Search

Prevalence of type II diabetes and cardiometabolic diseases is increasing worldwide and early identification of their complications could reduce healthcare costs. An early complication of diabetes is small fiber neuropathy that can be diagnosed through assessment of sweat dysfunction. In this context, the Sudoscan™ technology developed by Impeto Medical provides early diagnosis, rapid and non-invasive analysis of sudomotor functions. This technology is based on measurements of skin current density via the imposition of low amplitude voltages (4 to 1.5V) between electrodes applied to the skin and measuring the low current generated. These electrodes are sensitive to the composition of the sweat produced by the eccrine glands when stimulated. To optimize the electrode materials and the diagnosis, a better insight into the origin of the electrochemical signals is needed by mimicking the in vivo results through the use of a model electrochemical cell reproducing physiological sweat conditions. In this paper, the electrode surface was modified with polymeric membranes to mimic the role of the filter of the skin and to get similar results to those obtained by Sudoscan™. Then, the composition of the electrolyte was changed by optimizing its viscosity to reduce the flow of Cl − ions to the electrode surface. The electrochemical behavior of the electrodes, measured in terms of current-voltage studied in artificial sweat, were compared to those of the Sudoscan™ technology.

International audience; A non-invasive device based on measurements of electrochemical skin conductance can detect small fiber neuropathy, a sweat gland dysfunction implicated in several diseases. The measurement is related to sweat composition and notably to chloride concentration. To optimize the electrode material, in vitro experiments are performed in mimetic sweat solutions. This work reports on the resistance to pitting corrosion of biocompatiblestainless steels (AISI 304L, AISI 430, AISI 430T, D2205) in sweat mimicking electrolyte at pH 7 with variable chloride concentration, to determine the most sensitive material to sweat composition. AISI 430 is promising due to its high sensitivity to chloride concentration variations.

An electrochemical sensor detects the risk of diabetes and prediabetes; low potentials are applied to nickel electrodes and electrical responses are measured. Although the contact of nickel with skin is short, the risk of allergical reactions cannot be discarded. SS 304L, with lower Ni content, was tested in carbonate buffer solutions containing chloride, lactate and urea to investigate its sensitivity to different parameters in sweat and compare it to nickel. The results show that SS 304L is a suitable material for the assessment of sudomotor dysfunction due to its high capacity to detect the deviation in Cl− concentration. Sensitivity of SS 304L to Cl− is much higher than for nickel.

Sudomotor dysfunction is a major clinical manifestation of diabetic autonomic neuropathy and is an early sign of prediabetes. SUDOSCAN™, a noninvasive and quick method was developed to assess sudomotor function based on measurement of the electrical current response of the skin when different rectangular pulses of low voltage amplitudes are applied on nickel electrodes. Electrochemical skin conductance is then calculated from the resulting voltage and the generated current. This leads to an accurate noninvasive way to predict dysglycemia, including type II diabetes, without fasting requirement due to the sensitivity of Ni electrodes to human eccrine glands sweat.

We have studied the electrochemical kinetics of anodic Ni dissolution as a function of chloride ion concentration, at pH 5, 6 and 7, in order to mimic the conditions of sweat samples. Our results show that the rate-determining step for Ni dissolution in the mentioned pH range is the transfer of one first electron, as suggested by the Tafel slopes close to 0.120 V/decade. However, the reaction order in chloride ion varies from ca. 2 at pH 7 to values close to unity for pH values between 5 and 6. This finding is very important for sensor applications in sweat fluids since the sensitivity of the Ni electrode to chloride ions is higher in neutral solutions (pH ca. 7) compared to that in slightly acid solutions (pH between 5 and 6). Small variations in pH in real samples are expected so this change in sensitivity should be considered when sensing chloride ions in sweat fluids.

The surface ageing of nickel electrodes was studied in the frame of the development of non-invasive biomedical devices, dedicated to the detection of sudomotor dysfunction manifested by an alteration of the ionic balance in human sweat. In this kind of technology, low voltage potentials with variable amplitudes are applied to nickel electrodes, placed on skin regions with a high density of sweat glands, and the electrical responses are measured. The trick is that nickel electrodes play alternately the role of anode and cathode, thus the analysis of the temporal evolution of the physico-chemical properties of nickel is of prime importance to ensure the good performance of the device. Electrochemical measurements coupled to surface chemical characterizations (X-ray photoelectron spectroscopy (XPS), Time of Flight-Secondary Ion Mass Spectrometry (ToF-SIMS)) were performed on pure Ni samples, immersed in buffered chloride solutions mimicking human sweat. The shapes of voltammograms, recorded in a restricted anodic potential range, show that the nickel surface was gradually passivated as a function of the number of scans. This was confirmed by XPS data, with the formation of a 1 nm thick duplex layer composed by nickel hydroxide (outermost layer) and nickel oxide (inner layer). In a negative extended potential range, though the electrochemical behavior of electrodes was not modified upon cycling the potential, XPS data show that the inner layer was thickening, indicating a surface degradation of the nickel electrode. Below pitting potentials, adsorbed chloride was only hardly detected by XPS, and the surface composition of the nickel samples was similar after treatments in chloride or chloride-free buffered solutions. In a larger potential range enabling to reach the breakdown potential, the highly chemically sensitive ToF-SIMS characterization pointed out that the surface concentration of adsorbed chloride was higher in pits than elsewhere on the surface sample.

Key to putting prevention of diabetes into practice is finding the people with increased risk. Several tools are currently in use: oral glucose tolerance test, fasting glucose measurement and a number of questionnaires to identify those with increased risk. Each has its own advantages and disadvantages. One new tool that can identify those with increased diabetes risk is the EZSCAN™. This new diagnostic device developed by Impeto Medical uses the sweat gland function to detect risk for insulin resistance and diabetes. The basic pathophysiology behind this technology is supported by the growing number of clinical studies worldwide which show a strong association between small nerve neuropathies to insulin resistance and diabetes risk. Because the EZSCAN™ test takes only three minutes to run, is noninvasive and easy to operate, it is an ideal diagnostic tool for both the medical and paramedical setting. Several applications are possible: the EZSCAN™ can be used to monitor insulin resistance-based treatment, to diagnose increased diabetes risk and to aid proposing diabetes prevention programmes. EZSCAN™ has the potential to become a very useful tool in diabetes risk diagnostics. Br J Diabetes Vasc Dis 2011;11:204-209

EZSCAN(®) (Impeto Medical, Paris, France), a noninvasive device that assesses sweat gland dysfunction using reverse iontophoresis, also detects early dysglycemia. Given the interrelationships among dysglycemia, vasculopathy, and neuropathy, EZSCAN may detect kidney disease in diabetes (DKD).An EZSCAN score (0-100) was calculated using a proprietary algorithm based on the chronoamperometry analysis. We measured the score in 50 Chinese type 2 diabetes patients without DKD (urinary albumin-creatinine ratio [ACR]2.5 mg/mmol in men or ACR3.5 mg/mmol in women and estimated glomerular filtration rate [eGFR]90 mL/min/1.73 m(2)) and 50 with DKD (ACR ≥25 mg/mmol and eGFR60 mL/min/1.73 m(2)). We used spline analysis to determine the threshold value of the score in detecting DKD and its sensitivity and specificity.EZSCAN scores were highly correlated with log values of eGFR (r=0.67, P0.0001) and ACR (r=-0.66, P0.0001). Using a cutoff value of 55, the score had 94% sensitivity, 78% specificity, and a likelihood ratio of 4.2 to detect DKD with a positive predictive value of 81% and a negative predictive value of 93%. On multivariable analysis, DKD was independently associated with EZSCAN score (β=-0.72, P=0.02), smoking status (1=never, 0=current/former) (β=-2.37, P=0.02), retinopathy (1=yes, 0=no) (β=3.019, P=0.01), triglycerides (β=2.56, P=0.013), and blood hemoglobin (β=-0.613, P=0.04). Patients without DKD but low EZSCAN score (n=10) had longer duration of disease (median [interquartile range], 13 [9-17] vs. 8 [4-16] years; P=0.017) and were more likely to have retinopathy (36.7% vs. 5.1%, P=0.02), lower eGFR (98 [95.00-103] vs. 106 [98.5-115], P=0.036), and treatment with renin-angiotensin system blockers (81.8% vs. 25.6%, P=0.002) than those with a normal score.EZSCAN may detect high-risk subjects for DKD in Chinese populations.

Aims: This study done in subjects with an initial normal glucose tolerance (NGT) was to assess the ability of EZSCAN, a new device developed to evaluate sudomotor function, to predict future abnormalities in glucose tolerance. Methods: South Asian (Indian) subjects (n= 69, 48% male, mean age 42 ± 9 years, mean BMI 28 ± 5 kg/m 2 ) diagnosed as NGT with a previous oral glucose tolerance test (OGTT, T0) underwent a frequently sampled OGTT (FSOGTT), 8 months later (T8). At both times EZSCAN tests were done. Using the AUC glucose and AUC insulin measured by the FSOGTT, subjects were categorised as normal, high AUC insulin or isolated high AUC glucose . Odds ratio (OR) for having high AUC insulin or isolated high AUC glucose vs normal was computed by logistic regression analysis using EZSCAN risk classification at T0 as independent variable ( 65%=high risk). Results: At T8, 11 and 5 subjects developed impaired glucose tolerance and diabetes respectively. OR of having high AUC insulin or isolated high AUC glucose in the different risk groups was 6.19 (CI 95% 1.50 – 25.48, p = 0.0116) for high risk vs no risk and 3.0 (CI 95% 0.98 – 9.19, p = 0.0545) for intermediate risk vs no risk. Sensitivity of EZSCAN for early detection of these abnormalities in glucose tolerance was 77% while it was 14% for fasting plasma glucose and 66% for HbA 1C . Conclusions: Assessment of sudomotor function by EZSCAN, a sensitive method when compared with the con - ventional methods may be very useful to identify and manage subjects at risk for developing glucose intolerance.

Low DC active current through nickel electrodes applied on skin in places like hands, forehead and feet provides a novel non invasive diagnostic tool using reverse iontophoresis. This work describes the electrochemistry reactions involved and some medical applications, such as diagnostics of neuropathy, diabetes and cardiac diseases. Finally we provide evidence for the utility of this method through large clinical studies.

Small fiber neuropathy is a dysfunction caused by diseases such as type II diabetes and cystic fibrosis. Nowadays, it is possible to analyze neuropathy with SudoscanTM technology (Impeto Medical Inc.) which provides a rapid and non-invasive early diagnosis. This technology is based on measurements of the electrochemical conductance of the skin viathe imposition of low amplitude voltages between electrodes applied to the skin and measuring the low current generated. The output measurement is related to the sweat composition associated to glands innervations and their permeability to chloride and proton ions [1]. The results obtained with this in vivo technology show a typical anode current response (curve J-E) with a significant offset and a linear part. The characteristic shape of the J-E graph easily indicates the type of disease and its progress [2]. To have a deeper understanding of the mechanisms occurring at electrodes and optimize the sensitivity of the instrument, in vitro experiments were performed in mimetic electrolytic solutions of sweat. Preliminary in vitro experiments led to same shapes than in vivo but with larger current densities (≈ 50 times greater than those obtained in vivo). This phenomenon is probably due to the high resistivity of a human body and the difference of the electrodes system between in vitro and in vivo measurements. For these reasons, it was necessary to modify in vitro conditions to get similar current densities and mimic realistically in vivo conditions. To this end, major modifications in the in vitro system were realized: (i) Concerning the in vitro configuration: the electrodes arrangement was changed and 3 identical electrodes were used leading to a decrease in the current densities by a factor of 10 (ii) To simulate the body resistance and, consequently, to decrease the current densities in vitro, the electrolyte composition was optimized by increasing its viscosity to reduce the flux of chloride ions to the electrode surface. The new composition allowed to reach current densities close to those obtained in vivo [3]. The aim of this work was to find the optimized electrolyte, mimicking sweat in terms of composition and the resistance of the human body under in vitroconditions. Then, the goal was to go deeper in the knowledge on the mechanism governing the electrode response to sweat. For this, linear voltammetry and electrochemical impedance spectroscopy were implemented to study the influence of sweat components such as pH, chloride concentration, buffer and carbonate concentration on a nickel model electrode [4]. Finally, different stainless steel electrodes were tested. Such electrodes are required because they are not allergenic and less expensive than nickel, but they need to be sensible to ions detection in sweat, with reproducible results allowing the early detection of diseases. References: [1] A. Calmet, H. Ayoub, V. Lair, and S. Griveau, Actual. Chim., vol. 390, pp. 48–49, 2014. [2] P. Brunswick and N. Bocquet, “Système d’analyse électrophysiologique,” 0753461. [3] A. Calmet, K. Khalfallah, H. Ayoub, V. Lair, S. Griveau, P. Brunswick, F. Bedioui, and M. Cassir, Electrochim. Acta, vol. 140, pp. 37–41, Sep. 2014. [4] H. Ayoub , S. Griveau, V. Lair, P. Brunswick, M. Cassir, and F. Bedioui, Electroanalysis, vol. 22, no. 21, pp. 2483–2490, Nov. 2010.