The Impact of Metabolic Control on Limb Differences in Peripheral Neuropathy: A Pilot Study

Background: Hyperglycemia is thought to be one of the most common causes of peripheral neuropathy. Pathology of the peripheral nervous system can involve sensory nerves, motor nerves, or autonomic nerves. It is typically believed that hyperglycemia-induced neuropathies follow a length-dependent pattern, generally affecting the feet and toes first, with the hands and fingers involved at a later stage. Sudomotor function, which is the body’s ability to regulate sweat production through the autonomic nervous system, is often one of the earliest signs of autonomic dysfunction. There is limited information on the inter-limb differences in peripheral neuropathy, and the precise impact of metabolic control on individual limbs has yet to be clarified. Thus, the present study aims to explore the relationships between glucose regulation and peripheral neuropathy across all four limbs, using sudomotor activity as a measure of nerve functional status. Methods: Electronic medical record data from 34 individuals of a private practice clinic were included in this study. Fasting blood glucose and hemoglobin A1c (HbA1c) were used as indices of metabolic control. Sudomotor function was assessed using the Sudoscan device and serves as an important indicator of peripheral autonomic nerve function. Sudomotor function is measured in electrochemical skin conductance (ESC), with a lower ESC representing greater peripheral neuropathy. Results: There were no differences in patient demographics or clinical laboratory values between men and women (all P > 0.05), except that men were taller (P < 0.001) and heavier (P = 0.021) compared to women. The right hand had a lower ESC than the left hand (P < 0.001), left foot (P < 0.001), and right foot (P < 0.001). The left hand had a lower ESC than the left foot (P = 0.005) and the right foot (P = 0.003). There was a significant negative relationship between fasting blood glucose concentrations and ESC in the left hand (r = -0.363; P = 0.035), right hand (r = -0.474; P = 0.005), and right foot (r = -0.385; P = 0.024). Conclusion: Contrary to popular belief, the results of the present investigation suggest that hands have more severe peripheral autonomic neuropathy compared to the feet. Lastly, there is a direct linear relationship between degree of peripheral autonomic neuropathy and fasting blood glucose and age. Indeed, current findings suggest a potential need for a shift in clinical practice, where more detailed testing of the hands and arms could detect early signs of neuropathy before it becomes more clinically evident in the legs. Keywords: Hyperglycemia; Sudomotor function; Diabetes; Sudoscan