Epigenetic alterations in type 1 diabetes and their association with poor glycemic control: the SED1-EPI substudy

Type 1 diabetes (T1D) is an autoimmune disease characterized by β-cell destruction and insulin deficiency. Circulating microRNAs (miRNAs) are promising biomarkers for disease monitoring and complication risk assessment. This study aimed to describe the epigenetic profile in a multicenter Spanish T1D cohort and its association with clinical variables. We analyzed plasma samples from 125 participants (76 T1D, 49 controls) recruited across nine Spanish hospitals. Eight candidate miRNAs from a prior Asturias cohort study were quantified using RT-PCR. Associations with clinical and biochemical parameters were explored, and enrichment analysis was performed to investigate affected biological pathways. Of the miRNAs analyzed, only hsa-miR-200a-3p was significantly overexpressed in T1D versus controls (p = 0.035). In T1D patients, hsa-miR-200a-3p, hsa-miR-1-3p, and hsa-miR-340-5p showed positive correlations with HbA1c, while hsa-miR-224-5p correlated with body mass index (BMI). Poor glycemic control (HbA1c ≥ 7.5%) was associated with higher expression of hsa-miR-1-3p, hsa-miR-200a-3p, and hsa-miR-340-5p. No significant expression differences were found according to comorbidity or hypertension status. hsa-miR-200a-3p emerges as a potential biomarker for β-cell stress in long-standing T1D, while hsa-miR-1-3p and hsa-miR-340-5p may reflect glycemic control status and vascular risk. These findings support further evaluation of these miRNAs in larger, clinically diverse T1D cohorts.

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Journal
Scientific Reports
Published
2026-03-13
DOI
https://doi.org/10.1038/s41598-026-42995-x
Primary Topic
Diabetes and associated disorders
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article

Epigenetic alterations in type 1 diabetes and their association with poor glycemic control: the SED1-EPI substudy

Ana Chico Ballesteros, Marta Botella Serrano, Fátima Illán, Berta Rodés Soldevila et al.
Scientific Reports
Diabetes and associated disorders
article

Epigenetic alterations in type 1 diabetes and their association with poor glycemic control: the SED1-EPI substudy

Ana Chico Ballesteros, Marta Botella Serrano, Fátima Illán, Berta Rodés Soldevila, Ignacio Díez López, Florentino Carral San Laureano, Juan Angel Hernandez Bayo, Elisenda Climent Biescas, Isolina Riaño Galán, Alfonso Calle Pascual, Francisca Payeras Mas, Antonio Picó, Francisco Madueño, José Manuel García López, José Alfonso Arranz Martín, Coral Montalbán, Elsa Fernandez Rubio, Paolo Rossetti, Miguel Ángel Brito-Sanfiel, Benito Blanco Samper, Wifredo P. Ricart, Alfonso González, M Ferrer-Lozano, Ismael Capel Flores, S. Azriel Mira, Manuel Pérez Maraver, Fidel J. Enciso, Lluís Forga Llenas, José Ramón Domínguez Escribano, Daniel Antonio de Luis, María Caimari, Fernando Gomez-Peralta, Laura Oleaga, Alfonso María Lechuga Sancho, Elsa Villa-Fernández, Clara Rosario Fuentes Gómez, Estefanía Santos, Francisco Javier Arroyo Díez, Juan Pedro López-Siguero, Carlos Sánchez Juan, Noemí González Pérez de Villar, Visitación Álvarez, María Clemente León, A. Riesgo García, Antonio López-Guzmán, Purificación Ros Pérez, Isabel Serrano-Olmedo, Gemma Carreras González, Belén Roldán, Paloma Cabanas Rodríguez, Antonio Hernández Mijares, Gonzalo Díaz Soto, Edelmiro Luis Menéndez-Torre, Teresa Pedro, Ignacio Conget, M. Ángeles Martínez de Salinas Santamaría, SED1 study investigators SED, Miguel García-Villarino, Antonio M. Hernández Martínez, Martín López de la Torre, Alberto Moreno Carazo, Carmen Lambert, Carmiña Fajardo Montañana, Marta Hernández García, Itxaso Rica, Francisco Javier Ampudia Blasco, Pablo Abellán, Belen Dalama Gómez, Orosia Bandrés Nivela, Luz Ma López Jiménez, Roque Cardona, Pedro Pujante, Ignacio Llorente Gómez, Ana Lucía Gómez-Gila, Víctor M. Andía Melero, Reyes Luna Cano, Ana Megia Colet, Manuel Ángel Gargallo Fernández, Diego Bellido Guerrero, Francisco Javier del Cañizo Gómez, Francisco M. Morales-Pérez, Lluís Masmiquel Comas
article en

Abstract

Type 1 diabetes (T1D) is an autoimmune disease characterized by β-cell destruction and insulin deficiency. Circulating microRNAs (miRNAs) are promising biomarkers for disease monitoring and complication risk assessment. This study aimed to describe the epigenetic profile in a multicenter Spanish T1D cohort and its association with clinical variables. We analyzed plasma samples from 125 participants (76 T1D, 49 controls) recruited across nine Spanish hospitals. Eight candidate miRNAs from a prior Asturias cohort study were quantified using RT-PCR. Associations with clinical and biochemical parameters were explored, and enrichment analysis was performed to investigate affected biological pathways. Of the miRNAs analyzed, only hsa-miR-200a-3p was significantly overexpressed in T1D versus controls (p = 0.035). In T1D patients, hsa-miR-200a-3p, hsa-miR-1-3p, and hsa-miR-340-5p showed positive correlations with HbA1c, while hsa-miR-224-5p correlated with body mass index (BMI). Poor glycemic control (HbA1c ≥ 7.5%) was associated with higher expression of hsa-miR-1-3p, hsa-miR-200a-3p, and hsa-miR-340-5p. No significant expression differences were found according to comorbidity or hypertension status. hsa-miR-200a-3p emerges as a potential biomarker for β-cell stress in long-standing T1D, while hsa-miR-1-3p and hsa-miR-340-5p may reflect glycemic control status and vascular risk. These findings support further evaluation of these miRNAs in larger, clinically diverse T1D cohorts.

Scientific Reports
Universitat Jaume I (ES), Universidade da Coruña (ES), Hebron University (PS), Hospital Sant Joan de Déu Barcelona (ES), UF Health Shands Hospital (US), Universidad de Oviedo (ES), Catholic University of Ávila (ES), Universidad Francisco de Vitoria (ES), Gobierno del Principado de Asturias (ES), Hospital Universitario La Paz (ES), Hospital de Sant Pau (ES), Bellvitge University Hospital (ES), Hospital Universitari Arnau de Vilanova (ES), University Hospital Complex Of Vigo (ES), Hospital General Universitario Gregorio Marañón (ES), Hospital Clínico San Carlos (ES), Hospital General De Segovia (ES), Hospital Son Llatzer (ES), Hospital Universitario Nuestra Señora de Candelaria (ES), Hospital Universitario Virgen Macarena (ES), Hospital General Universitario Morales Meseguer (ES), Hospital Universitari Sant Joan D'Alacant (ES), Hospital de Basurto (ES), Hospital General Nuestra Señora del Prado (ES), Hospital Universitario de Guadalajara (ES), Hospital de La Ribera (ES), Hospital Clínico Universitario de Valencia (ES), Ferrer Grupo (Spain) (ES), Complejo Hospitalario de Navarra (ES), Marqués de Valdecilla University Hospital (ES), Centro de Salud Casa del Barco (ES), Institut de Recerca Biomèdica Catalunya Sud (ES), Hospital Royo Villanova (ES), Fundación Hospital Manacor (ES), Hospital Universitario Puerta de Hierro Majadahonda (ES), Hospital Universitario Príncipe de Asturias (ES), Hospital Regional Universitario de Málaga (ES), Hospital Universitario Miguel Servet (ES), Hospital Clínic de Barcelona (ES), Hospital Universitario de Burgos (ES), Hospital Universitario Virgen de las Nieves (ES), Complejo Hospitalario de Jaén (ES), Hospital Arnau de Vilanova (ES), Hospital de Sabadell (ES), Hospital General Universitari de Castelló (ES), Hospital Universitario Doctor Peset (ES), Vall d'Hebron Hospital Universitari (ES), Hospital General Universitario De Valencia (ES), Hospital Materno-Infantil (ES), Hospital Universitario de La Princesa (ES), Hospital Universitario Central de Asturias (ES), Hospital de Mataró (ES), Hospital de Cruces (ES), Hospital General Universitario de Alicante Doctor Balmis (ES), Centro de Implantología Cirugía Oral y Maxilofacial (ES), Hospital Universitario Puerto Real (ES), Hospital San Pedro (ES), Fundación Hospital Provincial de Castellón (ES), Hospital Universitario Puerta del Mar (ES), Hospital Universitario Virgen de la Arrixaca (ES), Hospital Universitario Son Espases (ES), Hospital Universitario Virgen del Rocío (ES), Hospital Universitari Germans Trias i Pujol (ES), Hospital Universitari de Girona Doctor Josep Trueta (ES), Complejo Hospitalario Universitario de Albacete (ES), Hospital Clínico Universitario Virgen de la Victoria (ES), Hospital Clínico Universitario de Valladolid (ES), Complejo Hospitalario de Cáceres (ES), Hospital Universitario Infanta Sofía (ES), Hospital Universitario Ramón y Cajal (ES), Hospital Perpetuo Socorro (ES), Hospital Universitario Infanta Leonor (ES), Hospital Provincial de Conxo (ES), Complejo Hospitalario Universitario de Ferrol (ES), Universidad de Burgos (ES)
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Diabetes and associated disorders
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