Timed evaluation of the Neuropad test may expand its use in the detection of diabetic neuropathy

Aims: To test the diagnostic performance of a new approach using the Neuropad patch sudomotor function test to detect diabetic peripheral neuropathy (DPN).

Methods: The Neuropad patch was applied to the plantar aspect of the metatarsal head I/II of the feet of 518 individuals with type 2 diabetes using the traditional approach (visual assessment of color change after 10 minutes) and a novel approach (quantitative assessment of color change every minute for at least 10 minutes using a hand-held digital color analyzer). Diagnostic performance was evaluated by comparing area under the ROC curve (AUC), sensitivity, and specificity. DPN was diagnosed using different cutoffs for a modified Neuropathy Disability Score (NDS) and Neuropathy Symptoms Score (NSS).

Results: Using a DPN definition of NSS + NSS ≥ 4 points, the slope of the color change at the 4th minute showed an AUC of 0.81, 81% sensitivity, and 76.3% specificity to detect DPN, while the traditional approach yielded in 0.62, 81.8%, and 41.7%, respectively. Using another DPN definition (NDS ≥ 6 points or NDS ≥ 3 points + NSS ≥ 5 points), no difference in diagnostic performance was observed.

Conclusions: This study presents a different approach to quantitatively assess Neuropad with better diagnostic performance than the visual methods and a shorter detection time, which may be beneficial for new DPN screening strategies.

Comments: The Neuropad test is a simple test that visually assesses sweat gland function by indicating the amount of moisture produced by the sweat glands through a color change from blue to pink. Previous reports have suggested that it is more useful for ruling out DPN than for detecting it timely. Others have developed a quantitative assessment of the color change using a scanner, but this has not yet made the leap from research to clinical application. Therefore, the study by Yang et al. is a welcome addition as it provides a method to assess the temporal component of sweat production using this simple test that could be integrated in future iterations of sudomotor function tests. However, the relatively arbitrary, if not questionable, DPN definitions used in the present study and the absence of more objective quantitative tests are a limitation that reduces the generalizability of the reported diagnostic performance indices, especially regarding the early detection of asymptomatic DPN stages.

Further research could evaluate associations between the timed Neuropad evaluation and quantitative nerve function and morphology measures as well as with diabetic foot ulcer indices such as time to first ulcer. It is worth noting that the Neuropad test should be considered a surrogate rather than a direct marker of DPN, as the sweat secretory system is innervated by autonomic branches of the peripheral nervous system that may not be affected in the same way as somatosensory nerve fibers in people with diabetes.

Gidon J Bönhof

Reference: Yang Z, Zhao S, Lv Y, Xiang L, Zhang X, Feng Z, Liu Z, Li R. A New Quantitative Neuropad for Early Diagnosis of Diabetic Peripheral Neuropathy. Diabetes Metab Res Rev. 2024 Nov;40(8):e70010. doi: 10.1002/dmrr.70010. PMID: 39560299.

🔗 https://onlinelibrary.wiley.com/doi/10.1002/dmrr.70010