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

Lorenza Nisticò, Dario Iafusco, Alfonso Galderisi, Corrado Fagnani, Rodolfo Cotichini, Virgilia Toccaceli, Maria Antonietta Stazi, Valentino Cherubini, Antonio Iannilli, Anna Maria Paparusso, Luciano Cavallo, Clara Zecchino, Gianpaolo De Filippo, Luigi Gargantini, Silvana Salardi, Stefano Zucchini, Giulio Maltoni, Bruno Pasquino, Peter Kaufmann, Fabio BuziElena Prandi, Francesco Gallo, Mario Cicchetti, Enzo Castaldo, Felice Citriniti, Franco Chiarelli, Stefano Tumini, Alessia Di Stefano, Domenico Sperlì, Rosaria De Marco, Patrizia Banin, Sonia Toni, Lorenzo Lenzi, Maurizio Del Vecchio, Renata Lorini, Giuseppe D'Annunzio, Dario Ingletto, Andrea Scaramuzza, Gian Vincenzo Zuccotti, Giuseppe Chiumello, Franco Meschi, Riccardo Bonfanti, Giulio Frontino, Filippo De Luca, Fortunato Lombardo, Giusy Salzano, Lorenzo Iughetti, Adriana Franzese, Pietro Buono, Ilaria De Simone, Francesco Prisco, Alessandra Cocca, Franco Cadario, Carla M. Monciotti, Valentina Savio, Francesca Cardella, Maurizio Vanelli, Giovanni Chiari, Katrin Errico, Brunella Iovane, Valeria Calcaterra, Francesco Citro, Sandro Cantoni, Alberto Marsciani, Marco Cappa, Patrizia I. Patera, Riccardo Schiaffini, Nicoletta Sulli, Marialuisa Spoletini, Franco Cerutti, Ivana Rabbone, Sabrina Sicignano, Vittoria Cauvin, Maria Bellizzi, Giorgio Tonini, Elena Faleschini, Alessandro Salvatoni, Leonardo Pinelli, Claudio Maffeis, Giovanna Contreas

Research output: Contribution to journalArticle

23 Citations (Scopus)

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.

Original languageEnglish
JournalJournal of Clinical Endocrinology and Metabolism
Volume97
Issue number8
DOIs
Publication statusPublished - Aug 2012

Fingerprint

Twin Studies
Medical problems
Type 1 Diabetes Mellitus
Italy
Insulin
Recurrence
Glutamate Decarboxylase
Structural Models
Incidence
Epidemiology
Pediatrics
Islets of Langerhans
Phosphoric Monoester Hydrolases
Autoantibodies
Tyrosine
Registries
Environmental impact
Outcome Assessment (Health Care)
Genetic Background
Confidence Intervals

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

Emerging effects of early environmental factors over genetic background for type 1 diabetes susceptibility : Evidence from a nationwide Italian twin study. / Nisticò, Lorenza; Iafusco, Dario; Galderisi, Alfonso; Fagnani, Corrado; Cotichini, Rodolfo; Toccaceli, Virgilia; Stazi, Maria Antonietta; Cherubini, Valentino; Iannilli, Antonio; Paparusso, Anna Maria; Cavallo, Luciano; Zecchino, Clara; De Filippo, Gianpaolo; Gargantini, Luigi; Salardi, Silvana; Zucchini, Stefano; Maltoni, Giulio; Pasquino, Bruno; Kaufmann, Peter; Buzi, Fabio; Prandi, Elena; Gallo, Francesco; Cicchetti, Mario; Castaldo, Enzo; Citriniti, Felice; Chiarelli, Franco; Tumini, Stefano; Di Stefano, Alessia; Sperlì, Domenico; De Marco, Rosaria; Banin, Patrizia; Toni, Sonia; Lenzi, Lorenzo; Del Vecchio, Maurizio; Lorini, Renata; D'Annunzio, Giuseppe; Ingletto, Dario; Scaramuzza, Andrea; Zuccotti, Gian Vincenzo; Chiumello, Giuseppe; Meschi, Franco; Bonfanti, Riccardo; Frontino, Giulio; De Luca, Filippo; Lombardo, Fortunato; Salzano, Giusy; Iughetti, Lorenzo; Franzese, Adriana; Buono, Pietro; De Simone, Ilaria; Prisco, Francesco; Cocca, Alessandra; Cadario, Franco; Monciotti, Carla M.; Savio, Valentina; Cardella, Francesca; Vanelli, Maurizio; Chiari, Giovanni; Errico, Katrin; Iovane, Brunella; Calcaterra, Valeria; Citro, Francesco; Cantoni, Sandro; Marsciani, Alberto; Cappa, Marco; Patera, Patrizia I.; Schiaffini, Riccardo; Sulli, Nicoletta; Spoletini, Marialuisa; Cerutti, Franco; Rabbone, Ivana; Sicignano, Sabrina; Cauvin, Vittoria; Bellizzi, Maria; Tonini, Giorgio; Faleschini, Elena; Salvatoni, Alessandro; Pinelli, Leonardo; Maffeis, Claudio; Contreas, Giovanna.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 97, No. 8, 08.2012.

Research output: Contribution to journalArticle

Nisticò, L, Iafusco, D, Galderisi, A, Fagnani, C, Cotichini, R, Toccaceli, V, Stazi, MA, Cherubini, V, 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, F, Rabbone, I, Sicignano, S, Cauvin, V, Bellizzi, M, Tonini, G, Faleschini, E, Salvatoni, A, Pinelli, L, Maffeis, C & Contreas, G 2012, 'Emerging effects of early environmental factors over genetic background for type 1 diabetes susceptibility: Evidence from a nationwide Italian twin study', Journal of Clinical Endocrinology and Metabolism, vol. 97, no. 8. https://doi.org/10.1210/jc.2011-3457
Nisticò, Lorenza ; Iafusco, Dario ; Galderisi, Alfonso ; Fagnani, Corrado ; Cotichini, Rodolfo ; Toccaceli, Virgilia ; Stazi, Maria Antonietta ; Cherubini, Valentino ; Iannilli, Antonio ; Paparusso, Anna Maria ; Cavallo, Luciano ; Zecchino, Clara ; De Filippo, Gianpaolo ; Gargantini, Luigi ; Salardi, Silvana ; Zucchini, Stefano ; Maltoni, Giulio ; Pasquino, Bruno ; Kaufmann, Peter ; Buzi, Fabio ; Prandi, Elena ; Gallo, Francesco ; Cicchetti, Mario ; Castaldo, Enzo ; Citriniti, Felice ; Chiarelli, Franco ; Tumini, Stefano ; Di Stefano, Alessia ; Sperlì, Domenico ; De Marco, Rosaria ; Banin, Patrizia ; Toni, Sonia ; Lenzi, Lorenzo ; Del Vecchio, Maurizio ; Lorini, Renata ; D'Annunzio, Giuseppe ; Ingletto, Dario ; Scaramuzza, Andrea ; Zuccotti, Gian Vincenzo ; Chiumello, Giuseppe ; Meschi, Franco ; Bonfanti, Riccardo ; Frontino, Giulio ; De Luca, Filippo ; Lombardo, Fortunato ; Salzano, Giusy ; Iughetti, Lorenzo ; Franzese, Adriana ; Buono, Pietro ; De Simone, Ilaria ; Prisco, Francesco ; Cocca, Alessandra ; Cadario, Franco ; Monciotti, Carla M. ; Savio, Valentina ; Cardella, Francesca ; Vanelli, Maurizio ; Chiari, Giovanni ; Errico, Katrin ; Iovane, Brunella ; Calcaterra, Valeria ; Citro, Francesco ; Cantoni, Sandro ; Marsciani, Alberto ; Cappa, Marco ; Patera, Patrizia I. ; Schiaffini, Riccardo ; Sulli, Nicoletta ; Spoletini, Marialuisa ; Cerutti, Franco ; Rabbone, Ivana ; Sicignano, Sabrina ; Cauvin, Vittoria ; Bellizzi, Maria ; Tonini, Giorgio ; Faleschini, Elena ; Salvatoni, Alessandro ; Pinelli, Leonardo ; Maffeis, Claudio ; Contreas, Giovanna. / Emerging effects of early environmental factors over genetic background for type 1 diabetes susceptibility : Evidence from a nationwide Italian twin study. In: Journal of Clinical Endocrinology and Metabolism. 2012 ; Vol. 97, No. 8.
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title = "Emerging effects of early environmental factors over genetic background for type 1 diabetes susceptibility: Evidence from a nationwide Italian twin study",
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.",
author = "Lorenza Nistic{\`o} and Dario Iafusco and Alfonso Galderisi and Corrado Fagnani and Rodolfo Cotichini and Virgilia Toccaceli and Stazi, {Maria Antonietta} and Valentino Cherubini and Antonio Iannilli and Paparusso, {Anna Maria} and Luciano Cavallo and Clara Zecchino and {De Filippo}, Gianpaolo and Luigi Gargantini and Silvana Salardi and Stefano Zucchini and Giulio Maltoni and Bruno Pasquino and Peter Kaufmann and Fabio Buzi and Elena Prandi and Francesco Gallo and Mario Cicchetti and Enzo Castaldo and Felice Citriniti and Franco Chiarelli and Stefano Tumini and {Di Stefano}, Alessia and Domenico Sperl{\`i} and {De Marco}, Rosaria and Patrizia Banin and Sonia Toni and Lorenzo Lenzi and {Del Vecchio}, Maurizio and Renata Lorini and Giuseppe D'Annunzio and Dario Ingletto and Andrea Scaramuzza and Zuccotti, {Gian Vincenzo} and Giuseppe Chiumello and Franco Meschi and Riccardo Bonfanti and Giulio Frontino and {De Luca}, Filippo and Fortunato Lombardo and Giusy Salzano and Lorenzo Iughetti and Adriana Franzese and Pietro Buono and {De Simone}, Ilaria and Francesco Prisco and Alessandra Cocca and Franco Cadario and Monciotti, {Carla M.} and Valentina Savio and Francesca Cardella and Maurizio Vanelli and Giovanni Chiari and Katrin Errico and Brunella Iovane and Valeria Calcaterra and Francesco Citro and Sandro Cantoni and Alberto Marsciani and Marco Cappa and Patera, {Patrizia I.} and Riccardo Schiaffini and Nicoletta Sulli and Marialuisa Spoletini and Franco Cerutti and Ivana Rabbone and Sabrina Sicignano and Vittoria Cauvin and Maria Bellizzi and Giorgio Tonini and Elena Faleschini and Alessandro Salvatoni and Leonardo Pinelli and Claudio Maffeis and Giovanna Contreas",
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month = "8",
doi = "10.1210/jc.2011-3457",
language = "English",
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journal = "Journal of Clinical Endocrinology and Metabolism",
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TY - JOUR

T1 - Emerging effects of early environmental factors over genetic background for type 1 diabetes susceptibility

T2 - Evidence from a nationwide Italian twin study

AU - Nisticò, Lorenza

AU - Iafusco, Dario

AU - Galderisi, Alfonso

AU - Fagnani, Corrado

AU - Cotichini, Rodolfo

AU - Toccaceli, Virgilia

AU - Stazi, Maria Antonietta

AU - Cherubini, Valentino

AU - Iannilli, Antonio

AU - Paparusso, Anna Maria

AU - Cavallo, Luciano

AU - Zecchino, Clara

AU - De Filippo, Gianpaolo

AU - Gargantini, Luigi

AU - Salardi, Silvana

AU - Zucchini, Stefano

AU - Maltoni, Giulio

AU - Pasquino, Bruno

AU - Kaufmann, Peter

AU - Buzi, Fabio

AU - Prandi, Elena

AU - Gallo, Francesco

AU - Cicchetti, Mario

AU - Castaldo, Enzo

AU - Citriniti, Felice

AU - Chiarelli, Franco

AU - Tumini, Stefano

AU - Di Stefano, Alessia

AU - Sperlì, Domenico

AU - De Marco, Rosaria

AU - Banin, Patrizia

AU - Toni, Sonia

AU - Lenzi, Lorenzo

AU - Del Vecchio, Maurizio

AU - Lorini, Renata

AU - D'Annunzio, Giuseppe

AU - Ingletto, Dario

AU - Scaramuzza, Andrea

AU - Zuccotti, Gian Vincenzo

AU - Chiumello, Giuseppe

AU - Meschi, Franco

AU - Bonfanti, Riccardo

AU - Frontino, Giulio

AU - De Luca, Filippo

AU - Lombardo, Fortunato

AU - Salzano, Giusy

AU - Iughetti, Lorenzo

AU - Franzese, Adriana

AU - Buono, Pietro

AU - De Simone, Ilaria

AU - Prisco, Francesco

AU - Cocca, Alessandra

AU - Cadario, Franco

AU - Monciotti, Carla M.

AU - Savio, Valentina

AU - Cardella, Francesca

AU - Vanelli, Maurizio

AU - Chiari, Giovanni

AU - Errico, Katrin

AU - Iovane, Brunella

AU - Calcaterra, Valeria

AU - Citro, Francesco

AU - Cantoni, Sandro

AU - Marsciani, Alberto

AU - Cappa, Marco

AU - Patera, Patrizia I.

AU - Schiaffini, Riccardo

AU - Sulli, Nicoletta

AU - Spoletini, Marialuisa

AU - Cerutti, Franco

AU - Rabbone, Ivana

AU - Sicignano, Sabrina

AU - Cauvin, Vittoria

AU - Bellizzi, Maria

AU - Tonini, Giorgio

AU - Faleschini, Elena

AU - Salvatoni, Alessandro

AU - Pinelli, Leonardo

AU - Maffeis, Claudio

AU - Contreas, Giovanna

PY - 2012/8

Y1 - 2012/8

N2 - 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.

AB - 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.

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U2 - 10.1210/jc.2011-3457

DO - 10.1210/jc.2011-3457

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JF - Journal of Clinical Endocrinology and Metabolism

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