MiRNAs profile as biomarkers of nutritional therapy for the prevention of type 2 diabetes mellitus: from the CORDIOPREV study

Authors: JIMENEZ-LUCENA, ROSA - University Hospital Reina Sofia; ALCALA-DIAZ, JUAN - University Hospital Reina Sofia; RONCERO-RAMOS, IRENE - University Hospital Reina Sofia; LOPEZ-MORENO, JAVIER - University Hospital Reina Sofia; CAMARGO, ANTONIO - University Hospital Reina Sofia; GOMEZ-DELGADO, FRANCISCO - University Hospital Reina Sofia; QUINTANA-NAVARRO, GRACIA - University Hospital Reina Sofia; VALS-DELGADO, CRISTINA - University Hospital Reina Sofia; RODRIGUEZ-CANTALEJO, FERNANDO - University Hospital Reina Sofia; LUQUE, RAUL - Instituto De Salud Carlos Iii; DELGADO-LISTA, JAVIER - University Hospital Reina Sofia; ORDOVAS, JOSE - Tufts University; PEREZ-MARTINEZ, PABLO - University Hospital Reina Sofia; RANGEL-ZUNIGA, ORIOL - University Hospital Reina Sofia; LOPEZ-MIRANDA, JOSE - University Hospital Reina Sofia

Submitted to: Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/30/2020
Publication Date: 7/13/2020
Citation: Jimenez-Lucena, R., Alcala-Diaz, J.F., Roncero-Ramos, I., Lopez-Moreno, J., Camargo, A., Gomez-Delgado, F., Quintana-Navarro, G., Vals-Delgado, C., Rodriguez-Cantalejo, F., Luque, R.M., Delgado-Lista, J., Ordovas, J.M., Perez-Martinez, P., Rangel-Zuniga, O.A., Lopez-Miranda, J. 2020. MiRNAs profile as biomarkers of nutritional therapy for the prevention of type 2 diabetes mellitus: from the CORDIOPREV study. Clinical Nutrition. https://doi.org/10.1016/j.clnu.2020.06.035.
DOI: https://doi.org/10.1016/j.clnu.2020.06.035

Interpretive Summary: Type 2 diabetes mellitus (T2DM) is one of the leading public health problems. The number of patients with diabetes is increasing dramatically due to the increase in the incidence and prevalence of obesity, mainly associated with western dietary and other lifestyle habits. Complications related to T2DM lead to a deterioration in the patients' quality of life, and subjects with T2DM have higher cardiovascular morbidity and mortality compared with non-diabetic subjects. Prevention is vital for reducing the risk of developing T2DM. This is possible with changes in lifestyle factors such as adopting healthy dietary and physical activity habits and decreasing or removing smoking, alcohol intake, depression, and stress. Therefore, it is essential to identify individuals at high risk of developing diabetes and provide them with dietary advice to prevent the disease. For this purpose, new biomarkers are needed to guide the selection of suitable diets at a personalized level. In this context, miRNAs (small single-stranded non-coding RNA molecules containing about 22 nucleotides) are emerging as promising biomarkers to predict the development of several diseases, including T2DM. The aim of this work conducted by investigators in Spain and at the HNRCA in Boston was to study whether miRNAs could be used to select the nutritional therapy to prevent T2DM development in patients with cardiovascular disease from the CORDIOPREV study. The results show that blood circulating miRNAs could be used in clinical practice as a new tool for selecting the most suitable diet to prevent T2DM development in patients with cardiovascular disease.

Technical Abstract: BACKGROUND AND AIM: The incidence of type 2 diabetes mellitus (T2DM) has increased worldwide. One of the first actions to reduce the risk of this disease is to implement healthy dietary models; however, no universal dietary strategies have so far been established. In addition, MicroRNAs (miRNAs) are emerging as new biomarkers to predict disease. We aimed to study whether miRNAs could be used to select the nutritional therapy to prevent T2DM development in patients with cardiovascular disease. METHODS: All patients from the CORDIOPREV study without T2DM at baseline according to the American Diabetes Association (ADA) diagnostic criteria (n = 462) were included in the present study. Of them, after a median dietary intervention period of 60 months with two diets (Low fat or Mediterranean diets), 107 developed T2DM and 355 subjects did not develop the disease. The plasma levels of 24 miRNAs were measured at baseline by qRT-PCR. The risk of T2DM was evaluated by Cox regression analysis based on the plasma levels of the miRNAs at baseline and according to the dietary intervention. Finally, pathways analyses were carried out to identify target genes regulated by the miRNAs studied and cellular processes which could be associated with T2DM development. RESULTS: Cox regression analyses showed that patients with low plasma levels of miR-145 at baseline showed a higher risk of developing T2DM after consumption of an LFHCC diet. In addition, patients with low levels of miR-29a, miR-28-3p and miR-126 and high plasma levels of miR-150 at baseline showed a higher risk of developing T2DM after consumption of the Med diet. Finally, pathways analysis showed an interaction of miR-126 and miR-29a in the modulation of FoxO, TNF-alpha, PI3K-AKT, p53 and mTOR signaling, associated with T2DM development. CONCLUSION: Our results suggest that circulating miRNAs could be used in clinical practice as a new tool for selecting the most suitable diet to prevent type 2 diabetes mellitus development in patients with cardiovascular disease.