A unique plasma microRNA profile defines type 2 diabetes progression

Abstract

A major unmet medical need to better manage Type 2 Diabetes (T2D) is the accurate disease prediction in subjects who show glucose dysmetabolism, but are not yet diagnosed as diabetic. We investigated the possibility to predict/monitor the progression to T2D in these subjects by retrospectively quantifying blood circulating microRNAs in plasma of subjects with i) normal glucose tolerance (NGT, n = 9); ii) impaired glucose tolerance (IGT, n = 9), divided into non-progressors (NP, n = 5) and progressors (P, n = 4) based on subsequent diabetes occurrence, and iii) newly diagnosed T2D (n = 9). We found that impaired glucose tolerance associated with a global increase of plasma circulating microRNAs. While miR-148 and miR-222 were specifically modulated in diabetic subjects and correlated with parameters of glucose tolerance, the most accentuated microRNA dysregulation was found in NP IGT subjects, with increased level of miR-122, miR-99 and decreased level of let-7d, miR-18a, miR-18b, miR-23a, miR-27a, miR-28 and miR-30d in comparison with either NGT or T2D. Interestingly, several of these microRNAs significantly correlated with parameters of cholesterol metabolism. In conclusion, we observed the major perturbation of plasma circulating microRNA in NP pre-diabetic subjects and identified a unique microRNA profile that may become helpful in predicting diabetic development.

Regulation of insulin resistance by targeting the insulin‐like growth factor 1 receptor with microRNA‐122‐5p in hepatic cells

“…Then, the relative level of miR-122 was found to be increased significantly, and that of IGF-1R protein, conversely, decreased in the liver of DM rats. Recent studies have indicated that accentuated miRNA dysregulation was found in impaired glucose tolerance and diabetes subjects with an increased level of miR-122 (de Candia et al, 2017;Ye et al, 2018). These previous studies and our in vivo data suggest that miR-122 may be involved in T2D and hepatic IR.…”

“…(C) miR-122 relative expression. Recent studies have indicated that accentuated miRNA dysregulation was found in impaired glucose tolerance and diabetes subjects with an increased level of miR-122 (de Candia et al, 2017;Ye et al, 2018). Data are presented as the mean ± standard deviation.…”

“…Silencing of miR-122 was reported to inhibit fat synthesis in diabetic animals, promote fatty acid degradation, and effectively reduce blood lipid levels (Esau et al, 2006). Furthermore, miR-122 was elevated in plasma in Zucker diabetic fatty rats (Delic et al, 2016), and also in patients with T2D and impaired glucose tolerance (de Candia et al, 2017). Furthermore, miR-122 was elevated in plasma in Zucker diabetic fatty rats (Delic et al, 2016), and also in patients with T2D and impaired glucose tolerance (de Candia et al, 2017).…”

“…In breast cancer cells, miR-122 was found to inhibit the glucose oxidation capacity by modulating pyruvate kinase (Fong et al, 2015). Furthermore, miR-122 was elevated in plasma in Zucker diabetic fatty rats (Delic et al, 2016), and also in patients with T2D and impaired glucose tolerance (de Candia et al, 2017). All these findings suggested a close correlation between miR-122 and T2D, but there are few reports on the specific mechanisms of miR-122 affecting glucose metabolism.…”

MicroRNAs 342 and 450 together with NOX‐4 activity and their association with coronary artery disease in diabetes

“…In the current work, we first investigated the expression of miRNA 342 amongst T2D patients, CAD patients (with its subtypes), and T2D with CAD (with its subtypes), where its expression was significantly upregulated in all the groups studied, especially those suffering from T2D with CAD clots, when compared with the respective control group. The differential expression of miRNA 342 in DM has been identified before, where the levels of several miRNAs, one of which was miRNA 342, were found to be differential among non‐glucose tolerant, T2D, and intermediate stages of impaired glucose tolerance …”