of drugs for diabetic neuropathy in a group of Turkish
Selcuk Mistik, M.D. Assistant Professor
Erciyes University Medical Faculty, Department of Family Medicine
Dilek Toprak, M.D. Assistant Professor
Kocatepe University Medical Faculty, Department of Family
Murat Aksu, M.D. Associate Professor
Erciyes University Medical Faculty,
Department of Neurology
Erciyes University Medical Faculty
Department of Family Medicine
38039 Kayseri, TURKEY
Phone: 00 90 352 4374937 / 23851
00 90 532 3438450
Fax: 00 90 352 4375285
Diabetic neuropathy is a disease of peripheral
nerves that occurs in at least 50% of patients who have had
diabetes for 25 years. A study to figure out the probable
markers of early diabetic neuropathy was carried out. The
major point to be investigated was the use of drugs for diabetic
neuropathy either in the presence or absence of the diagnosis
of diabetic neuropathy by a performed EMG. This research was
carried out in 2002 in Afyon province, Turkey. A questionnaire
of 36 questions was administered. A total of 204 diabetic
patients were involved in the study where 72 (35.3%) were
male and 132 (64.7%) were female. Only 3 of the patients were
Type1 diabetes mellitus. The mean duration of diabetes mellitus
was 6.92 ± 5.60 years. There were no patients using
carbamazepine, metoclopramide or diphenhydramine, where one
(0.5%) was using amitriptyline, 46 (22.7%) were using B1+B6
or combined vitamins, and only six (3%) were using gabapentin.
Our study demonstrates the necessity of diagnosis and treatment
of diabetic neuropathy.
Keywords. Diabetic neuropathy, treatment
Diabetes mellitus is a common condition and
diabetic neuropathy is a disease of peripheral nerves that
occurs in at least 50 percent of patients who have had diabetes
for 25 years (1). The syndrome includes symmetrical distal
polyneuropathy, asymmetrical proximal motor neuropathy, focal
asymmetrical mono- or polymononeuropathies, or autonomic neuropathy
(1). The aetiology is uncertain. However, there are four hypotheses.
These are; hyperglycemia-polyol-myoinositol hypothesis, microvascular
hypothesis, structural changes at the node of Ranvier, and
vasculitic neuropathy (1-4).
The clinical features, which are classified
under four items, may present with a wide range of symptoms.
The first, symmetrical distal polyneuropathies, includes pain
and paresthesias usually in the lower extremities, decreased
vibration and position sense, sensory ataxia, loss of ankle
jerks, painful or painless foot ulceration, dissociated sensory
loss of pain and temperature sensation, development of Charcot
joints in the lower extremities, painless distension of the
bladder and Argyll Robertson pupils. Sudden asymmetrical weakness
of the pelvic musculature, and slowly progressive weakness
of the proximal limb-girdle musculature are named as asymmetrical
proximal motor neuropathies. The third, focal asymmetrical
mono- or polymononeuropathies, includes paralysis of extraocular
muscles, painful dysesthesias involving the lower thorax or
upper abdominal wall, weakness of intercostal abdominal muscles,
and involvement of nerves at risk of compression. The fourth
item, autonomic neuropathies, include postural hypotension,
resting tachycardia, silent myocardial infarction, atonic,
painless distended bladder with overflow incontinence, male
impotence with failure of ejaculation, reduced vaginal lubrication
and dyspareunia in the female, incoordination of oesophageal
peristalsis, gastric hypomobility, pylorospasm, intestinal
hypomobility and constipation, intestinal incoordination and
diarrhoea, anorectal dysfunction with incontinence, meiosis
and failure of reaction to light- an Argyll Robertson-like
Progressive nerve degeneration is reflected
in reduction in amplitude of compound muscle action potential
and a progressive slowing of conduction velocity in multiple
nerves (5). Therefore, in addition to a detailed neurological
examination, electromyography is a necessary diagnostic test
in the diagnosis of diabetic neuropathy.
Intensive diabetic therapy markedly delays or
prevents the clinical manifestation of diabetic neuropathy
(6). Maintenance of ideal body weight is another requirement.
There are many drugs used for symptomatic treatment in diabetic
neuropathy. Tricyclics such as amitriptyline, carbamazepine,
and gabapentin are used for painful neuropathy. Intravenous
lidocaine can be used for patients with intractable pain.
Fluorohydrocortisone, indomethacin, a combination of diphenhydramine
and cimetidine, and liquorice containing glycyrrhizic acid
can be used for autonomic dysfunction and postural hypotension.
Bethanechol can be used to promote detrussor contraction,
and to accelerate delayed oesophageal emptying. Imipramine
may prevent retrograde ejaculation, and impotence may be treated
with Sildenafil citrate. Metoclopramide may be used for delayed
gastric emptying, and tetracycline for diarrhoea (1,7).
The aim of this study was to define the drugs
used for diabetic neuropathy in a primary care setting, and
whether these drugs are used with or without EMG confirmation.
Another objective of the study was to define whether there
are drugs which are prescribed to diabetic patients but have
no proven therapeutic value for diabetic neuropathy.
This research was carried out in 2002 in Afyon,
Turkey. Afyon has a central population of 150,000 and a total
population of approximately 840,000. The subjects involved
in the study were chosen from a diabetes mellitus centre working
in cooperation with the Afyon General Hospital. The centre
is working for the care of the voluntarily submitted diabetes
mellitus patients who are the members of three of the four
social security organizations in Turkey, and has been established
two years ago. There are nearly five hundred patients who
are being periodically examined in the centre.
The research group was composed of diabetes
mellitus patients who had admitted to the diabetes centre
during a three month period. All of the patients gave oral
informed consent. The study included 204 patients.
Interviews were performed face-to-face by a
family physician, who is a staff member of the centre, and
a staff nurse who is trained in diabetes mellitus. A questionnaire
of 36 questions was administered. The questionnaire inquired
about age, level of education, occupation, addiction of tobacco,
social security, type of diabetes mellitus, the drugs which
are used for diabetes mellitus and the other drugs which are
permanently used, duration of diabetes mellitus from the onset
of disease, presence of other chronic diseases and their names,
and 16 other questions to define the presence of diabetic
The drugs, which are used by the patients, are
classified into nine groups as: oral anti-diabetics, insulin,
amitriptyline, carbamazepine, metoclopramide, diphenhydramine,
B1 and B6 vitamins, gabapentin, and as others to attain a
better evaluation. The questions to define the presence of
diabetic neuropathy are taken from the questions which Feldman
et al. have used (8).
The results were stored and processed on a computer
running SPSS version 10.0. Standard deviation was used for
In the study group, there were 72 (35.3%) men
and 132 (64.7) women. The average age was 59.75 ± 21.57.
The patients' levels of education were as follows: 26.9% were
illiterates, 11.4% could read and write, 43.8 were primary
school graduates, 5.5% were secondary school graduates, 6.0%
were high school (lycee) graduates, and 6.5% were university
graduates. The general distribution of social security types
was as follows: 51% government employees' social security,
39.7% social security of self-employed professionals, 3.1%
social security organization of employees, and 6.2% were using
other social security organizations. There were 1.6% type
1 diabetes mellitus patients and the remaining 98.4% was type
2 diabetes mellitus. Only 12.7% had tobacco addiction in the
There were only 27.1% of patients with no additional
chronic disease, however 66.8% of them had a chronic disease.
Hypertension was the most commonly seen additional chronic
disease, which was present in 98 (48%) patients. The second
and third most common chronic diseases were: 17 (8%) coronary
heart disease patients and 14 (6%) hyperlipemia patients.
The list of concomitant diseases is in Table1. The average
duration of diabetes mellitus was 6.92 ± 5.60 years.
The answers to the questions administered for
defining diabetic neuropathy were as follows: 27.1% had numbness
in legs or feet, 30.5% had burning pain in legs or feet, 5.9%
have feet too sensitive to touch, 34.7% get muscle cramps,
24.6% have prickling feeling in legs or feet, only 2% feel
hurt when the bed covers touch their feet, 2.5% patients are
not able to tell hot water from cold, 2.5% patients have open
sores on their feet, 53% feel weak most of the time, 24.4%
have worse symptoms at night, 27.4%'s legs are hurt when they
walk, 74% can sense their feet while they walk, 22.7% have
dry feet or skin with cracks, only 3.4% have performed EMG,
1% have been told that they have diabetic neuropathy, and
1% had an amputation.
There were 165 (80.9%) patients using oral antidiabetics,
37 (18.1%) using insulin, and 1 (0.5%) patient was using both
insulin and oral antidiabetics. There were no patients using
carbamazepine, metoclopramide or diphenhydramine, where 1(0.5%)
was using amitriptyline, 46(22.7%) were using B1+B6 or combined
vitamins, and only 6(3%) are using gabapentin (Table2). The
list of the other drugs used by the patients is in Table 3.
It has been projected that 300 million individuals
would be affected with diabetes by the year
2025 (9). The progression of diabetic retinopathy and nephropathy
can be slowed or prevented with tight glucose and blood pressure
control. Neuropathy remains a major problem causing significant
impairment (10). It has been stated in various studies that
diabetic patients have neuropathy in varying percentages such
as: 7-25% in one year after the onset of disease, 50% 25 years
after the onset of disease (11,12). In our study group, all
of the patients have diabetes mellitus over a period of one
year, and two patients have diabetes mellitus for more than
Diabetic neuropathy is a progressive process that starts from
the onset of the disease. It may be either symptomatic or
without the presence of any notable symptoms, which in case
do not eliminate the presence of the disease. When we consider
the percentages of the symptoms that are probably the markers
of neuropathy, we have a wide range of percentages varying
from 2% to 53%. It is not possible to state the certain number
of patients with neuropathy without performing EMG on the
patients. However there may be patients with some kind of
presenting symptoms and yet not considered to have neuropathy
on a performed EMG.
The major point that we should be interested
in might be the evaluation of the presence of other possible
causes of neuropathies. Forty-six patients (22.6%) in our
study group are using either B1+B6 or combined vitamins. It
has been shown in many studies that these vitamins are of
no use in diabetic neuropathy, but only useful in the neuropathies
due to the lack of these vitamins (11,12). Most physicians
still prefer to prescribe vitamins in case of possible diabetic
There were no patients using carbamazepine,
in the study group; indicating that probably carbamazepine
is not a drug of choice for painful neuropathy by physicians,
and on the other hand the patients were probably not evaluated
for the presence of painful neuropathy, or the patients' perception
of pain was so low that it was not mentioned as a complaint.
The use of drugs such as amitriptyline and gabapentin are
low as well, likely due to similar conditions. There are several
studies that have shown the effectiveness of both of the drugs
in painful diabetic neuropathy with relief of pain varying
from 50% to 67% (13,14). It has been stated that carbamazepine
was the first of this class of drugs to be studied in clinical
trials and has been longest in use for treatment of neuropathic
pain (15). Antidepressants and anticonvulsants are used widespread
for the relief of pain in diabetic neuropathy, with the expression
that gabapentin is an expensive drug although it offers a
symptomatic treatment with less adverse effects when compared
to amitriptyline (13,16). In our study group there were only
7 (3.4%) patients using any of these three drugs, which is
probably not compliant with the actual number of patients
with painful diabetic neuropathy as we observe symptoms reaching
to 53%, which indicates that approximately 100 patients could
be receiving symptomatic treatment.
In conclusion, questions regarding diabetic
neuropathy should be asked of the patients in order to define
the presence of symptoms and drugs should be prescribed for
relief of pain. In order to improve the life quality of the
patients, a physician should prescribe drugs for neuropathy
following the diagnosis of diabetic neuropathy.
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TABLE 1. List of concomitant diseases
||No. of records
Benign Prostate Hyperplasia
Chronicle Obstructive Pulmonary Disease
Congestive Heart Failure
Coronary Artery Disease
TABLE 2. List of separately inquired drugs
|Separately inquired drugs
|No. of records
TABLE 3. Use of other drugs
||No. of records
||No. of records
Iron III hydroxate polymaltose