Circulating microRNAs in Diabetes Progression: Discovery, Validation, and Research Translation

Abstract

Diabetes, in all of its forms, is a disease state that demonstrates wide ranging pathological effects throughout the body. Until now, the only method of diagnosing and monitoring the progression of diabetes was through the measurement of blood glucose. Unfortunately, beta cell dysfunction initiates well before the clinical onset of diabetes, and so the development of an effective biomarker signature is of paramount importance to predict and monitor the progression of this disease. MicroRNAs (miRNAs/miRs) are small (18-22 nucleotide) noncoding (nc)RNAs that post-transcriptionally regulate endogenous gene expression by targeted inhibition or degradation of messenger (m)RNA. Recently, miRNAs have shown great promise as biomarkers as some exhibit differential expression in multiple disease states, including type 1 and type 2 diabetes (T1D/T2D). Furthermore, miRNAs are quite stable in circulation, resistant to freeze-thaw and pH-mediated degradation, and are relatively easy to detect using quantitative (q)PCR. Here, we discuss microRNAs that may form a diabetes biomarker signature. To identify these transcripts we outline miRNAs that play a central role in pancreas development and diabetes, as well as previously identified miRNAs with differential expression in individuals with T1D and T2D. Validation and refinement of a miRNA biomarker signature for diabetes would allow identification and intervention of individuals at risk of this disease, as well as stratification and monitoring of patients with established diabetes.