Diagnostic Tools, Biomarkers, and Treatments in Diabetic polyneuropathy and Cardiovascular Autonomic Neuropathy

Abstract

: The various manifestations of diabetic neuropathy including distal symmetric sensorimotor polyneuropathy (DSPN) and cardiovascular autonomic neuropathy (CAN) are among to the most prevalent chronic complications of diabetes. Major clinical complications of diabetic neuropathies such as neuropathic pain, chronic foot ulcers, and orthostatic hypotension are associated with considerable morbidity, increased mortality, and diminished quality of life. Despite the substantial individual and socioeconomic burden, the strategies to diagnose and treat diabetic neuropathies remain insufficient. This review provides an overview on the current clinical aspects and recent advances in exploring local and systemic biomarkers of both DSPN and CAN assessed in human studies (such as biomarkers of inflammation and oxidative stress) to better understand the underlying pathophysiology and to improve early detection. Current therapeutic options for DSPN are (I) causal treatment including lifestyle modification, optimal glycemic control, and multifactorial risk intervention; (II) pharmacotherapy derived from pathogenetic concepts; and (III) analgesic treatment against neuropathic pain. Recent advances in each category are discussed including non-pharmacological approaches such as electrical stimulation. Finally, the current therapeutic options for cardiovascular autonomic complications are provided. These insights should contribute to a broader understanding of the various manifestations of diabetic neuropathies from both the research and clinical perspectives.

Skin Advanced Glycation End Products among Subjects with Type 2 Diabetes Mellitus with or without Distal Sensorimotor Polyneuropathy

“…Indeed, skin AGEs were increased in both small and large nerve fibre impairments. As regards the former, reduced temperature and pinprick sensation (estimates of small nerve fibres [ 14 , 15 ]) were seen in participants with higher skin AGE levels. The same was seen for parameters assessing the latter (abnormal VPT and monofilament).…”

“…Finally, 10 g Semmes Weinstein monofilaments were used on 10 foot sites [ 14 , 15 ] bilaterally. The monofilament score was the number of correct answers [ 14 ].…”

“…The monofilament score was the number of correct answers [ 14 ]. Abnormality was defined as monofilament score < 8, using the lower of the two measurements [ 14 , 15 ].…”

BOND study: a randomised double-blind, placebo-controlled trial over 12 months to assess the effects of benfotiamine on morphometric, neurophysiological and clinical measures in patients with type 2 diabetes with symptomatic polyneuropathy

“…2 3 However, DSPN frequently remains an underdiagnosed and undertreated condition as therapy options are limited. 4 Current established options for the management of DSPN are mainly based on control of risk factors such as hyperglycaemia and symptomatic treatment to alleviate neuropathic pain. 5 Near-normal glycaemic control is crucial to delay the development of DSPN in people with type 1 diabetes, although it may not be sufficient to prevent or reverse DSPN.…”

“…Moreover, it is unclear whether analgesic compounds may also alleviate non-painful symptoms such as paraesthesia or numbness, which are frequently reported by patients with DSPN. 4 The available evidence for the effectiveness of pathogenetically oriented disease-modifying pharmacotherapy is still limited. 4 Currently only three agents derived from the pathophysiological pathways implicated in the development and progression of DSPN are available in several countries: α-lipoic acid, benfotiamine and actovegin, whereas other agents such as aldose reductase inhibitors, nerve growth factor, protein kinase C (PKC) ß inhibitor, long-acting (PEGylated) C-peptide or vitamin E were not effective in DSPN.…”