Loss of protective sensation is the best-known neuropathic pathway to a diabetic foot ulcer, but it is not the earliest one. Long before a 10-gram monofilament goes unfelt, the small unmyelinated C-fibres that supply the sweat glands of the sole can fail. The result is sudomotor dysfunction: reduced plantar sweating, dry and fissured skin, and a loss of the skin’s mechanical resilience. Over the past decade, several groups have asked whether measuring that sweat-gland function adds anything to conventional foot screening. The answer emerging from the literature is that it identifies risk earlier than standard tests, though with different trade-offs in accuracy.
Why Sweat Gland Function Matters in the Foot at Risk
Plantar sweat glands are innervated by sympathetic cholinergic small fibres, which are among the first nerve populations damaged in diabetes. When they degenerate, the stratum corneum loses hydration, and callus and fissures follow — both recognised precursors of ulceration. Balasubramanian and colleagues, writing in Frontiers in Endocrinology in 2020, reviewed the neurovascular interactions in the diabetic foot and argued that small-fibre loss and cutaneous microcirculatory impairment are interdependent: as thermoregulatory and vasodilatory small-fibre function is lost, the skin’s microvascular response to injury is compromised in parallel.
Mechanistic work has since sharpened this picture. Guo and colleagues, publishing in MedComm in 2025, examined sweat glands from patients with diabetic foot ulcers and from a murine model of diabetic neuropathy. They found that sweat glands can remain structurally intact while functionally impaired, with transcriptomic and proteomic evidence of a hypoxia-driven change in the gland microenvironment and disrupted neurovascular networks adjacent to the glands. This helps explain why a foot can look anatomically normal yet sweat abnormally.
What the Screening Studies Show
Two testing approaches dominate the evidence. The indicator plaster method (marketed as Neuropad) is a colour-changing adhesive pad applied to the plantar surface; failure to change colour within a set time indicates reduced sweating. Electrochemical skin conductance (ESC), measured with the Sudoscan device, quantifies chloride flux from sweat glands in microsiemens.
The most informative prospective data come from Panagoulias and colleagues, reported in Frontiers in Endocrinology in 2020. Across six years of follow-up in 308 people with diabetes and no ulcer history, 55 developed a foot ulcer — an annual incidence of 2.97%. After adjustment for age, sex and diabetes duration, an abnormal indicator plaster test carried a hazard ratio of 3.32 (95% CI 1.46–7.55) for subsequent ulceration, comparable to a neuropathy disability score of 6 or more (HR 2.78) and a vibration perception threshold of 25 volts or greater (HR 2.59). The tests differed markedly in character: the plaster test was highly sensitive (0.86) but poorly specific (0.49), while the disability score and vibration threshold were specific (0.87 and 0.89) but insensitive (0.40 and 0.39). In other words, sudomotor testing is a screening test, and the conventional measures are confirmatory ones.
For ESC, Gautier and colleagues published a multicentre retrospective analysis of 2,157 patients across four French tertiary centres in Frontiers in Endocrinology in 2025. Foot ESC fell progressively across IWGDF risk grades, with an area under the curve of 0.82 for identifying grade 3 (highest-risk) patients, though performance was limited in early-stage disease. Notably, ESC flagged at-risk individuals within grade 0 — patients whom the standard classification had judged low-risk. An earlier cross-sectional study by Sheshah and colleagues in the Journal of Diabetes and Metabolic Disorders (2016), in 296 patients, found that a foot ESC below 70 µS detected neuropathy defined by a vibration threshold of 25 volts or more with 100% sensitivity.
Where the Evidence Is Weaker
These tests are not uniformly strong. García-Ulloa and colleagues, in BMJ Open Diabetes Research & Care (2022), studied 2,243 patients with type 2 diabetes of less than five years’ duration and found sudomotor abnormalities in 27.6%. Against monofilament and tuning-fork examination as the reference, however, Sudoscan performed poorly (AUC 0.495; sensitivity 24%, specificity 71%) — a reminder that small-fibre and large-fibre tests measure different things and should not be treated as interchangeable.
Sudomotor abnormality is also not purely neurogenic. Lv and colleagues, in Diabetes, Metabolic Syndrome and Obesity (2023), assessed 511 patients with type 2 diabetes and found sudomotor dysfunction in 75.1%. Lower-limb arterial ischaemia — defined by abnormal ankle-brachial index, toe-brachial index or transcutaneous oxygen tension — was an independent risk factor (OR 1.75), with low transcutaneous oxygen tension conferring the strongest association (OR 2.23). An abnormal sweat test therefore does not exclude perfusion assessment.
Supporting this, Vouillarmet and colleagues reported in Medicina (2024) that among 172 patients stratified by IWGDF grade, those with a prior ulcer history were more likely to have severe sudomotor dysfunction (OR 2.73) and retinopathy (OR 3.15), suggesting these markers may help refine existing risk categories.
Clinical Summary
Sudomotor testing detects small-fibre damage that precedes loss of protective sensation, and prospective data link an abnormal result to roughly a threefold increase in subsequent ulceration risk. Its high sensitivity and modest specificity suit it to initial screening rather than definitive diagnosis, and it complements — but does not replace — monofilament testing, vibration perception, and vascular assessment. As Tentolouris and colleagues concluded in their 2024 narrative review in Hormones, no single test identifies the at-risk foot; the practical value of sudomotor assessment lies in adding an early, objective signal to a multimodal examination.
References
- Panagoulias GS, Eleftheriadou I, Papanas N, et al. Dryness of Foot Skin Assessed by the Visual Indicator Test and Risk of Diabetic Foot Ulceration: A Prospective Observational Study. Frontiers in Endocrinology. 2020;11:625. doi:10.3389/fendo.2020.00625
- Gautier JF, Riveline JP, Potier L, et al. Electrochemical skin conductance: a tool for risk stratification and early anticipation of diabetic foot ulcers. Frontiers in Endocrinology. 2025;16:1437858. doi:10.3389/fendo.2025.1437858
- Sheshah E, Madanat A, Al-Greesheh F, et al. Electrochemical skin conductance to detect sudomotor dysfunction, peripheral neuropathy and the risk of foot ulceration among Saudi patients with diabetes mellitus. Journal of Diabetes and Metabolic Disorders. 2016;15:29. doi:10.1186/s40200-016-0252-8
- García-Ulloa AC, Almeda-Valdes P, Cuatecontzi-Xochitiotzi TE, et al. Detection of sudomotor alterations evaluated by Sudoscan in patients with recently diagnosed type 2 diabetes. BMJ Open Diabetes Research & Care. 2022;10(6):e003005. doi:10.1136/bmjdrc-2022-003005
- Lv Y, Yang Z, Xiang L, et al. Lower Limb Arterial Ischemia: An Independent Risk Factor of Sudomotor Dysfunction in Type 2 Diabetes. Diabetes, Metabolic Syndrome and Obesity. 2023;16:883-891. doi:10.2147/DMSO.S402797
- Vouillarmet J, Josset-Lamaugarny A, Moret M, et al. Impairment of Microcirculation Parameters in Patients with a History of Diabetic Foot Ulcers. Medicina. 2024;61(1):2. doi:10.3390/medicina61010002
- Tentolouris A, Stergioti A, Eleftheriadou I, Siafarikas C, Tsilingiris D. Screening tools for diabetic foot ulcers: a narrative review. Hormones. 2024;24(1):71-83. doi:10.1007/s42000-024-00598-z
- Balasubramanian G, Vas P, Chockalingam N, Naemi R. A Synoptic Overview of Neurovascular Interactions in the Foot. Frontiers in Endocrinology. 2020;11:308. doi:10.3389/fendo.2020.00308
- Guo X, Zhang C, Wang Y, et al. Hypoxia-Driven Neurovascular Impairment Underlies Structural-Functional Dissociation in Diabetic Sudomotor Dysfunction. MedComm. 2025;6(5):e70173. doi:10.1002/mco2.70173
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