OC23 - SED1-EPI study: Validation of the results obtained in the DM1-Asturias cohort

Background/Introduction Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of pancreatic β-cells, leading to insulin deficiency. Its development results from a combination of environmental, immunological, metabolic, and epigenetic factors, with a growing focus in recent years on the analysis of miRNA expression. The SED1 study aims to analyze the profile and management of Spanish patients with T1D to assess factors that may influence disease control. The SED1-EPI substudy aims to identify epigenetic changes associated with the presence of T1D and its comorbidities. Purpose Our objective is to validate the findings of the DM1-Asturias study (PMID:37244952) in the Spanish SED1 cohort. Specifically, we analyze changes in miRNA expression levels and their relationship with metabolic control. Methods A total of 115 plasma samples were collected, 76 volunteers with T1D and 39 controls from across Spain. The differential expression of seven miRNAs that had previously been studied in the DM1-Asturias cohort was analysed by using RT-PCR, together with the demographic data of the volunteers. Results After analyzing the differential expression of 7 circulating miRNAs in the plasma, statistically significant differences were found in the expression of hsa-miR- 200a-3p, with higher expression observed in T1D compared to controls(p = 0.035). Although no statistically significant, higher expression levels of hsa-miR-141 were also observed in T1D volunteers(p = 0.097). Additionally, correlations between miRNA expression and anthropometric and biochemical parameters were analyzed. BMI showed a positive correlation with the expression of hsa-miR-224-5p(p=0.049). HbA1c levels were also positively correlated with the expression of hsa-miR-1-3p(p=0.035) and hsa-miR-340-5p(p=0.016). Conclusion(s) We have validated, in a national cohort, the findings from the epigenetic analysis of the DM1-Asturias. In particular, we confirmed the correlation between hsa-miR-1-3p and HbA1c levels, suggesting its potential involvement in various stages of diabetes development and its complications. Additionally, we examined miR-200 family expression and its association with BMI, as this family is linked to beta-cell function in diabetes. Although we could not establish a relationship between the expression of these miRNAs and the presence of comorbidities, a better understanding of the epigenetic status of people with T1D could facilitate a better disease control.