Tilburg University
'Numbness of the feet' is a poor indicator for polyneuropathy in type 2 diabetic patients
van de Poll-Franse, L.; Valk, G.D.; Dekker, J.H.; Heine, R.J.; van Eijk, J.T. M.
Published in:
Diabetic Medicine: Journal of the British Diabetic Association
Publication date:
2000
Link to publication
Citation for published version (APA):
Franse, L. V., Valk, G. D., Dekker, J. H., Heine, R. J., & van Eijk, J. T. M. (2000). 'Numbness of the feet' is a
poor indicator for polyneuropathy in type 2 diabetic patients. Diabetic Medicine: Journal of the British Diabetic
Association, 17(2), 105-110.
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`Numbness of the feet' is a poor indicator for
polyneuropathy in Type 2 diabetic patients
L. V. Franse*, G. D. Valk*, J. H. Dekker*, R. J. Heine*² and J. T. M. van Eijk³
Abstract
*Institute for Research in Extramural Medicine,
Vrije Universiteit, Amsterdam, The Netherlands
²Department of Endocrinology, Academisch
Ziekenhuis Vrije Universiteit, Amsterdam, The
Netherlands
³Department of Medical Sociology, Universiteit
van Maastricht, The Netherlands
Received 10 November 1998; revised 2 September
1999; accepted 17 October 1999
Aims To identify neuropathic sensory symptoms associated with a clinical
neurological examination (CNE) and to investigate whether these symptoms
could be used as a diagnostic or screening tool for diabetic polyneuropathy in
general practice.
Methods Five hundred and eighty-eight patients with Type 2 diabetes,
recruited from 26 general practices in the Netherlands, underwent a CNE and
completed a diabetes symptom checklist that included 10 items on neuropathic
sensory symptoms. Linear regression analyses were performed to assess the
association between neuropathic symptoms and CNE. Receiver operating
characteristic (ROC) curves were created to assess the diagnostic properties of
neuropathic symptoms.
Results In this population, with a mean age of 66.8 years, 32% were
identi®ed with diabetic polyneuropathy according to the CNE. Variables that
showed the strongest association with CNE score were age (b = 0.41),
symptoms of sensory alteration (b = 0.27), and the item `numbness of the feet'
(b = 0.35) in particular. ROC curves showed that prediction of diabetic
polyneuropathy from these symptoms was unsatisfying. The sensitivity and
speci®city of daily symptoms of `numbness of the feet' were 28% and 93%,
respectively, in patients < 68 years, and 22% and 92%, respectively, in
patients > 68 years.
Conclusions Identi®cation of neuropathic sensory symptoms is not useful as a
diagnostic or even a screening tool in the assessment of diabetic neuropathy in
daily practice. Therefore, the results reported in this paper mandate an annual
foot examination by the general practitioner.
Diabet. Med. 17, 105±110 (2000)
Keywords diabetic
neuropathies,
healthcare, Type 2 diabetes mellitus
neurological
examination,
primary
Abbreviations CNE, clinical neurological examination; GP, general practi-
tioner
Introduction
Foot ulceration and lower limb amputation are common
complications of diabetes. In a primary healthcare setting,
Correspondence to: Lonneke Franse MPH, Institute for Research in Extramural
Medicine, Vrije Universiteit, Van der Boechorststraat 7, 1081 BT Amsterdam,
The Netherlands. E-mail: lv.franse.emgo@med.vu.nl
ã 2000 British Diabetic Association. Diabetic Medicine, 17, 105±110
one in every seven (14.3%) patients with Type 2 diabetes
was found to have an active foot ulcer (Wagner stage 1 or 2:
super®cial to deep ulcer) or pre-ulcer (Wagner stage 0: hard
skin with or without macerating changes) [1,2]. Diabetesrelated amputations accounted for 46.9% of the total
number of lower extremity amputations (n = 6680) in the
Netherlands in 1991 and 1992 [3].
105
106
`Numbness of feet' and polyneuropathy · L. V. Franse et al.
Early diagnosis of diabetic polyneuropathy can reduce
patient morbidity by allowing preventive therapeutic
interventions, including patient education and regular foot
examinations [4,5]. Established tests to identify patients at
risk for developing diabetic foot complications are tests of
warm and cold thermal perception [6], and nerve conduction [7]. These involve the use of expensive equipment and
are not quick or easy. For the detection of diabetic
polyneuropathy in daily clinical practice, a simple,
sensitive and inexpensive screening method is the clinical
neurological examination (CNE) which includes pinprick
sense, light touch sense, vibration sense and ankle jerk.
This simple CNE has recently been validated and shown to
be adequate for use in daily clinical practice [8,9].
Despite the fact that guidelines recommend an annual
foot examination by the general practitioner (GP) for
patients with diabetes [10,11], chart reviews reveal that
foot assessment for neuropathy is only seldom performed
[12]. Only one-third of all GPs perform a CNE, owing to
lack of time. Instead, the identi®cation of patients with
diabetic polyneuropathy in daily practice is often based on
interpretation of the symptoms reported by the patient.
Symptoms of sensory alteration have been associated with
both the CNE and the neurophysiological examination
[13]. The question arises as to whether or not patient
history can replace the CNE in daily clinical practice.
The aim of this study was to identify neuropathic sensory
symptoms associated with CNE outcome and to investigate whether those symptoms could be used as a diagnostic
or screening tool for diabetic polyneuropathy in general
practice.
Patients and methods
Five hundred and eighty-eight patients with Type 2 diabetes
were recruited from 26 general practices in the Netherlands.
Participants were identi®ed by their GP. Known and newly
diagnosed patients with Type 2 diabetes who received diabetes
care in general practice and were able to complete a
questionnaire in Dutch were eligible, if the diagnostic evidence
met the criteria of the Dutch College of General Practitioners for
Type 2 diabetes [10]. Patients were excluded if they received
diabetes care in hospital outpatient clinics, but not if they were
under specialist care for retinopathy or cardiovascular comorbidity. Participating GPs were known to refer about 30% of
their Type 2 diabetes patients to hospital outpatient clinics for
diabetes care [14]. Patients with other aetiological factors that
might in¯uence sensory functions of the skin of the lower
extremities (e.g. alcohol abuse, use of neurotoxic drugs,
abnormal kidney function) were excluded from the analyses.
One patient was excluded for this reason (serum creatinine
333 mmol/l).
Patients who agreed to participate and gave written informed
consent were included in the study. Forty-nine refused to
participate. They did not differ from the participating patients in
age or sex, but their diabetes duration was on average 2 years'
longer (P = 0.025).
The study was approved by the Medical Ethics Committee of
the Academic Hospital of the Vrije Universiteit in Amsterdam,
The Netherlands.
Measurements
Participants were sent a diabetes symptom checklist to complete
before the clinical examination. These were performed by a
trained research fellow at the practice of the patient's GP. The
checklist was not looked at before the examination. Blood
samples were drawn within 1 week after the clinical examination, after an overnight fast. Glycated haemoglobin (HbA1c)
was determined by ion-exchange high-performance liquid
chromatography, using a Modular Diabetes Monitoring
System (Bio-Rad, Veenendaal, the Netherlands).
Assessment of the severity of symptoms
The Type 2 Diabetes Symptom Checklist (DSC-Type 2) was
used to measure the severity of neuropathic sensory symptoms.
This comprises 34 questions, and measures the occurrence of
physical and psychological symptoms related to Type 2 diabetes
and its possible complications. Ten concern symptoms related to
sensory polyneuropathy. Grootenhuis and Valk factor-analysed
the 10 questions included in the DSC-Type 2 [13,15] and found
two dimensions (factors): the ®rst apparently represent symptoms of sensory alteration (tingling sensations in the hands/
®ngers, numbness ± diminished sensation ± of the hands, strange
sensation in the legs or feet, tingling sensation in the lower legs,
numbness ± diminished sensation ± of the feet, tingling sensation
in the arms/legs at night), while the second dimension represents
symptoms of neuropathic pain (shooting pain in the legs,
burning pain in the legs, pain in the legs during walking, burning
pain in the calves at night).
The patients were asked how often the symptoms had
occurred during the past month. The answers were scored as 0
± not at all; 1 ± one or more times per month; 2 ± one or more
times per week; 3 ± daily. The total score for the sensory
alteration dimension could thus vary between 0 and 18 and the
total score for the neuropathic pain dimension could vary
between 0 and 12.
Scoring system for the clinical neurological examination
All patients underwent a CNE as described by Valk et al. [9],
modi®ed by excluding assessments of muscle strength and great
toe joint position sense [16]. All tests were scored based on two
similar results out of three tests. Pinprick sense and light touch
sense (cotton wool) of the dorsum of the feet were tested on the
mid-foot and compared to proximal sensation (ankles).
Vibration sense (128 Hz tuning fork) of ®rst toes was compared
to vibration sense of ankles, and vibration sense of ankles was
compared to vibration sense of patella. Ankle jerks were
compared to knee re¯exes. Pinprick sense, light touch sense,
vibration sense of toes and ankles, and ankle re¯exes were
separately scored for both feet as 0 ± normal, 1 ± impaired in
comparison with proximal and 2 ± absent; summing up to a
maximum score of 20. Additionally, light touch sense was
related to the anatomical level below which it was impaired, and
ã 2000 British Diabetic Association. Diabetic Medicine, 17, 105±110
Original articles
was scored as 0 ± no abnormalities, 1 ± toe, 2 ± mid-foot, 3 ±
ankle, 4 ± mid-calf and 5 ± knee. If there was a difference at this
level between the right and the left side, the more abnormal side
was scored. The outcome of the total score of the CNE (the sum
of the scores of the sensory modalities, the ankle re¯exes, and the
anatomical level below which light touch sense was impaired)
could vary between 0 and 25. As muscle strength and position
sense do not add to the total score, the actual distribution of the
modi®ed CNE score was assumed to be the same as in the
original description.
Valk et al. [8] determined the best diagnostic polyneuropathy
cut-off point on the scale of measurement to achieve maximum
sensitivity (87.0%) and reasonable speci®city (62.2%) to be > 4
for the CNE. Therefore, a total score higher than 4 was graded as
polyneuropathy.
Statistical analyses
Results were analysed with SPSS for Windows software (SPSS,
Chicago, IL) [17]. Linear regression analysis was applied to
assess the univariate association between the different variables
and the CNE outcome. Standardized residuals plots showed that
linear regression analyses were appropriate. In addition, linear
regression analyses with natural log transformed, normally
distributed variables showed no different results.
Two-by-two contingency tables were formed for various cutoff points to examine the performance characteristics of
neuropathic symptoms as a diagnostic tool for neuropathy
(CNE > 4). Sensitivity and speci®city data were summarized in
Receiver operating characteristics (ROC) curves. ROC curve
analyses used MedCalc for Windows software (Mariakerke,
Belgium).
Results
The characteristics of the study population are shown in
Table 1. Thirty-two per cent of the participants had a CNE
score > 4 and were graded as polyneuropathy. In univariate regression analyses, age, diabetes duration, symptoms of pain, and symptoms of sensory alteration were
signi®cantly associated with the CNE score (Table 2).
Analyses of the association between the single items of
neuropathic symptoms and CNE score were performed to
investigate whether one question would show a stronger
association and have the same or better diagnostic
properties compared to a complete dimension or checklist.
The single item `numbness of the feet' showed the strongest
association with CNE score, stronger than the complete
subdimensions `sensory alteration' or `pain'. The other
nine items were all signi®cant, but the association with
CNE score was weaker; the standardized b varied from
0.09 to 0.23 (data not shown).
As age showed the strongest association with CNE score,
the diagnostic value of subdimensions `pain', and `sensory
alteration', and the single item `numbness of the feet'
according to age were examined by dichotomizing age by
its median value (68 years).
Figures 1,2,3 present the ROC curve analyses of the
predictive value of `pain', `sensory alteration', and `numbness of the feet' for a CNE score > 4 in patients < 68 years
and patients > 68 years. For symptoms of `pain', the area
Table 2 Univariate linear regression analyses with the clinical
neurological examination as outcome variable
Variable
Age (years)
Sex, male
Diabetes duration (years)
HbA1c (%)
Neuropathic symptom(s)
Pain (4 items)
Sensory alteration (6 items)
Numbness of the feet (1 item)
Standardized
coef®cients/beta
P
0.41
± 0.04
0.13
0.08
< 0.001
0.34
0.002
0.06
0.16
0.27
0.35
< 0.001
< 0.001
< 0.001
Table 1 Characteristics of the Type 2 diabetic patients (n = 588)
Variable
Age (years)
Sex (men)
Diabetes duration (years)
HbA1c (%)
CNE-score (0±25)
CNE > 4 (neuropathy)
Neuropathic symptoms score
Pain (0±12)
Sensory alteration (0±18)
66.8 6 10.4²
47% (276)³
5 (2±10)§
7.3 6 1.4²
4 (0±6)§
32% (190)³
0 (0±3)§
1 (0±6)§
CNE, clinical neurological examination.
²Mean 6 SD. ³Per cent (n). §20th to 80th percentile.
ã 2000 British Diabetic Association. Diabetic Medicine, 17, 105±110
107
Figure 1 Receiver operating characteristic curve for neuropathic
symptoms of `pain'.
108
`Numbness of feet' and polyneuropathy · L. V. Franse et al.
under the curve (AUC) for both age groups was not
signi®cantly different from 0.5. Symptoms of sensory
alteration and `numbness of the feet' both showed better
performance characteristics, but the AUC was never
greater than 0.66. At the cut-off point `daily symptoms of
numbness of the feet', 28% of the patients < 68 years with
CNE > 4 (polyneuropathy) were detected as such (sensitivity), and 93% of the patients with CNE < 4 were
categorized with no polyneuropathy according to this
symptom (speci®city) (Fig. 3). For those > 68 years, the
sensitivity and speci®city were virtually the same, 22% and
92%, respectively. However, as the prevalence of polyneuropathy was signi®cantly higher among those
> 68 years compared to those < 68 years (P < 0.001)
(Table 3), the positive predictive value of `daily symptoms
of numbness of the feet' was higher in those > 68 years
(71.7%) compared to those < 68 years (41.4%).
In the younger age group, 200 (89.7%) patients who had
neverhadsymptomsof`numbnessofthefeet'duringthepast
month were identi®ed with no polyneuropathy according to
the CNE score. Of the 23 (10.3%) patients who never had
symptoms of `numbness of the feet', but were identi®ed with
polyneuropathy, 19 had aCNEscore < 8,twohad ascore of
10 and two had a score of 12 (data not shown).
A previously reported validation study mainly involved
relatively younger patients [8]. Additional analysis revealed that in the present study, 40% of the patients
> 68 years were identi®ed with an impaired or absent
vibration sense, whereas only 10% of those < 68 years had
an impaired or absent vibration sense (data not shown).
Figure 2 Receiver operating characteristic curve for neuropathic
symptoms of `sensory alteration'.
100
Sensitivity (%)
80
< 68
60
≥ 68
40
Area under curve (95% CI)
< 68: 0.66 (0.57– 0.75)
≥ 68: 0.59 (0.50– 0.68)
20
0
0
20
40
60
80
1-specificity (%)
Figure 3 Receiver operating characteristic curve for neuropathic
symptoms of `numbness of the feet'.
100
Discussion
This study demonstrates that the identi®cation of neuropathic sensory symptoms cannot replace the CNE as a
diagnostic tool in the assessment of early diabetic
polyneuropathy in Type 2 diabetic patients in general
practice. Although symptoms of pain, sensory alteration
and `numbness of the feet' in particular, showed a
signi®cant association with CNE score, the prediction of
polyneuropathy from the neuropathic symptoms was not
satisfactory.
Table 3 Prevalence of polyneuropathy (clinical neurological examination (CNE) score > 4) by age and frequency of symptoms of `numbness of the
feet'
CNE score > 4 (neuropathy)
How often in the past month have you had symptoms of `numbness of the feet'?
< 68 years (n = 286)
> 68 years (n = 302)
Not at all
One or more times per month
One or more times per week
Daily
P-trend
Total prevalence of neuropathy
23 (10.3%)
5 (22.7%)
3 (27.3%)
12 (41.4%)
< 0.001
15.0% (n = 43)
90 (41.7%)
8 (53.3%)
16 (64.0%)
33 (71.7%)
< 0.001
48.7% (n = 147)
ã 2000 British Diabetic Association. Diabetic Medicine, 17, 105±110
Original articles
The results of this study con®rm earlier ®ndings in a
hospital setting using the same symptom checklist [13].
Among 68 patients referred to the neurologist with
suspected polyneuropathy, symptoms of sensory alteration
showed a stronger association with CNE score than
symptoms of pain [13]. Dyck et al. [18] also found that
the number of neuropathic symptoms was signi®cantly
associated with the neurological abnormality score according to the Neurological Disability Score but did not
make a distinction between the different dimensions of
sensory alteration and pain.
The weak association, found between diabetes duration
and the CNE score was explained by the association of age
with CNE score (data not shown). Other studies have been
found to be inconsistent with regard to the association of
diabetic neuropathy with age, duration of diabetes and
hyperglycaemia [19±23].
ROC curves showed that prediction of diabetic polyneuropathy from the different neuropathic symptoms was
unsatisfactory. The discriminating ability of symptoms of
pain was not better than chance. The ROC curves of
symptoms of sensory alteration and `numbness of the feet'
showed better discriminating abilities, but were still poor.
Daily symptoms of `numbness of the feet' had high
speci®city, but low sensitivity. To calculate the positive
and negative predictive values of a diagnostic instrument,
the prevalence (prior odds) of a `disease' in the studied
population is also important [24]. As the prevalence of
polyneuropathy differed more than 30% between the two
age groups, the positive and negative predictive values were
also different. Although the positive predictive value of
`daily symptoms of numbness of the feet' was highest
among those > 68 years, in this age group 28% of the
patients who reported daily symptoms still did not have
objective evidence of diabetic neuropathy while 45% of
patients who did not report daily symptoms of `numbness
of the feet', did. Feldman et al. [25] also concluded that
symptoms might not always indicate underlying neuropathy, ®nding that an equal number of patients with and
without diabetic neuropathy answered up to six relevant
questions positively.
Almost 90% of those aged < 68 years who never had
symptoms of `numbness of the feet' had no evidence of
diabetic polyneuropathy at examination. The `missed'
10% who did have diabetic polyneuropathy had relatively
low CNE scores. This suggests that asking younger Type 2
patients about `numbness of the feet' might be a useful
screening instrument. However, as there are no longitudinal data of the consequences of not performing a CNE
among the 10% that do not have complaints but suffer a
mild neuropathy, even avoiding CNE is this group is
inadvisable.
The limitations of the present study should be considered. Patients receiving diabetes care in hospital outpatient clinics were excluded. Although this does not
ã 2000 British Diabetic Association. Diabetic Medicine, 17, 105±110
109
in¯uence the conclusions in the general practice population, these cannot be extrapolated to hospital clinic
patients or indeed to patients unable to complete a
questionnaire in Dutch. It is possible that the patients
referred to a specialist for diabetes care had a worse HbA1c,
explaining the fairly good HbA1c values seen in the study
population. Although, the 49 participants who refused
participation had a longer duration of Type 2 diabetes, it is
unlikely that this in¯uenced the main outcome as diabetes
duration was weakly associated with CNE outcome.
The allocation of `aching in the calves when walking' to
the domain of polyneuropathic pain is open to criticism. It
is debatable whether one item can differentiate between
neuropathic pain and peripheral vascular pain. Based on
content, and also for statistical reasons, the allocation of
this item to the pain dimension seemed plausible at the time
of development and validation of the symptom checklist
[13,15].
There is no gold standard for the assessment of
polyneuropathy, with which new tests can be compared.
Although warm and cold thermal perception [6], and nerve
conduction tests [7] are extensively studied and generally
accepted, they are not very suitable for use in daily clinical
practice.
It is questionable whether a CNE cut-off score > 4 for
diabetic neuropathy is useful in older patients as it is well
documented (and con®rmed in the present study) that
vibration sense in the elderly is often absent [26,27].
Raising the CNE cut-off point to > 8 for the diagnosis of
neuropathy in patients > 68 years decreased the prevalence of neuropathy in this subgroup to 18%. However, it
did not change the sensitivity or speci®city of the question
`numbness of the feet' and therefore did not change the
outcome of interest.
In conclusion, identi®cation of neuropathic sensory
symptoms is not useful as a diagnostic or even a screening
tool in the assessment of diabetic neuropathy in daily
practice. Therefore, the results reported in this paper
mandate an annual foot examination by the general
practitioner.
Acknowledgements
The authors would like to thank Jos Twisk PhD for his help
in the statistical analyses.
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