BioProject

Diabetic neuropathy (DN) is a common complication of diabetes. While multiple pathways are implicated in the pathophysiology of DN, there are no specific treatments for DN and currently it is not possible to predict DN onset or progression. More...

Diabetic neuropathy (DN) is a common complication of diabetes. While multiple pathways are implicated in the pathophysiology of DN, there are no specific treatments for DN and currently it is not possible to predict DN onset or progression. To examine gene expression signatures related to DN, microarray experiments were performed on a subset of human sural nerves collected during a 52-week clinical trial of acetyl-L-carnitine. A series of bioinformatics analyses analyzed differential gene expression and identified gene networks and pathways potentially responsible for the progression of DN. We identified 532 differentially expressed genes (DEGs) between patient samples with progressing or non-progressing DN, which were functionally enriched in pathways involving defense and inflammatory responses and lipid metabolism. A literature-derived co-citation network of the DEGs revealed gene sub-networks centered on apolipoprotein E (APOE), jun oncogene (JUN), leptin (LEP), serpin peptidase inhibitor E Type 1 (SERPINE1) and peroxisome proliferator-activated receptor gamma (PPARG). DEGs were used to predict DN progression in a test set of patients. Ridge-regression classification models with 14 DEGs achieved an overall accuracy of 92%, correctly classifying the progression status of 11 out of 12 patients. To our knowledge, this is the first study to identify transcriptional changes associated with DN progression in human sural nerves biopsies and describe their potential utility for molecular prediction of DN. Our results identifying the unique gene signature of patients with progressive DN will facilitate the development of new mechanism-based diagnostics and therapies. Overall design: 18 progressor and 17 non-progressor at 52 weeks Less...