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Journal of International Medical
http://imr.sagepub.com/content/32/5/558
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DOI: 10.1177/147323000403200515
2004 32: 558 Journal of International Medical Research
S Takayama, Y Takahashi, M Osawa and Y Iwamoto
Control in Type 2 Diabetes
Acute Painful Neuropathy Restricted to the Abdomen following Rapid Glycaemic

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The Journal of International Medical Research
2004; 32: 558 562
558
Acute Painful Neuropathy Restricted to
the Abdomen Following Rapid Glycaemic
Control in Type 2 Diabetes
S TAKAYAMA
1
, Y TAKAHASHI
2
, M OSAWA
1
AND Y IWAMOTO
1
1
Diabetes Centre, Tokyo Womens Medical University School of Medicine, Tokyo, Japan;
2
Internal Medicine, Daini Hospital, Tokyo Womens Medical University, Tokyo, Japan
A 46-year-old Japanese man with type 2
diabetes mellitus, whose only diabetic
complication was simple retinopathy,
developed acute painful neuropathy. This
presented as paresthesia and hyper-
esthesia restricted to the abdomen. The
patients haemoglobin A
1c
had dropped
from 12% to 7.5% within 5 months,
following a rapid improvement in
glycaemic control. On investigation, there
were no indications of disease in the intra-
abdominal area. Nerve conduction studies
were consistent with mild sensorimotor
peripheral and autonomic neuropathy.
The patient required medication
(mexiletine, sulpiride and imipramine
hydrochloride) to control the pain.
Four months after presentation, the
symptoms showed a dramatic improve-
ment and the treatment for pain relief was
discontinued without any recurrence of
paresthesia or hyperesthesia in the
patients abdomen. This was a very
unusual case of diabetic post-treatment
painful neuropathy in which the
prominent features were severe pain,
paresthesia and hyperesthesia restricted to
the abdomen.
KEY WORDS: TYPE 2 DIABETES; HYPERESTHESIA; PAIN; PARESTHESIA; NEUROPATHY
Introduction
In patients with diabetes mellitus, painful
sensation and/or paresthesia are sometimes
precipitated by insulin treatment or strict
glycaemic control. The phenomenon is
generally called post-treatment painful
neuropathy, and it is regarded as an entity
of diabetic neuropathy.
1,2
The cause of post-
treatment painful neuropathy and the
reason why an individual might be
predisposed to develop it are unknown; the
prevalence is generally thought to be low.
2
One hypothesis suggests that post-treatment
painful neuropathy results from adequate
diabetic control promoting nerve
regeneration and that the pain may be
related to the ectopic generation of impulses
in regenerating axon sprouts.
3
Post-
treatment painful neuropathy usually
develops several weeks after a rapid
improvement in glycaemic control, and
presents as dramatic and severe pain in the
lower extremities. This usually subsides
within a year.
2
This paper presents a very unusual case of
acute painful neuropathy following a rapid
improvement in glycaemic control in which
the prominent feature was a severe pain
restricted to the abdomen.
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Case report
A Japanese man aged 46 years was
diagnosed with type 2 diabetes in 1999. He
drank alcohol and did not smoke. He was
treated with glimepiride (3 mg/day), vogli-
bose (0.2 mg/day) and buformine (50 mg/day),
but his haemoglobin A
1c
(HbA
1c
) was 9 12%
because he did not control his diet. In April
2003, he adopted a healthier lifestyle by
commencing a strict diet and omitting
alcohol. Subsequently, his HbA
1c
had fallen
from 12% to 7.5% by August 2003, and he
developed pain, paresthesia and hyperesthesia
in his abdomen; these symptoms did not
affect other areas (end of June 2003). In
August 2003, the patient underwent general
clinical examination, an abdominal
ultrasound examination and assessment for
tumour markers (-fetoprotein [AFP],
carcinoembryonic antigen [CEA] and
carbohydrate antigenic determinant 19-9
[CA19-9]), which revealed no intra-
abdominal pathology.
On neurological examination, his cranial
nerve, knee jerk reflex and Achilles tendon
reflex were normal. In terms of the sensory
system, Fig. 1 shows that the dermatome
involved in the abnormal sensation
(paresthesia and hyperesthesia) was both
anterior sides of the thoracic (Th) spinal nerves
at levels 8 11. There were no other areas with
559
S Takayama, Y Takahashi, M Osawa et al.
Focal pain in the abdomen following rapid glycaemic control
FIGURE 1: The distribution of thoracic (Th) spinal nerves showing the abnormal
sensation (paresthesia and hyperesthesia) dermatome at levels 8 11 (shaded area)
associated with post-treatment painful neuropathy in a 46-year-old Japanese man
with type 2 diabetes following a rapid improvement in glycaemic control
Th1
Th2
Th3
Th4
Th5
Th6
Th7
Th8
Th9
Th10
Th11
Th12
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abnormal sensation. There were no eruptions
on the skin of his trunk. Nerve conduction
studies were consistent with mild sensorimotor
peripheral neuropathy (motor nerve con-
duction velocity: right ulnar nerve 43.0 m/s,
right peroneal nerve 42.8 m/s; sensory nerve
conduction velocity: right ulnar nerve 48.6 m/s,
right sural nerve 46.5 m/s), and there was a
dysfunction of the autonomic nervous system
(heart rate variation on deep breathing:
9 beats/min). There was an osteophyte at the
Th10 level, but no evidence of spinal cord
compression on magnetic resonance imaging
(MRI) of the thoracic spine. With regard to
other diabetic complications, simple
retinopathy was found, but there was no
evidence of nephropathy.
At the end of August 2003, the patient
commenced treatment with mexiletine
(150 mg/day), sulpiride (150 mg/day) and
imipramine hydrochloride (30 mg/day) for
pain relief. Three weeks after treatment, his
symptoms showed a dramatic improvement,
and these drugs were discontinued at the end
of November 2003. There was no subsequent
recurrence of paresthesia and hyperesthesia
in his abdomen.
Discussion
This is a very unusual case of acute painful
neuropathy following a rapid improvement
in glycaemic control (HbA
1c
reduced from
12% to 7.5% within 5 months); the prominent
features were severe pain, paresthesia and
hyperesthesia restricted to the abdomen. We
speculate that the symptoms in this case
may have been caused by diabetic post-
treatment painful neuropathy.
The aetiology and pathogenesis of post-
treatment painful neuropathy are still
unclear. Previous studies have reported
arterio-venous shunting and proliferating
new vessels in acute painful neuropathy
following rapid glycaemic control.
4,5
Suzuki
et al.
6
reported that all five patients with
diabetic post-treatment painful neuropathy
in their study were identified as having a
mitochondrial tRNA (Leu) mutation at
position 3243. These observations cannot
completely explain the clinical course and
sites of pain sensation associated with post-
treatment painful neuropathy, however.
Greater care should be taken when
commencing strict glycaemic control in
diabetic patients with prolonged hyper-
glycaemia and previous neuropathy.
2,7
In this case, we had to discriminate
between a diagnosis of post-treatment
painful neuropathy or one of truncal
neuropathy. The latter usually presents with
pain and dysesthesia in areas of the chest or
abdomen or both.
8
The pathogenesis of
diabetic truncal neuropathy is also not
known with certainty, although it is widely
thought to be due to an ischaemic change
because it frequently has a sudden onset.
9
Clinically, the differential diagnosis of
diabetic truncal or post-treatment painful
neuropathy is very difficult. This is because
the clinical courses of diabetic truncal and
post-treatment painful neuropathy are very
similar and the symptoms of both often
subside within a year without medication. In
this particular case, it was also difficult to
differentiate between diabetic truncal
neuropathy and post-treatment painful
neuropathy. It is clear that symptoms of each
of these types of diabetic neuropathy are
triggered by a rapid improvement in
glycaemic control.
Polyneuropathy affecting the limbs,
usually in a distal or stocking and glove
distribution, has long been recognized in
diabetes mellitus.
10
Usual painful diabetic
neuropathy is just one of a myriad of
secondary conditions that may result from
poor glycaemic control. The sites of symptoms
of usual painful diabetic neuropathy also
560
S Takayama, Y Takahashi, M Osawa et al.
Focal pain in the abdomen following rapid glycaemic control
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References
1 Ellenberg M: Diabetic neuropathy precipitating
after institution of diabetic control. Am J Med Sci
1958; 236: 466 471.
2 Takahashi Y, Takayama S, Ito T, Inoue Y,
Omori Y: Clinical features of eighty-six patients
with post-treatment painful neuropathy. J Jpn
Diab Soc 1998; 41: 165 170.
3 Llewelyn JG, Thomas PK, Fonseca V, King RH,
Dandona P: Acute painful diabetic neuropathy
precipitated by strict glycaemic control. Acta
Neuropathol (Berl) 1986; 72: 157 163.
4 Kihara M, Zollman PJ, Smithson IL, Lagerlund T,
Low PA: Hypoxic effect of exogenous insulin on
normal and diabetic peripheral nerve. Am J
Physiol 1994; 266: E980 E985.
5 Tesfaye S, Malik R, Harris N, Jakubowski JJ,
Mody C, Rennie IG, et al: Arterio-venous
shunting and proliferating new vessels in
acute painful neuropathy of rapid glycaemic
control (insulin neuritis). Diabetologia 1996; 39:
329 335.
6 Suzuki Y, Kadowaki H, Katagiri H, Suematsu M,
Atsumi Y, Hosokawa K, et al: Posttreatment
neuropathy in diabetic subjects with mito-
chondrial tRNA (Leu) mutation. Diabetes Care
1994; 17: 777 778.
7 Wilson JL, Sokol DK, Smith LH, Snook RJ,
Waguespack SG, Kincaid JC: Acute painful
neuropathy (insulin neuritis) in a boy following
rapid glycemic control for type 1 diabetes
mellitus. J Child Neurol 2003; 18: 365 367.
8 Stewart JD: Diabetic truncal neuropathy:
topography of the sensory deficit. Ann Neurol
1989; 25: 233 238.
9 Parry GJ, Floberg J: Diabetic truncal
neuropathy presenting as abdominal hernia.
Neurology 1989; 39: 1488 1490.
10 Ellenberg M: Diabetic neuropathy: clinical
aspects. Metabolism 1976; 25: 1627 1655.
11 Inoue Y, Takahashi Y, Oowada K, Hirata Y:
Clinical features of diabetics with painful post-
treatment neuropathy. Ann Jpn Soc Res Diab
Complicat 1990; 3: 72 78.
561
S Takayama, Y Takahashi, M Osawa et al.
Focal pain in the abdomen following rapid glycaemic control
show a distal or stocking and glove
distribution. The symptom (pain) areas
associated with post-treatment painful
neuropathy not only have a distal
distribution, however, but they may often be
found in other areas. Takahashi et al.
2
reported that the pain sites of post-treatment
painful neuropathy were the lower
extremities, with pain spreading evenly
throughout the body. Patients with post-
treatment painful neuropathy were
significantly thinner than patients without
post-treatment painful neuropathy at the
beginning of diabetic treatment. They also
had a greater impairment of the patella
tendon reflex and motor nerve conduction
velocity in the ulnar and peroneal nerves
and more sensory nerve symptoms.
11
The
present case is very unusual in terms of the
localization of the symptoms of pain.
Painful neuropathy is the transmission of
painful stimuli from the peripheral nerve
fibres (C-fibres) to the higher centres. A
recent study reported that pain from the
abnormal stimulation of C-fibres was caused
by an abnormality of the tetrodotoxin-
resistant sodium channels in post-treatment
painful neuropathy.
12
Alternatively,
abnormal opioid receptors in higher centres
have been shown to influence pain
sensitivity in chronic hyperglycaemia.
13
It is
not known which of these theories is correct,
and we also do not know which peripheral
nerve C-fibres may influence the painful
stimulation associated with post-treatment
painful neuropathy. In this case, there was
an osteophyte at the Th10 level, but there
was no evidence of spinal cord compression
on MRI and the symptoms of pain were not
stimulated by exercise. The osteophyte was
not considered to influence the symptoms,
therefore.
There is still much to learn about post-
treatment painful neuropathy and diabetes,
including which peripheral nerve C-fibres
may influence the painful stimulation.
Received for publication 29 March 2004 Accepted subject to revision 6 April 2004
Revised accepted 9 May 2004
Copyright 2004 Cambridge Medical Publications
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562
S Takayama, Y Takahashi, M Osawa et al.
Focal pain in the abdomen following rapid glycaemic control
12 Hirade M, Yasuda H, Omatsu-Kanbe M,
Kikkawa R, Kitasato H: Tetrodotoxin-resistant
sodium channels of dorsal root ganglion
neurons are readily activated in diabetic rats.
Neuroscience 1999; 90: 933 939.
13 Ohsawa M, Mizoguchi H, Narita M, Kamei J,
Nagase H, Tseng LF: Effects of a mu-opioid
receptor agonist on G-protein activation in
streptozotocin-induced diabetic mice. Eur J
Pharmacol 2000; 28: 55 58.
Address for correspondence
Dr S Takayama
8-1 Kawada-cho, Shinjuku-ku, Tokyo162-8666, Japan.
E-mail: s-taka@ceres.dti.ne.jp
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