Peripheral Neuropathy in Diabetes Mellitus: Pathogenetic Mechanisms and Diagnostic Options

Abstract

Diabetic neuropathy (DN) is one of the main microvascular complications of both type 1 and type 2 diabetes mellitus. Sometimes, this could already be present at the time of diagnosis for type 2 diabetes mellitus (T2DM), while it appears in subjects with type 1 diabetes mellitus (T1DM) almost 10 years after the onset of the disease. The impairment can involve both somatic fibers of the peripheral nervous system, with sensory-motor manifestations, as well as the autonomic system, with neurovegetative multiorgan manifestations through an impairment of sympathetic/parasympathetic conduction. It seems that, both indirectly and directly, the hyperglycemic state and oxygen delivery reduction through the vasa nervorum can determine inflammatory damage, which in turn is responsible for the alteration of the activity of the nerves. The symptoms and signs are therefore various, although symmetrical painful somatic neuropathy at the level of the lower limbs seems the most frequent manifestation. The pathophysiological aspects underlying the onset and progression of DN are not entirely clear. The purpose of this review is to shed light on the most recent discoveries in the pathophysiological and diagnostic fields concerning this complex and frequent complication of diabetes mellitus.

Peripheral sensory neuropathy is associated with circulating angiopoietins in type 2 diabetes patients in Ghana

“…In this study, the prevalence of PSN by VPT and DNE were 20.6 % and 35.6 % in T2DM patients and 2.8 % and 3.7 % in nondiabetic controls respectively. The prevalence of PSN in non-diabetic controls in our study is consistent with the report of peripheral neuropathies in the general population, which is within the range of 1 – 7 % [21] , and this has been attributed to alcoholism [22] , vitamin deficiency [23] , chronic exposure to recreational drugs and heavy metal [24] and medications [8] , [21] . The prevalence of PSN in T2DM patients in the current study is consistent with our previous studies in T2DM patients that reported the prevalence of PSN to be 15.2 % using VPT ≥ 25 [6] and 16.6 % using VPT > 97.5th percentile of age and gender-adjusted cut-off [17] .…”

“…The manifestations of PSN in diabetes patients depend on the type of nerve fibre involved (small or large) and the organs that these nerves supply. PSN may be presented as symmetric sensory-motor axonal neuropathy, proximal asymmetric painful motor neuropathy, mononeuropathy, and autonomic neuropathy which mainly involves small nerve fibres [8] , [6] . There have been several metabolic, inflammatory and cellular signalling defects have been postulated to underline the development of PSN in diabetes patients.…”

“…There have been several metabolic, inflammatory and cellular signalling defects have been postulated to underline the development of PSN in diabetes patients. Prominent among these pathophysiological processes of nerve damage in diabetes patients include microangiopathy leading to disruption of the blood-nerve barrier, lipid peroxidation and oxidative stress [8] , [9] .…”

Effect of the SARS-CoV-2 pandemic on metabolic control in patients with type 2 diabetes: a 5-year cohort follow-up managed by a dynamic multidisciplinary team in Northeastern Mexico

“…The higher prevalence of this complication is linked to an increased risk of diabetic neuropathy with advancing age. Age greater than 60 years is associated with a heightened risk of developing diabetic neuropathy due to biological aging processes such as alterations in nerve vasculature, increased advanced glycation end products, and decreased resistance to oxidative stress products [ 44 ].…”

Impact of Type 1 Versus Type 2 Diabetes on Developing Herpes Zoster and Post-herpetic Neuralgia: A Population-based Cohort Study

“…Okamoto et al ( 30 ) indicated that the CMI of VZV in individuals with diabetes was significantly lower than that in healthy controls, which explains why people with diabetes are more likely to develop HZ. Persistent inflammation in patients with DM leads to nerve damage and increased pain sensitivity, which might contribute to the increased incidence of PHN in patients with DM ( 31 ). Ma et al ( 32 ) proposed that autoimmune pathogenesis resulted in impaired function of monocyte/macrophage in patients with T1DM.…”