New Perspective in Diabetic Neuropathy: From the Periphery to the Brain, a Call for Early Detection, and Precision Medicine

Abstract

Diabetic peripheral neuropathy (DPN) is a common chronic complication of diabetes mellitus. It leads to distressing and expensive clinical sequelae such as foot ulceration, leg amputation, and neuropathic pain (painful-DPN). Unfortunately, DPN is often diagnosed late when irreversible nerve injury has occurred and its first presentation may be with a diabetic foot ulcer. Several novel diagnostic techniques are available which may supplement clinical assessment and aid the early detection of DPN. Moreover, treatments for DPN and painful-DPN are limited. Only tight glucose control in type 1 diabetes has robust evidence in reducing the risk of developing DPN. However, neither glucose control nor pathogenetic treatments are effective in painful-DPN and symptomatic treatments are often inadequate. It has recently been hypothesized that using various patient characteristics it may be possible to stratify individuals and assign them targeted therapies to produce better pain relief. We review the diagnostic techniques which may aid the early detection of DPN in the clinical and research environment, and recent advances in precision medicine techniques for the treatment of painful-DPN.

Keywords: diabetic neuropathy; diagnosis diabetic neuropathy; painful diabetic neuropathy; painful diabetic neuropathy treatment; stratified medicine.

Figure 1

Hyperglycaemia-driven Schwann cell stress and neuronal damage. Hyperglycaemia and dyslipidemia lead to reduction of neuronal support from Schwann cells and microvessels. Disruption of neuronal support by Schwann cells and the vascular system contributes to neuropathy, in conjunction with the direct effects of hyperglycaemia on neurons. ER, endoplasmic reticulum; NADPH, Nicotinamide adenine dinucleotide phosphate; Ros, reactive oxygen species; Rns, reactive nitrogen species. Reproduced and permission gained from Sloan et al. (7).

Figure 2

Treatment algorithm for painful-DPN. Reproduced and permission gained from Tesfaye et al. (103).