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the study population , their glycemic status verification , and other possible causes of neuropathy were considered and have been described earlier ( 7 ) .
blood samples were drawn and measured for cholesterols , triglycerides , creatinine , fasting plasma glucose , and hba1c .
standardized motor and sensory nerve conduction studies were performed on the right peroneal and sural nerve by a neurophysiologist blinded to the individuals group identity .
thermal threshold tests were performed with thermotest equipment ( somedic ab , hrby , sweden ) by using the method of limits ( 8) .
procedures were developed ( 9 ) and modified ( 10 ) from published guidelines ( 11 ) . the intraepidermal nerve fiber density ( ienfd )
denotes the number of fibers per millimeter of epidermal length ( mean counts in three sections ) .
data are presented as numbers ( n ) and proportions ( % ) , and distribution as mean and sd or median and interquartile range ( iqr ) .
differences between groups were tested by anova and subsequent student t test for normally distributed variables . for nonnormally distributed variables
, the kruskal - wallis test was applied with subsequent mann - whitney u testing .
the study population , their glycemic status verification , and other possible causes of neuropathy were considered and have been described earlier ( 7 ) .
blood samples were drawn and measured for cholesterols , triglycerides , creatinine , fasting plasma glucose , and hba1c .
standardized motor and sensory nerve conduction studies were performed on the right peroneal and sural nerve by a neurophysiologist blinded to the individuals group identity .
standardized motor and sensory nerve conduction studies were performed on the right peroneal and sural nerve by a neurophysiologist blinded to the individuals group identity .
thermal threshold tests were performed with thermotest equipment ( somedic ab , hrby , sweden ) by using the method of limits ( 8) .
procedures were developed ( 9 ) and modified ( 10 ) from published guidelines ( 11 ) . the intraepidermal nerve fiber density ( ienfd )
denotes the number of fibers per millimeter of epidermal length ( mean counts in three sections ) .
data are presented as numbers ( n ) and proportions ( % ) , and distribution as mean and sd or median and interquartile range ( iqr ) .
differences between groups were tested by anova and subsequent student t test for normally distributed variables . for nonnormally distributed variables
, the kruskal - wallis test was applied with subsequent mann - whitney u testing .
people with igt showed no significant metabolic differences compared with ngt , whereas patients with diabetes had metabolic perturbations compared with both ngt and igt ( table 1 ) .
clinical characteristics of the study population by glycemic status sural nerve conduction did not differ between igt and ngt .
people with igt had a lower conduction velocity ( cv ) of the peroneal nerve than those with ngt .
the cv of the peroneal and sural nerve was lower in t2d patients compared with ngt individuals ( table 1 ) .
there were no differences in heat or cold thresholds between igt and ngt ( table 1 ) .
the proportion of abnormal heat thresholds was significantly higher in individuals with t2d than ngt and igt .
ienfd did not differ significantly between igt and ngt ( table 1 ) , but was significantly lower in t2d compared with ngt .
women had higher ienfd than men ( median = 4.8 fibers / mm [ iqr 3.26.4 fibers / mm ] vs. 2.7 fibers / mm [ 1.64.7 fibers / mm ] ; p < 0.001 )
. however , there was no interaction between sex and small or large nerve fiber function ( data not shown ) .
people with igt showed no significant metabolic differences compared with ngt , whereas patients with diabetes had metabolic perturbations compared with both ngt and igt ( table 1 ) .
people with igt had a lower conduction velocity ( cv ) of the peroneal nerve than those with ngt .
the cv of the peroneal and sural nerve was lower in t2d patients compared with ngt individuals ( table 1 ) .
there were no differences in heat or cold thresholds between igt and ngt ( table 1 ) .
the proportion of abnormal heat thresholds was significantly higher in individuals with t2d than ngt and igt .
ienfd did not differ significantly between igt and ngt ( table 1 ) , but was significantly lower in t2d compared with ngt .
women had higher ienfd than men ( median = 4.8 fibers / mm [ iqr 3.26.4 fibers / mm ] vs. 2.7 fibers / mm [ 1.64.7 fibers / mm ] ; p < 0.001 )
. however , there was no interaction between sex and small or large nerve fiber function ( data not shown ) .
igt individuals did not show different large and small nerve fiber function compared with ngt . as expected , patients with t2d had poorer small and large nerve fiber function than ngt and igt .
it is not clear if neuropathy is found in the prediabetic individuals with igt ( 24,6 ) .
a high prevalence of igt in individuals with idiopathic neuropathy has been reported ( 1,12 ) , but these were individuals with existing neuropathy and in whom glycemic status was subsequently assessed .
the retrospective study design is less appropriate for ascribing igt as a potential cause of neuropathy .
a reduction in ienfd has been reported in individuals with diabetes without clinical or electrophysiological indications of nerve dysfunction ( 13 ) .
in addition , it has been reported that there is a loss of ienfd in individuals with igt ( 14,15 ) , suggestive of small nerve fiber dysfunction being present in a prediabetic stage . in a population - based study , neuropathy
was marginally increased in igt , but the measure of neuropathy was rather crude and mainly on large fibers ( 4 ) .
one recent similar study showed no difference between igt and ngt ( 6 ) ; however , no detailed measures of small nerve fiber function , particularly ienfd , were assessed .
first , our study is limited by a relatively small group size , which probably reduced the power to detect differences in ienfd between groups .
however , our study provides detailed assessment of nerve function in individuals with igt and ngt without any trend in results suggesting differences between the two groups .
second , the cross - sectional design did not enable us to study cause and effect . moreover , when assessing ienfd , we used thin sections of 5 m as compared with thick 50-m sections suggested by published guidelines
. however , it still allows for group comparison between ngt , igt , and t2d within our study , but hampers comparisons to studies using thicker sections .
our study has the following strengths : all individuals were recruited consecutively from a population - based sample , were well defined in terms of glycemic status with a strict definition of igt based on two oral glucose tolerance tests , and were all of the same age . to avoid bias ,
neurophysiological measurements were performed by personnel blinded for the glucose status of participants . in conclusion , we found no significant differences in large and small nerve function between igt and ngt .
it is not clear if neuropathy is found in the prediabetic individuals with igt ( 24,6 ) .
a high prevalence of igt in individuals with idiopathic neuropathy has been reported ( 1,12 ) , but these were individuals with existing neuropathy and in whom glycemic status was subsequently assessed .
the retrospective study design is less appropriate for ascribing igt as a potential cause of neuropathy .
a reduction in ienfd has been reported in individuals with diabetes without clinical or electrophysiological indications of nerve dysfunction ( 13 ) .
in addition , it has been reported that there is a loss of ienfd in individuals with igt ( 14,15 ) , suggestive of small nerve fiber dysfunction being present in a prediabetic stage . in a population - based study
, neuropathy was marginally increased in igt , but the measure of neuropathy was rather crude and mainly on large fibers ( 4 ) .
one recent similar study showed no difference between igt and ngt ( 6 ) ; however , no detailed measures of small nerve fiber function , particularly ienfd , were assessed .
first , our study is limited by a relatively small group size , which probably reduced the power to detect differences in ienfd between groups
. however , our study provides detailed assessment of nerve function in individuals with igt and ngt without any trend in results suggesting differences between the two groups .
second , the cross - sectional design did not enable us to study cause and effect . moreover , when assessing ienfd , we used thin sections of 5 m as compared with thick 50-m sections suggested by published guidelines
. however , it still allows for group comparison between ngt , igt , and t2d within our study , but hampers comparisons to studies using thicker sections .
our study has the following strengths : all individuals were recruited consecutively from a population - based sample , were well defined in terms of glycemic status with a strict definition of igt based on two oral glucose tolerance tests , and were all of the same age . to avoid bias ,
neurophysiological measurements were performed by personnel blinded for the glucose status of participants . in conclusion , we found no significant differences in large and small nerve function between igt and ngt .
objectiveto assess small and large nerve fiber function in people with normal glucose tolerance ( ngt ) , impaired glucose tolerance ( igt ) , and type 2 diabetes ( t2d).research design and methodsparticipants were recruited consecutively from a population - based cohort : ngt ( n = 39 ) , igt ( n = 29 ) , and t2d ( n = 51 ) . 
 electrophysiological measures included nerve conduction studies and thermal thresholds . 
 intraepidermal nerve fiber density ( ienfd ) in skin biopsies was calculated.resultsthere was no difference between igt and ngt in sural nerve conduction , ienfd , and thermal thresholds . 
 ienfd was significantly lower in t2d ( median = 2.8 fibers / mm [ interquartile range 1.14.7 fibers / mm ] ) than ngt individuals ( 4.5 fibers / mm [ 3.46.1 fibers / mm ] ; p < 0.05 ) . 
 t2d participants had poorer nerve conduction and higher heat thresholds than ngt and igt.conclusionslarge and small nerve function in people with igt did not differ from those with ngt . 
 our finding does not support the existence of neuropathy in a prediabetic stage .