Uncovering sensory axonal dysfunction in asymptomatic type 2 diabetic neuropathy

Abstract

This study investigated sensory and motor nerve excitability properties to elucidate the development of diabetic neuropathy. A total of 109 type 2 diabetes patients were recruited, and 106 were analyzed. According to neuropathy severity, patients were categorized into G0, G1, and G2+3 groups using the total neuropathy score-reduced (TNSr). Patients in the G0 group were asymptomatic and had a TNSr score of 0. Sensory and motor nerve excitability data from diabetic patients were compared with data from 33 healthy controls. Clinical assessment, nerve conduction studies, and sensory and motor nerve excitability testing data were analyzed to determine axonal dysfunction in diabetic neuropathy. In the G0 group, sensory excitability testing revealed increased stimulus for the 50% sensory nerve action potential (P<0.05), shortened strength-duration time constant (P<0.01), increased superexcitability (P<0.01), decreased subexcitability (P<0.05), decreased accommodation to depolarizing current (P<0.01), and a trend of decreased accommodation to hyperpolarizing current in threshold electrotonus. All the changes progressed into G1 (TNSr 1–8) and G2+3 (TNSr 9–24) groups. In contrast, motor excitability only had significantly increased stimulus for the 50% compound motor nerve action potential (P<0.01) in the G0 group. This study revealed that the development of axonal dysfunction in sensory axons occurred prior to and in a different fashion from motor axons. Additionally, sensory nerve excitability tests can detect axonal dysfunction even in asymptomatic patients. These insights further our understanding of diabetic neuropathy and enable the early detection of sensory axonal abnormalities, which may provide a basis for neuroprotective therapeutic approaches.

Early sensory neurophysiological changes in prediabetes

“…We found that sensory superexcitability was positively correlated with fasting plasma glucose and HbA1c in all participants. Similar correlations between nerve excitability parameters (superexcitability and late subexcitability) and clinical profiles have been discovered in diabetes patients 26,41 . However, aggressive glycemic control is an effective approach to reduce the risk of polyneuropathy only in type 1 diabetes patients 11 .…”

“…These changes were not affected by acute plasma glucose concentration, but were related to glycemic variability. Our previous study also reported downward shifting of the sensory recovery cycle and “fanning out” of TE progress from asymptomatic to symptomatic diabetes. These findings suggest functional changes precede structural changes in diabetes polyneuropathy; they can also explain why the NCS is not a sensitive tool for clinical detection or screening.…”

“…Kiernan et al 16 established a protocol measuring the "sensory" axonal nerve excitability, and confirmed its efficacy in studying the electrophysiology and channel function of sensory axons. Clinical application has been studied for different neurological diseases, such as cervical radiculopathy 18 , cisplatin-induced neuropathy [19][20][21] , uremic polyneuropathy 22,23 and diabetic neuropathies [24][25][26] . In previous nerve excitability tests among diabetes patients, the excitability parameters of sensory nerves changed earlier than those of motor nerves 26 and were correlated with glycated hemoglobin (HbA1c) in individuals with asymptomatic diabetes 25,26 .…”

Altered peripheral nerve structure and function in latent autoimmune diabetes in adults

“…The present study was undertaken to investigate the pathophysiology of peripheral nerve disease in LADA compared to type 1 and 2 diabetes. Nerve function was assessed using nerve excitability techniques, which provides insight into the function of the ion channels, pumps, and exchangers of the axonal membrane and have previously demonstrated changes in both type 1 and type 2 diabetes . A healthy control cohort was also recruited to examine underlying causes of nerve dysfunction in LADA.…”

“…Nerve function was assessed using nerve excitability techniques, which provides insight into the function of the ion channels, pumps, and exchangers of the axonal membrane and have previously demonstrated changes in both type 1 and type 2 diabetes. [6][7][8][9][10][11] A healthy control cohort was also recruited to examine underlying causes of nerve dysfunction in LADA. To accompany nerve electrophysiology, nerve structure was investigated using high-resolution ultrasound to assess cross-sectional fascicular area.…”