Circulating miRNAs as a Predictive Biomarker of the Progression from Prediabetes to Diabetes: Outcomes of a 5-Year Prospective Observational Study

Abstract

<jats:p>Due to a global increase in the prevalence of type 2 diabetes mellitus (T2DM), there is an urgent need for early identification of prediabetes, as these people have the highest risk of developing diabetes. Circulating miRNAs have shown potential as progression biomarkers in other diseases. This study aimed to conduct a baseline comparison of serum-circulating miRNAs in prediabetic individuals, with the distinction between those who later progressed to T2DM and those who did not. The expression levels of 798 miRNAs using NanoString technology were examined. Spearman correlation, receiver operating characteristic (ROC) curve analysis, and logistic regression modeling were performed. Gene ontology (GO) and canonical pathway analysis were used to explore the biological functions of the miRNA target genes. The study revealed that three miRNAs were upregulated in the serum samples of patients who later progressed to T2DM. Pathway analysis showed that the miRNA target genes were mainly significantly enriched in neuronal NO synthase (nNOS) signaling in neurons, amyloid processing, and hepatic cholestasis. ROC analysis demonstrated that miR-491-5p, miR-1307-3p, and miR-298 can be introduced as a diagnostic tool for the prediction of T2DM (area under the curve (AUC) = 94.0%, 88.0%, and 84.0%, respectively). Validation by real-time quantitative polymerase chain reaction (qRT-PCR) confirmed our findings. The results suggest that circulating miRNAs can potentially be used as predictive biomarkers of T2DM in prediabetic patients.</jats:p>

Emerging roles of exosomal miRNAs in diabetes mellitus

“…The AUC values were 0.867 (95% CI: 0.820-0.914, p < .001), 0.910 (95% CI: 0.873-0.948, p < .001), and 0.897 (95% CI: 0.858-0.936, p < .001), respectively. Furthermore, Sidorkiewicz et al 162 demonstrated that exosomal miR-491-5p, miR-1307-3p, and miR-298 can be used as novel biomarkers for predicting the progression from prediabetes to T2DM, and the AUC values were 0.940, 0.880, and 0.840, respectively. Interestingly, exosomal miR-NAs are closely associated with the gender difference of DM.…”

A Preliminary Study Showing the Impact of Genetic and Dietary Factors on GC–MS-Based Plasma Metabolome of Patients with and without PROX1-Genetic Predisposition to T2DM up to 5 Years Prior to Prediabetes Appearance

“…A daily energy intake was also similar for all participants (1991.8 ± 529.7 kcal) with 20.4% ± 4.4% (19.4% ± 1.4% vs. 21.6% ± 4.3% for LR vs. HR, p = 0.4) of energy from protein, 33.6% ± 5.8% (33.9% ± 10.0% vs. 31.7% ± 5.3% for LR vs. HR, p = 0.9) from fat and 42.0% ± 6.3% (41.4% ± 6.2% vs. 42.7% ± 6.8% for LR vs. HR, p = 0.9) from carbohydrates. Five years after the first examination, subjects from the 1000 PLUS cohort were called for a follow-up visit [22]. Seven individuals from the risk carriers group responded to this call, and for six of them, we observed worsening of selected clinical parameters assessing glucose homeostasis (e.g., fasting plasma glucose, HOMA-IR, HbA1c), indicating the development of prediabetic state manifested by increased (within the range of 100-125 mg/dL) fasting plasma glucose (three individuals) or increased (within the range of 5.7-6.4%) HbA1c value (two individuals) or insulin resistance (HOMA-IR = 4.6, one individual).…”

“…To complement previous meal-challenge metabolomics results, in the present work, metabolites were measured in samples from the same patients using GC-MS. Of note, participants of this study were recruited from the cross-sectional study called 1000 PLUS, which has been described in details previously [21]. We have recently performed 5-years of follow-up visits with the individuals from the 1000 PLUS cohort [22]. Interestingly, half of the risk carriers from the present study participated in the follow-up visit, and we observed that their parameters assessing glucose homeostasis (e.g., fasting plasma glucose, HOMA-IR, HbA1c) have worsened, indicating the development of a prediabetic state.…”

Chronic Microvascular Complications in Prediabetic States—An Overview

“…Their omnipresence in body fluids and the proven relationship of changes in their concentrations at the onset of the disease, during the progression and under treatment of carbohydrate metabolism disorders, make biomolecules a potential prognostic, diagnostic and progressive biomarker [ 95 ]. Sidorkiewicz et al performed a baseline comparison of serum-circulating miRNAs in prediabetic individuals, distinguishing between those who later progressed to T2DM and those who did not [ 96 ]. Abnormal expression of long noncoding RNA (lncRNA) and mRNA in people with prediabetes has been shown, and it has been proven that lncRNAs are involved in the entire biological process of prediabetes [ 97 , 98 , 99 ].…”