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2. Incidence of Type 1 diabetes and factors associated with presence and severity of ketoacidosis at onset in children

Author

Tumini, S. Baki, S. Kosteria, I. Giuseppe, I.D. Levantini, G.

Subjects
endocrine system diseases, nutritional and metabolic diseases
Abstract

Background and aim: To assess the incidence of Type 1 Diabetes Mellitus (T1DM) during the period 2012-2017, the frequency and severity of ketoacidosis (DKA) at diabetes onset, and the factors associated with DKA in children and adolescents younger than 18 years old in the Abruzzo region, Italy. Methods: All incident cases of T1DM (0-17 years old) diagnosed between January 2012 and December 2017 were included. Data about the patients were obtained from two independent sources; insulin prescriptions and medical records. Clinical data at diabetes onset, as well as demographic and non-demographic data, including center of first hospitalization, distance to regional reference center and number of pediatricians (per 1000 residents younger than 18 years) were collected and evaluated. Results: During 2012-2017 period, 177 patients were diagnosed with T1DM. In 2012, T1DM incidence was 15.6 per 100,000/year; in 2013, 16.4 per 100,000/year; in 2014, 11.6 per 100,000/year; in 2015, 14.2 per 100,000/year; in 2016, 16.2 per 100,000/year and in 2017, 12.2 per 100,000/year. DKA was present in 29.3% of patients, 6.9% with severe DKA. The DKA presence was correlated to age (p

Published
2022

4. Recommendations for recognizing, risk stratifying, treating, and managing children and adolescents with hypoglycemia

Author

Stefano Zucchini, Stefano Tumini, Andrea Enzo Scaramuzza, Riccardo Bonfanti, Maurizio Delvecchio, Roberto Franceschi, Dario Iafusco, Lorenzo Lenzi, Enza Mozzillo, Stefano Passanisi, Claudia Piona, Ivana Rabbone, Novella Rapini, Andrea Rigamonti, Carlo Ripoli, Giuseppina Salzano, Silvia Savastio, Riccardo Schiaffini, Angela Zanfardino, Valentino Cherubini, Diabetes Study Group of the Italian Society for Pediatric Endocrinology Diabetes, Albino Claudia Accursia, Aloe Monica, Anzelotti Maria Teresa, Arnaldi Claudia, Barbetti Fabrizio, Bassi Marta, Berioli Maria Giulia, Bernardini Luca, Bertelli Enrica, Biagioni Martina, Bobbio Adriana, Bombaci Bruno, Bonfanti Riccardo, Bonura Clara, Bracciolini Giulia Patrizia, Bruzzese Mariella, Bruzzi Patrizia, Buono Pietro, Buscarino Piera, Cadario Francesco, Calcaterra Valeria, Calzi Elena, Cappa Marco, Cardani Roberta, Cardella Francesca, Cardinale Giuliana Marcella, Casertano Alberto, Castorani Valeria, Cauvin Vittoria, Cenciarelli Valentina, Ceruti Franco, Cherubini Valentino, Chiarelli Francesco, Chiari Giovanni, Cianfarani Stefano, Cicchetti Mario, Cipriano Paola, Cirillo Dante, Citriniti Felice, Coccioli Maria Susanna, Confetto Santino, Contreas Giovanna, Coro Anna, Correddu Antonella, Corsini Elisa, Crino’ Antonino, d’Annunzio Giuseppe, De Berardinis Fiorella, De Donno Valeria, De Filippo Gianpaolo, De Marco Rosaria, De Sanctis Luisa, Del Duca Elisabetta, Delvecchio Maurizio, Deodati Annalisa, Di Bonito Procolo, Di Candia Francesca, Faleschini Elena, Fattorusso Valentina, Favia Anna, Federico Giovanni, Felappi Barbara, Ferrari Mara, Ferrito Lucia, Fichera Graziella, Fontana Franco, Fornari Elena, Franceschi Roberto, Franco Francesca, Franzese Adriana, Frongia Anna Paola, Frontino Giulio, Gaiero Alberto, Galassi Sabrina Maria, Gallo Francesco, Gargantini Luigi, Giani Elisa, Gortan Anna Jolanda, Graziani Vanna, Grosso Caterina, Gualtieri Antonella, Guasti Monica, Guerraggio Lucia Paola, Guzzetti Chiara, Iafusco Dario, Iannicelli Gennaro, Iezzi Maria Laura, Ignaccolo Maria Giovanna, Innaurato Stefania, Inzaghi Elena, Iovane Brunella, Iughetti Lorenzo, Kaufmann Peter, La Loggia Alfonso, Lambertini Anna Giulia, Lapolla Rosa, Lasagni Anna, Lazzaro Nicola, Lazzeroni Pietro, Lenzi Lorenzo, Lera Riccardo, Levantini Gabriella, Lezzi Marilea, Lia Rosanna, Liguori Alice, Lo Presti Donatella, Lombardo Fortunato, Lonero Antonella, Longhi Silvia, Lorubbio Antonella, Lucchesi Sonia, Maccioni Rosella, Macedoni Maddalena, Macellaro Patrizia Cristiana, Madeo Simona Filomena, Maffeis Claudio, Mainetti Benedetta, Maltoni Giulio, Mameli Chiara, Mammì Francesco, Manca Bitti Maria Luisa, Mancioppi Valentina, Manco Melania, Marigliano Marco, Marino Monica, Marsciani Alberto, Matteoli Maria Cristina, Mazzali Elena, Minute Marta, Minuto Nicola, Monti Sara, Morandi Anita,, Morganti Gianfranco, Morotti Elisa, Mozzillo Enza, Musolino Gianluca, Olivieri Francesca, Ortolani Federica, Pampanini Valentina, Pardi Daniela, Pascarella Filomena, Pasquino Bruno, Passanisi Stefano, Patera Ippolita Patrizia, Pedini Annalisa, Pennati Maria Cristina, Peruzzi Sonia, Peverelli Paola, Pezzino Giulia, Piccini Barbara, Piccinno Elvira Eugenia Rosaria, Piona Claudia, Piredda Gavina, Piscopo Alessia, Pistone Carmelo, Pozzi Erica, Prandi Elena, Predieri Barbara, Prudente Sabrina, Pulcina Anna, Rabbone Ivana, Randazzo Emioli, Rapini Novella, Reinstadler Petra, Riboni Sara, Ricciardi Maria Rossella, Rigamonti Andrea, Ripoli Carlo, Rossi Virginia, Rossi Paolo, Rutigliano Irene, Sabbion Alberto, Salvatoni Alessandro, Salvo Caterina, Salzano Giuseppina, Sanseviero Mariateresa, Savastio Silvia, Savini Rosanna, Scanu Mariapiera, Scaramuzza Andrea Enzo, Schiaffini Riccardo, Schiavone Maurizio, Schieven Eleonardo, Scipione Mirella, Secco Andrea, Silvestri Francesca, Siri Giulia, Sogno Valin Paola, Sordelli Silvia, Spiri Daniele, Stagi Stefano, Stamati Filomena Andreina, Suprani Tosca, Talarico Valentina, Tiberi Valentina, Timpanaro Tiziana Antonia Lucia, Tinti Davide, Tirendi Antonina, Tomaselli Letizia Grazia, Toni Sonia, Torelli Cataldo, Tornese Gianluca, Trada Michela,, Trettene Adolfo Andrea, Tumini Stefano, Tumminelli Marilena, Valerio Giuliana, Vandelli Sara, Ventrici Claudia, Zampolli Maria, Zanatta Manuela, Zanfardino Angela, Zecchino Clara, Zonca Silvia, and Zucchini Stefano

Subjects
adolescents, automated insulin delivery, children, hypoglycemia, glucagon, oral glucose, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

There has been continuous progress in diabetes management over the last few decades, not least due to the widespread dissemination of continuous glucose monitoring (CGM) and automated insulin delivery systems. These technological advances have radically changed the daily lives of people living with diabetes, improving the quality of life of both children and their families. Despite this, hypoglycemia remains the primary side-effect of insulin therapy. Based on a systematic review of the available scientific evidence, this paper aims to provide evidence-based recommendations for recognizing, risk stratifying, treating, and managing patients with hypoglycemia. The objective of these recommendations is to unify the behavior of pediatric diabetologists with respect to the timely recognition and prevention of hypoglycemic episodes and the correct treatment of hypoglycemia, especially in patients using CGM or advanced hybrid closed-loop systems. All authors have long experience in the specialty and are members of the Italian Society of Pediatric Endocrinology and Diabetology. The goal of treating hypoglycemia is to raise blood glucose above 70 mg/dL (3.9 mmol/L) and to prevent further decreases. Oral glucose at a dose of 0.3 g/kg (0.1 g/kg for children using “smart pumps” or hybrid closed loop systems in automated mode) is the preferred treatment for the conscious individual with blood glucose

Published
2024
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5. Sulfonylurea treatment outweighs insulin therapy in short-term metabolic control of patients with permanent neonatal diabetes mellitus due to activating mutations of the KCNJ11 (KIR6.2) gene

Author

Tonini, G., Bizzarri, C., Bonfanti, R., Vanelli, M., Cerutti, F., Faleschini, E., Meschi, F., Prisco, F., Ciacco, E., Cappa, M., Torelli, C., Cauvin, V., Tumini, S., Iafusco, D., Barbetti, F., and Early-Onset Diabetes Study Group of the Italian Society of Paediatric Endocrinology and Diabetology

Published
2006
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10. Effectiveness and safety of long-term treatment with sulfonylureas in patients with neonatal diabetes due to KCNJ11 mutations: an international cohort study

Author

Bowman P., Sulen A., Barbetti F., Beltrand J., Svalastoga P., Codner E., Tessmann E. H., Juliusson P. B., Skrivarhaug T., Pearson E. R., Flanagan S. E., Babiker T., Thomas N. J., Shepherd M. H., Ellard S., Klimes I., Szopa M., Polak M., Iafusco D., Hattersley A. T., Njolstad P. R., Aisenberg J., Akkurt I., Abdul-Latif H., Al-Abdullah A., Barak L., Van Den Bergh J., Bertrand A. -M., Bizzarri C., Bonfanti R., Bruel H., Burrows A., Cadario F., Cameron F. J., Carson D., Cartigny M., Cauvin V., Cave H., Chakera A., Chetan R., Chiari G., Couch B., Coutant R., Cummings E., Dankovcikova A., Davis L., Deiss D., Delvecchio M., Faleschini E., Fauret A. -L., Finn R., Ford T., Franco E. D., Gallen B. D., Gasperikova D., Guntamukkala P., Hakeem V., Hasegawa S., Hathout E. H., Heffernan E., Hill D., Ho J., Hoarau M., Holl R., Hoddinott R., Houghton J., Howard N., Hughes N., Hunter I., Hogasen A. K., Kuulasmaa H., Ioacara S., Iotova V., Irgens H., Jaap A., Jones K., Kapellen T., Kaufman E., Klinge A., Klupa T., Krishnaswamy R., Lafferty T., LeGault L., Lambert P., Malecki M. T., Malievsky O., Mathew R., Mathews F., McVie R., Menzel U., Metz C., Meulen J. V. D., Modgil G., Mul D., Muther S., Nuboer R., O'Connell S. M., O'Riordan S., Palko M., Patel K. A., Pesavento R., Piccinno E., Pillai J. K., Pruhova S., Punthakee Z., Rabbone I., Raile K., Rincon M., Rose D., Sanchez J., Sandereson S., Saxena V., Schebek M., Schmidt D., Shehadeh N., Shiels J. P. H., Silva J. M. C. L., Stanik J., Tinklin T., Tjora E., Tumini S., Tuomi T., Uehara A., Velde R. V. D., Vermeulen G., Visser U., Voorhoeve P., Walker J., Weill J., Weisner T., Werner A., Williams T., Woodhead H., oddegard R., Bowman, Pamela, Sulen, Åsta, Barbetti, Fabrizio, Beltrand, Jacque, Svalastoga, Pernille, Codner, Ethel, Tessmann, Ellen H, Juliusson, Petur B, Skrivarhaug, Torild, Pearson, Ewan R, Flanagan, Sarah E, Babiker, Tarig, Thomas, Nicholas J, Shepherd, Maggie H, Ellard, Sian, Klimes, Iwar, Szopa, Magdalena, Polak, Michel, Iafusco, Dario, Hattersley, Andrew T, Njølstad, Pål R, Aisenberg, Javier, Akkurt, Ilker, Abdul-Latif, Hussein, Al-Abdullah, Anee, Barak, Lubomir, Van Den Bergh, Joop, Bertrand, Anne-Marie, Bizzarri, Carla, Bonfanti, Riccardo, Bruel, Henri, Burrows, Anthony, Cadario, Francesco, Cameron, Fergus J., Carson, Denni, Cartigny, Maryse, Cauvin, Vittoria, Cave, Helene, Chakera, Ali, Chetan, Ravi, Chiari, Giovanni, Couch, Bob, Coutant, Régi, Cummings, Elizabeth, Dankovcikova, Adriana, Davis, Liz, Deiss, Dorothee, Delvecchio, Maurizio, Faleschini, Elena, Fauret, Anne-Laure, Finn, Roisin, Ford, Tamsin, Franco, Elisa De, Gallen, Bastian De, Gasperíková, Daniela, Guntamukkala, Padma, Hakeem, Vaseem, Hasegawa, Shinji, Hathout, Eba H., Heffernan, Emmeline, Hill, David, Ho, Josephine, Hoarau, Marie, Holl, Reinhard, Hoddinott, Rebecca, Houghton, Jane, Howard, Neville, Hughes, Natalie, Hunter, Ian, Høgåsen, Anne Kirsti, Kuulasmaa, Helena, Iocara, Sorin, Iotova, Violeta, Irgens, Henrik, Jaap, Alan, Jones, Kenneth, Kapellen, Thoma, Kaufman, Ellen, Klinge, Andrea, Klupa, Tomasz, Krishnaswamy, Ramaiyer, Lafferty, Tony, Legault, Laurent, Lambert, Paul, Malecki, Maciej T, Malievsky, Olag, Mathew, Revi, Mathews, France, Mcvie, Robert, Menzel, Ulrike, Metz, Chantale, Meulen, John Van Der, Modgil, Gita, Mul, Dick, Muther, Silvia, Nuboer, Roo, O'Connell, Susan M., O'Riordan, Stephen, Palko, Miroslav, Patel, Kashyap Amratlal, Pesavento, Roberta, Piccinno, Elvira, Pillai, Janani Kumaraguru, Pruhova, Stephanka, Punthakee, Zubin, Rabbone, Ivana, Raile, Klemen, Rincon, Marielisa, Rose, Danette, Sanchez, Janine, Sandereson, Susan, Saxena, Vinay, Schebek, Martin, Schmidt, Dorothee, Shehadeh, Naim, Shiels, Julian P. H., Silva, Jose M. C. L, Stanik, Juraj, Tinklin, Tracy, Tjora, Erling, Tumini, Stefano, Tuomi, Tiinamaija, Uehara, Akiko, Velde, Robert Van der, Vermeulen, Guido, Visser, Uma, Voorhoeve, Paul, Walker, Jan, Weill, Jaque, Weisner, Tobia, Werner, Andrea, Williams, Toni, Woodhead, Helen, Øddegård, Rønnaug, Bowman, P., Sulen, A., Barbetti, F., Beltrand, J., Svalastoga, P., Codner, E., Tessmann, E. H., Juliusson, P. B., Skrivarhaug, T., Pearson, E. R., Flanagan, S. E., Babiker, T., Thomas, N. J., Shepherd, M. H., Ellard, S., Klimes, I., Szopa, M., Polak, M., Iafusco, D., Hattersley, A. T., Njolstad, P. R., Aisenberg, J., Akkurt, I., Abdul-Latif, H., Al-Abdullah, A., Barak, L., Van Den Bergh, J., Bertrand, A. -M., Bizzarri, C., Bonfanti, R., Bruel, H., Burrows, A., Cadario, F., Cameron, F. J., Carson, D., Cartigny, M., Cauvin, V., Cave, H., Chakera, A., Chetan, R., Chiari, G., Couch, B., Coutant, R., Cummings, E., Dankovcikova, A., Davis, L., Deiss, D., Delvecchio, M., Faleschini, E., Fauret, A. -L., Finn, R., Ford, T., Franco, E. D., Gallen, B. D., Gasperikova, D., Guntamukkala, P., Hakeem, V., Hasegawa, S., Hathout, E. H., Heffernan, E., Hill, D., Ho, J., Hoarau, M., Holl, R., Hoddinott, R., Houghton, J., Howard, N., Hughes, N., Hunter, I., Hogasen, A. K., Kuulasmaa, H., Ioacara, S., Iotova, V., Irgens, H., Jaap, A., Jones, K., Kapellen, T., Kaufman, E., Klinge, A., Klupa, T., Krishnaswamy, R., Lafferty, T., Legault, L., Lambert, P., Malecki, M. T., Malievsky, O., Mathew, R., Mathews, F., Mcvie, R., Menzel, U., Metz, C., Meulen, J. V. D., Modgil, G., Mul, D., Muther, S., Nuboer, R., O'Connell, S. M., O'Riordan, S., Palko, M., Patel, K. A., Pesavento, R., Piccinno, E., Pillai, J. K., Pruhova, S., Punthakee, Z., Rabbone, I., Raile, K., Rincon, M., Rose, D., Sanchez, J., Sandereson, S., Saxena, V., Schebek, M., Schmidt, D., Shehadeh, N., Shiels, J. P. H., Silva, J. M. C. L., Stanik, J., Tinklin, T., Tjora, E., Tumini, S., Tuomi, T., Uehara, A., Velde, R. V. D., Vermeulen, G., Visser, U., Voorhoeve, P., Walker, J., Weill, J., Weisner, T., Werner, A., Williams, T., Woodhead, H., and Oddegard, R.

Subjects
Endocrinology, Endocrinology, Diabetes and Metabolism, Internal Medicine
Abstract

Background: KCNJ11 mutations cause permanent neonatal diabetes through pancreatic ATP-sensitive potassium channel activation. 90% of patients successfully transfer from insulin to oral sulfonylureas with excellent initial glycaemic control; however, whether this control is maintained in the long term is unclear. Sulfonylurea failure is seen in about 44% of people with type 2 diabetes after 5 years of treatment. Therefore, we did a 10-year multicentre follow-up study of a large international cohort of patients with KCNJ11 permanent neonatal diabetes to address the key questions relating to long-term efficacy and safety of sulfonylureas in these patients. Methods: In this multicentre, international cohort study, all patients diagnosed with KCNJ11 permanent neonatal diabetes at five laboratories in Exeter (UK), Rome (Italy), Bergen (Norway), Paris (France), and Krakow (Poland), who transferred from insulin to oral sulfonylureas before Nov 30, 2006, were eligible for inclusion. Clinicians collected clinical characteristics and annual data relating to glycaemic control, sulfonylurea dose, severe hypoglycaemia, side-effects, diabetes complications, and growth. The main outcomes of interest were sulfonylurea failure, defined as permanent reintroduction of daily insulin, and metabolic control, specifically HbA 1c and sulfonylurea dose. Neurological features associated with KCNJ11 permanent neonatal diabetes were also assessed. This study is registered with ClinicalTrials.gov, number NCT02624817. Findings: 90 patients were identified as being eligible for inclusion and 81 were enrolled in the study and provided long-term (>5·5 years cut-off) outcome data. Median follow-up duration for the whole cohort was 10·2 years (IQR 9·3–10·8). At most recent follow-up (between Dec 1, 2012, and Oct 4, 2016), 75 (93%) of 81 participants remained on sulfonylurea therapy alone. Excellent glycaemic control was maintained for patients for whom we had paired data on HbA 1c and sulfonylurea at all time points (ie, pre-transfer [for HbA 1c ], year 1, and most recent follow-up; n=64)—median HbA 1c was 8·1% (IQR 7·2–9·2; 65·0 mmol/mol [55·2–77·1]) before transfer to sulfonylureas, 5·9% (5·4–6·5; 41·0 mmol/mol [35·5–47·5]; p

Published
2018

14. Insulin pump failures in Italian children with Type 1 diabetes: retrospective 1-year cohort study

Author

Rabbone, I., Minuto, N., Bonfanti, R., Marigliano, M., Cerutti, F., Cherubini, V., d(')Annunzio, G., Frongia, A. P., Iafusco, D., Ignaccolo, G., Lombardo, F., Schiaffini, R., Toni, S., Tumini, S., Zucchini, S., Pistorio, A., Scaramuzza, A. E., Scaramuuzza, A. E., Lera, R., Secco, A., Bobbio, A., Bechaz, M., Piccinno, E., Natale, M. P., Ortolani, F., Zecchino, C., Lonero, A., Maltoni, G., Pasquino, B., Gallo, F., Frongia, P., Ripoli, C., Lo Presti, D., Timpanaro, T., Citriniti, F., Suprani, T., Carinci, S., Cipriano, P., Lazzaro, N., De Donno, V., Gallarotti, F., Lenzi, L., Piccini, B., Vittorio, L., Russo, C., Borea, R., Mamm(`i), F., Bruzzese, M., Ventrici, C., Salzano, G., Frontino, G., Bonura, C., Favalli, V., Scaramuzza, A., Zuccotti, G. V., Ferrari, M., Iughetti, L., Predieri, B., Franzese, A., Mozzillo, E., Buono, P., Confetto, S., Zanfardino, A., Cadario, F., Savastio, S., Fiorito, C., Barbieri, P., Piredda, G., Cardella, F., Ropolo, R., Federico, G., Marchi, B., Benevento, D., Carducci, C., Mancabitti, M. L., Delvecchio, M., Lapolla, R., Gaiero, A., Fichera, G., Ignaccolo, M. G., Tinti, D., Cauvin, V., Franceschi, R., Biagioni, M., Salvatoni, A., Scolari, A., Maffeis, C., Sabbion, A., Arnaldi, C., Tosini, D., Rabbone, I, Minuto, N., Bonfanti, R., Marigliano, M., Cerutti, F., Cherubini, V., D'Annunzio, G., Frongia, A. P., Iafusco, Dario, Ignaccolo, G., Lombardo, F., Schiaffini, R., Toni, S., Tumini, S., Zucchini, S., Pistorio, A., Scaramuzza, A. E., Rabbone, I., Iafusco, D., Lera, R., Secco, A., Bobbio, A., Bechaz, M., Piccinno, E., Natale, M. P., Ortolani, F., Zecchino, C., Lonero, A., Maltoni, G., Pasquino, B., Gallo, F., Frongia, P., Ripoli, C., Lo Presti, D., Timpanaro, T., Citriniti, F., Suprani, T., Carinci, S., Cipriano, P., Lazzaro, N., De Donno, V., Gallarotti, F., Lenzi, L., Piccini, B., Vittorio, L., Russo, C., Borea, R., Mammi, F., Bruzzese, M., Ventrici, C., Salzano, G., Frontino, G., Bonura, C., Favalli, V., Scaramuzza, A., Zuccotti, G. V., Ferrari, M., Iughetti, L., Predieri, B., Franzese, A., Mozzillo, E., Buono, P., Confetto, S., Zanfardino, A., Cadario, F., Savastio, S., Fiorito, C., Barbieri, P., Piredda, G., Cardella, F., Ropolo, R., Federico, G., Marchi, B., Benevento, D., Carducci, C., Mancabitti, M. L., Del Vecchio, M., Lapolla, R., Gaiero, A., Fichera, G., Ignaccolo, M. G., Tinti, D., Cauvin, V., Franceschi, R., Biagioni, M., Salvatoni, A., Scolari, A., Maffeis, C., Sabbion, A., Arnaldi, C., Tosini, D., Rabbone, Minuto, Mammì, F., and Mozzillo, Enza.

Subjects
Blood Glucose, Male, Pediatrics, Adolescent, Blood Glucose Self-Monitoring, Child, Child, Preschool, Diabetes Mellitus, Type 1, Equipment Failure, Female, Humans, Infant, Insulin, Italy, Retrospective Studies, Insulin Infusion Systems, type 1 diabetes, medicine.medical_treatment, Endocrinology, Diabetes and Metabolism, Internal Medicine, Endocrinology, 0302 clinical medicine, Retrospective Studie, Medicine, 030212 general & internal medicine, Diabetes, Diabetology, failure, Diabetes and Metabolism, children and adolescents, insulin pump, Cohort study, Type 1, Human, Insulin pump, medicine.medical_specialty, Disease duration, 030209 endocrinology & metabolism, 03 medical and health sciences, Diabetes mellitus, Diabetes Mellitus, Preschool, Type 1 diabetes, business.industry, Diabetes, Type1, Pump, Insulin, Type1, Retrospective cohort study, Pump, medicine.disease, Surgery, Insulin Infusion System, business
Abstract

Aims Insulin pump failure and/or malfunction requiring replacement have not been thoroughly investigated. This study evaluated pump replacement in children and adolescents with Type 1 diabetes using insulin pump therapy. Methods Data were collected for all participants younger than 19 years, starting insulin pump therapy before 31 December 2013. For each child, age, disease duration, date of insulin pump therapy initiation, insulin pump model, failure/malfunction/replacement yes/no and reason were considered for the year 2013. Results Data were returned by 40 of 43 paediatric centres belonging to the Diabetes Study Group of the Italian Society of Paediatric Endocrinology and Diabetology. In total, 1574 of 11 311 (13.9%) children and adolescents with Type 1 diabetes were using an insulin pump: 29.2% Animas VIBE™, 9.4% Medtronic MiniMed 715/515™, 34.3% Medtronic MiniMed VEO™, 24.3% Accu-Check Spirit Combo™ and 2.8% other models. In 2013, 0.165 insulin pump replacements per patient-year (11.8% due to pump failure/malfunction and 4.7% due to accidental damage) were recorded. Animas VIBE™ (22.1%) and Medtronic MiniMed VEO™ (17.7%) were the most replaced. Conclusions In a large cohort of Italian children and adolescents with Type 1 diabetes, insulin pump failure/malfunction and consequent replacement are aligned with rates previously reported and higher in more sophisticated pump models. This article is protected by copyright. All rights reserved.

Published
2017

15. Organization and regional distribution of centers for the management of children and adolescents with diabetes in Italy

Author

Giorgetti C., Ferrito L., Zallocco F., Iannilli A., Cherubini V., Maghnie M., Rabbone I., Lera R., De Luna L., Kienberger B., Gualtieri A., Zecchino C., Piccino E., Ortolani F., Zucchini S., Maltoni G., Pasquino B., Reinstadler P., Prandi E., Zattoni V., Gallo F., Morganti G., Guerraggio L., Ripoli C., Frongia M., Pusceddu P., La Loggia A., Scanu P., Cardinale G., Ponzi G., Tomaselli L. G., Rapisarda V., Citriniti F., Soprani T., Tumini S., Lazzaro N., De Donno V., Banin P., Toni S., Lenzi L., Mainetti B., Coccioli M. S., D'Annunzio G., Minuto N., Montani E., Maccioni R., Marongiu U., Beccaria L., Bruzzese M., Mammi F., Pardi D., Lombardo F., Ventrici C., Scaramazza A., Ferrari M., Bonfanti R., Rigamonti A., Iughetti L., Predieri B., Iafusco D., Confetto S., Zanfardino A., Prisco F., Francese A., De Nitto E., Cadario F., Milia A., Piredda G., Mereu L., Soro M., Correddu A., Pipia A., Monciotti C., Cardella F., De Berardinis F., Santoro G., Chiari G., Berioli M. G., Federico G., Zanette G., Marsciani A., Pedini A., Patera I. P., Schiaffini R., Bitti M., Lidano R., Pietrosanti S., Delvecchio M., Trada M., Marinaro A., Meloni G., Galero A., Fichera G., Bulciolu P., Ignaccolo G., Cauvin V., Franceschi R., Faleschini E., Tornese G., Salvatoni A., Cardani R., Maffeis C., Marigliano M., Sabbion A., Arnaldi C., Giorgetti, Chiara, Ferrito, Lucia, Zallocco, Federica, Iannilli, Antonio, Cherubini, Valentino, Maghnie, Mohamad, Rabbone, Ivana, Lera, R., De Luna, L., Kienberger, B., Gualtieri, A., Zecchino, C., Piccino, E., Ortolani, F., Zucchini, S., Maltoni, G., Pasquino, B., Reinstadler, P., Prandi, E., Zattoni, V., Gallo, F., Morganti, G., Guerraggio, L., Ripoli, C., Frongia, M., Pusceddu, P., La Loggia, A., Scanu, P., Cardinale, G., Ponzi, G., Tomaselli, L. G., Rapisarda, V., Citriniti, F., Soprani, T., Tumini, S., Lazzaro, N., De Donno, V., Banin, P., Toni, S., Lenzi, L., Mainetti, B., Coccioli, M. S., D’Annunzio, G., Minuto, N., Montani, E., Maccioni, R., Marongiu, U., Beccaria, L., Bruzzese, M., Mammì, F., Pardi, D., Lombardo, F., Ventrici, C., Scaramazza, A., Ferrari, M., Bonfanti, R., Rigamonti, A., Iughetti, L., Predieri, B., Iafusco, Dario, Confetto, S., Zanfardino, A., Prisco, Francesco, Francese, A., De Nitto, E., Cadario, F., Milia, A., Piredda, G., Mereu, L., Soro, M., Correddu, A., Pipia, A., Monciotti, C., Cardella, F., De Berardinis, F., Santoro, G., Chiari, G., Berioli, M. G., Federico, G., Zanette, G., Marsciani, A., Pedini, A., Patera, I. P., Schiaffini, R., Bitti, M., Lidano, R., Pietrosanti, S., Delvecchio, M., Trada, M., Marinaro, A., Meloni, G., Galero, A., Fichera, G., Bulciolu, P., Rabbone, I., Ignaccolo, G., Cauvin, V., Franceschi, R., Faleschini, E., Tornese, G., Salvatoni, A., Cardani, R., Maffeis, C., Marigliano, M., Sabbion, A., Arnaldi, C., Study Group for Diabetes of, Isped, Tornese, Gianluca, Giorgetti, C., Ferrito, L., Zallocco, F., Iannilli, A., Cherubini, V., Maghnie, M., D'Annunzio, G., Mammi, F., Iafusco, D., and Prisco, F.

Subjects
Male, medicine.medical_specialty, Type 1 diabete, Adolescent, MEDLINE, Staffing, Distribution (economics), Legislation, diabetes, children, T1D, Italy, Pediatrics, Regional Medical Program, Prevalence, Surveys and Questionnaire, Medicine, Regional legislation, Practice Patterns, Physicians', Disease management (health), Child, Organization of care, Pediatric diabetes centers, Type 1 diabetes, Pediatrics, Perinatology and Child Health, business.industry, Incidence, Incidence (epidemiology), Research, Disease Management, Perinatology and Child Health, medicine.disease, Diabetes Mellitus, Type 1, diabete, Family medicine, Female, Organizational structure, Pediatric diabetes center, business, Delivery of Health Care, Human
Abstract

Background: The incidence of type 1 diabetes in childhood is increasing by 3 % per year, placing growing demands on healthcare professionals and medical expenditures. Aim of this study wars to assess the organization of care to children with diabetes in Italy. Methods: During 2012 a structured questionnaire was sent to all of the members of Italian Society of Paediatric Endocrinology and Diabetology (ISPED). Questions examined organizational structure of Centers, personnel dedicated to the care of children with diabetes, number of subjects followed, local legal legislation supporting centres. Results: A total of 68 centers taking care to 15,563 children and adolescents with diabetes under 18 years of age were identified with a prevalence of 1.4 per 1,000 people. A wide variation in the organizational background was also reported. Fourty-four centers were organized as outpatient departments, 17 as simple units, 5 as complex units and 2 as simple departmental structures. Most centers had a multidisciplinary team. Ten out of twenty Italian regions had introduced supportive regional legislation, but it was fully applied only in six of them. Conclusion: Great differences between regions were found in organizational structures, staffing levels and supportive legislation. The national legislation on diabetes was broadly implemented throughout the country regions. Further efforts are needed to improve standards and consistency of pediatric diabetes care in Italy.

Published
2015

16. Increasing burden, younger age at onset and worst metabolic control in migrant than in Italian children with type 1 diabetes: An emerging problem in pediatric clinics

Author

Cadario, F1, Cerutti, F, Savastio, S, Rabbone, I, Tumini, S, Bruno, G, Lera, R, Cherubini, V, Bechaz, M, Zucchini, S, Prandi, E, Zattoni, V, Coccioli, S, Frongia, A, La Loggia, A, Lo Presti, D, Citrini, F, Suprani, T, Dedonno, V, Vergerio, A, Banin, P, Toni, S, Piccini, B, Barni, F, Pescamona, M, Cardinale, G, Lombardo, F, Bonfanti, R, Scaramuzza, A, Iughetti, Lorenzo, Franzese, A, Iafusco, D, Guercio Nuzio, S, Abiuso, C, Monciotti, C, Cardella, F, Vanelli, M, Chiari, G, Calcaterra, V, De Giorgi, G, Zanette, G, Marsciani, A, Patera, P, Manca Bitti, M, Delvecchio, M, Trada, M, Aimar, A, Gaiero, A, Tinti, D, Fontana, F, Guerraggio, L, Cauvin, V, Gargantini, L, Salvatoni, A, Trivellin, V, Maffeis, C, Marigliano, M, Arnaldi, C., Cadario, F, Cerutti, F, Savastio, S, Rabbone, I, Tumini, S, Bruno, G, Italian Society of Pediatric, Endocrinology, Diabetology Study, Group, Iafusco, Dario, Italian Society of pediatric Endocrinology and Diabetology Study group, (SIEDP), and Bonfanti, R

Subjects
Male, Age of onset, Children immigration, Environment factors, Type 1 diabetes, Pediatrics, medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, TYPE I (INSULIN-DEPENDENT) DIABETES MELLITUS, Disease, Statistics, Nonparametric, Endocrinology, HLA Antigens, Weight loss, Interquartile range, Diabetes mellitus, Prevalence, Internal Medicine, medicine, Humans, Insulin, Genetic Predisposition to Disease, Child, Alleles, Glycemic, Transients and Migrants, Settore MED/38 - Pediatria Generale e Specialistica, business.industry, Case-control study, Infant, General Medicine, medicine.disease, Diabetes Mellitus, Type 1, Italy, Case-Control Studies, Child, Preschool, Female, medicine.symptom, business, Type 1 diabetes Children immigration Age of onset Environment factors
Abstract

To assess burden and clinical features of type 1 diabetes in migrant with respect to Italian children. Prevalent children with type 1 diabetes were identified through a multicenter study, including 46 pediatric outpatients diabetic clinics. A nested case–control study was also performed, comparing features at diabetes onset and after 1 year of insulin treatment in 84 migrants and 75 Italian children with onset in 2011, matched for age and sex. Out of 7,812 children cared for by pediatric diabetologists, 761 (10 %) were migrant and 548 of them were born in Italy. Age at diagnosis was lower in migrants born in Italy (5.1 years, interquartile range (IQR) 2.2–7.7) than in those born in their original countries (7.8 years, IQR 5.3–10.3) and in Italians (9.8 years, IQR 5.9–13.0, p\0.001). At diabetes onset, migrants had lower frequencies of positivities of markers of b-cell autoimmunity (96 vs. 99.5 %, p\0.01), higher values of weight loss (11 vs. 7 %, p\0.01), HbA1c (70 vs. 58 mmol/mol, p\0.001), and insulin requirement (0.70 ± 0.03 vs. 0.63 ± 0.10 UI/kg/die, p = 0.05) and lower levels of 25-OH vitamin D3 (15.0 ± 2.8 vs. 20.8 ± 1.3, p = 0.03). Moreover, they experienced higher frequencies of hospitalizations during the first year of disease (19.2 vs. 2.7 %, p\0.001). Burden of type 1 diabetes in migrant children is increasing in Italy, with younger age at onset and different clinical features than in Italian children. Higher hospitalization rates and poorer glycemic control over the first year underline that approach to diabetes care in migrants needs to be improved.

Published
2014

17. Health-related quality of life and treatment preferences in adolescents with type 1 diabetes. The VIPKIDS study

Author

Cherubini V, Gesuita R, Bonfanti R, Frongia AP, Iafusco D, Iannilli A, Lombardo F, Rabbone I, Sabbion A, Salvatoni A, Scaramuzza A, Schiaffini R, Sulli N, Toni S, Tumini S, Mosca A, Carle F, VIPKIDS Study G.r.o.u.p., FRANZESE, ADRIANA, Cherubini, V, Gesuita, R, Bonfanti, R, Franzese, Adriana, Frongia, Ap, Iafusco, D, Iannilli, A, Lombardo, F, Rabbone, I, Sabbion, A, Salvatoni, A, Scaramuzza, A, Schiaffini, R, Sulli, N, Toni, S, Tumini, S, Mosca, A, Carle, F, VIPKIDS Study, G. r. o. u. p., Franzese, A, Iafusco, Dario, and VIPKIDS Study, Group

Subjects
Male, medicine.medical_specialty, Pediatrics, Activities of daily living, Adolescent, Health Status, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, MEDLINE, Infusions, Subcutaneous, Insulin Infusion Systems, Endocrinology, Quality of life, CSII Quality of life Diabetes in childhood. Devices Psychological aspects, Surveys and Questionnaires, Diabetes mellitus, Devices, Diabetes in childhood, Psychological aspects, Internal Medicine, medicine, Humans, Insulin, Child, Health related quality of life, Type 1 diabetes, business.industry, Reproducibility of Results, Patient Preference, General Medicine, medicine.disease, humanities, Diabetes Mellitus, Type 1, Quality of Life, Physical therapy, Female, Observational study, business
Abstract

A multi-centre, observational, cross-sectional study was carried out to determine whether the healthrelated quality of life (HRQOL) of adolescents with type 1 diabetes is affected by different insulin treatment systems, and which features of HRQOL are impacted by the respective insulin treatment. The study regarded 577 adolescents, aged 10–17 years, with type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII) (n = 306) or multiple daily injections (MDI) (n = 271). The Insulin Delivery System Rating Questionnaire was validated in Italian and was self-completed by the subjects during a routine visit to the centres. Subjects were compared following the domains of the questionnaire. Good HRQOL was seen in subjects treated with either MDI or CSII. Significant differences were not found in the domains for general diabetes, including diabetes worries, social burden and psychological well-being. Multiple quantile regression analysis showed that CSII confers significant advantages in terms of HRQOL with improvements in treatment satisfaction, perceived clinical efficacy and reduction in treatment interference with daily activities.This favourable impact was more evident in subjects reporting lower HRQOL scores, suggesting that CSII may be especially useful for individuals perceiving a poor HRQOL. Analysis of the domains indicated that CSII was associated with a higher HRQOL than MDI. Life-course HRQOL evaluation using a standardised questionnaire can ensure better chronic disease management. This is particularly important when providing individualized care for adolescents, as they become increasingly responsible for managing their diabetes.

Published
2014

18. Erratum: Organization and regional distribution of centers for the management of children and adolescents with diabetes in Italy (Ital J Pediatr (2015) 41 (74) DOI:10.1186/s13052-015-0179-6)

Author

Giorgetti, C., Ferrito, L., Zallocco, F., Iannilli, A., Cherubini, V., Maghnie, M., Rabbone, I., Lera, R., De Luna, L., Kienberger, B., Gualtieri, A., Zecchino, C., Piccino, E., Ortolani, F., Zucchini, S., Maltoni, G., Pasquino, B., Reinstadler, P., Prandi, E., Zattoni, V., Gallo, F., Morganti, G., Guerraggio, L., Ripoli, C., Frongia, M., Pusceddu, P., La Loggia, A., Scanu, P., Cardinale, G., Ponzi, G., Tomaselli, L. G., Rapisarda, V., Citriniti, F., Soprani, T., Tumini, S., Lazzaro, N., De Donno, V., Banin, P., Toni, S., Lenzi, L., Mainetti, B., Coccioli, M. S., D(')Annunzio, G., Minuto, N., Montani, E., Maccioni, R., Marongiu, U., Beccaria, L., Bruzzese, M., Mamm(`i), F., Pardi, D., Lombardo, F., Ventrici, C., Scaramazza, A., Ferrari, M., Bonfanti, R., Rigamonti, A., Iughetti, L., Predieri, B., Iafusco, D., Confetto, S., Zanfardino, A., Prisco, F., Francese, A., De Nitto, E., Cadario, F., Milia, A., Piredda, G., Mereu, L., Soro, M., Correddu, A., Pipia, A., Monciotti, C., Cardella, F., De Berardinis, F., Santoro, G., Chiari, G., Berioli, M. G., Federico, G., Zanette, G., Marsciani, A., Pedini, A., Patera, I. P., Schiaffini, R., Bitti, M., Lidano, R., Pietrosanti, S., Delvecchio, M., Trada, M., Marinaro, A., Meloni, G., Gaiero, A., Fichera, G., Bulciolu, P., Ignaccolo, G., Cauvin, V., Franceschi, R., Faleschini, E., Tornese, G., Salvatoni, A., Cardani, R., Maffeis, C., Marigliano, M., Sabbion, A., and Arnaldi, C.

Subjects
children, type 1 diabetes, children, adolescents, adolescents
Published
2016

19. Dandy-Walker malformation and Wisconsin syndrome: novel cases add further insight into the genotype-phenotype correlations of 3q23q25 deletions

Author

Ferraris, A, Bernardini, L, Sabolic Avramovska, V, Zanni, G, Loddo, S, Sukarova Angelovska, E, Parisi, V, Capalbo, A, Tumini, S, Travaglini, L, Mancini, F, Duma, F, Barresi, S, Novelli, A, Mercuri, E, Tarani, L, Italian CBCD Study Group, Bertini, E, Dallapiccola, B, Collaborators: Arrigoni F, Valente E. M., Borgatti, R, Romaniello, R, Accorsi, P, Fazzi, E, Giordano, L, Pinelli, L, Biancheri, R, Mirabelli, M, Rossi, A, Briguglio, M, Tortorella, G, Chiapparini, L, D' Arrigo, S, Moroni, I, Pantaleoni, C, Spaccini, L, Uziel, G, D' Amico, A, Del Giudice, E, Pichiecchio, A, Signorini, S, Battini, R, Casarani, M, Colafati, S, Digilio, Mc, Leuzzi, V, Micalizzi, A, Romani, M, Spalice, A, Vitiello, G, Cirillo, Margherita, Simonati, A., Ferraris, A, Bernardini, L, Sabolic Avramovska, V, Zanni, G, Loddo, S, Sukarova Angelovska, E, Parisi, V, Capalbo, A, Tumini, S, Travaglini, L, Mancini, F, Duma, F, Barresi, S, Novelli, A, Mercuri, E, Tarani, L, Italian, CBCD Study Group, and DEL GIUDICE, Ennio

Subjects
Dandy-Walker malformation, Wisconsin syndrome, 3q deletion, ZIC1-ZIC4 genes, Hemizygosity, 0302 clinical medicine, Dandy–Walker syndrome, Ptosis, Genetics(clinical), Pharmacology (medical), Child, Genetics (clinical), Medicine(all), Genetics, 0303 health sciences, 030305 genetics & heredity, Zinc Fingers, General Medicine, Single Nucleotide, Penetrance, Phenotype, Child, Preschool, Pair 3, Female, Chromosomes, Human, Pair 3, medicine.symptom, Chromosome Deletion, zic1-zic4 genes, Human, Adult, wisconsin syndrome, dandy-walker malformation, Biology, ZIC1, Polymorphism, Single Nucleotide, Chromosomes, 03 medical and health sciences, Young Adult, Wisconsin, Settore MED/39 - NEUROPSICHIATRIA INFANTILE, medicine, Humans, Polymorphism, Preschool, Genetic Association Studies, Research, medicine.disease, Blepharophimosis, Human genetics, Face, Dandy-Walker Syndrome, 030217 neurology & neurosurgery, Transcription Factors
Abstract

Background The Dandy-Walker malformation (DWM) is one of the commonest congenital cerebellar defects, and can be associated with multiple congenital anomalies and chromosomal syndromes. The occurrence of overlapping 3q deletions including the ZIC1 and ZIC4 genes in few patients, along with data from mouse models, have implicated both genes in the pathogenesis of DWM. Methods and results Using a SNP-array approach, we recently identified three novel patients carrying heterozygous 3q deletions encompassing ZIC1 and ZIC4. Magnetic resonance imaging showed that only two had a typical DWM, while the third did not present any defect of the DWM spectrum. SNP-array analysis in further eleven children diagnosed with DWM failed to identify deletions of ZIC1-ZIC4. The clinical phenotype of the three 3q deleted patients included multiple congenital anomalies and peculiar facial appearance, related to the localization and extension of each deletion. In particular, phenotypes resulted from the variable combination of three recognizable patterns: DWM (with incomplete penetrance); blepharophimosis, ptosis, and epicanthus inversus syndrome; and Wisconsin syndrome (WS), recently mapped to 3q. Conclusions Our data indicate that the 3q deletion is a rare defect associated with DWM, and suggest that the hemizygosity of ZIC1-ZIC4 genes is neither necessary nor sufficient per se to cause this condition. Furthermore, based on a detailed comparison of clinical features and molecular data from 3q deleted patients, we propose clinical diagnostic criteria and refine the critical region for WS.

Published
2013

20. Combined therapy with insulin and rGH in thirteen Italian patients with type 1 diabetes (T1DM) and growth disorders

Author

Zucchini, S., Pozzobon, G., Bonfanti, R., Vannelli, S., Rabbone, I., Maghnie, M., Bizzarri, C., Tumini, S., Lenzi, L., Maggio, M. C., Iafusco, D., Marigliano, M., Cherubini, V., Iughetti, Lorenzo, Zucchini, S, Pozzobon, G, Bonfanti, R, Vannelli, S, Rabbone, I, Maghnie, M, Bizzarri, C, Tumini, S, Lenzi, L, Maggio, M C, Iafusco, D, Marigliano, M, Cherubini, V, and Iughetti, L

Subjects
Settore MED/38 - Pediatria Generale E Specialistica, type 1 diabetes, T1DM, GH, Insulin, GH
Abstract

Background: Combined GH and insulin therapy are rarely prescribed in pediatric pts because the association of GHD and T1DM is rare and maybe for the difficulties in managing a double therapy with opposite effects on glucose metabolism. Objective and hypotheses: To investigate on the attitude of pediatric endo-diabetologists in treating these pts. Methods: Data were collected from over 50 centres belonging to the ISPED. The inclusion criterion was based on the double therapy for at least 6 months with insulin due to T1DM, and rGH, due to growth impairment. Results: Most centres stated that the use of combined therapy was considered uncomfortable and frequently avoided, whereas 10 centres reported the treatment of 13 pts (7M, 6F). In 7 pts T1DM was the first diagnosis (age at onset from 1.5 to 9.5 yrs) and they were treated with insulin (group 1) and with rGH subsequently (after 0.5-9.75 yrs) due to idiopathic GHD in 4 pts, Turner s. in 1 pt, Leri-Weill s. in 1 pt and bone dysplasia in 1 pt. In 6 pts rGH therapy was started first (age at start 2.5-12 yrs) due to idiopathic GHD in 4 pts, organic GHD in 1 pt and Turner s. in 1 pt. Height SDS at the start of rGH therapy ranged from -2.5 to -3.9. Longest duration of rGH therapy was 7 yrs and 5 pts are still treated. Insulin schedule was with MDI in 10 pts and with CSII in the remaining 3. In the 7 pts of group 1, mean insulin dose increased during the first 6 months after rGH start from 0.68 to 1.06 U/kg (p=0.03). HbA1c was not modified after 6 months compared to the baseline value (7.62±0.8 vs 7.76±0.57). In the pt with Leri-Weill s. rGH therapy was stopped due to impaired metabolic control. No significant side-effects during the treatment were reported. Conclusions: Double therapy with insulin and GH is uncommonly performed in pediatric patients. Despite a higher insulin requirement, metabolic control in patients with T1DM was not impaired significantly by the simultaneous treatment. Our data suggest that GH is not an absolute contraindication for treatment of children with T1DM and growth disorders.

Published
2012

21. Infant and toddler type 1 diabetes: complications after 20 years' duration

Author

Salardi S, Porta M, Maltoni G, Rubbi F, Rovere S, Cerutti F, Tumini S, Cauvin V, Diabetes Study Group of the Italian Society of Paediatric Endocrinology, Diabetology, IAFUSCO, Dario, Salardi, S, Porta, M, Maltoni, G, Rubbi, F, Rovere, S, Cerutti, F, Iafusco, Dario, Tumini, S, Cauvin, V, Diabetes Study Group of the Italian Society of Paediatric, Endocrinology, and Diabetology

Abstract

OBJECTIVE: To compare the effect of the prepubertal duration of diabetes on the occurrence of complications in two groups of patients after the same number of years of the disease. RESEARCH DESIGN AND METHODS: This multicenter study enrolled 105 patients aged 16-40.3 years; 53 were prepubertal at diagnosis (aged 0-3) and 52 were pubertal (Tanner stage) and aged 9-14.9. The mean duration of disease was 19.8 and 19.5 years for prepubertal and pubertal patients, respectively. In all patients, retinal photographs were taken and centrally graded. Urinary albumin excretion (UAE; 86 case subjects), blood pressure (BP; 89 case subjects), and lifetime HbA(1c) (72 case subjects) were also evaluated. RESULTS: The prevalence of diabetic retinopathy (DR) was higher in pubertal than in prepubertal patients, both for any grade DR (71 vs. 40%, P = 0.002) and for mild or more severe DR (P = 0.005). The prevalence of abnormal UAE was not different in the two groups. Hypertension was found only in three patients, all pubertal at diagnosis. In the small group with moderate-to-severe DR, lifetime HbA(1c) levels, as percentages above the upper normal reference value, were higher (P < 0.01) in prepubertal than in pubertal patients. CONCLUSIONS: If diabetes is diagnosed in infants or toddlers and the prepubertal duration of diabetes is very long, the patients seem to be protected against DR. This protection disappears if lifetime metabolic control is bad. Instead, when onset is at puberty, the DR risk is higher and less dependent on metabolic control and may be influenced by age-related factors, such as BP.

Published
2012

22. Severe hypoglycemia and ketoacidosis over one year in Italian pediatric population with type 1 diabetes mellitus: a multicenter retrospective observational study

Author

Cherubini, V, Pintaudi, B, Rossi, Mc, Lucisano, G, Pellegrini, F, Chiumello, G, Frongia, Ap, Monciotti, C, Patera, Ip, Toni, S, Zucchini, S, Nicolucci, A, Lera, R, Iannilli, A, Giorgetti, C, Cesaretti, A, Paparusso, Am, Alessandrelli, Mc, Scipione, M, Balsamo, C, Gallo, F, Lo Presti, D, Passanisi, S, Tumini, S, Cipriano, P, Lazzaro, N, Vergerio, A, Banin, P, Lenzi, L, Coccioli, Ms, D'Annunzio, G, Bruzzese, M, Lombardo, F, Salzano, G, Bonfanti, R, Frontino, G, Battaglino, R, Iughetti, Lorenzo, Predieri, Barbara, Cadario, F, Savastio, S, Zabadneh, N, Zanella, C, Mozzo, E, Tiozzo, S, Benevento, D, Calcaterra, V, Larizza, D, Delvecchio, M, Trada, M, Rabbone, I, Sicignano, S, Cauvin, V, Franceschi, R, Gargantini, L, Pennati, C, Bianchi, G, Salvatoni, A, Maffeis, C, Marigliano, M, Sabbion, A, Arnaldi, C, Tosini, D, Tossi, Mc, Valentini, M, D'Alonzo, D, Pirozzoli, C, Di Nardo, B, Memmo, R, and Cianci, A.

Subjects
Male, medicine.medical_specialty, Children and adolescents, endocrine system diseases, Adolescent, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Insulin, Isophane, Medicine (miscellaneous), NPH insulin, TYPE I (INSULIN-DEPENDENT) DIABETES MELLITUS, Internal medicine, Diabetes mellitus, medicine, Humans, Hypoglycemic Agents, Insulin, Child, Retrospective Studies, Glycated Hemoglobin, Type 1 diabetes, Severe hypoglycemia, Nutrition and Dietetics, business.industry, Incidence (epidemiology), Incidence, Infant, Retrospective cohort study, Diabetes ketoacidosis, Ketosis, medicine.disease, Hypoglycemia, Ketoacidosis, Surgery, Diabetes Mellitus, Type 1, Italy, Child, Preschool, Regular insulin, Female, Cardiology and Cardiovascular Medicine, business
Abstract

Background and aims: Evaluation of incidence and correlates of severe hypoglycemia (SH) and diabetes ketoacidosis (DKA) in children and adolescents with T1DM. Methods and results: Retrospective study conducted in 29 diabetes centers from November 2011 to April 2012. The incidence of SH and DKA episodes and their correlates were assessed through a questionnaire administered to parents of patients aged 0e18 years. Incidence rates and incident rate ratios (IRRs) were estimated through multivariate Poisson regression analysis and multilevel analysis. Overall, 2025 patients were included (age 12.4 � 3.8 years; 53% males; diabetes dura- tion 5.6 � 3.5 years; HbA1c 7.9 � 1.1%). The incidence of SH and DKA were of 7.7 and 2.4 events/ 100 py, respectively. The risk of SH was higher in females (IRR Z 1.44; 95%CI 1.04e1.99), in pa- tients using rapid acting analogues as compared to regular insulin (IRR Z 1.48; 95%CI 0.97e2.26) and lower for patients using long acting analogues as compared to NPH insulin (IRR Z 0.40; 95% CI 0.19e0.85). No correlations were found between SH and HbA1c levels. The risk of DKA was higher in patients using rapid acting analogues (IRR Z 4.25; 95%CI 1.01e17.86) and increased with insulin units needed (IRR Z 7.66; 95%CI 2.83e20.74) and HbA1c levels (IRR Z 1.63; 95% CI 1.36e1.95). Mother' sa ge was inversely associated with the risk of both SH (IRRZ 0.95; 95%CI 0.92e0.98) and DKA (IRR Z 0.94; 95%CI 0.88e0.99). When accounting for center effect, the risk of SH associated with the use of rapid acting insulin analogues was attenuated (IRR Z 1.48; 95%CI 0.97e2.26); 33% and 16% of the residual variance in SH and DKA risk was ex- plained by center effect. Conclusion: The risk of SH and DKA is mainly associated with treatment modalities and strongly depends on the practice of specialist centers.

Published
2014

23. Epidemiology of diabetic ketoacidosis in Italy

Author

Cherubini, V, Gesuita, R, Sternardi, S, Ferrito, L, Lenzi, L, Iannilli, A, Piccini, B, Skrami, E, Nicolucci, A, Pintaudi, B, Toni, S, Lera, R, De Luna, L, Kienberger, B, Gualtieri, A, Zecchino, C, Piccino, E, Ortolani, F, Zucchini, S, Maltoni, G, Pasquino, B, Reinstadler, P, Prandi, E, Zattoni, V, Gallo, F, Morganti, G, Guerraggio, L, Ripoli, C, Frongia, M, Pusceddu, P, La Loggia, A, Scanu, P, Cardinale, G, Ponzi, G, Tomaselli, L, G, Rapisarda, V, Citriniti, F, Soprani, T, Tumini, S, Lazzaro, N, De Donno, V, Banin, P, Mainetti, B, Coccioli, Ms, D'Annunzio, G, Minuto, N, Montani, E, Maccioni, R, Marongiu, U, Beccaria, L, Bruzzese, M, Mammì, F, Pardi, D, Lombardo, F, Ventrici, C, Scaramazza, A, Ferrari, M, Bonfanti, R, Rigamonti, A, Iughetti, L, Predieri, B, Iafusco, D, Confetto, S, Zanfardino, A, Prisco, F, Franzese, A, De Nitto, E, Cadario, F, Milia, A, Piredda, G, Mereu, L, Soro, M, Correddu, A, Pipia, A, Monciotti, C, Cardella, F, De Berardinis, F, Santoro, G, Chiari, G, Berioli, M, Federico, G, Zanette, G, Marsciani, A, Pedini, A, Patera, I, P, Schiaffini, R, Bitti, M, Lidano, R, Pietrosanti, S, Delvecchio, M, Trada, M, Marinaro, A, Meloni, G, Galero, A, Fichera, G, Bulciolu, P, Rabbone, I, Ignaccolo, G, Cauvin, V, Franceschi, R, Faleschini, E, Tornese, G, Salvatoni, Alessandro, Cardani, R, Maffeis, C, Marigliano, M, Sabbion, A, and Arnaldi, C.

Published
2014

24. Diabetes Incidence in 0- to 14-Year Age-Group in Italy

Author

CARLE F, GESUITA R, BRUNO G, COPPA GV, FALORNI A, LORINI R, MARTINUCCI ME, POZZILLI P, PRISCO F, SONGINI M, TENCONI MT, CHERUBINI V, THE RIDI STUDY GROUP, PIFFER S, FRANCHINI S, BIANCHI L, CERUTTI F, MERLETTI F, PAGANO G, COTELLESSA M, MINICUCCI L, BARBIERI P, D’ANNUNZIO G, BAZZANO S, TONI S, REALI MS, MEDICI A, IUGHETTI L, PREDIERI B, BALLI F, VISALLI N, SEBASTIANI L, MARIETTI G, SANTEUSANIO F, DE GIORGI G, SANTILLI E, IANNILLI A, PINELLI A, MASCIOLI G, ALTOBELLI E, CHIARELLI F, TUMINI S, IAFUSCO D, DE FELICE E, INGENITO N, CASU A, FRONGIA P, MARINARO A., DEVOTI, Gabriele, Carle, F, Gesuita, R, Bruno, G, Coppa, Gv, Falorni, A, Lorini, R, Martinucci, Me, Pozzilli, P, Prisco, F, Songini, M, Tenconi, Mt, Cherubini, V, THE RIDI STUDY, Group, Piffer, S, Franchini, S, Bianchi, L, Cerutti, F, Merletti, F, Pagano, G, Cotellessa, M, Minicucci, L, Barbieri, P, Devoti, Gabriele, D’Annunzio, G, Bazzano, S, Toni, S, Reali, M, Medici, A, Iughetti, L, Predieri, B, Balli, F, Visalli, N, Sebastiani, L, Marietti, G, Santeusanio, F, DE GIORGI, G, Santilli, E, Iannilli, A, Pinelli, A, Mascioli, G, Altobelli, E, Chiarelli, F, Tumini, S, Iafusco, D, DE FELICE, E, Ingenito, N, Casu, A, Frongia, P, and Marinaro, A.

Subjects
incidence, registry, Type 1 diabetes mellitu
Abstract

Objective. The Registry for Type 1 Diabetes Mellitus in Italy (RIDI) Study Group was established to coordinate the registries of type 1 diabetes in Italy. This report is based on 3,606 children younger than 15 years diagnosed with type 1 diabetes and prospectively registered during 1990-1999 by nine centers, covering > 35% of the Italian population. Research design and methods. Registries were pooled in four geographic macro-areas: north, central, south and insular. The completeness of registration was assessed by the capture-recapture method. Poisson regression analysis was used to evaluate temporal trend in incidence. Results. Large variation in incidence were confirmed not only between Sardegna and the mainland but also among peninsular areas. In Sardegna, there was an excess of boys (the boy-to-girl incidence ratio was 1.4). The overall incidence showed average increases of 3.6% (p

Published
2004

25. Emerging effects of early environmental factors over genetic background for type 1 diabetes susceptibility: Evidence from a nationwide Italian twin study

Author

Nisticò, L, Iafusco, D, Galderisi, A, Fagnani, C, Cotichini, R, Toccaceli, V, Stazi, Ma, Study Group on Diabetes of the Italian Society of Pediatric Endocrinology, Collaborators: Cherubini V, D. i. a. b. e. t. o. l. o. g. y., Iannilli, A, Paparusso, Am, Cavallo, L, Zecchino, C, de Filippo, G, Gargantini, L, Salardi, S, Zucchini, S, Maltoni, G, Pasquino, B, Kaufmann, P, Buzi, F, Prandi, E, Gallo, F, Cicchetti, M, Castaldo, E, Citriniti, F, Chiarelli, F, Tumini, S, Di Stefano, A, Sperlì, D, De Marco, R, Banin, P, Toni, S, Lenzi, L, Del Vecchio, M, Lorini, R, D'Annunzio, G, Ingletto, D, Scaramuzza, A, Zuccotti, Gv, Chiumello, G, Meschi, F, Bonfanti, R, Frontino, G, de Luca, F, Lombardo, F, Salzano, G, Iughetti, L, Franzese, A, Buono, P, De Simone, I, Prisco, F, Cocca, A, Cadario, F, Monciotti, Cm, Savio, V, Cardella, F, Vanelli, M, Chiari, G, Errico, K, Iovane, B, Calcaterra, V, Citro, F, Cantoni, S, Marsciani, A, Cappa, M, Patera, Pi, Schiaffini, R, Sulli, N, Spoletini, M, Cerutti, Franco, Rabbone, I, Sicignano, S, Cauvin, V, Bellizzi, M, Tonini, G, Faleschini, E, Salvatoni, A, Pinelli, L, Maffeis, C, Contreas, G., Nisticò, L, Iafusco, D, Galderisi, A, Fagnani, C, Cotichini, R, Toccaceli, V, Stazi, Ma, and the Study Group on Diabetes of the Italian Society of Pediatric Endocrinology and, Diabetology

Subjects
Adult, Male, Endocrinology, Diabetes and Metabolism, Biochemistry, Endocrinology, Clinical Biochemistry, Biochemistry (medical), medicine.medical_specialty, Adolescent, Child, Child, Preschool, Diabetes Mellitus, Type 1, Environment, Female, Humans, Infant, Kaplan-Meier Estimate, Twins, Dizygotic, Twins, Monozygotic, Genetic Predisposition to Disease, type 1 diabetes, Concordance, Population, Twins, Context (language use), Monozygotic, Internal medicine, Diabetes mellitus, Diabetes Mellitus, Dizygotic, medicine, Preschool, education, Type 1 diabetes, education.field_of_study, business.industry, medicine.disease, Twin study, Zygosity, Diabetes and Metabolism, Cohort, Environmental Exposures, business, Type 1
Abstract

Context:The incidence of type 1 diabetes has been increasing over time.Objective:We estimated the genetic and environmental components of type 1 diabetes susceptibility in a twin cohort of recent-onset cases to explore the sources of changing disease epidemiology.Design:We linked the population-based Italian Twin Registry with 14803 type 1 diabetes records from 36 pediatric diabetes care centers throughout Italy, except Sardinia, and identified 173 diabetic twins. Patients were positive for at least one autoantibody to islet cell, glutamate decarboxylase, tyrosine phosphatase, insulin, or zinc transporter 8 and were insulin dependent since their diagnosis. Zygosity was determined by DNA genotyping or by questionnaire.Outcome Measures:We estimated proband-wise concordance, cotwin recurrence risk with Kaplan-Meier method, and genetic and environmental proportions of susceptibility variance by structural equation models.Results:We recruited 104 diabetic twins (53 males) from 88 pairs (34 monozygotic, 54 dizygotic) and one triplet. The mean age at diagnosis was 8.1 yr (range 1.1-20.5 yr), and the median year of diagnosis was 2002. Proband-wise concordances were 45.5 and 16.4% in monozygotic and dizygotic pairs (P = 0.01). Recurrence risks in monozygotic and dizygotic cotwins were 37 and 12% after 10 yr from the proband's diagnosis (P = 0.005). Genetic contribution to type 1 diabetes susceptibility was 40% (95% confidence interval 8-78), and the shared and individual-specific environmental components were 51% (14-77) and 9% (4-19), respectively.Conclusions:In addition to the moderate genetic effects on type 1 diabetes susceptibility, our results draw attention to the substantial shared environmental effects, suggesting that exposures in fetal or early postnatal life may contribute to the increasing incidence of the disease.

Published
2012

27. Potential celiac disease in type 1 diabetes: a multicenter study

Author

Franzese, A, Iafusco, D, Spadaro, R, Cavaliere, O, Prisco, F, Auricchio, R, Troncone, R, Valerio, G, the Study Group on Diabetes of Italian Society of Pediatric Endocrinology, Diabetology: LERA, R, Cherubini, V, Biagioni, M, Pasquino, B, Gallo, F, Suprani, T, Tumini, S, Lazzaro, N, Toni, S, D'Annunzio, G, Emmanuele, V, Bruzzese, M, Lombardo, F, Bonfanti, R, Tronconi, Gm, Iughetti, L, Monciotti, C, Cardella, F, Chiari, G, Vanelli, M, Calcaterra, V, Federico, Giovanni, Crinò, A, Cappa, M, Patera, I, Negro, I, Delvecchio, M, Rabbone, I, Fontana, F, Guerraggio, L, Salvatoni, A, Costantini, C, and Pinelli, L.

Published
2011

28. Potential celiac disease in type 1 diabetes: a multicenter study

Author

Franzese, A., Iafusco, D., Spadaro, R., Cavaliere, O., Prisco, F., Auricchio, R., Troncone, R., Valerio, G., Lera, R., Fontana, F., Cherubini, V., Biagioni, M., Pasquino, B., Gallo, F., Suprani, T., Tumini, S., Lazzaro, N., Toni, S., D'Annunzio, G., Emmanuele, V., Bruzzese, M., Lombardo, F., Bonfanti, R., Tronconi, G. M., Iughetti, L., Monciotti, C., Cardella, F., Chiari, G., Vanelli, M., Calcaterra, V., Federico, G., Crino, A., Cappa, M., Patera, I., Negro, I., Delvecchio, M., Rabbone, I., Guerraggio, L., Salvatoni, A., Costantini, C., Pinelli, L., Franzese, A, Iafusco, D, Spadaro, R, Cavaliere, O, Prisco, F, Auricchio, R, Troncone, R, Valerio, G, Bonfanti, R, Study Group on diabetes of Italian Society of pediatric Endocrinology and, Diabetology, Franzese, Adriana, D., Iafusco, R., Spadaro, O., Cavaliere, F., Prisco, Auricchio, Renata, Troncone, Riccardo, G., Valerio, S. o., Diabete, Diabetology, Iafusco, Dario, THE STUDY GROUP ON DIABETES OF ITALIAN SOCIETY OF, Pediatric, and ENDOCRINOLOGY AND DIABETOLOGY, Isped

Subjects
Male, medicine.medical_specialty, Adolescent, endocrine system diseases, Endocrinology, Diabetes and Metabolism, Disease, Adolescent, Celiac Disease, Serology, Diet, Gluten-Free, Endocrinology, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Humans, Child, Type 1 diabetes, complications/epidemiology, Diet, Routine screening, business.industry, epidemiology/etiology, Child, Child, Infant, nutritional and metabolic diseases, Potential celiac disease, General Medicine, Autoimmune disorders, medicine.disease, Preschool, Cross-Sectional Studies, Diabetes Mellitu, Celiac disease, humanities, Gluten-Free, Female, Humans, Infant, Male, Celiac Disease, Child, Preschool, Cross-Sectional Studies, Diabetes Mellitus, Type 1, Female, Multicenter study, Immunology, Gluten free, business, Type 1
Abstract

Aims To describe the prevalence of potential celiac disease (pot-CD) in young patients with type 1 diabetes mellitus (T1DM) and characterize their clinical features. Methods This cross-sectional multicenter study involved 8717 T1DM patients from 31 Italian centers. Information was collected on the total number of T1DM patients, CD patients and pot-CD patients. The following data were collected on pot-CD patients: gender, age at T1DM diagnosis, age at the first CD serological positivity, presence of CD-related symptoms, presence of other autoimmune disorders and treatment with gluten free diet (GFD). One thousand-three-hundred-sixty-one patients who were positive for CD serology were the control group. Results CD serological positivity was found in 7.2% T1DM patients. Prevalence of pot-CD was 12.2% ( n =77) among CD positive patients: symptoms were present in 12/77; a third autoimmune disorder was found in 15 patients. Prevalence of pot-CD in the control population was 8.4% ( n =114; p =0.005). No difference was found with regard to clinical features. Only few symptomatic patients were on GFD both in T1DM and control patients. Conclusions A higher prevalence of pot-CD was found in T1DM patients, that may be ascribed to the routine screening, although the influence of genetic factors cannot be excluded.

Published
2011

29. Permanent diabetes during the first year of life: multiple gene screening in 54 patients

Author

Russo, L, Iafusco, D, Brescianini, S, Nocerino, V, Bizzarri, C, Toni, S, Cerutti, F, Monciotti, C, Pesavento, R, Iughetti, L, Bernanrdini, L, Bonfanti, R, Gargantini, L, Vanelli, M, AGUILAR BRYAN, L, Stazi, Ma, Grasso, V, Colombo, C, Barbetti, F, the EARLY DIABETES STUDY GROUP LERA, R, Cherubini, V, Fifi, Ar, Torelli, C, Frezza, E, Cavallo, L, Zucchini, S, Pasquino, B, Kaufmann, P, Frongia, P, Zedda, N, Ripoli, C, LA LOGGIA, A, LO PRESTI, D, Pocecco, M, Chiarelli, F, Tumini, S, DEL DONNO, M, DE MARCO MR, Lenzi, L, Lorini, R, D'Annunzio, G, Lombardo, F, Meschi, F, Franzese, A, Buono, P, Prisco, F, Cadario, F, Cardella, F, Calcaterra, V, DE GIORGI, G, Federico, Giovanni, Cappa, M, Sulli, N, MANCA BITTI ML, Delvecchio, M, Cotellessa, M, Rabbone, I, Cauvin, V, Bellizzi, M, Tonini, G, Salvatoni, A, and Pinelli, L.

Published
2011

30. Age-period-cohort analysis of 1990-2003 incidence time trends of childhood diabetes in Italy: the RIDI study

Author

Bruno, G, Maule, M, Merletti, F, Novelli, G, Falorni, A, Iannilli, A, Iughetti, Lorenzo, Altobelli, E, D'Annunzio, G, Piffer, S, Pozzilli, P, Iafusco, D, Songini, M, Roncarolo, F, Toni, S, Carle, F, Cherubini, V, Cerutti, F, Franchini, S, Bianchi, L, Lorini, R, Minuto, N, Sacco, S, Ramondetti, F, Predieri, Barbara, Reali, S, Medici, A, Biagioni, M, Gesuita, R, Santeusanio, F, De Giorgi, G, Visalli, N, Bizzarri, C, Chiarelli, F, Tumini, S, Prisco, F, Confetto, S, Frongia, P, and Marinaro, A.

Subjects
Cohort Studies, Type 1 diabetes, incidence
Published
2010

36. Diabetes incidence in 0- to 14-year age-group in Italy: a 10-year prospective study

Author

Carle, Flavia, Gesuita, Rosaria, Bruno, Graziella, Coppa, Giovanni V, Falorni, Alberto, Lorini, Renata, Martinucci, Marco E, Pozzilli, Paolo, Prisco, Francesco, Songini, Marco, Tenconi, Maria T, Cherubini, Valentino, RIDI Study Group (Piffer, S, Franchini, S, Bianchi, L, Cerutti, F, Merletti, F, Pagano, G, Cotellessa, M, Minicucci, L, Barbieri, P, Devoti, G, D’Annunzio, G, Bazzano, S, Toni, S, Reali, Ms, Medici, A, Iughetti, L, Predieri, B, Balli, F, Visalli, N, Sebastiani, L, Marietti, G, Santeusanio, F, De Giorgi, G, Santilli, E, Iannilli, A, Pinelli, A, Mascioli, G, Altobelli, E, Chiarelli, F, Tumini, S, Iafusco, D, De Felice, E, Ingenito, N, Casu, A, Frongia, P, and Marinaro, A)

Subjects
Male, Adolescent, Child, Child, Preschool, Demography, Diabetes Mellitus, Type 1, Female, Humans, Incidence, Infant, Italy, Registries, Sex Characteristics, Diabetes Mellitus, Preschool, Type 1
Abstract

The Registry for Type 1 Diabetes Mellitus in Italy (RIDI) Study Group was established to coordinate the registries of type 1 diabetes in Italy. This report is based on 3,606 children younger than 15 years diagnosed with type 1 diabetes and prospectively registered during 1990-1999 by nine centers, covering35% of the Italian population.Registries were pooled in four geographic macro-areas: north, central, south, and insular. The completeness of registration was assessed by the capture-recapture method. Poisson regression analysis was used to evaluate temporal trend in incidence.Large variations in incidence were confirmed not only between Sardegna and the mainland but also among peninsular areas. In Sardegna, there was an excess of boys (the boy-to-girl incidence ratio was 1.4). The overall incidence showed average increases of 3.6% (P0.001) and 3.7% (P0.001) per year in peninsular Italy and in Sardegna, respectively. Significant increases in incidence rates were found in boys aged 10-14 years (6.7%, 95% CI 0.5-13.3) and in girls aged 5-9 years (6.6%, 0.5-13.1) living in the southern area. The incidence rate also increased in boys aged 10-14 years (5.0%, 0.3-10) and in girls aged 0-4 years (4.9%, 0.8-9.1) living in Sardegna.Italy is a country with large geographical variations in incidence rates of type 1 diabetes. However, the rates are evenly increasing both in the mainland and Sardegna, suggesting that similar environmental factors are operating over populations that have different genetic backgrounds.

Published
2004

41. WHO Multinational Project for Childhood Diabetes. WHO Diamond Project Group

Author

Muntoni, S, Silvetti, M, Songini, M, Masile, P, Tronci, P, Vigneri, R, Squatrito, Sebastiano, Purrello, Francesco, Italia, S, Arpi, M, Chiarelli, F, Verrotti, A, Capani, F, Tumini, S, Morgese, G, Chiumello, G, Meschi, F, Bognetti, E, Balzano, E, Russo, G, Tenconi, M, Devoti, G, Fratino, P, Lorini, R, Pagano, G, Bruno, G, Pisu, E, Merletti, F, Pinelli, L, Gonfiantini, E, and Maffels, C

Published
1990

46. Vascular endothelial growth factor (VEGF) in children, adolescents and young adults with Type 1 diabetes mellitus: relation to glycaemic control and microvascular complications.

Author

Chiarelli, F., Spagnoli, A., Basciani, F., Tumini, S., Mezzetti, A., Cipollone, F., Cuccurullo, F., Morgese, G., and Verrotti, A.

Subjects
GROWTH factors, DIABETES, PEOPLE with diabetes, PHYSIOLOGY
Abstract

SUMMARY Aims To evaluate serum levels of vascular endothelial growth factor (VEGF) in a large group of children, adolescents and young adults with Type 1 diabetes mellitus to investigate whether increased VEGF concentrations are associated with long-term glycaemic control and microvascular complications. Methods The study involved 196 patients with Type 1 diabetes mellitus (age range 2–24 years, onset of diabetes before the age of 12 years, duration of disease longer than 2 years), without clinical and laboratory signs of microvascular complications; they were divided into three groups (group 1 – n = 37, age < 6 years; group 2 – n = 71, age 6–12 years; group 3 – n = 88–age > 12 years). Fifty-three adolescents and young adults (age 16.1–29.7) with different grades of diabetic retinopathy and microalbuminuria were also selected (group 4). A total of 223 healthy controls were matched for age and sex with each group of patients with diabetes mellitus. Results VEGF serum levels were significantly increased in pre-school and pre-pubertal children with diabetes as well as in pubertal patients compared to controls. VEGF concentrations were markedly increased in adolescents and young adults with microvascular complications compared with both healthy controls and diabetic patients without retinopathy or nephropathy. Multivariate analysis showed that elevation of VEGF in serum was an independent correlate of complications. One-year mean HbA1c values were significantly correlated with VEGF concentrations (r = 0.372; P < 0.01). Children with HbA1c levels greater than 10% had significantly higher VEGF concentrations when compared with matched patients whose HbAlc levels were lower than 10%. In poorly controlled diabetic children (HbA1c > 10%), long-term (2 years) improvement of glycaemic control (aiming at HbA1c < 7%) resulted in a significant reduction of VEGF... [ABSTRACT FROM AUTHOR]

Published
2000
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47. Increased circulating nitric oxide in young patients with type 1 diabetes and persistent microalbuminuria: relation to glomerular hyperfiltration.

Author

Chiarelli, Francesco, Cipollone, Francesco, Romano, Ferdinando, Tumini, Stefano, Costantini, Fabrizio, di Ricco, Laura, Pomilio, Mariapina, Pierdomenico, Sante D., Marini, Matteo, Cuccurullo, Franco, Mezzetti, Andrea, Chiarelli, F, Cipollone, F, Romano, F, Tumini, S, Costantini, F, di Ricco, L, Pomilio, M, Pierdomenico, S D, and Marini, M

Subjects
NITRIC oxide, PEOPLE with diabetes, GLOMERULAR filtration rate, HYPERGLYCEMIA
Abstract

Hyperglycemia has been causally linked to vascular and glomerular dysfunction by a variety of biochemical mechanisms, including a glucose-dependent abnormality in nitric oxide (NO) production and action. NO is a candidate for mediating hyperfiltration and the increased vascular permeability induced by diabetes. Serum nitrite and nitrate (NO2-+ NO3-) concentrations were assessed as an index of NO production in 30 adolescents and young adults with type 1 diabetes, 15 with and 15 without microalbuminuria (albumin excretion rate [AER] between 20 and 200 microg/min), compared with a well-balanced group of healthy control subjects. In all subjects, glomerular filtration rate (GFR) was determined by radionuclide imaging. Our study showed that NO2- + NO3- serum content and GFR values were significantly higher in microalbuminuric diabetic patients than in the other 2 groups. GFR was significantly and positively related to AER levels (r2 = 0.75, P < 0.0001), whereas NO2- + NO3- serum content was independently associated with both AER and GFR values (beta = 2.086, P = 0.05, beta = 1.273, P = 0.0085, respectively), suggesting a strong link between circulating NO, glomerular hyperfiltration, and microalbuminuria in young type 1 diabetic patients with early nephropathy. Interestingly, mean HbA1c, serum concentration was significantly higher in microalbuminuric than in normoalbuminuric diabetic subjects (P < 0.05) and was independently associated with AER values, suggesting a role for chronic hyperglycemia in the genesis of diabetic nephropathy. Moreover, HbA1c serum concentration was significantly and positively related to NO2 + NO3 serum content (r2 = 0.45, P = 0.0063) and GFR values (r2 = 0.57, P = 0.0011), suggesting that chronic hyperglycemia may act through a mechanism that involves increased NO generation and/or action. In conclusion, we suggest that in young type 1 diabetic patients with early nephropathy, chronic hyperglycemia is associated with an increased NO biosynthesis and action that contributes to generating glomerular hyperfiltration and persistent microalbuminuria. [ABSTRACT FROM AUTHOR]

Published
2000
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