Sudomotor dysfunction in diabetic peripheral neuropathy (DPN) and its testing modalities: A literature review

Long term consequences of diabetes mellitus (DM) may include multi-organ complications such as retinopathy, cardiovascular disease, neuronal, and kidney damage. One of the most prevalent complication is diabetic peripheral neuropathy (DPN), occurring in half of all diabetics, and is the main cause of disability globally with profound impact on a patient's quality of life. Small fiber neuropathy (SFN) can develop in the pre-diabetes stage preceding large fiber damage in DPN. Asymptomatic SFN is difficult to diagnose in early stages, with sudomotor dysfunction considered one of the earliest manifestations of autonomic neuropathy. Early detection is crucial as it can prevent potential cardiovascular events. Although punch skin biopsy is the gold-standard method for SFN diagnosis, implementation as routine screening is hindered due to its invasive, impractical, and time-consuming nature. Other sudomotor testing modalities, most of which evaluate the postganglionic cholinergic sympathetic nervous system, have been developed with varying sensitivity and specificity for SFN diagnosis. Here, we provide an overview on the general mechanism of DPN, the importance of sudomotor assessment for early detection of autonomic dysfunction in DPN, the benefits and disadvantages of current testing modalities, factors that may affect testing, and the importance of future discoveries on sudomotor testing for successful DPN diagnosis.