Circulating miRNAs as Predictive Biomarkers of Type 2 Diabetes Mellitus Development in Coronary Heart Disease Patients from the CORDIOPREV Study

Abstract

Circulating microRNAs (miRNAs) have been proposed as type 2 diabetes biomarkers, and they may be a more sensitive way to predict development of the disease than the currently used tools. Our aim was to identify whether circulating miRNAs, added to clinical and biochemical markers, yielded better potential for predicting type 2 diabetes. The study included 462 non-diabetic patients at baseline in the CORDIOPREV study. After a median follow-up of 60 months, 107 of them developed type 2 diabetes. Plasma levels of 24 miRNAs were measured at baseline by qRT-PCR, and other strong biomarkers to predict diabetes were determined. The ROC analysis identified 9 miRNAs, which, added to HbA1c, have a greater predictive value in early diagnosis of type 2 diabetes (AUC = 0.8342) than HbA1c alone (AUC = 0.6950). The miRNA and HbA1c-based model did not improve when the FINDRISC was included (AUC = 0.8293). Cox regression analyses showed that patients with low miR-103, miR-28-3p, miR-29a, and miR-9 and high miR-30a-5p and miR-150 circulating levels have a higher risk of disease (HR = 11.27; 95% CI = 2.61–48.65). Our results suggest that circulating miRNAs could potentially be used as a new tool for predicting the development of type 2 diabetes in clinical practice.

The link between diabetes and atherosclerosis

“…miRNAs have been proposed as surrogate markers of the prediabetes state, 38,39 diabetes and cardiovascular complications, 40 being detectable in a stable form in blood circulation and biological fluids. Many studies have revised the involvement of miRNAs in the vascular complications of diabetes 29 as well as in atherosclerosis, 41 determining a branch of investigation deserving special attention due to potential diagnostic and therapeutic implications.…”

MicroRNAs in Vascular Eye Diseases

“…In addition to diagnosing DR through histological examination of the fundus vasculature, circulating miRNAs were found to play critical roles in DR development, suggesting that miRNAs could also serve as new biomarkers in detecting or predicting the progress of retinopathy and furthermore, the overall progress of DM [139][140][141]. Analysis of circulating miRNAs from serum or plasma samples of DM patients both with and without DR showed altered expression levels of many miRNAs throughout different patient populations (e.g., ages, type of DM, years after onset, etc.,) [142].…”

MicroRNA single‐nucleotide polymorphisms and diabetes mellitus: A comprehensive review

“…Lv et al identified a correlation between serum miR‐130b level changes and the severity of DN . Jimenez et al proposed a new model (9 miRNAs + Finnish Diabetes Risk Score + HbA1C) that use both HbA1C and miRNA to improve sensitivity and specificity and increase the predictive value of developing DM …”