In This Issue of Diabetes

Circulating MicroRNAs Correlating With HbA 1c in Type 1 DiabetesAccording to Satake et al. (p.1013), a series of plasma microRNAs (miRNAs) may be associated with variations in HbA1c and their dysregulation might contribute to complications in type 1 diabetes.However, the conclusions come with a caveat: there are likely numerous possible mechanisms and pathways through which disruption of miRNAs might impact risk of complications in the disease.Using two panels of patients with type 1 diabetes, the authors report an initial investigation with sequencing technology into 2,083 miRNAs present in plasma samples.Reportedly, the patients had a median HbA1c level of 8.3% (interquartile range 7.9-9.2),allowing the authors to look for correlations between the measure and miRNA levels.After fi ltering and normalization, they identifi ed 54 candidate miRNAs that had statistically signifi cant correlation with HbA1c levels.Moving onto a second panel of patients with type 1 diabetes, they then attempted to replicate the fi ndings with quantitative RT-PCR.The authors managed to assay 48 of the candidates and found that 26 were detectable in more than half of the patients.Of these, 10 correlated with HbA1c at P < 0.05, with 5 positively correlating and 5 negatively correlating with HbA1c.Four candidates reportedly correlated very strongly with HbA1c.The authors then turned to KEGG pathway analysis to try to uncover putative pathways that might be involved-and this is where it gets complicated-reportedly fi nding as many as 50 unique pathways that might be involved.The authors go on to explore a number of the pathways and the different ways they may be involved in various diabetes complications.Author Andrzej S. Krolewski told Diabetes: "Researchers should be aware that hyperglycemia may have pleiotropic effects on many pathways through new mechanisms such as dysregulation of circulating candidate miRNAs.A novel fi nding of our research is that one of these pathways is the axon guidance pathway.This pathway may play a role in the development of microvascular complications."