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

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

Abstract

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.

Article Details

Volume / Issue Vol. 16, Issue 1
Published March 13, 2026
ISSN 2045-2322
Publisher Nature Portfolio

Journal Info

Scientific Reports

Nature Portfolio

ISSN: 2045-2322 Open Access Life Sciences

Authors (82)

A

Ana Victoria García

C

Carmen Lambert

E

Elsa Villa-Fernández

M

Miguel García-Villarino

I

Isabel Serrano-Olmedo

E

Elsa Fernández Rubio

A

Ana Megia Colet

M

Miguel Brito-Sanfiel

F

Francisca Payeras Mas

E

Estefanía Santos

M

M. Ángeles Martínez de Salinas Santamaría

F

Fernando Gómez-Peralta

E

Edelmiro Menéndez-Torre

P

Pedro Pujante

F

Francisco Tinahones Madueño

F

Florentino Carral San Laureano

M

Martín López de la Torre

A

Alberto Moreno Carazo

J

Javier Acha Pérez Hospital

O

Orosia Bandrés Nivela

L

Lluís Masmiquel Comas

I

Ignacio Llorente Gómez

J

Juan Angel Hernández Bayo

C

Coral Montalbán

D

Daniel de Luis

G

Gonzalo Díaz Soto

A

Antonio López-Guzmán

L

Luz Ma López Jiménez

V

Visitacion Alvarez

B

Benito Blanco Samper

A

Ana Chico Ballesteros

B

Belen Dalama Gómez

I

Ignacio Conget

M

Manuel Pérez Maraver

B

Berta Soldevila

I

Ismael Capel Flores

M

Marta Hernández García

W

Wifredo Ricart

E

Elisenda Climent Biescas

F

Francisco Javier Ampudia Blasco

A

Antonio Hernández Mijares

C

Carlos Sánchez Juan

A

Antonio Picó

J

José Ramón Domínguez Escribano

C

Carmiña Fajardo Montañana

T

Teresa Pedro

P

Pablo Abellán

P

Paolo Rossetti

Computational Biology

F

Francisco M. Morales-Pérez

F

Fidel Enciso

A

Alfonso Soto González

D

Diego Bellido Guerrero

R

Reyes Luna Cano

J

José Manuel García López

V

Víctor M. Andía Melero

J

José Alfonso Arranz Martín

S

Sharona Azriel Mira

M

Marta Botella Serrano

A

Alfonso Calle Pascual

F

Francisco Javier del Cañizo Gómez

M

Manuel Ángel Gargallo Fernández

F

Fátima Illán

A

Antonio M. Hernández Martínez

L

Lluis Forga Llenas

C

Clara Rosario Fuentes Gómez

A

Amelia Oleaga

J

Juan Pedro López-Siguero

A

Ana Lucía Gómez-Gila

A

Alfonso María Lechuga Sancho

M

Marta Ferrer Lozano

I

Isolina Riaño Galán

M

María Caimari

R

Roque Cardona

M

María Clemente León

G

Gemma Carreras González

F

Francisco Javier Arroyo Diez

P

Paloma Cabanas Rodríguez

B

Belén Roldán

N

Noemí González Pérez de Villar

P

Purificación Ros Pérez

I

Itxaso Rica

I

Ignacio Diez López