchialla P., Arena S., Buzzetti R., Avogaro A., Consoli A., Formoso G., Grossi G., Pucci A., Sesti G., Andreozzi F., Capobianco G., Gatti A., Bonadonna R., Zavaroni I., Cas A.D., Felace G., Volsi P.L., Leto G., Sorice G.P., Morano S., Bossi A.C., Duratorre E., Morpurgo P.S., Orsi E., Querci F., Boemi M., D'Angelo F., Petrelli M., Aimaretti G., Karamouzis I., Cavalot F., Saglietti G., Cazzetta G., Cervone S., Devangelio E., Lamacchia O., Di Benedetto A., Frittitta L., Giordano C., Piro S., Rizzo M., Chianetta R., Mannina C., Anichini R., Penno G., Solini A., Fattor B., Bonora E., Cigolini M., Lapolla A., Chilelli N.C., Poli M., Simioni N., and Frison V.

Subjects
Blood Glucose, Male, Glycated Hemoglobin A, Endocrinology, Diabetes and Metabolism, Blood Pressure, Type 2 diabetes, 030204 cardiovascular system & hematology, Settore MED/13 - Endocrinologia, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Glucosides, Clinical endpoint, Medicine, Dapagliflozin, GLP-1 analogue, Middle Aged, Treatment Outcome, glycaemic control, antidiabetic drug, dapagliflozin, observational study, Combination, Original Article, Drug Therapy, Combination, Female, Type 2, medicine.drug, Adult, medicine.medical_specialty, 030209 endocrinology & metabolism, Glucagon-Like Peptide-1 Receptor, 03 medical and health sciences, Drug Therapy, GLP‐1 analogue, Internal medicine, Diabetes mellitus, Internal Medicine, Diabetes Mellitus, Humans, Hypoglycemic Agents, Benzhydryl Compounds, Aged, Retrospective Studies, Glycated Hemoglobin, Body Weight, Diabetes Mellitus, Type 2, Diabetic Angiopathies, Exenatide, Liraglutide, business.industry, Retrospective cohort study, Original Articles, medicine.disease, Blood pressure, chemistry, Propensity score matching, business, Antidiabetic drug, dapagliflozin, GLP-1 analogue, glycaemic control, observational study
Abstract

Aims According to cardiovascular outcome trials, some sodium‐glucose contransporter‐2 inhibitors (SGLT2i) and glucagon‐like peptide‐1 receptor agonists (GLP‐1RA) are recommended for secondary cardiovascular prevention in type 2 diabetes (T2D). In this real‐world study, we compared the simultaneous reductions in HbA1c, body weight and systolic blood pressure after initiation of dapagliflozin or GLP‐1RA as second or a more advanced line of therapy. Materials and methods DARWIN‐T2D was a retrospective multi‐centre study conducted at diabetes specialist clinics in Italy that compared T2D patients who initiated dapagliflozin or GLP‐1RA (exenatide once weekly or liraglutide). Data were collected at baseline and at the first follow‐up visit after 3 to 12 months. The primary endpoint was the proportion of patients achieving a simultaneous reduction in HbA1c, body weight and systolic blood pressure. To reduce confounding, we used multivariable adjustment (MVA) or propensity score matching (PSM). Results Totals of 473 patients initiating dapagliflozin and 336 patients initiating GLP‐1RA were included. The two groups differed in age, diabetes duration, HbA1c, weight and concomitant medications. The median follow‐up was 6 months in both groups. Using MVA or PSM, the primary endpoint was observed in 30% to 32% of patients, with no difference between groups. Simultaneous reduction of HbA1c, BP and SBP by specific threshold, as well as achievement of final goals, did not differ between groups. GLP‐1RA reduced HbA1c by 0.3% more than the reduction achieved with dapagliflozin. Conclusion In routine specialist care, initiation of dapagliflozin can be as effective as initiation of a GLP‐1RA for attainment of combined risk factor goals.

Published
2019

5. Dietary intake and major food sources of polyphenols in people with type 2 diabetes: The TOSCA.IT Study

Author

Vitale, M, Masulli, M, Rivellese, A, Bonora, E, Cappellini, F, Nicolucci, A, Squatrito, S, Antenucci, D, Barrea, A, Bianchi, C, Bianchini, F, Fontana, L, Fornengo, P, Giorgino, F, Gnasso, A, Mannucci, E, Mazzotti, A, Nappo, R, Palena, A, Pata, P, Perriello, G, Potenziani, S, Radin, R, Ricci, L, Romeo, F, Santini, C, Scarponi, M, Serra, R, Timi, A, Turco, A, Vedovato, M, Zavaroni, D, Grioni, S, Riccardi, G, Vaccaro, O, Cocozza, S, Auciello, S, Cigolini, M, Pichiri, I, Brangani, C, Tomasetto, E, Sinagra, T, Longhitano, S, Tropea, V, Ballardini, G, Babini, A, Ripani, R, Gregori, G, Dolci, M, Bruselli, L, Salutini, I, Mori, M, Baccetti, F, Lapolla, A, Sartore, G, Burlina, S, Chilelli, N, Buzzetti, R, Venditti, C, Carlone, A, Galluzzo, A, Giordano, C, Torregrossa, V, Corsi, L, Cuneo, G, Corsi, S, Tizio, B, Galluzzo, G, Citro, G, Natale, M, Salvatore, V, Di Cianni, G, Lacaria, E, Russo, L, Iannarelli, R, De Gregorio, A, Sciarretta, F, D'Andrea, S, Montani, V, Cannarsa, E, Dolcetti, K, Cordera, R, Bonabello, L, Mazzucchelli, C, Giorda, C, Bonetto, C, Baldassarre, M, Iovine, C, Ciano, O, Dall'Aglio, E, Mancastroppa, G, Grimaldi, F, Tonutti, L, Boemi, M, D'Angelo, F, Leotta, S, Lauro, D, Rinaldi, M, Cignarelli, M, La Macchia, O, Fariello, S, Tomasi, F, Zamboni, C, Dozio, N, Trevisan, R, Scaranna, C, Del Prato, S, Miccoli, R, Garofolo, M, Pugliese, G, Salvi, L, Rangel, G, Anichini, R, Tedeschi, A, Corsini, E, Cucinotta, D, Di Benedetto, A, Giunta, L, Ruffo, M, Bossi, A, Carpinter, R, Dotta, F, Ceccarelli, E, Bartolo, P, Caselli, C, Luberto, A, Calbucci, G, Consoli, A, Ginestra, F, Calabrese, M, Zogheri, A, Laviola, L, Ippolito, C, Tarantino, L, Avogaro, A, Carallo, C, Scicchitano, C, Livraga, S, Perin, P, Forrnengo, P, Prinzis, T, De Cosmo, S, Bacci, S, Lamanna, C, Lettina, G, Aiello, A, Lalli, C, Franzetti, I, Petrachi, F, Asprino, V, Capra, C, Forte, E, Reggiani, G, Forlani, G, Montesi, L, Mazzella, N, Piatti, P, Monti, L, Stuccillo, M, Auletta, P, Petraroli, E, Capobianco, G, Romano, G, Cutolo, M, De Simone, G, Caiazzo, G, Nunziata, P, Sorrentino, S, Amelia, U, Calatola, P, Capuano, G, Vitale M., Masulli M., Rivellese A. A., Bonora E., Cappellini F., Nicolucci A., Squatrito S., Antenucci D., Barrea A., Bianchi C., Bianchini F., Fontana L., Fornengo P., Giorgino F., Gnasso A., Mannucci E., Mazzotti A., Nappo R., Palena A. P., Pata P., Perriello G., Potenziani S., Radin R., Ricci L., Romeo F., Santini C., Scarponi M., Serra R., Timi A., Turco A. A., Vedovato M., Zavaroni D., Grioni S., Riccardi G., Vaccaro O., Cocozza S., Auciello S., Cigolini M., Pichiri I., Brangani C., Tomasetto E., Sinagra T., Longhitano S., Tropea V., Ballardini G., Babini A. C., Ripani R., Gregori G., Dolci M., Bruselli L., Salutini I., Mori M., Baccetti F., Lapolla A., Sartore G., Burlina S., Chilelli N. C., Buzzetti R., Venditti C., Carlone A., Galluzzo A., Giordano C., Torregrossa V., Corsi L., Cuneo G., Corsi S., Tizio B., Galluzzo G., Citro G., Natale M., Salvatore V., Di Cianni G., Lacaria E., Russo L., Iannarelli R., De Gregorio A., Sciarretta F., D'Andrea S., Montani V., Cannarsa E., Dolcetti K., Cordera R., Bonabello L. A., Mazzucchelli C., Giorda C. B., Bonetto C., Baldassarre M. P. A., Iovine C., Ciano O., Dall'Aglio E., Mancastroppa G., Grimaldi F., Tonutti L., Boemi M., D'Angelo F., Leotta S., Lauro D., Rinaldi M. E., Cignarelli M., La Macchia O., Fariello S., Tomasi F., Zamboni C., Dozio N., Trevisan R., Scaranna C., Del Prato S., Miccoli R., Garofolo M., Pugliese G., Salvi L., Rangel G., Anichini R., Tedeschi A., Corsini E., Cucinotta D., Di Benedetto A., Giunta L., Ruffo M. C., Bossi A. C., Carpinter R., Dotta F., Ceccarelli E., Bartolo P. D., Caselli C., Luberto A., Calbucci G., Consoli A., Ginestra F., Calabrese M., Zogheri A., Laviola L., Ippolito C., Tarantino L., Avogaro A., Carallo C., Scicchitano C., Livraga S., Perin P. C., Forrnengo P., Prinzis T., De Cosmo S., Bacci S., Lamanna C., Lettina G., Aiello A., Lalli C., Franzetti I., Petrachi F., Asprino V., Capra C., Forte E., Reggiani G. M., Forlani G., Montesi L., Mazzella N., Piatti P. M., Monti L., Stuccillo M., Auletta P., Petraroli E., Capobianco G., Romano G., Cutolo M., De Simone G., Caiazzo G., Nunziata P., Sorrentino S., Amelia U., Calatola P., Capuano G., Vitale, M, Masulli, M, Rivellese, A, Bonora, E, Cappellini, F, Nicolucci, A, Squatrito, S, Antenucci, D, Barrea, A, Bianchi, C, Bianchini, F, Fontana, L, Fornengo, P, Giorgino, F, Gnasso, A, Mannucci, E, Mazzotti, A, Nappo, R, Palena, A, Pata, P, Perriello, G, Potenziani, S, Radin, R, Ricci, L, Romeo, F, Santini, C, Scarponi, M, Serra, R, Timi, A, Turco, A, Vedovato, M, Zavaroni, D, Grioni, S, Riccardi, G, Vaccaro, O, Cocozza, S, Auciello, S, Cigolini, M, Pichiri, I, Brangani, C, Tomasetto, E, Sinagra, T, Longhitano, S, Tropea, V, Ballardini, G, Babini, A, Ripani, R, Gregori, G, Dolci, M, Bruselli, L, Salutini, I, Mori, M, Baccetti, F, Lapolla, A, Sartore, G, Burlina, S, Chilelli, N, Buzzetti, R, Venditti, C, Carlone, A, Galluzzo, A, Giordano, C, Torregrossa, V, Corsi, L, Cuneo, G, Corsi, S, Tizio, B, Galluzzo, G, Citro, G, Natale, M, Salvatore, V, Di Cianni, G, Lacaria, E, Russo, L, Iannarelli, R, De Gregorio, A, Sciarretta, F, D'Andrea, S, Montani, V, Cannarsa, E, Dolcetti, K, Cordera, R, Bonabello, L, Mazzucchelli, C, Giorda, C, Bonetto, C, Baldassarre, M, Iovine, C, Ciano, O, Dall'Aglio, E, Mancastroppa, G, Grimaldi, F, Tonutti, L, Boemi, M, D'Angelo, F, Leotta, S, Lauro, D, Rinaldi, M, Cignarelli, M, La Macchia, O, Fariello, S, Tomasi, F, Zamboni, C, Dozio, N, Trevisan, R, Scaranna, C, Del Prato, S, Miccoli, R, Garofolo, M, Pugliese, G, Salvi, L, Rangel, G, Anichini, R, Tedeschi, A, Corsini, E, Cucinotta, D, Di Benedetto, A, Giunta, L, Ruffo, M, Bossi, A, Carpinter, R, Dotta, F, Ceccarelli, E, Bartolo, P, Caselli, C, Luberto, A, Calbucci, G, Consoli, A, Ginestra, F, Calabrese, M, Zogheri, A, Laviola, L, Ippolito, C, Tarantino, L, Avogaro, A, Carallo, C, Scicchitano, C, Livraga, S, Perin, P, Forrnengo, P, Prinzis, T, De Cosmo, S, Bacci, S, Lamanna, C, Lettina, G, Aiello, A, Lalli, C, Franzetti, I, Petrachi, F, Asprino, V, Capra, C, Forte, E, Reggiani, G, Forlani, G, Montesi, L, Mazzella, N, Piatti, P, Monti, L, Stuccillo, M, Auletta, P, Petraroli, E, Capobianco, G, Romano, G, Cutolo, M, De Simone, G, Caiazzo, G, Nunziata, P, Sorrentino, S, Amelia, U, Calatola, P, Capuano, G, Vitale M., Masulli M., Rivellese A. A., Bonora E., Cappellini F., Nicolucci A., Squatrito S., Antenucci D., Barrea A., Bianchi C., Bianchini F., Fontana L., Fornengo P., Giorgino F., Gnasso A., Mannucci E., Mazzotti A., Nappo R., Palena A. P., Pata P., Perriello G., Potenziani S., Radin R., Ricci L., Romeo F., Santini C., Scarponi M., Serra R., Timi A., Turco A. A., Vedovato M., Zavaroni D., Grioni S., Riccardi G., Vaccaro O., Cocozza S., Auciello S., Cigolini M., Pichiri I., Brangani C., Tomasetto E., Sinagra T., Longhitano S., Tropea V., Ballardini G., Babini A. C., Ripani R., Gregori G., Dolci M., Bruselli L., Salutini I., Mori M., Baccetti F., Lapolla A., Sartore G., Burlina S., Chilelli N. C., Buzzetti R., Venditti C., Carlone A., Galluzzo A., Giordano C., Torregrossa V., Corsi L., Cuneo G., Corsi S., Tizio B., Galluzzo G., Citro G., Natale M., Salvatore V., Di Cianni G., Lacaria E., Russo L., Iannarelli R., De Gregorio A., Sciarretta F., D'Andrea S., Montani V., Cannarsa E., Dolcetti K., Cordera R., Bonabello L. A., Mazzucchelli C., Giorda C. B., Bonetto C., Baldassarre M. P. A., Iovine C., Ciano O., Dall'Aglio E., Mancastroppa G., Grimaldi F., Tonutti L., Boemi M., D'Angelo F., Leotta S., Lauro D., Rinaldi M. E., Cignarelli M., La Macchia O., Fariello S., Tomasi F., Zamboni C., Dozio N., Trevisan R., Scaranna C., Del Prato S., Miccoli R., Garofolo M., Pugliese G., Salvi L., Rangel G., Anichini R., Tedeschi A., Corsini E., Cucinotta D., Di Benedetto A., Giunta L., Ruffo M. C., Bossi A. C., Carpinter R., Dotta F., Ceccarelli E., Bartolo P. D., Caselli C., Luberto A., Calbucci G., Consoli A., Ginestra F., Calabrese M., Zogheri A., Laviola L., Ippolito C., Tarantino L., Avogaro A., Carallo C., Scicchitano C., Livraga S., Perin P. C., Forrnengo P., Prinzis T., De Cosmo S., Bacci S., Lamanna C., Lettina G., Aiello A., Lalli C., Franzetti I., Petrachi F., Asprino V., Capra C., Forte E., Reggiani G. M., Forlani G., Montesi L., Mazzella N., Piatti P. M., Monti L., Stuccillo M., Auletta P., Petraroli E., Capobianco G., Romano G., Cutolo M., De Simone G., Caiazzo G., Nunziata P., Sorrentino S., Amelia U., Calatola P., and Capuano G.

Abstract

Purpose: Proper evaluation of polyphenols intake at the population level is a necessary step in order to establish possible associations with health outcomes. Available data are limited, and so far no study has been performed in people with diabetes. The aim of this work was to document the intake of polyphenols and their major food sources in a cohort of people with type 2 diabetes and in socio-demographic subgroups. Methods: We studied 2573 men and women aged 50–75 years. Among others, anthropometry was measured by standard protocol and dietary habits were investigated by food frequency questionnaire (EPIC). The intake of polyphenols was evaluated using US Department of Agriculture and Phenol-Explorer databases. Results: The mean total polyphenol intake was 683.3 ± 5.8 mg/day. Non-alcoholic beverages represented the main food source of dietary polyphenols and provided 35.5% of total polyphenol intake, followed by fruits (23.0%), alcoholic beverages (14.0%), vegetables (12.4%), cereal products and tubers (4.6%), legumes (3.7%) and oils (2.1%); chocolate, cakes and nuts are negligible sources of polyphenols in this cohort. The two most important polyphenol classes contributing to the total intake were flavonoids (47.5%) and phenolic acids (47.4%). Polyphenol intake increased with age and education level and decreased with BMI; furthermore, in the northern regions of Italy, the polyphenol intake was slightly, but significantly higher than in the central or southern regions. Conclusions: The study documents for the first time the intake of polyphenols and their main food sources in people with diabetes using validated and complete databases of the polyphenol content of food. Compared with published data, collected in people without diabetes, these results suggest a lower intake and a different pattern of intake in people with diabetes.

Published
2018

6. Effects on the incidence of cardiovascular events of the addition of pioglitazone versus sulfonylureas in patients with type 2 diabetes inadequately controlled with metformin (TOSCA.IT): a randomised, multicentre trial

Author

Vaccaro, O, Masulli, M, Nicolucci, A, Bonora, E, Del Prato, S, Maggioni, A, Rivellese, A, Squatrito, S, Giorda, C, Sesti, G, Mocarelli, P, Lucisano, G, Sacco, M, Signorini, S, Cappellini, F, Perriello, G, Babini, A, Lapolla, A, Gregori, G, Giordano, C, Corsi, L, Buzzetti, R, Clemente, G, Di Cianni, G, Iannarelli, R, Cordera, R, La Macchia, O, Zamboni, C, Scaranna, C, Boemi, M, Iovine, C, Lauro, D, Leotta, S, Dall'Aglio, E, Cannarsa, E, Tonutti, L, Pugliese, G, Bossi, A, Anichini, R, Dotta, F, Di Benedetto, A, Citro, G, Antenucci, D, Ricci, L, Giorgino, F, Santini, C, Gnasso, A, De Cosmo, S, Zavaroni, D, Vedovato, M, Consoli, A, Calabrese, M, di Bartolo, P, Fornengo, P, Riccardi, G, D'Angelo, F, Giansanti, R, Tanase, L, Lanari, L, Testa, I, Pancani, F, Ranchelli, A, Vagheggi, P, Scatona, A, Fontana, L, Laviola, L, Tarantino, L, Ippolito, C, Gigantelli, V, Manicone, M, Conte, E, Trevisan, R, Rota, R, Dodesini, A, Reggiani, G, Montesi, L, Mazzella, N, Forlani, G, Caselli, C, Di Luzio, R, Mazzotti, A, Aiello, A, Barrea, A, Musto, A, D'Amico, F, Sinagra, T, Longhitano, S, Trowpea, V, Sparti, M, Italia, S, Lisi, E, Grasso, G, Pezzino, V, Insalaco, F, Carallo, C, Scicchitano, C, De Franceschi, M, Calbucci, G, Ripani, R, Cuneo, G, Corsi, S, Romeo, F, Lesina, A, Comoglio, M, Bonetto, C, Robusto, A, Nada, E, Asprino, V, Cetraro, R, Impieri, M, Lucchese, G, Donnarumma, G, Tizio, B, Lenza, L, Paraggio, P, Tomasi, F, Dozio, N, Scalambra, E, Mannucci, E, Lamanna, C, Cignarelli, M, Macchia, O, Fariello, S, Sorrentino, M, Franzetti, I, Radin, R, Annunziata, F, Bonabello, L, Durante, A, Dolcino, M, Gallo, F, Mazzucchelli, C, Aleo, A, Melga, P, Briatore, L, Maggi, D, Storace, D, Cecoli, F, D'Ugo, E, Pupillo, M, Baldassarre, M, Salvati, F, Minnucci, A, De Luca, A, Zugaro, A, Santarelli, L, Bosco, A, Petrella, V, La Verghetta, G, D'Andrea, S, Giuliani, A, Polidoro, W, Sperandio, A, Sciarretta, F, Pezzella, A, Carlone, A, Potenziani, S, Venditti, C, Foffi, C, Carbone, S, Cipolloni, L, Moretti, C, Leto, G, Serra, R, Petrachi, F, Romano, I, Lacaria, E, Russo, L, Goretti, C, Sannino, C, Dolci, M, Bruselli, L, Mori, M, Baccetti, F, Del Freo, M, Cucinotta, D, Giunta, L, Ruffo, M, Cannizzaro, D, Pintaudi, B, Perrone, G, Pata, P, Ragonese, F, Lettina, G, Mancuso, T, Coppolino, A, Piatti, P, Monti, L, Stuccillo, M, Lucotti, P, Setola, M, Crippa, G, Loi, C, Oldani, M, Bottalico, M, Pellegata, B, Bonomo, M, Menicatti, L, Resi, V, Bertuzzi, F, Disoteo, E, Pizzi, G, Annuzzi, G, Capaldo, B, Nappo, R, Auciello, S, Turco, A, Costagliola, L, Corte, G, Vallefuoco, P, Nappi, F, Vitale, M, Cocozza, S, Ciano, O, Massimino, E, Garofalo, N, Avogaro, A, Guarneri, G, Fedele, D, Sartore, G, Chilelli, N, Burlina, S, Bonsembiante, B, Galluzzo, A, Torregrossa, V, Mancastroppa, G, Arsenio, L, Cioni, F, Caronna, S, Papi, M, Santeusanio, F, Calagreti, G, Timi, A, Tantucci, A, Marino, C, Ginestra, F, Di Biagio, R, Taraborelli, M, Miccoli, R, Bianchi, C, Garofolo, M, Politi, K, Penno, G, Livraga, S, Calzoni, F, Corsini, E, Tedeschi, A, Gagliano, M, Ippolito, G, Salutini, E, Cervellino, F, Natale, M, Salvatore, V, Zampino, A, Sinisi, R, Arcangeli, A, Zogheri, A, Guizzotti, S, Longo, R, Pellicano, F, Scolozzi, P, Termine, S, Luberto, A, Ballardini, G, Trojani, C, Mazzuca, P, Bruglia, M, Ciamei, M, Genghini, S, Zannoni, C, Rangel, G, Salvi, L, Zappaterreno, A, Cordone, S, Simonelli, P, Meggiorini, M, Frasheri, A, Di Pippo, C, Maglio, C, Mazzitelli, G, Rinaldi, M, Galli, A, Romano, M, D'Angelo, P, Suraci, C, Bacci, S, Palena, A, Genovese, S, Mancino, M, Rondinelli, M, Capone, F, Calabretto, E, Bulgheroni, M, Bucciarelli, L, Ceccarelli, E, Fondelli, C, Santacroce, C, Guarino, E, Nigi, L, Lalli, C, Di Vizia, G, Scarponi, M, Montani, V, Di Bernardino, P, Romagni, P, Dolcetti, K, Forte, E, Tamburo, L, Perin, P, Prinzis, T, Gruden, G, Bruno, G, Zucco, C, Perotta, M, Marena, S, Monsignore, S, Panero, F, Ponzi, F, Carpinteri, R, Casagrande, M, Coletti, M, Balini, A, Filopanti, M, Madaschi, S, Pulcina, A, Grimaldi, F, Venturini, G, Agus, S, Pagnutti, S, Guidotti, F, Cavarape, A, Cigolini, M, Pichiri, I, Brangani, C, Fainelli, G, Tomasetto, E, Zoppini, G, Galletti, A, Perrone, D, Capra, C, Bianchini, F, Ceseri, M, Di Nardo, B, Sasso, E, Bartolomei, B, Suliman, I, Fabbri, G, Romano, G, Maturo, N, Nunziata, G, Capobianco, G, De Simone, G, Villa, V, Rota, G, Pentangelo, C, Carbonara, O, Caiazzo, G, Cutolo, M, Sorrentino, T, Mastrilli, V, Amelia, U, Masi, S, Corigliano, G, Gaeta, I, Armentano, V, Calatola, P, Capuano, G, Angiulli, B, Auletta, P, Petraroli, E, Iodice, C, Agrusta, M, Vaccaro O., Masulli M., Nicolucci A., Bonora E., Del Prato S., Maggioni A. P., Rivellese A. A., Squatrito S., Giorda C. B., Sesti G., Mocarelli P., Lucisano G., Sacco M., Signorini S., Cappellini F., Perriello G., Babini A. C., Lapolla A., Gregori G., Giordano C., Corsi L., Buzzetti R., Clemente G., Di Cianni G., Iannarelli R., Cordera R., La Macchia O., Zamboni C., Scaranna C., Boemi M., Iovine C., Lauro D., Leotta S., Dall'Aglio E., Cannarsa E., Tonutti L., Pugliese G., Bossi A. C., Anichini R., Dotta F., Di Benedetto A., Citro G., Antenucci D., Ricci L., Giorgino F., Santini C., Gnasso A., De Cosmo S., Zavaroni D., Vedovato M., Consoli A., Calabrese M., di Bartolo P., Fornengo P., Riccardi G., D'Angelo F., Giansanti R., Tanase L., Lanari L., Testa I., Pancani F., Ranchelli A., Vagheggi P., Scatona A., Fontana L., Laviola L., Tarantino L., Ippolito C., Gigantelli V., Manicone M., Conte E., Trevisan R., Rota R., Dodesini A. R., Reggiani G. M., Montesi L., Mazzella N., Forlani G., Caselli C., Di Luzio R., Mazzotti A., Aiello A., Barrea A., Musto A., D'Amico F., Sinagra T., Longhitano S., Trowpea V., Sparti M., Italia S., Lisi E., Grasso G., Pezzino V., Insalaco F., Carallo C., Scicchitano C., De Franceschi M. S., Calbucci G., Ripani R., Cuneo G., Corsi S., Romeo F., Lesina A., Comoglio M., Bonetto C., Robusto A., Nada E., Asprino V., Cetraro R., Impieri M., Lucchese G., Donnarumma G., Tizio B., Lenza L., Paraggio P., Tomasi F., Dozio N., Scalambra E., Mannucci E., Lamanna C., Cignarelli M., Macchia O. L., Fariello S., Sorrentino M. R., Franzetti I., Radin R., Annunziata F., Bonabello L. A., Durante A., Dolcino M., Gallo F., Mazzucchelli C., Aleo A., Melga P., Briatore L., Maggi D., Storace D., Cecoli F., D'Ugo E., Pupillo M., Baldassarre M. P. A., Salvati F., Minnucci A., De Luca A., Zugaro A., Santarelli L., Bosco A., Petrella V., La Verghetta G. G., D'Andrea S., Giuliani A. E., Polidoro W. L., Sperandio A., Sciarretta F., Pezzella A., Carlone A., Potenziani S., Venditti C., Foffi C., Carbone S., Cipolloni L., Moretti C., Leto G., Serra R., Petrachi F., Romano I., Lacaria E., Russo L., Goretti C., Sannino C., Dolci M., Bruselli L., Mori M. L., Baccetti F., Del Freo M., Cucinotta D., Giunta L., Ruffo M. C., Cannizzaro D., Pintaudi B., Perrone G., Pata P., Ragonese F., Lettina G., Mancuso T., Coppolino A., Piatti P. M., Monti L., Stuccillo M., Lucotti P., Setola M., Crippa G. V., Loi C., Oldani M., Bottalico M. L., Pellegata B., Bonomo M., Menicatti L. S. M., Resi V., Bertuzzi F., Disoteo E. O., Pizzi G., Annuzzi G., Capaldo B., Nappo R., Auciello S. M., Turco A. A., Costagliola L., Corte G. D., Vallefuoco P., Nappi F., Vitale M., Cocozza S., Ciano O., Massimino E., Garofalo N., Avogaro A., Guarneri G., Fedele D., Sartore G., Chilelli N. C., Burlina S., Bonsembiante B., Galluzzo A., Torregrossa V., Mancastroppa G., Arsenio L., Cioni F., Caronna S., Papi M., Santeusanio F., Calagreti G., Timi A., Tantucci A., Marino C., Ginestra F., Di Biagio R., Taraborelli M., Miccoli R., Bianchi C., Garofolo M., Politi K. S., Penno G., Livraga S., Calzoni F., Mancastroppa G. L. F., Corsini E., Tedeschi A., Gagliano M. S., Ippolito G., Salutini E., Cervellino F., Natale M., Salvatore V., Zampino A., Sinisi R., Arcangeli A., Zogheri A., Guizzotti S., Longo R., Pellicano F., Scolozzi P., Termine S., Luberto A., Ballardini G., Trojani C., Mazzuca P., Bruglia M., Ciamei M., Genghini S., Zannoni C., Rangel G., Salvi L., Zappaterreno A., Cordone S., Simonelli P., Meggiorini M., Frasheri A., Di Pippo C., Maglio C., Mazzitelli G., Rinaldi M. E., Galli A., Romano M., D'Angelo P., Suraci C., Bacci S., Palena A. P., Genovese S., Mancino M., Rondinelli M., Capone F., Calabretto E., Bulgheroni M., Bucciarelli L., Ceccarelli E., Fondelli C., Santacroce C., Guarino E., Nigi L., Lalli C., Di Vizia G., Scarponi M., Montani V., Di Bernardino P., Romagni P., Dolcetti K., Forte E., Tamburo L., Perin P. C., Prinzis T., Gruden G., Bruno G., Zucco C., Perotta M., Marena S., Monsignore S., Panero F., Ponzi F., Carpinteri R., Casagrande M. L., Coletti M. F., Balini A., Filopanti M., Madaschi S., Pulcina A., Grimaldi F., Venturini G., Agus S., Pagnutti S., Guidotti F., Cavarape A., Cigolini M., Pichiri I., Brangani C., Fainelli G., Tomasetto E., Zoppini G., Galletti A., Perrone D., Capra C., Bianchini F., Ceseri M., Di Nardo B., Sasso E., Bartolomei B., Suliman I., Fabbri G., Romano G., Maturo N., Nunziata G., Capobianco G., De Simone G., Villa V., Rota G., Pentangelo C., Carbonara O., Caiazzo G., Cutolo M., Sorrentino T., Mastrilli V., Amelia U., Masi S., Corigliano G., Gaeta I., Armentano V., Calatola P., Capuano G., Angiulli B., Auletta P., Petraroli E., Iodice C. E., Agrusta M., Vaccaro, O, Masulli, M, Nicolucci, A, Bonora, E, Del Prato, S, Maggioni, A, Rivellese, A, Squatrito, S, Giorda, C, Sesti, G, Mocarelli, P, Lucisano, G, Sacco, M, Signorini, S, Cappellini, F, Perriello, G, Babini, A, Lapolla, A, Gregori, G, Giordano, C, Corsi, L, Buzzetti, R, Clemente, G, Di Cianni, G, Iannarelli, R, Cordera, R, La Macchia, O, Zamboni, C, Scaranna, C, Boemi, M, Iovine, C, Lauro, D, Leotta, S, Dall'Aglio, E, Cannarsa, E, Tonutti, L, Pugliese, G, Bossi, A, Anichini, R, Dotta, F, Di Benedetto, A, Citro, G, Antenucci, D, Ricci, L, Giorgino, F, Santini, C, Gnasso, A, De Cosmo, S, Zavaroni, D, Vedovato, M, Consoli, A, Calabrese, M, di Bartolo, P, Fornengo, P, Riccardi, G, D'Angelo, F, Giansanti, R, Tanase, L, Lanari, L, Testa, I, Pancani, F, Ranchelli, A, Vagheggi, P, Scatona, A, Fontana, L, Laviola, L, Tarantino, L, Ippolito, C, Gigantelli, V, Manicone, M, Conte, E, Trevisan, R, Rota, R, Dodesini, A, Reggiani, G, Montesi, L, Mazzella, N, Forlani, G, Caselli, C, Di Luzio, R, Mazzotti, A, Aiello, A, Barrea, A, Musto, A, D'Amico, F, Sinagra, T, Longhitano, S, Trowpea, V, Sparti, M, Italia, S, Lisi, E, Grasso, G, Pezzino, V, Insalaco, F, Carallo, C, Scicchitano, C, De Franceschi, M, Calbucci, G, Ripani, R, Cuneo, G, Corsi, S, Romeo, F, Lesina, A, Comoglio, M, Bonetto, C, Robusto, A, Nada, E, Asprino, V, Cetraro, R, Impieri, M, Lucchese, G, Donnarumma, G, Tizio, B, Lenza, L, Paraggio, P, Tomasi, F, Dozio, N, Scalambra, E, Mannucci, E, Lamanna, C, Cignarelli, M, Macchia, O, Fariello, S, Sorrentino, M, Franzetti, I, Radin, R, Annunziata, F, Bonabello, L, Durante, A, Dolcino, M, Gallo, F, Mazzucchelli, C, Aleo, A, Melga, P, Briatore, L, Maggi, D, Storace, D, Cecoli, F, D'Ugo, E, Pupillo, M, Baldassarre, M, Salvati, F, Minnucci, A, De Luca, A, Zugaro, A, Santarelli, L, Bosco, A, Petrella, V, La Verghetta, G, D'Andrea, S, Giuliani, A, Polidoro, W, Sperandio, A, Sciarretta, F, Pezzella, A, Carlone, A, Potenziani, S, Venditti, C, Foffi, C, Carbone, S, Cipolloni, L, Moretti, C, Leto, G, Serra, R, Petrachi, F, Romano, I, Lacaria, E, Russo, L, Goretti, C, Sannino, C, Dolci, M, Bruselli, L, Mori, M, Baccetti, F, Del Freo, M, Cucinotta, D, Giunta, L, Ruffo, M, Cannizzaro, D, Pintaudi, B, Perrone, G, Pata, P, Ragonese, F, Lettina, G, Mancuso, T, Coppolino, A, Piatti, P, Monti, L, Stuccillo, M, Lucotti, P, Setola, M, Crippa, G, Loi, C, Oldani, M, Bottalico, M, Pellegata, B, Bonomo, M, Menicatti, L, Resi, V, Bertuzzi, F, Disoteo, E, Pizzi, G, Annuzzi, G, Capaldo, B, Nappo, R, Auciello, S, Turco, A, Costagliola, L, Corte, G, Vallefuoco, P, Nappi, F, Vitale, M, Cocozza, S, Ciano, O, Massimino, E, Garofalo, N, Avogaro, A, Guarneri, G, Fedele, D, Sartore, G, Chilelli, N, Burlina, S, Bonsembiante, B, Galluzzo, A, Torregrossa, V, Mancastroppa, G, Arsenio, L, Cioni, F, Caronna, S, Papi, M, Santeusanio, F, Calagreti, G, Timi, A, Tantucci, A, Marino, C, Ginestra, F, Di Biagio, R, Taraborelli, M, Miccoli, R, Bianchi, C, Garofolo, M, Politi, K, Penno, G, Livraga, S, Calzoni, F, Corsini, E, Tedeschi, A, Gagliano, M, Ippolito, G, Salutini, E, Cervellino, F, Natale, M, Salvatore, V, Zampino, A, Sinisi, R, Arcangeli, A, Zogheri, A, Guizzotti, S, Longo, R, Pellicano, F, Scolozzi, P, Termine, S, Luberto, A, Ballardini, G, Trojani, C, Mazzuca, P, Bruglia, M, Ciamei, M, Genghini, S, Zannoni, C, Rangel, G, Salvi, L, Zappaterreno, A, Cordone, S, Simonelli, P, Meggiorini, M, Frasheri, A, Di Pippo, C, Maglio, C, Mazzitelli, G, Rinaldi, M, Galli, A, Romano, M, D'Angelo, P, Suraci, C, Bacci, S, Palena, A, Genovese, S, Mancino, M, Rondinelli, M, Capone, F, Calabretto, E, Bulgheroni, M, Bucciarelli, L, Ceccarelli, E, Fondelli, C, Santacroce, C, Guarino, E, Nigi, L, Lalli, C, Di Vizia, G, Scarponi, M, Montani, V, Di Bernardino, P, Romagni, P, Dolcetti, K, Forte, E, Tamburo, L, Perin, P, Prinzis, T, Gruden, G, Bruno, G, Zucco, C, Perotta, M, Marena, S, Monsignore, S, Panero, F, Ponzi, F, Carpinteri, R, Casagrande, M, Coletti, M, Balini, A, Filopanti, M, Madaschi, S, Pulcina, A, Grimaldi, F, Venturini, G, Agus, S, Pagnutti, S, Guidotti, F, Cavarape, A, Cigolini, M, Pichiri, I, Brangani, C, Fainelli, G, Tomasetto, E, Zoppini, G, Galletti, A, Perrone, D, Capra, C, Bianchini, F, Ceseri, M, Di Nardo, B, Sasso, E, Bartolomei, B, Suliman, I, Fabbri, G, Romano, G, Maturo, N, Nunziata, G, Capobianco, G, De Simone, G, Villa, V, Rota, G, Pentangelo, C, Carbonara, O, Caiazzo, G, Cutolo, M, Sorrentino, T, Mastrilli, V, Amelia, U, Masi, S, Corigliano, G, Gaeta, I, Armentano, V, Calatola, P, Capuano, G, Angiulli, B, Auletta, P, Petraroli, E, Iodice, C, Agrusta, M, Vaccaro O., Masulli M., Nicolucci A., Bonora E., Del Prato S., Maggioni A. P., Rivellese A. A., Squatrito S., Giorda C. B., Sesti G., Mocarelli P., Lucisano G., Sacco M., Signorini S., Cappellini F., Perriello G., Babini A. C., Lapolla A., Gregori G., Giordano C., Corsi L., Buzzetti R., Clemente G., Di Cianni G., Iannarelli R., Cordera R., La Macchia O., Zamboni C., Scaranna C., Boemi M., Iovine C., Lauro D., Leotta S., Dall'Aglio E., Cannarsa E., Tonutti L., Pugliese G., Bossi A. C., Anichini R., Dotta F., Di Benedetto A., Citro G., Antenucci D., Ricci L., Giorgino F., Santini C., Gnasso A., De Cosmo S., Zavaroni D., Vedovato M., Consoli A., Calabrese M., di Bartolo P., Fornengo P., Riccardi G., D'Angelo F., Giansanti R., Tanase L., Lanari L., Testa I., Pancani F., Ranchelli A., Vagheggi P., Scatona A., Fontana L., Laviola L., Tarantino L., Ippolito C., Gigantelli V., Manicone M., Conte E., Trevisan R., Rota R., Dodesini A. R., Reggiani G. M., Montesi L., Mazzella N., Forlani G., Caselli C., Di Luzio R., Mazzotti A., Aiello A., Barrea A., Musto A., D'Amico F., Sinagra T., Longhitano S., Trowpea V., Sparti M., Italia S., Lisi E., Grasso G., Pezzino V., Insalaco F., Carallo C., Scicchitano C., De Franceschi M. S., Calbucci G., Ripani R., Cuneo G., Corsi S., Romeo F., Lesina A., Comoglio M., Bonetto C., Robusto A., Nada E., Asprino V., Cetraro R., Impieri M., Lucchese G., Donnarumma G., Tizio B., Lenza L., Paraggio P., Tomasi F., Dozio N., Scalambra E., Mannucci E., Lamanna C., Cignarelli M., Macchia O. L., Fariello S., Sorrentino M. R., Franzetti I., Radin R., Annunziata F., Bonabello L. A., Durante A., Dolcino M., Gallo F., Mazzucchelli C., Aleo A., Melga P., Briatore L., Maggi D., Storace D., Cecoli F., D'Ugo E., Pupillo M., Baldassarre M. P. A., Salvati F., Minnucci A., De Luca A., Zugaro A., Santarelli L., Bosco A., Petrella V., La Verghetta G. G., D'Andrea S., Giuliani A. E., Polidoro W. L., Sperandio A., Sciarretta F., Pezzella A., Carlone A., Potenziani S., Venditti C., Foffi C., Carbone S., Cipolloni L., Moretti C., Leto G., Serra R., Petrachi F., Romano I., Lacaria E., Russo L., Goretti C., Sannino C., Dolci M., Bruselli L., Mori M. L., Baccetti F., Del Freo M., Cucinotta D., Giunta L., Ruffo M. C., Cannizzaro D., Pintaudi B., Perrone G., Pata P., Ragonese F., Lettina G., Mancuso T., Coppolino A., Piatti P. M., Monti L., Stuccillo M., Lucotti P., Setola M., Crippa G. V., Loi C., Oldani M., Bottalico M. L., Pellegata B., Bonomo M., Menicatti L. S. M., Resi V., Bertuzzi F., Disoteo E. O., Pizzi G., Annuzzi G., Capaldo B., Nappo R., Auciello S. M., Turco A. A., Costagliola L., Corte G. D., Vallefuoco P., Nappi F., Vitale M., Cocozza S., Ciano O., Massimino E., Garofalo N., Avogaro A., Guarneri G., Fedele D., Sartore G., Chilelli N. C., Burlina S., Bonsembiante B., Galluzzo A., Torregrossa V., Mancastroppa G., Arsenio L., Cioni F., Caronna S., Papi M., Santeusanio F., Calagreti G., Timi A., Tantucci A., Marino C., Ginestra F., Di Biagio R., Taraborelli M., Miccoli R., Bianchi C., Garofolo M., Politi K. S., Penno G., Livraga S., Calzoni F., Mancastroppa G. L. F., Corsini E., Tedeschi A., Gagliano M. S., Ippolito G., Salutini E., Cervellino F., Natale M., Salvatore V., Zampino A., Sinisi R., Arcangeli A., Zogheri A., Guizzotti S., Longo R., Pellicano F., Scolozzi P., Termine S., Luberto A., Ballardini G., Trojani C., Mazzuca P., Bruglia M., Ciamei M., Genghini S., Zannoni C., Rangel G., Salvi L., Zappaterreno A., Cordone S., Simonelli P., Meggiorini M., Frasheri A., Di Pippo C., Maglio C., Mazzitelli G., Rinaldi M. E., Galli A., Romano M., D'Angelo P., Suraci C., Bacci S., Palena A. P., Genovese S., Mancino M., Rondinelli M., Capone F., Calabretto E., Bulgheroni M., Bucciarelli L., Ceccarelli E., Fondelli C., Santacroce C., Guarino E., Nigi L., Lalli C., Di Vizia G., Scarponi M., Montani V., Di Bernardino P., Romagni P., Dolcetti K., Forte E., Tamburo L., Perin P. C., Prinzis T., Gruden G., Bruno G., Zucco C., Perotta M., Marena S., Monsignore S., Panero F., Ponzi F., Carpinteri R., Casagrande M. L., Coletti M. F., Balini A., Filopanti M., Madaschi S., Pulcina A., Grimaldi F., Venturini G., Agus S., Pagnutti S., Guidotti F., Cavarape A., Cigolini M., Pichiri I., Brangani C., Fainelli G., Tomasetto E., Zoppini G., Galletti A., Perrone D., Capra C., Bianchini F., Ceseri M., Di Nardo B., Sasso E., Bartolomei B., Suliman I., Fabbri G., Romano G., Maturo N., Nunziata G., Capobianco G., De Simone G., Villa V., Rota G., Pentangelo C., Carbonara O., Caiazzo G., Cutolo M., Sorrentino T., Mastrilli V., Amelia U., Masi S., Corigliano G., Gaeta I., Armentano V., Calatola P., Capuano G., Angiulli B., Auletta P., Petraroli E., Iodice C. E., and Agrusta M.

Abstract

Background The best treatment option for patients with type 2 diabetes in whom treatment with metformin alone fails to achieve adequate glycaemic control is debated. We aimed to compare the long-term effects of pioglitazone versus sulfonylureas, given in addition to metformin, on cardiovascular events in patients with type 2 diabetes. Methods TOSCA.IT was a multicentre, randomised, pragmatic clinical trial, in which patients aged 50–75 years with type 2 diabetes inadequately controlled with metformin monotherapy (2–3 g per day) were recruited from 57 diabetes clinics in Italy. Patients were randomly assigned (1:1), by permuted blocks randomisation (block size 10), stratified by site and previous cardiovascular events, to add-on pioglitazone (15–45 mg) or a sulfonylurea (5–15 mg glibenclamide, 2–6 mg glimepiride, or 30–120 mg gliclazide, in accordance with local practice). The trial was unblinded, but event adjudicators were unaware of treatment assignment. The primary outcome, assessed with a Cox proportional-hazards model, was a composite of first occurrence of all-cause death, non-fatal myocardial infarction, non-fatal stroke, or urgent coronary revascularisation, assessed in the modified intention-to-treat population (all randomly assigned participants with baseline data available and without any protocol violations in relation to inclusion or exclusion criteria). This study is registered with ClinicalTrials.gov, number NCT00700856. Findings Between Sept 18, 2008, and Jan 15, 2014, 3028 patients were randomly assigned and included in the analyses. 1535 were assigned to pioglitazone and 1493 to sulfonylureas (glibenclamide 24 [2%], glimepiride 723 [48%], gliclazide 745 [50%]). At baseline, 335 (11%) participants had a previous cardiovascular event. The study was stopped early on the basis of a futility analysis after a median follow-up of 57·3 months. The primary outcome occurred in 105 patients (1·5 per 100 person-years) who were given pioglitazone and 108 (1·5 p

Published
2017

8. Gestational Diabetes Mellitus and Future Cardiovascular Risk: An Update

Author

Burlina, S., Dalfrà, M. G., Chilelli, N. C., and Lapolla, A.

Subjects
Article Subject
Abstract

The prevalence of gestational diabetes mellitus is increasing in parallel with the rising prevalence of type 2 diabetes and obesity around the world. Current evidence strongly suggests that women who have had gestational diabetes mellitus are at greater risk of cardiovascular disease later in life. Given the growing prevalence of gestational diabetes mellitus, it is important to identify appropriate reliable markers of cardiovascular disease and specific treatment strategies capable of containing obesity, diabetes, and metabolic syndrome in order to reduce the burden of cardiovascular disease in the women affected.

Published
2016
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13. Long-term effect of pioglitazone vs glimepiride on lipoprotein oxidation in patients with type 2 diabetes: a prospective randomized study

Author

Marco Roverso, Nino Cristiano Chilelli, Olga Vaccaro, Giovanni Sartore, Raffaella Marin, Silvia Burlina, Roberta Seraglia, Annunziata Lapolla, Eugenio Ragazzi, Chiara Cosma, Sartore, G., Chilelli, N. C., Seraglia, R., Ragazzi, E., Marin, R., Roverso, M., Cosma, C., Vaccaro, O., Burlina, S., and Lapolla, A.

Subjects
Blood Glucose, Glycation End Products, Advanced, Male, Endocrinology, Diabetes and Metabolism, Type 2 diabetes, 030204 cardiovascular system & hematology, Diabete, chemistry.chemical_compound, Clinical trials, 0302 clinical medicine, Endocrinology, Oxidized lipids, Lipoprotein, medicine.diagnostic_test, Diabetes, General Medicine, Oxidized lipid, Lipid, Middle Aged, Lipids, Diabetes and Metabolism, Clinical trial, Lipoproteins, LDL, Sulfonylurea Compound, Lipoproteins, Mass spectrometry, Internal Medicine, lipids (amino acids, peptides, and proteins), Female, Lipoproteins, HDL, Oxidation-Reduction, medicine.drug, Human, medicine.medical_specialty, 030209 endocrinology & metabolism, 03 medical and health sciences, Diabetes mellitus, Internal medicine, medicine, Humans, Hypoglycemic Agents, Lipoprotein oxidation, Aged, Apolipoprotein A-I, Hypoglycemic Agent, Pioglitazone, business.industry, Cholesterol, Cholesterol, HDL, medicine.disease, Glimepiride, Sulfonylurea Compounds, chemistry, Diabetes Mellitus, Type 2, Thiazolidinediones, business, Lipid profile
Abstract

Aims: Type 2 diabetes (DM2) is associated to oxidative modifications of high-density lipoproteins (HDL), which can interfere with their function. Pioglitazone has proved effective in raising HDL cholesterol (HDL-C) and lowering small dense low-density lipoprotein (LDL), but no clinical studies have examined its effect on lipoprotein oxidation in patients with DM2. Methods: We assessed the effect of pioglitazone vs glimepiride after 1 year on HDL oxidation, expressed as relative abundance of peptides containing Met 112 O in ApoA-I (oxApoA-I) estimated by mass spectrometry (MALDI/TOF/TOF), in 95 patients with DM2. The oxLDL and AGE were quantified by ELISA. Results: Patients receiving pioglitazone showed a significant increase in the concentration of ApoA-I (Δ = 7.2 ± 14.8 mg/dL, p < 0.02) and a reduction in oxApoA-I (Δ = − 1.0 ± 2.6%, p < 0.02); this reduction was not significantly different from glimepiride. oxLDL showed a slight, but not significant increase in both treatment groups. Regression analysis showed a correlation between ΔoxApoA-I and ΔAGE (r = 0.30; p = 0.007) in all patients, while both of these parameters were unrelated to changes in HbA1c, HDL-C, duration of illness, or use of statins. Conclusions: Long-term treatment with pioglitazone was effective in reducing the oxidation of HDL, but not LDL in patients with DM2, while glimepiride didn’t. This finding seems to be associated to the change of glyco-oxidation status, not to any improvement in glycemic control or lipid profile. Trial registration: NCT00700856, ClinicalTrials.gov Registered June 18, 2008.

Published
2019

14. AGEs, rather than hyperglycemia, are responsible for microvascular complications in diabetes: a "glycoxidation-centric" point of view.

Author

Chilelli NC, Burlina S, and Lapolla A

Subjects
Animals, Diabetes Mellitus, Type 2 metabolism, Diabetes Mellitus, Type 2 physiopathology, Diabetes Mellitus, Type 2 therapy, Diabetic Nephropathies metabolism, Diabetic Nephropathies physiopathology, Diabetic Neuropathies metabolism, Diabetic Neuropathies physiopathology, Diabetic Retinopathy metabolism, Diabetic Retinopathy physiopathology, Glycation End Products, Advanced blood, Humans, Hyperglycemia prevention & control, Microvessels metabolism, Diabetes Mellitus, Type 2 complications, Diabetic Angiopathies physiopathology, Glycation End Products, Advanced metabolism, Microvessels physiopathology, Models, Biological, Oxidative Stress
Abstract

Aims: Advanced glycation end products (AGE) excess is one of the most important mechanisms involved in the pathophysiology of chronic diabetic complications. This review first summarizes the role of these compounds in microvascular pathogenesis, particularly in the light of recently proposed biochemical mechanisms for diabetic retinopathy, nephropathy and neuropathy. Then we focus on the relationship between AGE and metabolic memory, trying to clarify the former's role in the missing link between micro- and macrovascular complications., Data Synthesis: An excessive AGE formation has been demonstrated in the newly disclosed biochemical pathways involved in the microvascular pathobiology of type 2 diabetes, confirming the central role of AGE in the progression of diabetic neuropathy, retinopathy and nephropathy. As shown by recent studies, AGE seem to be not "actors", but "directors" of processes conducting to these complications, for at least two main reasons: first, AGE have several intra- and extracellular targets, so they can be seen as a "bridge" between intracellular and extracellular damage; secondly, whatever the level of hyperglycemia, AGE-related intracellular glycation of the mitochondrial respiratory chain proteins has been found to produce more reactive oxygen species, triggering a vicious cycle that amplifies AGE formation. This may help to explain the clinical link between micro- and macrovascular disease in diabetes, contributing to clarify the mechanisms behind metabolic memory., Conclusions: The pathophysiological cascades triggered by AGE have a dominant, hyperglycemia-independent role in the onset of the microvascular complications of diabetes. An effective approach to prevention and treatment must therefore focus not only on early glycemic control, but also on reducing factors related to oxidative stress, and the dietary intake of exogenous AGE in particular., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Published
2013
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