Electrochemical skin conductances values and clinical factors affecting sudomotor dysfunction in patients with prediabetes, type 1 diabetes, and type 2 diabetes: A single center experience.

BACKGROUND AND AIM: Sudomotor dysfunction is linked to small fibers damage. We investigated sudomotor dysfunction in a large group of participants with diabetes, prediabetes, and nondiabetic healthy subjects. This study aimed to complete knowledge on sudomotor dysfunction in this population, especially regarding the threshold values for the electrochemical skin conductance (ESC) and factors affecting it. MATERIALS AND METHODS: A total of 690 volunteers in four groups were included in the study (type 1 [T1DG]: n = 80, 61.3% women; type 2 diabetes [T2DG]: n = 438, 63.5% women; prediabetes [Pre-DG]: n = 88, 80.7% women; healthy control [HC-G]: n = 84, 67.5% women). All subjects were investigated for clinical diabetic peripheral polyneuropathy and sudomotor dysfunction. The characteristics of participants obtained from outpatient records were evaluated. We used the Sudoscan device to measure ESC which was normalized for BMI, to improve the discriminative capability of the method. RESULTS: Diabetic polyneuropathy was found in 17.5% of T1DG, 27.4% of T1DG, and 10.2% of Pre-DG. The mean ESC/BMI was lower in subgroups with diabetic polyneuropathy than those without. Mean ESC/BMI was lowest in T2DG and highest in HC-G but comparable in T1DG and Pre-DG. We accepted the "mean ESC/BMI-1 SD" in the HC-G as the threshold for sudomotor dysfunction. Accordingly, the prevalence of sudomotor dysfunction was 18.8%, 44.3%, 59.1%, and 15% in T1DG, T2DG, Pre-DG, and HC-G, respectively. In T2DG, sudomotor dysfunction was found in 66.7% of persons with retinopathy, of which 56.3% had clinical diabetic polyneuropathy. The prevalence of sudomotor dysfunction in subjects with peripheral artery disease, chronic kidney disease, cardiovascular disease, and hypertension was 46.7%, 47.4%, 43.4%, and 50%, respectively, and 42.9%, 38.9%, 45.5%, and 37.3% of whom in the same order detected with clinical diabetic polyneuropathy. Considering the entire group, a logistic regression model demonstrated that the variables associated with SMD were: retinopathy (OR: 2.969; 95% CI: 1.723, 5.114), female gender (OR: 1.952; 95% CI: 1.287, 2.962), and e-GFR (OR: 0.989; 95% CI: 0.981, 0.998). Since the rate of complications was very low in T1DG, excluding this group, a new model similarly revealed that retinopathy and female gender were associated with SMD, however, the association with e-GFR was disappeared. CONCLUSION: The prevalence of sudomotor dysfunction is high when established peripheral polyneuropathy was present in diabetes. Even though, sudomotor dysfunction can also occur before clinical polyneuropathy in both types of diabetes (T1DG: 18.8%, T2DG 44.3%), prediabetes (59.1%), and nondiabetic healthy subjects (15%). The variables associated with sudomotor dysfunction were retinopathy and female sex. Normalization of ESC for BMI would be a beneficial approach. However, before this method is included in the routine screening programs for diabetic polyneuropathy, large-scale and prospective studies are required to reach a consensus on the pathological threshold values.

Reduction in the Risk of Peripheral Neuropathy and Lower Decrease in Kidney Function with Metformin, Linagliptin or Their Fixed-Dose Combination Compared to Placebo in Prediabetes: A Randomized Controlled Trial.

OBJECTIVE: To compare the effect of glucose-lowering drugs on peripheral nerve and kidney function in prediabetes. METHODS: Multicenter, randomized, placebo-controlled trial in 658 adults with prediabetes treated for 1 year with metformin, linagliptin, their combination or placebo. Endpoints are small fiber peripheral neuropathy (SFPN) risk estimated by foot electrochemical skin conductance (FESC < 70 µSiemens) and estimated glomerular filtration rate (eGFR). RESULTS: Compared to the placebo, the proportion of SFPN was reduced by 25.1% (95% CI:16.3-33.9) with metformin alone, by 17.3% (95% CI 7.4-27.2) with linagliptin alone, and by 19.5% (95% CI 10.1-29.0) with the combination linagliptin/metformin (p < 0.0001 for all comparisons). eGFR remained +3.3 mL/min (95% CI: 0.38-6.22) higher with the combination linagliptin/metformin than with the placebo (p = 0.03). Fasting plasma glucose (FPG) decreased more with metformin monotherapy -0.3 mmol/L (95%CI: -0.48; 0.12, p = 0.0009) and with the combination metformin/linagliptin -0.2 mmol/L (95% CI: -0.37; -0.03) than with the placebo (p = 0.0219). Body weight (BW) decreased by -2.0 kg (95% CI: -5.65; -1.65, p = 0.0006) with metformin monotherapy, and by -1.9 kg (95% CI: -3.02; -0.97) with the combination metformin/linagliptin as compared to the placebo (p = 0.0002). CONCLUSIONS: in people with prediabetes, a 1 year treatment with metformin and linagliptin, combined or in monotherapy, was associated with a lower risk of SFPN, and with a lower decrease in eGFR, than treatment with placebo.

Sudomotor dysfunction in patients recovered from COVID-19.

Dysautonomia has been reported in COVID-19. Sweat function testing has been proposed to assess autonomic neuropathy. Fifty Indian patients consulting for neurological symptoms participated in this observational study. The NHS questionnaire for neurological symptoms was completed and electrochemical skin conductance was measured using Sudoscan. The 26% of patients with sweat dysfunction i) were older (p = 0.001), ii) were more frequently treated at home (p = 0.008), iii) were more likely to have received antiviral treatment (p = 0.0006), and iv) more frequently reported at least one motor, sensory or autonomic symptom (p = 0.04). This preliminary study suggests that patients with COVID-19 should be screened for dysautonomia.

Normative Values for Electrochemical Skin Conductance Measurements for Quantitative Assessment of Sudomotor Function in Healthy Indian Adults.

CONTEXT: Electrochemical skin conductance (ESC) test is a widely accepted objective technique for quantitatively assessing sudomotor dysfunction, which is one of the earliest-detected neurophysiologic abnormalities in diabetic patients with distal symmetric polyneuropathy. AIMS: This study aimed to provide normative data for ESC values among healthy Indian participants and assess the potential influence of age, sex, and body mass index (BMI) on ESC measurements. SETTINGS AND DESIGN: A sample of 217 healthy participants aged 18-75 years were recruited and assessed for parameters including age, gender, BMI, and ESC measurements of the hands and feet. STATISTICAL ANALYSIS USED: The Shapiro-Wilk test was used to assess the normality of the data. Pearson's correlation was used to evaluate the association between age, gender, and BMI, and ESC measurements. RESULTS: The mean age of the participants was 43.3 ± 13.2 years, and mean BMI was 26.0 ± 4.3 kg/m2. Mean ESC for the hands and feet was 68.9 ± 13.1 and 71 ± 12.9 micro-Siemens, respectively, and there was a significant correlation between values from the right and left hands and feet (r = 0.9, P < 0.0001). A significant correlation was also observed between ESC measurements of the hands and feet (r = 0.94, P < 0.0001). ESC values of both hands and feet declined with age. A weak but significant inverse correlation between ESC and age was observed for the hands (r = 0.02, P = 0.01) and for the feet (r = 0.12, P < 0.0001). There was no significant difference in hand or feet ESC measurement between male and female participants. No significant correlation was observed between BMI and ESC of hands or feet. Only age was identified as a significant determinant of ESC on multivariate logistic regression analysis. CONCLUSIONS: Normative values for Indians are lower than that reported for Caucasians.

Quick, non-invasive and quantitative assessment of small fiber neuropathy in patients receiving chemotherapy.

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a common, potentially severe and dose-limiting adverse effect; however, it is poorly investigated at an early stage due to the lack of a simple assessment tool. As sweat glands are innervated by small autonomic C-fibers, sudomotor function testing has been suggested for early screening of peripheral neuropathy. This study aimed to evaluate Sudoscan, a non-invasive and quantitative method to assess sudomotor function, in the detection and follow-up of CIPN. Eighty-eight patients receiving at least two infusions of Oxaliplatin only (45.4%), Paclitaxel only (14.8%), another drug only (28.4%) or two drugs (11.4%) were enrolled in the study. At each chemotherapy infusion the accumulated dose of chemotherapy was calculated and the Total Neuropathy Score clinical version (TNSc) was carried out. Small fiber neuropathy was assessed using Sudoscan (a 3-min test). The device measures the Electrochemical Skin Conductance (ESC) of the hands and feet expressed in microSiemens (µS). For patients receiving Oxaliplatin mean hands ESC changed from 73 ± 2 to 63 ± 2 and feet ESC from 77 ± 2 to 66 ± 3 µS (p < 0.001) while TNSc changed from 2.9 ± 0.5 to 4.3 ± 0.4. Similar results were observed in patients receiving Paclitaxel or another neurotoxic chemotherapy. During the follow-up, ESC values of both hands and feet with a corresponding TNSc < 2 were 70 ± 2 and 73 ± 2 µS respectively while they were 59 ± 1.4 and 64 ± 1.5 µS with a corresponding TNSc ≥ 6 (p < 0.0001 and p = 0.0003 respectively). This preliminary study suggests that small fiber neuropathy could be screened and followed using Sudoscan in patients receiving chemotherapy.

Sudomotor function as a tool for cardiorespiratory fitness level evaluation: comparison with maximal exercise capacity.

Physical inactivity is a modifiable risk factor for cardiovascular (CV) and metabolic disorders. VO2max is the best method to assess cardio-respiratory fitness level but it is poorly adopted in clinical practice. Sudomotor dysfunction may develop early in metabolic diseases. This study aimed at comparing established CV risk evaluation techniques with SUDOSCAN; a quick and non-invasive method to assess sudomotor function. A questionnaire was filled-in; physical examination and VO2max estimation using a maximal test on a bicycle ergometer were performed on active Finish workers. Hand and foot electrochemical skin conductance (ESC) were measured to assess sudomotor function. Subjects with the lowest fitness level were involved in a 12 month training program with recording of their weekly physical activity and a final fitness level evaluation. Significant differences in BMI; waist and body fat were seen according to SUDOSCAN risk score classification. Correlation between the risk score and estimated VO2max was r = -0.57, p < 0.0001 for women and -0.48, p < 0.0001 for men. A significant increase in estimated VO2max, in hand and foot ESC and in risk score was observed after lifestyle intervention and was more important in subjects with the highest weekly activity. SUDOSCAN could be used to assess cardio-metabolic disease risk status in a working population and to follow individual lifestyle interventions.

A new tool to detect kidney disease in Chinese type 2 diabetes patients: comparison of EZSCAN with standard screening methods.

BACKGROUND: 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). METHODS: 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 ACR <3.5 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 eGFR <60 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. RESULTS: EZSCAN scores were highly correlated with log values of eGFR (r=0.67, P<0.0001) and ACR (r=-0.66, P<0.0001). 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 (ß=-0.72, P=0.02), smoking status (1=never, 0=current/former) (ß=-2.37, P=0.02), retinopathy (1=yes, 0=no) (ß=3.019, P=0.01), triglycerides (ß=2.56, P=0.013), and blood hemoglobin (ß=-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. CONCLUSION: EZSCAN may detect high-risk subjects for DKD in Chinese populations.

Abnormal electrochemical skin conductance in cystic fibrosis.

BACKGROUND: Electrochemical skin conductance measurement is an active electrophysiologic method in which incremental low direct voltage is applied on the skin. It generates a current due to reverse iontophoresis which previous studies suggested to be mostly related to chloride anion movements. As sweat chloride movements upon electric stimulation were likely to be impaired in cystic fibrosis (CF) patients, we designed a proof-of-concept study to measure electrochemical skin conductance in CF patients and control subjects and to test the ability of this method to discriminate CF from controls. METHODS: Electrochemical skin conductance was measured in 41 adult patients with classical CF and 20 healthy control subjects. Patients placed their hands and feet on nickel electrodes and an incremental low direct voltage was applied on the anode during 2min. The resulting voltage on the cathode and the current generated between anode and cathode were measured and from them, two electrochemical skin conductance variables were calculated: ESC, obtained when a low voltage of 1.6V was applied, and dESC which took into account electrochemical skin conductances obtained when low and high voltages were applied. RESULTS: ESC measurements on hands and feet were significantly different in CF patients (on feet: 75±10µSi), as compared with control subjects (62±13µSi, p<0.0001); dESC was also significantly different and more discriminative in CF patients (on feet: 34±24µSi), as compared with control subjects (93±24µSi, p<0.0001). dESC measurement provided a diagnostic specificity of 1 and a sensitivity of 0.93. CONCLUSIONS: These results show that electrochemical skin conductance which is easily and rapidly measured is abnormal in CF patients. Trial registry name in the European Clinical Trials Database (eudraCT): "EZSCAN MUCO1: Mesure de la conductance cutanée par chronoampérométrie", N°EUDRACT: 2007-A00221-52.

Effect of doxycycline on sulfur mustard-induced respiratory lesions in guinea pigs.

Respiratory tract lesions induced by the chemical warfare agent sulfur mustard (SM) are characterized by epithelial damages associated with inflammatory cell infiltration. Here we evaluated the imbalance between gelatinase and tissue inhibitors of metalloproteinases (TIMPs), and we tested pretreatment with the protease inhibitor doxycycline. Guinea pigs were intoxicated intratracheally with SM and evaluated 24 h after exposure. Matrix metalloproteinase (MMP) gelatinase activity of bronchial lavage (BL) fluid from SM-exposed guinea pigs was high compared with controls, as shown by both zymography and biotinylated substrate degradation, whereas TIMP-1 and -2 levels by immunoblotting were similar. Extensive areas of lysis were evidenced by in situ zymography, indicating imbalance between gelatinases and inhibitors towards net proteolytic activity. Doxycycline pretreatment resulted in 1) decreased gelatinase activity (zymography, free gelatinase activity assay, and in situ zymography); 2) decreased inflammation (BL fluid cellularity and protein level); and 3) dramatic decrease in histological epithelial lesions. Our results suggest inadequate levels of TIMP to counteract increased gelatinase activity and further support a role for MMP gelatinases in SM-induced respiratory lesions. They also suggest that doxycycline may hold promise as a therapeutic tool.