Search

Your search keyword '"Barbetti, Fabrizio"' showing total 264 results
Start Over Author "Barbetti, Fabrizio" Publication Type Academic Journals
264 results on '"Barbetti, Fabrizio"'

2. 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
Full Text
View/download PDF

5. Monogenic diabetes clinic (MDC): 3-year experience

Author

Rapini, Novella, Patera, Patrizia I., Schiaffini, Riccardo, Ciampalini, Paolo, Pampanini, Valentina, Cristina, Matteoli M., Deodati, Annalisa, Bracaglia, Giorgia, Porzio, Ottavia, Ruta, Rosario, Novelli, Antonio, Mucciolo, Mafalda, Cianfarani, Stefano, and Barbetti, Fabrizio

Published
2023
Full Text
View/download PDF

7. Neonatal diabetes mellitus around the world: Update 2024.

Author

Barbetti, Fabrizio, Deeb, Asma, and Suzuki, Shigeru

Subjects
*HUMAN embryonic stem cells, *INDUCED pluripotent stem cells, *DIABETES in children, *GENETIC variation, *ETIOLOGY of diabetes
Abstract

Neonatal diabetes mellitus (NDM), defined as diabetes with an onset during the first 6 months of life, is a rare form of monogenic diabetes. The initial publications on this condition began appearing in the second half of the 1990s and quite surprisingly, the search for new NDM genes is still ongoing with great vigor. Between 2018 and early 2024, six brand new NDM‐genes have been discovered (CNOT1, FICD, ONECUT1, PDIA6, YIPF5, ZNF808) and three genes known to cause different diseases were identified as NDM‐genes (EIF2B1, NARS2, KCNMA1). In addition, NDM cases carrying mutations in three other genes known to give rise to diabetes during childhood have been also identified (AGPAT2, BSCL2, PIK3R1). As a consequence, the list of NDM genes now exceeds 40. This genetic heterogeneity translates into many different mechanism(s) of disease that are being investigated with state‐of‐the‐art methodologies, such as induced pluripotent stem cells (iPSC) and human embryonic stem cells (hESC) manipulated with the CRISPR technique of genome editing. This diversity in genetic causes and the pathophysiology of diabetes dictate the need for a variety of therapeutic approaches. The aim of this paper is to provide an overview on recent achievements in all aspects of this area of research. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

10. Improved Diagnosis of Rare Disease Patients through Systematic Detection of Runs of Homozygosity

Author

Renieri, Alessandra, Dursun, Ali, Matilla-Duenas, Antoni, Cormand, Bru, Rivolta, Carlo, Ayuso, Carmen, Espinós, Carmen, Scerri, Christian, Yalnizoglu, Dilek, Soler, Doriette, Morava, Eva, Barbetti, Fabrizio, Forzano, Francesca, Mari, Francesca, Muntoni, Francesco, Tort, Frederic, Houlden, Henry James, Tejada, Maria-Isabel, Senderek, Jan, Benitez, Javier, De La Calle, Javier Corral, Serra, Jordi, Millán, José Ma, Segovia, Jose, Gimeno Blanes, Juan Ramon, Armstrong, Judith, Ozgul, Koksal, Vilarinho, Laura, Montoliu, Lluis, Posada, Manuel, Mencarelli, Maria Antonietta, Mora, Marina, Bianchi, Paola, Seeman, Pavel, Elliott, Perry M., Ferlini, Alessandra, Brice, Alexis, Wirth, Brunhilde, Hanna, Mike, Tabrizi, Sarah, Klockgether, Thomas, Timmerman, Vincent, Straub, Volker, Kurul, Semra Hiz, Oktay, Yavuz, Gungor, Serdal, Yaramis, Ahmet, Yis, Uluc, Macaya, Alfons, Ribes, Antonia, Pujol, Aurora, Lázaro, Conxi, Grinberg, Daniel, Tizzano, Eduardo, Cardellach, Francesc, Palau, Francesc, Milà, Montse, Gallano, Pia, Artuch, Rafael, MartiSeves, Ramon, Villanueva, Gonzalo, Vidal, Silvia, Garrabou, Gloria, Balcells, Susanna, Urreizti, Roser, López, Estrella, Cuscó, Ivon, Valenzuela, Irene, Sabater, Maria, Matalonga, Leslie, Laurie, Steven, Papakonstantinou, Anastasios, Piscia, Davide, Mereu, Elisabetta, Bullich, Gemma, Thompson, Rachel, Horvath, Rita, Pérez-Jurado, Luis, Riess, Olaf, Gut, Ivo, van Ommen, Gert-Jan, Lochmüller, Hanns, and Beltran, Sergi

Published
2020
Full Text
View/download PDF

12. Editorial: Personalized therapies for monogenic diabetes.

Author

Delvecchio, Maurizio, Ming Liu, Rapini, Novella, and Barbetti, Fabrizio

Subjects
MATURITY onset diabetes of the young, TYPE 1 diabetes, TYPE 2 diabetes, GESTATIONAL diabetes, METABOLIC syndrome, INSULIN
Abstract

The editorial discusses personalized therapies for monogenic diabetes, focusing on three main clinical forms: Maturity Onset Diabetes of the Young (MODY), Neonatal Diabetes Mellitus (NDM), and Severe Insulin Resistance syndromes. The article highlights the genetic basis of these conditions and treatment options, such as oral hypoglycemic agents for MODY and NDM, and human recombinant IGF1 for Severe Insulin Resistance syndromes. Additionally, the editorial emphasizes the importance of precision medicine in managing monogenic diabetes and explores potential therapeutic targets through Mendelian randomization. [Extracted from the article]

Published
2024
Full Text
View/download PDF

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

Author

Aisenberg, Javier, Akkurt, Ilker, Abdul-Latif, Hussein, Al-Abdullah, Anees, Barak, Lubomir, Van Den Bergh, Joop, Bertrand, Anne-Marie, Bizzarri, Carla, Bonfanti, Riccardo, Bruel, Henri, Burrows, Anthony, Cadario, Francesco, Cameron, Fergus J., Carson, Dennis, Cartigny, Maryse, Cauvin, Vittoria, Cave, Helene, Chakera, Ali, Chetan, Ravi, Chiari, Giovanni, Couch, Bob, Coutant, Régis, 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, Ioacara, Sorin, Iotova, Violeta, Irgens, Henrik, Jaap, Alan, Jones, Kenneth, Kapellen, Thomas, Kaufman, Ellen, Klinge, Andreas, Klupa, Tomasz, Krishnaswamy, Ramaiyer, Lafferty, Tony, LeGault, Laurent, Lambert, Paul, Malecki, Maciej T, Malievsky, Olag, Mathew, Revi, Mathews, Frances, McVie, Robert, Menzel, Ulrike, Metz, Chantale, Meulen, John Van Der, Modgil, Gita, Mul, Dick, Muther, Silvia, Nuboer, Roos, 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, Klemens, 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, Jaques, Weisner, Tobias, Werner, Andrea, Williams, Toni, Woodhead, Helen, øddegård, Rønnaug, Bowman, Pamela, Sulen, Åsta, Barbetti, Fabrizio, Beltrand, Jacques, 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, and Njølstad, Pål R

Published
2018
Full Text
View/download PDF

17. Insulin: still a miracle after all these years

Author

Barbetti, Fabrizio and Taylor, Simeon I.

Subjects
Genetic testing -- Analysis, Autoimmunity -- Analysis, Autoantibodies -- Analysis, Type 2 diabetes -- Genetic aspects -- Analysis, Peptides -- Analysis, Medical research -- Analysis, Insulin -- Analysis, Genetic research, Genes, Medical schools, Antibodies, Hypoglycemic agents, Health care industry, Joslin Diabetes Center
Abstract

The discovery of insulin almost 100 years ago has resulted in a remarkable increase in lifespan and quality of life for patients with type 1 diabetes. The Joslin Medalist Study has allowed researchers to access and study patients (Medalists) with type 1 diabetes who have been insulin dependent for 50 years or more. In this issue of the JCI, Yu et al. evaluated HLA variants, autoantibody status, [beta] cell function, C-peptide release, and monogenetic diabetes genes in a cohort of Medalists. Postmortem analysis of pancreata from Medalists revealed the presence of insulin-positive [beta] cells in these patients. Moreover, some patients were still able to respond to metabolic stimuli despite long-term insulin dependence. Overall, the Medalist cohort was highly heterogenous, and genetic testing suggested that several patients would fall into categories other than type 1 diabetes on the basis of REVEL (rare exome variant ensemble learner) classification and may be able to transfer to other therapy options., Ground-breaking discovery: insulin As we approach the 100th anniversary of the discovery of insulin (1), we give thanks for the miraculous transformation of patients' lives resulting from that historical achievement [...]

Published
2019
Full Text
View/download PDF

20. Can HbA1c combined with fasting plasma glucose help to assess priority for GCK-MODY vs HNF1A-MODY genetic testing?

Author

Delvecchio, Maurizio, Salzano, Giuseppina, Bonura, Clara, Cauvin, Vittoria, Cherubini, Valentino, d’Annunzio, Giuseppe, Franzese, Adriana, Giglio, Sabrina, Grasso, Valeria, Graziani, Vanna, Iafusco, Dario, Iughetti, Lorenzo, Lera, Riccardo, Maffeis, Claudio, Maltoni, Giulio, Mantovani, Vilma, Menzaghi, Claudia, Patera, Patrizia I., Rabbone, Ivana, Reindstadler, Petra, Scelfo, Sabrina, Tinto, Nadia, Toni, Sonia, Tumini, Stefano, Lombardo, Fortunato, Nicolucci, Antonio, Barbetti, Fabrizio, and The Diabetes Study Group of the Italian Society of Pediatric Endocrinology and Diabetes (ISPED)

Published
2018
Full Text
View/download PDF

24. Case report: Better late than never, but sooner is better: switch from CSII to sulfonylureas in two patients with neonatal diabetes due to KCNJ11 variants.

Author

Mancioppi, Valentina, Pozzi, Erica, Zanetta, Sara, Missineo, Anna, Savastio, Silvia, Barbetti, Fabrizio, Mellone, Simona, Giordano, Mara, and Rabbone, Ivana

Subjects
INSULIN pumps, HYPOGLYCEMIC sulfonylureas, SULFONYLUREAS, PEOPLE with diabetes, GLYCOSYLATED hemoglobin, HYPERGLYCEMIA
Abstract

Neonatal diabetes mellitus (NDM) is a rare genetic disease characterized by severe hyperglycemia requiring insulin therapy with onsetmostly within the first 6 months and rarely between 6-12 months of age. The disease can be classified into transient (TNDM) or permanent neonatal diabetes mellitus (PNDM), or it can be a component of a syndrome. The most frequent genetic causes are abnormalities of the 6q24 chromosomal region and mutations of the ABCC8 or KCNJ11 genes coding for the pancreatic beta cell's potassium channel (KATP). After the acute phase, patients with ABCC8 or KCNJ11 mutations treated with insulin therapy can switch to hypoglycemic sulfonylureas (SU). These drugs close the KATP channel binding the SUR1 subunit of the potassium channel and restoring insulin secretion after a meal. The timing of this switch can be different and could affect long-term complications. We describe the different management and clinical outcome over the time of two male patients with NDM due to KCNJ11 pathogenetic variants. In both cases, continuous subcutaneous insulin infusion pumps (CSII) were used to switch therapy from insulin to SU, but at different times after the onset. The two patients kept adequate metabolic control after the introduction of glibenclamide; during the treatment, insulin secretion was evaluated with c-peptide, fructosamine, and glycated hemoglobin (HbA1c), which were within the normal range. In neonates or infants with diabetes mellitus, genetic testing is an indispensable diagnostic tool and KCNJ11 variants should be considered. A trial of oral glibenclamide must be considered, switching from insulin, the first line of NDM treatment. This therapy can improve neurological and neuropsychological outcomes, in particular in the case of earlier treatment initiation. A new modified protocol with glibenclamide administered several times daily according to continuous glucose monitoring profile indications, was used. Patients treated with glibenclamide maintain good metabolic control and prevent hypoglycemia, neurological damage, and apoptosis of beta cells during long-term administration. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

26. ISPAD Clinical Practice Consensus Guidelines 2022: The diagnosis and management of monogenic diabetes in children and adolescents.

Author

Greeley, Siri Atma W., Polak, Michel, Njølstad, Pål R., Barbetti, Fabrizio, Williams, Rachel, Castano, Luis, Raile, Klemens, Chi, Dung Vu, Habeb, Abdelhadi, Hattersley, Andrew T., and Codner, Ethel

Subjects
GENETICS of diabetes, DIAGNOSIS of diabetes, DIABETES prevention, LIPODYSTROPHY, MOLECULAR diagnosis, GENETICS, GENETIC mutation, MITOCHONDRIAL pathology, GENETIC testing, MEDICAL protocols, GENOMICS, AGE factors in disease, GENES, DISEASE management, INSULIN resistance, CHILDREN, ADOLESCENCE
Abstract

The article presents the discussion on addition of recently described subtypes of monogenic diabetes. Topics include use of increasingly available publicly accessible information about specific variants to allow for the appropriate classification of pathogenicity of gene variants; and referral to a specialist in monogenic diabetes or an interested clinical genetics unit suggested to guide specific management considerations.

Published
2022
Full Text
View/download PDF

31. Sulfonylurea-Insensitive Permanent Neonatal Diabetes Caused by a Severe Gain-of-Function Tyr330His Substitution in Kir6.2.

Author

McClenaghan, Conor, Rapini, Novella, De Rose, Domenico Umberto, Gao, Jian, Roeglin, Jacob, Bizzarri, Carla, Schiaffini, Riccardo, Tiberi, Eloisa, Mucciolo, Mafalda, Deodati, Annalisa, Perri, Alessandro, Vento, Giovanni, Barbetti, Fabrizio, Nichols, Colin G., and Cianfarani, Stefano

Subjects
ETIOLOGY of diabetes, DEVELOPMENTAL delay, NEONATAL diseases, FUNCTIONAL analysis, SULFONYLUREAS, ION channels
Abstract

Background/Aims: Mutations in KCNJ11, the gene encoding the Kir6.2 subunit of pancreatic and neuronal KATP channels, are associated with a spectrum of neonatal diabetes diseases. Methods: Variant screening was used to identify the cause of neonatal diabetes, and continuous glucose monitoring was used to assess effectiveness of sulfonylurea treatment. Electrophysiological analysis of variant KATP channel function was used to determine molecular basis. Results: We identified a previously uncharacterized KCNJ11 mutation, c.988T>C [p.Tyr330His], in an Italian child diagnosed with sulfonylurea-resistant permanent neonatal diabetes and developmental delay (intermediate DEND). Functional analysis of recombinant KATP channels reveals that this mutation causes a drastic gain-of-function, due to a reduction in ATP inhibition. Further, we demonstrate that the Tyr330His substitution causes a significant decrease in sensitivity to the sulfonylurea, glibenclamide. Conclusions: In this subject, the KCNJ11 (c.988T>C) mutation provoked neonatal diabetes, with mild developmental delay, which was insensitive to correction by sulfonylurea therapy. This is explained by the molecular loss of sulfonylurea sensitivity conferred by the Tyr330His substitution and highlights the need for molecular analysis of such mutations. [ABSTRACT FROM AUTHOR]

Published
2022
Full Text
View/download PDF

33. Seven mutations in the human insulin gene linked to permanent neonatal/infancy-onset diabetes mellitus

Author

Colombo, Carlo, Porzio, Ottavia, Liu, Ming, Massa, Ornella, Vasta, Mario, Salardi, Silvana, Beccaria, Luciano, Monciotti, Carla, Toni, Sonia, Pedersen, Oluf, Hansen, Torben, Federici, Luca, Pesavento, Roberta, Cadario, Francesco, Federici, Giorgio, Ghirri, Paolo, Arvan, Peter, Iafusco, Dario, and Barbetti, Fabrizio.

Subjects
Diabetes -- Genetic aspects, Pancreatic beta cells -- Health aspects, Pancreatic beta cells -- Research, Gene mutations -- Complications and side effects, Gene mutations -- Research, Infants (Newborn) -- Diseases, Infants (Newborn) -- Genetic aspects, Infants (Newborn) -- Risk factors
Abstract

Permanent neonatal diabetes mellitus (PNDM) is a rare disorder usually presenting within 6 months of birth. Although several genes have been linked to this disorder, in almost half the cases documented in Italy, the genetic cause remains unknown. Because the Akita mouse bearing a mutation in the Ins2 gene exhibits PNDM associated with pancreatic [beta] cell apoptosis, we sequenced the human insulin gene in PNDM subjects with unidentified mutations. We discovered 7 heterozygous mutations in 10 unrelated probands. In 8 of these patients, insulin secretion was detectable at diabetes onset, but rapidly declined over time. When these mutant proinsulins were expressed in HEK293 cells, we observed defects in insulin protein folding and secretion. In these experiments, expression of the mutant proinsulins was also associated with increased Grp78 protein expression and XBP1 mRNA splicing, 2 markers of endoplasmic reticulum stress, and with increased apoptosis. Similarly transfected INS-1E insulinoma cells had diminished viability compared with those expressing WT proinsulin. In conclusion, we find that mutations in the insulin gene that promote proinsulin misfolding may cause PNDM., Introduction Neonatal diabetes is a rare monogenic disorder associated with defects of pancreatic [beta] cell mass and/or function. The disorder is distinguished by 2 clinical variants--transient and permanent--caused by specific [...]

Published
2008

34. Lack of the architectural factor HMGA1 causes insulin resistance and diabetes in humans and mice

Author

Foti, Daniela, Chiefari, Eusebio, Fedele, Monica, Iuliano, Rodolfo, Brunetti, Leonardo, Paonessa, Francesco, Manfioletti, Guidalberto, Barbetti, Fabrizio, Brunetti, Arturo, Croce, Carlo M, Fusco, Alfredo, and Brunetti, Antonio

Abstract

Type 2 diabetes mellitus is a widespread disease, affecting millions of people globally. Although genetics and environmental factors seem to have a role, the cause of this metabolic disorder is largely unknown. Here we report a genetic flaw that markedly reduced the intracellular expression of the high mobility group A1 (HMGA1) protein, and adversely affected insulin receptor expression in cells and tissues from four subjects with insulin resistance and type 2 diabetes. Restoration of HMGA1 protein expression in subjects' cells enhanced INSR gene transcription, and restored cell-surface insulin receptor protein expression and insulin-binding capacity. Loss of Hmga1 expression, induced in mice by disrupting the Hmga1 gene, considerably decreased insulin receptor expression in the major targets of insulin action, largely impaired insulin signaling and severely reduced insulin secretion, causing a phenotype characteristic of human type 2 diabetes., Author(s): Daniela Foti [1, 7]; Eusebio Chiefari [1, 7]; Monica Fedele [2]; Rodolfo Iuliano [1]; Leonardo Brunetti [1]; Francesco Paonessa [1]; Guidalberto Manfioletti [3]; Fabrizio Barbetti [4]; Arturo Brunetti [5]; [...]

Published
2005
Full Text
View/download PDF

37. Neonatal diabetes mellitus due to complete glucokinase deficiency

Author

Njolstad, Pal, Sovik, Oddmund, Cuesta-Munoz, Antonio, Bjorkhaug, Lise, Massa, Ornella, Barbetti, Fabrizio, Undlien, Dag E., Shiota, Chiyo, Magnuson, Mark A., Molven, Anders, Matschinsky, Franz M., and Bell, Graeme I.

Subjects
Diabetes -- Causes of, Metabolism, Inborn errors of -- Case studies
Abstract

Medical scientists describe two newborn babies who developed diabetes because they had a complete absence of the enzyme glucokinase. This enzyme regulates the secretion of insulin in response to glucose ingestion.

Published
2001

40. Opposite Clinical Phenotypes of Glucokinase Disease: Description of a Novel Activating Mutation and Contiguous Inactivating Mutations in Human Glucokinase (GCK) Gene

Author

Barbetti, Fabrizio, Cobo-Vuilleumier, Nadia, Dionisi-Vici, Carlo, Toni, Sonia, Ciampalini, Paolo, Massa, Ornella, Rodriguez-Bada, Pablo, Colombo, Carlo, Lenzi, Lorenzo, Garcia-Gimeno, María A., Bermudez-Silva, Francisco J., de Fonseca, Fernando Rodriguez, Banin, Patrizia, Aledo, Juan C., Baixeras, Elena, Sanz, Pascual, and Cuesta-Muñoz, Antonio L.

Published
2009

43. Insights into the Structure and Regulation of Glucokinase from a Novel Mutation (V62M), Which Causes Maturity-onset Diabetes of the Young

Author

Gloyn, Anna L., Odili, Stella, Zelent, Dorothy, Buettger, Carol, Castleden, Harriet A.J., Steele, Anna M., Stride, Amanda, Shiota, Chyio, Magnuson, Mark A., Lorini, Renata, d'Annunzio, Giuseppe, Stanley, Charles A., Kwagh, Jae, van Schaftingen, Emile, Veiga-da-Cunha, Maria, Barbetti, Fabrizio, Dunten, Pete, Han, Yi, Grimsby, Joseph, Taub, Rebecca, Ellard, Sian, Hattersley, Andrew T., and Matschinsky, Franz M.

Published
2005
Full Text
View/download PDF

45. The application of precision medicine in monogenic diabetes.

Author

Barbetti, Fabrizio, Rapini, Novella, Schiaffini, Riccardo, Bizzarri, Carla, and Cianfarani, Stefano

Subjects
INDIVIDUALIZED medicine, DIABETES in children, DIABETES, GENETIC testing, AGE of onset
Abstract

Monogenic diabetes, a form of diabetes mellitus, is caused by a mutation in a single gene and may account for 1–2% of all clinical forms of diabetes. To date, more than 40 loci have been associated with either isolated or syndromic monogenic diabetes. While the request of a genetic test is mandatory for cases with diabetes onset in the first 6 months of life, a decision may be difficult for childhood or adolescent diabetes. In an effort to assist the clinician in this task, we have grouped monogenic diabetes genes according to the age of onset (or incidental discovery) of hyperglycemia and described the additional clinical features found in syndromic diabetes. The therapeutic options available are reviewed. Technical improvements in DNA sequencing allow for rapid, simultaneous analysis of all genes involved in monogenic diabetes, progressively shrinking the area of unsolved cases. However, the complexity of the analysis of genetic data requires close cooperation between the geneticist and the diabetologist, who should play a proactive role by providing a detailed clinical phenotype that might match a specific disease gene. [ABSTRACT FROM AUTHOR]

Published
2022
Full Text
View/download PDF

49. A rare cause of transient neonatal diabetes mellitus: Spontaneous HNF1B splice variant.

Author

Pezzino, Giulia, Ruta, Rosario, Rapini, Novella, Chiodo, Danilo Castellano, Mucciolo, Mafalda, Tomaselli, Letizia, Cianfarani, Stefano, and Barbetti, Fabrizio

Subjects
GENETICS of diabetes, NEWBORN screening, GENETIC mutation, HYPERGLYCEMIA, NEONATAL diseases, DIABETES, BLOOD sugar, GENETIC testing, INSULIN, TREATMENT effectiveness, GENES, CHROMOSOME abnormalities, CONTINUOUS glucose monitoring, C-peptide, CHILDREN
Abstract

The article focuses on a rare cause of transient neonatal diabetes mellitus (TNDM) related to a spontaneous splicing mutation in the HNF1B gene. Topics include the clinical case of an Italian patient with TNDM associated with this mutation, the necessity of genetic investigation in TNDM cases negative to common genetic causes, and the recommendation for a strict follow-up of glucose levels after remission in HNF1B-TNDM cases to detect early relapse of hyperglycemia.

Published
2024
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results