Figure 11.

Modified scheme of pathogenesis of diffuse diabetic neuropathy with inclusion of insulin signaling. According to this view, the disease process starts before impairment of glucose metabolism becomes apparent. Derangement of insulin signaling in PNS triggers and maintains the neuropathy at this stage. Postprandial and chronic hyperglycemia is not the least important factor of DPN, but they become involved at relatively advanced stages of DPN. C-peptide and IGFs insufficiencies represent another important set of pathogenic mechanisms; however, the role of these mechanisms in early DPN remains undetermined.