RAC1 and Hyperglycemia: In support, diabetes modulates transcription of matrix metalloproteinase MMP-9, an enzyme implicated in mitochondrial damage, via dynamic DNA methylation-hydroxymethylation of its promoter.9 Moreover, hyperglycemia has a direct impact on changes in the epigenome, and high DNA methylation and hydroxymethylation levels are observed in poorly controlled diabetic patients compared with healthy individuals.32 We recognize that Tets can further oxidize 5hmC to 5-formylcytosine, and 5-formylcytosine to 5-carboxylcytosine33; their role in regulation of Rac1 transcription cannot be ruled out.