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.
Authors
- Ana Chico Ballesteros
- Marta Botella Serrano
- Fátima Illán
- Berta Rodés Soldevila
- Ignacio Díez López (ORCID: https://orcid.org/0000-0001-7211-0135)
- Florentino Carral San Laureano (ORCID: https://orcid.org/0000-0002-2607-971X)
- Juan Angel Hernandez Bayo
- Elisenda Climent Biescas
- Isolina Riaño Galán (ORCID: https://orcid.org/0000-0003-2125-5101)
- Alfonso Calle Pascual
- Francisca Payeras Mas
- Antonio Picó (ORCID: https://orcid.org/0000-0002-7549-7563)
- Francisco Madueño (ORCID: https://orcid.org/0000-0001-7598-3003)
- José Manuel García López (ORCID: https://orcid.org/0000-0003-0923-2871)
- José Alfonso Arranz Martín (ORCID: https://orcid.org/0000-0002-0140-1522)
- Coral Montalbán
- Elsa Fernandez Rubio
- Paolo Rossetti (ORCID: https://orcid.org/0000-0002-2767-2996)
- Miguel Ángel Brito-Sanfiel (ORCID: https://orcid.org/0000-0002-4748-9777)
- Benito Blanco Samper
- Wifredo P. Ricart
- Alfonso González (ORCID: https://orcid.org/0000-0002-6139-4299)
- 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 (ORCID: https://orcid.org/0000-0002-1745-9315)
- María Caimari
- Fernando Gomez-Peralta
- Laura Oleaga (ORCID: https://orcid.org/0000-0001-9702-0451)
- Alfonso María Lechuga Sancho
- Elsa Villa-Fernández (ORCID: https://orcid.org/0000-0001-5702-8985)
- Clara Rosario Fuentes Gómez
- Estefanía Santos (ORCID: https://orcid.org/0000-0002-1194-7422)
- 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 (ORCID: https://orcid.org/0000-0003-2197-0607)
- 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
Institutions
- 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)
Publication Details
- Journal
- Scientific Reports
- Published
- 2026-03-13
- DOI
- https://doi.org/10.1038/s41598-026-42995-x
- Primary Topic
- Diabetes and associated disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00