Prevalence of Neuropathy in Prediabetes and Healthy Volunteers by Quantitative Assessment of Sudomotor Function
R. Gabriel1,2. JH. Calvet3, A. Vilier3, N. Boukichou2, J. Tuomilehto 2,4 on behalf of ePREDICE Study Group.
1Instituto de Salud Carlos III, Escuela Nacional de Sanidad, Madrid, Spain.
2. Evidem Consultores. ePREDICE Coordinating Centre, Madrid. Spain
3. IMPETO MEDICAL. Paris, France
4. Dasman Diabetes Institute. Kuwait City, Kuwait
Background
Sudomotor function is used to evaluate the peripheral autonomic system. Several studies have shown sudomotor dysfunction in diabetes and prediabetes. Measurement of Electrochemical Skin Conductance (ESC) based on the electrochemical reaction between the chloride ions in sweat and stainless steel plate electrodes is a simple, non-invasive, and quick method allowing assessment of sweat gland function. Previous studies have reported that ESC measurement correlates well with other validated sudomotor standards. However, sweat function is influenced by factors as age, gender, race, BMI, and glycaemic status. Therefore remains a need to describe the performance of this technology in the prediabetic stage.
Aim
1) To compare the Electrochemical Skin Conductance (ESC) values and distribution measured by SUDOSCAN in adult with prediabetes and healthy volunteers, 
2) To estimate the prevalence of Neuropathy and Cardiovascular Autonomic Neuropathy (CAN) among adult prediabetic subjects and healthy volunteers.
Method
Study populations. 447 prediabetic individuals (59% females), 45-74 years old, with IFG or IGT or IFG+IGT, recruited in the ongoing multicentre European Randomized Clinical Trial ePREDICE (Early Prevention of Diabetes Complications in People with Hyperglycaemia in Europe). 383 healthy volunteers (83% females), 22-65 years old. 
Measurements: SUDOSCAN test, HbA1c, OGTT-2h, BMI and waist circumference were measured at baseline. 
Neuropathy is defined according to SUDOSCAN results: a) No neuropathy: hands ESC ≥ 60 µS and feet ESC ≥ 70 µS; b) Neuropathy: hands ESC between 40 – 60 µS or feet ESC between 50-70 µS; and c) Severe neuropathy: hand ESC < 40 µS or feet ESC < 50 µS. Cardiovascular Autonomic Neuropathy (CAN) was defined according to CAN risk score: <30 no risk of CAN, ≥ 30 at risk of CAN. 
Results
Table 1. Percentage of neuropathy and CAN defined by SUDOSCAN in the two populations.
			          		                                      Prediabetics	Healthy volunteers	P value
Neuropathy as defined by SUDOSCAN, n (%)	        				                	<0.0001
 No neuropathy				                                310 (69)		     350 (91)	
Neuropathy				                                        117 (26)		          33 (9)	
Severe neuropathy		                  		            20 (5)		            0 (0)	
CAN risk score, n (%)								                                                        <0.0001
<30					                                            200 (44.7)		      382 (99)	
≥30					                                            203 (55.3)		             1 (1)	
P value for χ² test.

Table 2. Mean values of hands and feet ESC in groups of neuropathy in the two populations.
		                           No neuropathy		                        	Neuropathy	                                  Severe neuropa
		              Prediabetics	Healthy Volunteers	Prediabetics	Healthy Volunteers	Prediabetics	Healthy Volunteers
Hands ESC (µS)	75.7 ± 7.7		74.2 ± 6.8		56.0 ± 9.5		57.8 ± 4.5		37.1 ± 10.9		-
Feet ESC (µS)	83.0 ± 5.1		83.8 ± 4.9		73.3 ± 10.3		78.2 ± 6.1		65.6 ± 16.6		-

Percentage of neuropathy defined by SUDOSCAN in the two populations (No neuropathy: prediabetics n=310 (69%), healthy volunteers n=350 (91%); Neuropathy: prediabetics n=117 (26%), healthy volunteers n=33 (9%); and Severe neuropathy: prediabetics n=20 (5%), healthy volunteers n=0 (0%); p value comparing the two populations<0.0001).
Among patients with prediabetes percentage of neuropathy in groups of 2h OGTT (<7.8 mmol/l: no neuropathy 69%, neuropathy 26%, severe neuropathy 5%; 7.8-11 mmol/l : no neuropathy 72%, neuropathy 24%, severe neuropathy 4%; ≥11 mol/l: no neuropathy 35%, neuropathy 59%, severe neuropathy 6%).
Discussion
Overall prevalence of peripheral neuropathy is very high (31%) in the prediabetic population as compared to healthy volunteers (9%).   
SUDOSCAN is a simple, rapid, and highly reproducible test for use as a screening tool, and as an endpoint in clinical trials on neuropathy in prediabetes.