Diabetic peripheral neuropathy (DPN) is one of the most prevalent and debilitating complications of diabetes mellitus, affecting up to 50% of people living with the condition over their lifetime. It is a major driver of foot ulceration, lower limb amputation, and cardiovascular autonomic dysfunction, carrying significant burdens for both patients and healthcare systems. Early, accurate detection is therefore critical — yet standard neurological assessments can be time-consuming, require specialist equipment, and are poorly suited to routine clinical settings. Into this gap has stepped the Neuropad, a simple, point-of-care indicator test that detects sudomotor (sweat gland) dysfunction as a proxy marker for small autonomic nerve fibre damage. Understanding how it works, what the evidence says, and where it fits in clinical practice is essential for clinicians managing diabetes.
How Neuropad Works
Neuropad is a small adhesive plaster developed by TRIGOcare International and designed for application to the plantar (sole) surface of the foot. The pad contains anhydrous cobalt (II) chloride — a blue compound that undergoes a well-characterised colour change when it absorbs water. When applied to the skin for ten minutes, a normal sudomotor response causes the pad to turn from blue to pink, reflecting adequate moisture from sweat glands. An abnormal or incomplete colour change — the pad remaining blue or turning only partially pink — indicates reduced or absent sweating, which is a hallmark of small autonomic C-fibre dysfunction.
The test is patented as a ten-minute screening tool for early detection of diabetic foot syndrome. It is non-invasive, painless, and requires no specialised equipment beyond the plaster itself, making it readily deployable in primary care, diabetes clinics, or even as a patient self-test at home. At a list price of approximately £7.28 per test (as assessed by NICE), it is substantially more affordable than nerve conduction studies or skin biopsy.
The Scientific Basis: Sudomotor Dysfunction in Neuropathy
Sweating in the feet is regulated by postganglionic cholinergic sympathetic nerve fibres — small, unmyelinated C-fibres that are among the earliest structures damaged in diabetic neuropathy. Sudomotor dysfunction therefore represents an early and sensitive marker of neuropathic change, often preceding clinical symptoms and detectable deficits in large-fibre tests such as vibration perception or nerve conduction velocity.
This biological rationale lends Neuropad particular relevance to the detection of small-fibre neuropathy — a form of DPN that traditional assessments poorly capture. Established tools such as the Neuropathy Disability Score (NDS) and nerve conduction studies (NCS) predominantly assess large myelinated fibres, and can miss early small-fibre involvement entirely.
Diagnostic Performance
The evidence base for Neuropad has grown substantially over the past two decades, with numerous clinical studies examining its sensitivity, specificity, and correlation with established neuropathy markers.
A landmark 2008 study by Quattrini et al., published in Diabetologia, evaluated 57 diabetic patients using Neuropad alongside quantitative sensory testing, autonomic function assessments, and intra-epidermal nerve fibre density from skin biopsy. The results demonstrated meaningful correlations between Neuropad responses and the NDS, neuropathic symptom scores, cold detection thresholds, and deep-breathing heart rate variability — reflecting both somatic and autonomic neuropathic involvement.
Subsequent studies have further characterised its performance profile. Across assessments against large-fibre neuropathy markers — such as the NDS and peroneal motor nerve conduction velocity — Neuropad demonstrates high sensitivity (typically 80–95%) but moderate specificity (50–70%). This pattern makes it well-suited as a screening tool: a normal result reliably reduces the likelihood of clinically significant neuropathy, but an abnormal result warrants further investigation.
Importantly, diagnostic accuracy is meaningfully improved when Neuropad is assessed against small-fibre measures. A 2014 study by Ponirakis and colleagues found that, compared with corneal nerve fibre length — a sensitive marker of small-fibre damage assessed by corneal confocal microscopy — Neuropad achieved a sensitivity of 83% and specificity of 80%, with an area under the ROC curve (AUC) of 85%. This outperformed its performance against both the NDS (AUC 66%) and peroneal motor nerve conduction velocity (AUC 70%), underscoring the test’s specific utility for small C-fibre assessment.
An important refinement involves moving beyond simple binary (pink/blue) interpretation to quantifying the rate of colour change. A study examining automated image analysis (Sudometrics) demonstrated that continuous colour-change output substantially improved diagnostic accuracy, achieving high sensitivity and specificity for autonomic dysfunction (91% and 83% respectively) and small-fibre neuropathy (88% and 78%), compared with the weaker specificity of the categorical reading alone.
Research has also established Neuropad’s reproducibility. A study in 142 type 2 diabetic patients found a highly significant correlation (r = 0.91) between repeat measurements of time to complete colour change, indicating strong test-retest reliability.
Autonomic Neuropathy and Cardiovascular Risk
Beyond peripheral neuropathy, Neuropad has been evaluated as a tool for detecting cardiovascular autonomic neuropathy (CAN) — a potentially life-threatening condition associated with silent myocardial ischaemia, arrhythmia, and increased mortality. Time to complete colour change correlates significantly with the Valsalva ratio, a standard autonomic function test, as well as with symptoms of DPN and postural hypotension. A cut-off of fifteen minutes for complete colour change has been identified as an optimal threshold, improving specificity for both CAN and DPN without compromising sensitivity.
Given that CAN often goes undetected until advanced stages, the ability of a simple plaster to prompt further autonomic evaluation is clinically meaningful.
Limitations and Clinical Considerations
Neuropad is not without limitations. Its moderate specificity, particularly against large-fibre assessments, means a positive result should not be used in isolation for diagnosis. Environmental factors — ambient temperature, skin moisture, and humidity — may influence the rate and completeness of colour change, adding variability to qualitative readings. Age, BMI, renal function, and alcohol use have also been identified as potential confounders of sudomotor function independent of glycaemic status.
In elderly populations with diabetes or pre-diabetes, the KORA F4 survey found reasonable sensitivity but low specificity for polyneuropathy diagnosis, with a positive predictive value as low as 33.6%. This supports positioning Neuropad as a triage or exclusion test rather than a standalone diagnostic.
NICE evaluated Neuropad under its Medical Technologies Guidance programme (MTG38, 2018), recommending it as an option for detecting early DPN, particularly in settings where more specialised testing is unavailable. The guidance acknowledged its ease of use and potential value in identifying patients who require further assessment.
Conclusion
The Neuropad test occupies a valuable niche in the clinical assessment of diabetic neuropathy. By providing a simple, inexpensive, and non-invasive window into sudomotor and small C-fibre function, it enables early detection of neuropathic changes that traditional large-fibre assessments routinely miss. Its high sensitivity makes it particularly effective as a screening and exclusion tool, and its performance improves markedly when interpreted quantitatively or benchmarked against small-fibre measures. While it should not replace comprehensive neurological evaluation, Neuropad represents a practical and evidence-based addition to the diabetic foot assessment toolkit — one that can meaningfully support earlier intervention and reduce the risk of serious complications.