MicroRNA profiling and their pathways in South African individuals with prediabetes and newly diagnosed type 2 diabetes mellitus.

Tandi E Matsha,Andre P Kengne,Stanton Hector,Desiree L Mbu,Rajiv T Erasmus,Yandiswa Y Yako

doi:10.18632/oncotarget.25271

Abstract

Early identification of individuals with elevated risk of developing diabetes mellitus, followed by the implementation of effective prevention interventions can delay the onset of the disease and related complications. In this regard, recent studies have shown that miRNAs are useful as early markers of certain disease types, including diabetes. We used high throughput sequencing to assess miRNA expression profiles from whole blood of 12 individuals with screen-detected diabetes, 12 with prediabetes and 12 with normal glucose tolerance, matched for age, blood pressure, smoking and body mass index. We identified a total of 261 (57 novel) differentially expressed miRNA profiles between the study groups. Comparison of the miRNA expression profiles between prediabetess and diabetes revealed 25 common miRNA, but highlighted some interesting differences. For instance, three miRNAs (miR-126-3p, miR-28-3p miR-486-5p) were dysregulated in prediabetes compared to screen-detected diabetes. Target gene analysis showed thousands of potential genes and KEGG pathway analysis revealed 107 significant pathways of which some are involved signal transduction, cell-cell communications, cell growth and death, immune response, endocrine system and metabolic diseases. This first detailed African study has shown both known and novel differentially expressed miRNAs in relation to glucose tolerance.

Highlights

Diabetes mellitus (DM) is a major cause of morbidity and mortality worldwide and has resulted in deaths of approximately five million people aged between 20 and 79 years in 2015 according to the International diabetes federation [1]
The details of the ten most differentially expressed micro RNAs (miRNAs) can be found in Supplementary Table 2 which shows that miR-15b-5p remained amongst the ten most differentially expressed miRNA when screen-detected diabetes was compared to either normal glucose tolerance (NGT) or impaired glucose tolerance (IGT)
We employed high throughput sequencing to identify differentially expressed miRNAs associated with IGT and untreated diabetes in whole blood of South African mixed ancestry women, which in an earlier study we had established a high prevalence of undiagnosed IGT and DM [18)

Summary

Introduction

Diabetes mellitus (DM) is a major cause of morbidity and mortality worldwide and has resulted in deaths of approximately five million people aged between 20 and 79 years in 2015 according to the International diabetes federation [1]. Lifestyle modifications or drug www.oncotarget.com interventions can delay the onset of DM [5, 6], this is dependent on the identification of those at risk of progression to overt DM. This identification is heavily dependent on the diagnostic criteria which are continually revised and vary across stakeholders. In 2010 the ADA included HbA1c ranging from 5.7% to 6.4% as diagnostic criterion for prediabetes These realities validate the critical need for earlier and more efficient biomarkers for diabetes risk screening. Recent studies [7,8,9] have shown that micro RNAs (miRNAs) are useful as early markers of certain disease types, including diabetes

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