Therapy of

Diabetic Neuropathy
with Mecobalamin



Classification of Diabetic Neuropathy

1. Sensorimotor neuropathy:
Distal symmetric polyneuropathy
Focal neuropathy
Diabetic mononeuropathy (cranial, truncal,
peripheral nerves)
Mononeuropathy multiplex
Diabetic amyotrophy
Symptoms of Diabetic
Neuropathy

Sensorimotor neuropathy

Muscular symptoms: muscle weakness (not
fatigue), atrophy, balance problems, ataxic gait
Sensory symptoms: pain, paresthesia, numbness,
paralysis, cramping, nighttime falls.

Autonomic neuropathy
Gastrointestinal symptoms: dysphagia, bloating, nausea, a
vomiting, diarrhea, constipation, loss of bowel control
Genitourinary symptoms: loss of bladder control, urinary
tract infection, urinary frequency or dribbling, erectile
dysfunction, loss of libido, dyspareunia, vaginal dryness,
anorgasmia
Sudomotor (sweat glands) symptoms
Endocrine symptoms: hypoglycemic unawareness
Other symptoms: difficulty driving at night, depression,
anxiety, sleep disorders, cognitive changes

Distal symmetric polyneuropathy
Distal symmetric polyneuropathy, the most
common form of diabetic neuropathy, affects
approximately 40 percent of patients who have
had diabetes for 10 years or longer. Most often,
this neuropathy develops in the feet. The course is
chronic and progressive; in rare cases, however,
the neuropathy resolves spontaneously in 6 to 12
months.

Focal neuropathy
Diabetic mononeuropathy has an acute onset and
usually is asymmetric. Cranial, truncal, and
peripheral nerves are involved.
Patients with diabetic mononeuropathy may
develop visual changes or muscle weakness
involving cranial nerves III, IV, and VI, as well
as Bell's palsy.
The median, radial, and lateral popliteal nerves
are the most common sites of peripheral nerve
involvement.

Cardiovascular autonomic
neuropathy
Cardiovascular neuropathy is a result of damage
to vagal and sympathetic nerves.
Clinical findings may include syncope,
dizziness, fatigue, exercise intolerance,
persistent sinus tachycardia, no variation in
heart rate during activities, and bradycardia.
Vasomotor neuropathy
Vasomotor neuropathy frequently causes orthostatic
hypotension by affecting the splanchnic and peripheral
vascular beds.
Resultant peripheral vasomotor instability can manifest
as persistent hyperemia and peripheral edema. Loss of
sympathetic tone in the blood vessels results in maximal
vasodilation, which can lead to arteriovenous shunting in
the soft tissue and bone. Increased blood flow through the
bone causes calcium to wash from the cortical stores.
Defective bone homeostasis and bone demineralization
may result.
Sudomotor neuropathy
Sudomotor neuropathy may cause hyperhidrosis
and heat intolerance in the upper torso or
anhidrosis in the lower extremities. The skin of
the extremities may feel pruritic and may
display thinning, hair loss, dryness, cracks,
increased callus formation, and nail dystrophies.
MECOBALAMIN

Yi-Fei Zhang & Guang Ning
Shanghai Clinical Center for
Endocrine and Metabolic
Disease, Shanghai Institute
of Endocrinology and
Metabolism
Background
Mecobalamin, one of the coenzyme
forms of vitamins B12 acts as an
important cofactor in the activities of
B12 dependent methyltranferases.
Since the discovery of mecobalamin, it
has been applied mainly in the
treatment of hyperhomocysteinaemia
and peripheral neuropathy.
However, there is still lack of a
systemic review on the clinical
administration of mecobalamin and its
potential mechanism.


Objective
To review the mechanism, clinical
efficacy and safety of
mecobalamin in the treatment of
hyperhomocysteinaemia and
peripheral neuropathy

Methods
First, the potential mechanism,
pharmacokinetics and metabolism of
mecobalamin were clarified
In addition, the clinical
administration including efficacy,
safety and tolerability of
mecobalamin as monotherapy or
combined therapy in the treatment
of hyperhomocysteinaemia and
peripheral neuropathy were also
detailed.
Results
Although both monotherapy and combined
therapy can lower plasma/serum
homocysteine levels and improve the
neuropathic symptoms, combined therapy
with other B vitamins seems to be more
effective.
However, more precise, double blind and
randomised control studies are necessary
to confirm the efficacy of mecobalamin on
hyperhomocysteinaemia, peripheral
neuropathy interaction, and
cardiovascular, neurological and
osteoporotic mortality or morbidity.


Antihyperhomcysteinaemia
It is well-known that high levels of
plasma or serum Hcy are risk
factors for cardiovascular
diseases.
The deleterious effects of Hcy
include endothelial dysfunction,
arterial intimalmedial thickening,
arterial wall stiffening and a
procoagulant activity.

Many epidemiological studies
have shown a relationship
between total Hcy levels and
coronary artery disease, stroke,
peripheral vascular disease or
venous thrombosis.
Clinical data has also indicated
that hyperhomocysteinemia is
associated with an increased
incidence of chronic heart failure,
osteoporosis, neurodegenerative
disease, including dementia,
Parkinsons disease and stroke.

Although the exact pathomechanism
involved has not been fully
understood, DNA hypomethylation
maybe an important mechanism
linking hyperhomocysteinaemia and
various diseases mentioned above.
Because mecobalamin acts as an
important cofactor of methionine
synthesis, suplements of
mecobalamin enhance the efficiency
of the remethylation pathway,
consequently accelerating Hcy
consumption and reducing its
concentration.

Treatment for other
diseases
Clinical practice has also found effects of
mecocobalamin on male impotence and
infertility.
The administration of mecobalamin
increased the sperm concentration in 38%
of 26 infertile male patient and increased
the sperm motility in 50% of those
patients, consequently improving male
infertility.
Mecobalamin is also known to be useful
for the treatment of sleep disorder, which
may be because of its relationship with
the melatonin synthesis.


Conclusions
Mecobalamin has been aplied mainly in the
treatment of hyperhomocysteinaemia and
peripheral neurophaty.
The clinical effective dosage of
mecobalamin is 0,5-6 mg/day, which is safe
and easily tolerated.
The non oral administration route can be
used separately or together with the oral
route, however, therapeutic advantage of
the non oral route remains unclear.
Although both monotherapy and combined
therapy are beneficial in lowering plasma
Hcy levels and improve the neuropathic
symptoms, combined therapy with other B
vitamins seems to be more effective.

Effects of
Mecobalamin on
Diabetic
Neuropathies
LI Guang-wei (Dept. of Endocrinology, China-
Japan Friendship Hospital, Beijing)
Objective
To investigative the effect of
mecobalamin on
diabetic neuropathies.

Methods
One hundred and eight patients with
non insulin dependent diabetes
mellitus were involved in a
randomized positive control clinical
trial.
Sixty-two cases were treated with
mecobalamin 500g intramuscularly
3 tmes a week for 4 weeks, followed
by 500 ug orally three times a day for
additional 8 weeks
Forty-six cases were treated with
vitamin B12 in the same way and
served as controls.
Results
Twelve weeks after the treatment,
spontaneous pain and numbness of limbs
were improved by 73% and 75% in the
mecobalamin group, which were much higher
than those in the controls (36% and 45%)
respectively).
Hypoesthesia, hotness, coldness, oral
dryness and dysuria showed better response
in the mecobalamin group than in the
controls ( 55% vs 25%, 52% vs 18%, 59% vs
30%, 53% vs 19%, 63% vs 20%, respectively).
Mecobalamin also benefited nerve reflection
and conduction velocity to a certain extent.
No obvious side effects were found.

Conclusion
Mecobalamin might be worthy
of use as a safe agent in the
treatment of diabetic
neurophaties.
Discusion
As common complication of
diabetes mellitus, peripheral
neurophaty is characterized by
segmental demyelination of the
nerves.
Nerves undergo degeneration
because of the impaired axon
regeneration ability.
In clinics, the sensory nerve fibers
are more vulnerable.
Mecobalamin is another coenzym form of
vitamin B12. It is the active form of
vitamin B12.
Its methylated functional group can
directly participate in the mehtyl transfer
processes and promote the metabolism
of nucleic acid and protein in the
nervous system.
Some studies reported that, although the
cobamamide level remained normal in
the serum and the nervous system of the
diabetic patients, the mecobalamin level
in the nervous system decreased
dramatically.

Methylcobal can be transferred directly
into neurons, where it can induce the
synthesis of axoplasmic protein and
promote the regeneration of the
impaired axon segments.
Animal experiments showed that
mecobalamin could facilitate the repair
of the damaged myelin sheath and
increase the NCVs in diabetics rats by
accelerating the assembly of lecithin in
Schwann cells.
The amelioration rate of the
mecobalamin group was
significantly higher than that of
the control (vitamin B12) group.
Mecobalamin had no abvious side
effects on renal and liver
functions, serum lipids as well as
leukocyte and erythrocyte counts.





Thank you
for your attention