"Diabetes Newsletter" is also available at www.squarepharma.com.bd & www.ansulin.

com

Vol. 9 No. 1, February - April 2011

Inside Bangladesh
Electrophysiological Changes of Sensory Nerves in Patients with Type-2
Diabetes Mellitus of Different Duration

Background:
Peripheral neuropathy is a common complication of diabetes mellitus. Among the
diabetic neuropathies symmetrical sensory polyneuropathy is the most common one.
Abnormalities of sensory nerve conduction are features of diabetic nerve damage.
Significant association has been found between electrophysiological parameters of
sensory nerves and duration of metabolic derangement in patients with diabetic
neuropathy.

Objectives:
The present study was designed to characterize nerve conduction abnormalities of
sensory nerves in subjects with type 2 diabetes mellitus of different duration and also
to assess whether duration of diabetes has any influence on the sensory nerve
function.

Methods:
Forty-four type 2 diabetic subjects were included in two groups:- Group B1 consisted of
23 diabetic subjects having duration of diabetes for 5-10 years (shorter duration) and
Group B2 consisted of 21 diabetic subjects having duration of diabetes for 10-15 years
(longer duration). Twenty-five age and BMI matched healthy subjects without family
history of diabetes were included as Group A (control) subjects. Sensory nerve
conduction velocities, action potential amplitudes and latencies of ulnar and sural
nerves were measured by a standard NCV-EMG equipment.

Result:
No significant changes in sensory nerve conduction parameters were observed in the
group of diabetic subjects having shorter duration of diabetes. In the diabetic group
with relatively longer duration of diabetes some of the sensory nerve conduction
parameters were affected. Among them S SNAP and S NCV were significantly (P<0.01
and <0.05 respectively) reduced in diabetic group with relatively longer duration of
diabetes.

Conclusion:
The results of the study indicated that neuronal dysfunction for sensory nerves appears
after a prolonged exposure to hyperglycemia; there may also be some genetic and
biochemical basis (other than hyperglycemia) for early sensory sparing in type 2
diabetic population of Bangladesh.

Source: Electrophysiological Changes of Sensory Nerves in Patients with Type-2 Diabetes Mellitus of Different
Duration. Sharmeen Sultana, Noorzahan Begum, Liaquat Ali, Md Mosharrof Hossain, Nirmelendu Bikash
Bhowmik, Shahana Parveen, Zinia Perveen. Bangabandhu Sheikh Mujib Medical University Journal
 Comet 500, 750, 850 & 1gm
Diabetescope
Diabetescope Comet XR 500 & 1 gm
Metformin HCl tablets
Economic
Long-Term Insecurity
Metformin Linked to
Boosts Obesity
Vitamin B12 Deficiency Continuous
High Rates ofInsulin No ExtraSeen
Hypertension Benefit
in
During PCI in Diabetics
Youth With Diabetes
Researchers found that the stress of life in a competitive
social system without a strong welfare state may cause
Compared to subcutaneous insulin delivery, diabetics
people to overeat.
undergoing percutaneous coronary intervention (PCI)
Policies to reduce levels of obesity tend to focus on show no reduction in inflammatory markers with
encouraging people to look after themselves, but this continuous intravenous (IV) insulin.
study suggests that obesity has larger social causes. It
These patients typically have worse clinical outcomes
may be that the economic benefits of flexible and open
after the procedures than those without the disease,
markets come at a price to personal and public health
which could be a result of a rise in plasma inflammatory
which is rarely taken into account.
markers and oxidative stress.
Comparing four "market-liberal" English-speaking
To investigate the impact of normalizing glycemia,
countries - the United States, Britain, Canada and
researhers conducted a randomized controlled trial of
Australia - with seven relatively wealthy European
continuous versus standard insulin delivery in 70 patients
countries that traditionally offer stronger social protection
with Type 2 diabetes undergoing angioplasty with stent
- Finland, France, Germany, Italy, Norway, Spain and
implantation. Those given continuous intravenous insulin
Sweden - the team found that economic insecurity is
had a glucose target of less than 110 mg/dL and those
strongly linked to levels of obesity.
receiving standard subcutaneous insulin had a glucose
Countries with higher levels of job and income security target near 200 mg/dL.
were associated with lower levels of obesity. Basically,
Inflammatory and oxidative stress markers, including C-
hypothesis is that market-liberal reforms have stimulated
reactive protein, interleukin-6 and carbonyl were
competition in both the work environment and in what we
examined immediately after and 24 hours after the
consume, and this has undermined personal stability and
procedure. Markers increased in both groups.
security. The onset and increase of large-scale obesity
began during the 1980s, coinciding with the rise of The results showed that, although continuous
market-liberalism in the English-speaking countries. intravenous insulin for 24 hours increased insulin levels
and prevented hyperglycemia compared with standard-
The rise of obesity in wealthy societies has often been
control insulin treatment, it did not prevent the rise in
attributed to "fast food" - but researchers suggest that
inflammatory and oxidative stress markers.
economic influences were greater.
She added that although hyperglycemia was reduced, it
The team measured fast food's impact by using a price
wasn't accompanied by other benefits. Because IV
index . They calculated that the availability of fast food
insulin demands a trained nurse to be taking care of the
had only about half as much of an effect on the
patient for 24 hours, with multiple glycemic
prevalence of obesity as the effects of economic
measurements in order to adjust insulin infusion, the
insecurity.
procedure probably wouldn't be cost-effective.
Econ Hum Biol. July 27, 2010.
J Clin Endocrinol Metab. November 17, 2010.

Dibenol Sensulin 2 & 4 Rezulin

15/500 & 15/850

Glibenclamide 5 mg tablet Rosiglitazone 2 & 4 mg tablets Pioglitazone plus Metformin tablets

February - April 2011 Page-2

N E W S L E T T E R
 Secrin 1, 2, 3, 4
Glimepiride 1, 2, 3 & 4 mg tablets
Inhaled Corticosteroid Use May
Increase Risk for Diabetes Mellitus
High doses of inhaled corticosteroids commonly used in
patients with COPD are associated with an increase risk
of diabetes and of having to intensify therapy to include
insulin. Therefore, patients instituting therapy with high
doses of inhaled corticosteroids should be assessed for
possible hyperglycemia and treatment with high doses of
inhaled corticosteroids limited to situations where the
benefit is clear.
Although inhaled corticosteroids are recommended only
for patients with most severe COPD, current practice is
that they are prescribed to more than 70% of all patients
with COPD, including those with less severe disease.
Because the prevalence of COPD and diabetes both
increase with age, it is important to examine any possible
interaction between inhaled corticosteroid use and
worsened glycemic control.
Of 388,584 patients in the study cohort, 30,167
developed incident diabetes during 5.5 years of follow-up
(incidence rate, 14.2/1000/year), and 2099 patients
subsequently progressed from oral hypoglycemic
therapy to insulin treatment (incidence rate,
19.8/1000/year).
Participants with current use of inhaled corticosteroids
had a 34% increase in the rate of diabetes and in the
rate of diabetes progression. The highest inhaled
corticosteroid doses, equivalent to at least 1000 g/day
fluticasone, were associated with the greatest risk
increases. Limitations of this study include possible
residual confounding and possible underestimation of
incidence of diabetes.
Am J Med. 2010;123:1001-1006.
Comprid Sensimet
Comprid XR 30 1, 2, 4, 1 DS & 2 DS tablets
Gliclazide tablets Rosiglitazone + Metformin HCl
February - April 2011
N E W S L E
Diabetescope
Diab
Diab tt ope
ope
Polycystic Ovary
Metformin Syndrome
Reduces Ups
Metabolic
Young
Risks Women'sAntipsychotics
of Atypical Diabetes Risk
Even when young, women with polycystic ovary
syndrome (PCOS) are at increased risk of diabetes and
high cholesterol. Young women in their 20s, usually don't
followed closely. Studies have linked PCOS to several
risk factors for heart disease, as well as diabetes. But it's
still not clear whether PCOS, itself, is responsible. To
investigate, the authors looked at 1,127 women. The
women ranged in age from 20 to 32 at the beginning of
the study, and were followed for 18 years.
Fifty-three of the women had PCOS at the beginning of
the study. A dozen of them had developed type 2
diabetes by the end of the follow-up period and 18 had
dyslipidemia. On multivariate analysis, after adjustment
for potential confounding variables (including weight),
those rates translated to about twice the risk for both
diabetes and high cholesterol in women with PCOS vs
those without it.
The researchers also analyzed the risks for 31 normal-
weight women with PCOS at the study's outset. These
women were found to be at triple the risk of type 2
diabetes compared to normal-weight women without the
syndrome.
At year 14 of the study, 746 of the original study
participants were assessed for PCOS a second time.
Fifteen of the women still had it. These women with
"persistent" PCOS had a more than seven-fold greater
risk of developing type 2 diabetes during the subsequent
five years.
The fact that PCOS symptoms disappeared in many of
the women over time suggests that the syndrome
becomes less common with age. These women were still
at increased risk of diabetes, despite no longer having
PCOS.
Obstet Gynecol. Posted January 2011.
Tos 15 & 30
Pioglitazone 15 & 30 mg tablets
Page-3
T T E R
 what we haveInitiation
learnedofand
Insulin
hadTherapy for Type
to unlearn
Diabetic gastroparesis: what we have learned and had to unlearn in the past 5 years
Diabetic gastroparesis is a well established complication of
diabetes. Gastroparesis is defined as a syndrome
characterised by abnormal gastric function resulting in
delayed gastric emptying in the absence of mechanical
obstruction. What was first thought to be a rare
complication that occurs only in type 1 diabetes is now
known to occur in both type 1 and type 2 diabetes and to
occur more frequently than previously assumed. However,
the increasing availability of non-invasive tools to measure
gastric emptying has not only increased our ability to
diagnose the disease, but has also uncovered significant
gaps in our understanding of the pathophysiology of the
disease, the relationship between slow gastric emptying
and severity of symptoms, and the effectiveness of current
treatments. This review is aimed at summarising what has
been learned in the past 5 years, highlighting areas that are
still controversial and suggesting areas for future studies.
EPIDEMIOLOGY OF DIABETIC GASTROPARESIS
Gastroparesis is increasingly recognised as a significant
health problem. Patients admitted with gastroparesis
require more procedures, have a longer hospital stay and
incur higher charges than the mean. Though diabetic
gastroparesis has traditionally been associated with
advanced type 1 diabetes with poor glycaemic control, it is
increasingly being recognised in patients with type 2
diabetes. In a population-based survey of 423 patients with
diabetes (94.8% type 2 diabetes), a significantly higher
incidence of upper gastrointestinal symptoms in patients
with diabetes were reported.
Given the definition of gastroparesis, its diagnosis requires
a test to measure the rate of gastric emptying. The
prevalence of delayed gastric emptying in patients with
diabetes has been reported to be between 28% and 65%.
However, with the increased availability of gastric emptying
tests, it is now well established that there are subsets of
patients with delayed gastric emptying and no symptoms,
accelerated gastric emptying and identical symptoms to
patients with delayed gastric emptying, and symptoms with
normal gastric emptying. From a clinical perspective, the
term diabetic gastroparesis is therefore better limited to the
combination of a delay in gastric emptying of solids in the
absence of obstruction and upper gastrointestinal
symptoms including nausea, vomiting, bloating and early
satiety. Pain is often overlooked, but can be a predominant
symptom in a subset of patients with gastroparesis. A
recent community-based study from Olmsted County in the
USA using delayed gastric emptying and typical symptoms
as criteria for diagnosis showed a cumulative incidence of
4.8% in type 1 diabetes and 1% in type 2 diabetes as
compared with 0.1% in controls. The demographics of
diabetic gastroparesis, a disease affecting predominantly
young females of childbearing age, makes diabetic
gastroparesis a disease associated with considerable
morbidity and societal impact. In a single-centre study of
February - April 2011
N E W S L E
2 Diabete
in the past 5 years
patients with gastroparesis seen over 6 years, the mean
age of onset was 34 years and 82% of the patients were
women. The reasons for the female preponderance of
gastroparesis remain largely unknown. Gastric emptying is
slower overall in females with diabetes as compared with
males with diabetes. Some studies have shown that gastric
emptying is also slower in normal females. This raises the
possibility that females are closer to the threshold where a
decrease in gastric emptying becomes problematic.
However, a large randomised controlled study failed to
show any alteration in gastric transit in postmenopausal
females receiving oestrogen and progesterone
supplementation.
PATHOGENESIS
An increasingly controversial area is the relationship
between symptoms and gastric emptying. Most recent
studies show that the correlation between symptoms and
gastric emptying is poor.These data have been used to
suggest that gastric emptying should no longer be used to
define diabetic gastroparesis. However, given the increased
understanding of the complexity of gastric emptying and of
the association between defined changes at a cellular level
and changes in gastric emptying, it is possible that the poor
correlation reflects the non-specific nature of the symptoms
and the inability of current tests to measure different
aspects of gastric emptying.
Another controversial area is the role of hyperglycaemia in
gastric emptying. Acute changes in blood glucose are well
documented to alter gastric emptying. An acute increase in
blood glucose decreases fundic tone, decreases the
contractility of the mid and distal stomach and also alters
small bowel contractile activity. Hyperglycaemia has been
shown to stimulate localised pyloric contraction and inhibit
antral contraction, resulting in delayed gastric emptying. In
contrast to these relatively clear effects, the effect of
chronic hyperglycaemia on gastric emptying is much less
clear. The presence or absence of autonomic neuropathy
can also markedly alter the effect of hyperglycaemia on
gastric emptying.
Changes in gastric emptying also play an important role in
blood glucose homeostasis. The rate of gastric emptying is
a major determinant of the initial postprandial glycaemic
response both in healthy individuals and in patients with
type 1 or type 2 diabetes, and delayed gastric emptying can
cause postprandial hypoglycaemia in insulintreated
individuals. Hence gastric emptying is an important
consideration when developing new treatments to improve
glycaemia control in patients with diabetes. Another
consideration is the absorption kinetics of drugs, which can
be influenced by changes in gastric emptying.
Autonomic neuropathy was one of the first abnormalities
associated with diabetic gastroparesis. The sham feeding
test, used to evaluate the integrity of the vagus nerve,
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 what we have learned and had to unlearn in the past 5 years
shows a blunted pancreatic polypeptide response as well advantage of being able to be carried out in office settings.
as reduced gastric secretion in response to sham feeding in The gastric emptying breath test using, a stable (non-
patients with diabetic gastroparesis. Vagus nerve radioactive) isotope, has been well studied in both human
dysfunction is also thought to mediate some of the acute and animal models. The ratio of provides a reliable
effects of hyperglycaemia such as reduced pyloric measure of the gastric emptying rate. This test has been
relaxation, as a similar effect can be induced by validated in subjects with diabetes. Given the non-
subdiaphragmatic vagotomy. Pain, which is a predominant radioactive nature of the test, it can be used to measure
symptom in a subset of patients with diabetic gastroparesis, changes in gastric emptying over time and has a sensitivity
is often attributed to neuropathy. and specificity of 75% and 86%, respectively. A variation of
The pathogenesis of this complex disorder is still not well the octanoic acid technique is the Spirulina platensis
understood but involves abnormalities in multiple interacting breath test. The test was 89% sensitive and 80% specific in
identifying delayed gastric emptying using breath samples
cell types including the extrinsic nervous system, enteric
at 150 and 180 min when compared with gastric
nervous system, interstitial cells of Cajal (ICCs), smooth
scintigraphy.
muscles and immune cells.
Gastroduodenal manometry is invasive, expensive,
DIAGNOSIS
uncomfortable and of very limited availability. However,
Despite the poor correlation between currently available when available, it offers the ability to assess the frequency
methods to assess global gastric emptying and symptoms, and strength of antral and proximal intestinal contractility,
documentation of delayed gastric emptying to solids is antroduodenal coordination and the presence or absence of
required before a diagnosis of diabetic gastroparesis can be phase III of the migratory motor complex. This information
made. Abnormal gastric emptying still remains the only can help differentiate between predominantly neuropathic
objective marker of an underlying defect in the versus non-neuropathic processes, as well as predict
neuromuscular apparatus of the stomach. tolerability of gastric or small intestinal tube feedings.
Scintigraphy is the most common and widely available Transabdominal ultrasonography represents a simple non-
modality for measuring gastric emptying. It is, however, invasive technique to evaluate gastric function. However,
relatively expensive, associated with some radiation studies are still limited and the technique requires
exposure and, despite position papers published on the considerable technical expertise. When carried out
topic, still not standardised across medical centres. The correctly, transabdominal ultrasonography provides
standard technique involves scintigraphic determination of information on global gastric emptying, with high correlation
emptying of a solid meal. The American with scintigraphy, and also of accommodation and
Neurogastroenterology and Motility society recommends movement of intragastric contents. Two-dimensional
use of a (technetium) sulfur colloid-labelled egg sandwich ultrasound can indirectly measure gastric emptying by
as a test meal. It is required that scintigraphic measurement quantifying changes in antral area over time, and studies
continues to 4 h as this has been shown to improve the have shown increased antral area both in the fasting state
accuracy of the test. However, several centres continue to and after meals in diabetes. Three dimensional ultrasound
extrapolate gastric emptying data from 90-120 min provides better information of gastric pathophysiology by
readings. The results of tests shorter than 4 h should not be allowing assessment of intragastric meal distribution and
used to make a diagnosis of gastroparesis. In spite of these gastric volume, but is time consuming and requires an even
limitations, scintigraphy remains the test of choice and is more experienced operator. A particular problem with
considered the gold standard for comparison of newer transabdominal ultrasonography is that it is harder in obese
diagnostic modalities. Imaging should be obtained in patients, which can be an issue in patients with
relaxed environments and can be obtained sitting or obesityrelated type 2 diabetes.
standing as long as the same posture is maintained MRI of the stomach also correlates well with scintigraphy. It
throughout the test. Hyperglycaemia will delay gastric has the additional advantage over ultrasound in that it can
emptying and therefore needs to be tested for and differentiate solid and liquid components of intragastric
corrected before carrying out the test. Recent advances content, secretion and air. The utility of the test is currently
allow some separation of distal and proximal gastric limited by the speed with which images can be acquired
function. Single photon emission CT (SPECT)
imaging following labelling of the gastric
mucosa with is helpful in determining gastric Box 1 Pathophysiological mechanisms responsible for diabetic gastroparesis
volume and can be combined with 1. Autonomic neuropathy.
scintigraphy to measure gastric emptying and 2. Loss of neuronal nitric oxide synthase leading to loss of nitric oxide.
accommodation concurrently. 3. Increased oxidative stress with loss of upregulation of protective enzymes
such as haem oxygenase-1.
Gastric emptying tests that utilise non- 4. Loss of interstitial cells of Cajal with resultant gastric arrhythmia and delayed
radioactive forms of carbon incorporated in gastric emptying.
safely ingestible food or liquid products, 5. Smooth muscle atrophy and loss of IGF-1 from smooth muscle.
6. Loss of macrophages expressing haem oxygenase-1.
correlate well with scintigraphy and offer the

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N E W S L E T T E R
 The
what we have learned and prevention
had to unlearnofintype
the 2past
diabetes
5 years
using most of the current machines, the Box 2 Diagnosis
procedure cost and the time required for
interpretation. 1. 4 h gastric scintigraphy is the gold standard.
2. 13C-based breath tests can be used in the office setting.
Recently, a non-digestible capsule that 3. Ultrasonography is non-invasive and provides information on emptying as
records pH, pressure and temperature as it well as segmental function, but depends on operator expertise.
travels through the gastrointestinal tract has 4. Capsule allows measurement of pH, pressure, temperature and emptying at
been introduced. The change in pH between the same time.
5. MRI can help determine intragastric content and emptying without radiation
the distal stomach and proximal small
exposure, but still requires significant experience to interpret.
intestine allows documentation of egress of 6. SPECT imaging allows measurement of gastric emptying and accommodation
the capsule from the stomach and therefore concurrently.
documentation of the time from ingestion to
arrival in the small intestine. The human
gastroparesis should be to tighten glycaemic control, treat
pylorus prevents movement of particles bigger than 2-3 mm
symptoms and optimise nutritional intake. The effect of
from the stomach to the small intestine; therefore, emptying
erratic gastric emptying on glycaemic control is becoming
of the capsule probably coincides with onset of the phase III
increasingly clear. Therefore, there may be advantages to
migrating motor complex. It can discriminate between
the use of prokinetics even in the absence of significant
normal and delayed gastric emptying with a sensitivity of
symptom relief. Care must be taken, however, to exclude
87% and specificity of 92% compared with radiopaque
rapid gastric emptying which is being increasingly
markers.
recognised as occurring in a subset of patients with
A challenge to the development of new treatments is the diabetes.
lack of acceptance of tools in clinical trials to assess
It is important to asses the nutritional status of patients with
improvement on treatment by the agencies that approve
diabetic gastroparesis as they can have unintentional
new drugs. Non-radioactivebased gastric emptying
weight loss, dehydration and electrolyte imbalance
techniques are one option, as is the use of patient-reported
secondary to vomiting. Malnutrition can often be missed
outcome measures such as the Diabetes Bowel Symptom
due to the higher starting weight of patients with
Questionnaire, a useful measure of gastrointestinal
gastroparesis and type 2 diabetes.
symptoms and glycaemic control in patients with both type
1 and type 2 diabetes, and the Gastroparesis Cardinal In milder cases of malnutrition, oral nutrient drinks can be
Symptom index (GCSI), a patient reported outcome offered, but in malnourished patients with >5% weight loss
measure of symptoms of gastroparesis consisting of nine over 3 months one should consider enteral feeding to
commonly reported symptoms. bypass the dysfunctional stomach. A nasojejunal feeding
tube trial should be carried out for several days prior to
TREATMENT
placement of an endoscopic or surgical feeding tube as this
The past 5 years have seen significant advances in our may unmask any underlying small bowel dysmotility that
understanding of the cellular changes that give rise to would result in failure of tube feedings.
diabetic gastroparesis and the introduction of several new
The mainstay of treatment in patients with diabetic
diagnostic modalities. In contrast, there are fewer options
gastroparesis has been prokinetic medications. Both
available to treat diabetic gastroparesis than were available
metoclopramide and domperidone are dopamine-2 receptor
5 years ago. The available treatment options include
antagonists and equally effective in reducing symptoms.
nutritional support, improvement of gastric emptying using
Metoclopramide is also a weak 5-HT3 receptor antagonist
prokinetics, symptom control and, in refractory cases, use
and 5-HT4 receptor agonist. Domperidone does not cross
of a gastric electric stimulator, although the use of the latter
the bloodebrain barrier and is associated with fewer central
is still controversial.
nervous system effects. However, a well recognised
Nutritional support is often overlooked in patients with complication of metoclopramide is tardive dyskinesia. This
diabetic gastroparesis and there is a lack of randomised has limited its use. A recent study in rodents shows that
controlled trials assessing the effect of nutritional dopamine-3 receptor agonists inhibit stimulated pyloric
intervention on outcome. Patients are often advised to eat relaxation and gastric emptying, suggesting that dopamine-
small frequent meals, chew their food well, avoid fibre and 3 receptor antagonists given together with dopamine-2
consume a diet low in fat as studies have shown fat can receptor antagonists may be more effective in treating
slow gastric emptying in healthy volunteers. This advice symptoms.
makes physiological sense and should be given. However,
Erythromycin is a potent prokinetic agent which acts by
there are few data to show how these nutritional
activating the motilin receptor, probably on the cholinergic
interventions compare with other treatment modalities for neurons. It is a useful agent for short-term treatment of
gastroparesis or if they affect the natural history and patients in the hospital; however its long-term benefit is
outcome of patients with diabetic gastroparesis. limited due to development of tachyphylaxis. Several other
In the absence of drugs that target the underlying motilin agonists have been developed to avoid
mechanisms, the aims of treatment of diabetic tachyphylaxis. Mitemcinal (GM-611), a macrolide motilin

February - April 2011 Page-6

N E W S L E T T E R
 The prevention
what of type
we have learned and2 diabetes
had to unlearn in the past 5 years
receptor agonist with acid resistance, has been shown to
improve gastric emptying in patients with diabetic
gastroparesis. GSK962040 is a recently identified small
molecule motilin receptor agonist which selectively
activates the motilin receptor in humans and is being
evaluated to determine safety and tolerability in humans. An
issue with most motilin agonists is that they also increase
gastric tone and therefore can make symptoms worse even
when gastric emptying improves. They, of course, should
not be used in the subset of patients with rapid gastric
emptying. Several other agents have been evaluated for
their prokinetic effect, including SK-951, a benzofuran
derivative which improves gastric emptying in STZ-induced
diabetic dogs, and epalrestat, an aldose reductase inhibitor
which increases the amplitude of three cycles per minute
waves on EGG in patients with diabetic gastroparesis. The
5-HT4 agonists prucalopride and TD-5108 accelerate
gastric emptying but have not been tested in gastroparesis.
Ghrelin is an endogenous ligand for the growth hormone
secretagogue receptor expressed on the vagal afferent
neurons and enteric neurons in the stomach. Ghrelin has
been shown to improve gastric emptying in patients with
diabetic gastroparesis in a placebo-controlled study;
however, the mechanism by which it exerts the prokinetic
effect is unclear and it has a short half-life.
New drugs have recently been introduced to control
postprandial hyperglycaemia, such as amylin analogues
and glucagon like peptide-1 (GLP-1) receptor analogues
and agonists. These drugs can delay gastric emptying. The
amylin analogue pramlintide delays gastric emptying in both
patients with type 1 and type 2 diabetes. The effects of
pramlintide on gastric emptying appear to be mediated by
the vagal nerve supply to the stomach. Therefore, in
patients with vagal dysfunction, the delay in gastric
emptying induced by pramlintide may be reduced.
Exenatide is a GLP-1 mimetic used in type 2 diabetes and,
like the short-acting native GLP-1 hormone, can delay
gastric emptying, though this effect may be less
pronounced in patients in whom gastric emptying is already
delayed. Our current understanding is that the benefit of the
drugs on glycaemic control outweighs their effects on
gastric emptying, but these drugs need to be kept in mind
when assessing an abnormal gastric emptying study.
Nausea and vomiting are often the most debilitating
symptoms for patients with diabetic gastroparesis.
Phenothiazines such as prochlorperazine are one of the
most commonly utilised antiemetics. Other antiemetics such
as the 5-HT3 antagonists odansetron and granisetron
primarily developed for chemotherapy-induced nausea and
vomiting, cannabinoids, opioid agonists, benzodiazepines
and H1 receptor agonists, such as diphenhydramine, can
be used for symptomatic control of nausea and vomiting,
though they have not been evaluated in diabetic have been
shown to be effective in improving symptoms of nausea and
vomiting in some patients with delayed gastric emptying.
The neurokinin receptor antagonist aprepitant has recently
been shown to control vomiting effectively in a patient with
February - April 2011
N E W S L E
refractory diabetic gastroparesis. Similarly, the
antidepressant mirtazapine, which acts on the 5-HT3
receptor, has also been shown to be effective in a patient
with refractory gastroparesis. Among alternative treatments,
ginger and acupuncture have been evaluated. Acupuncture
has shown benefit in patients with diabetic gastroparesis.
Gastric electrical stimulation is being increasingly used for
patients with diabetic gastroparesis with refractory nausea
and vomiting. Initial work in the field focused on pacing the
stomach to increase gastric emptying. In contrast, currently
available gastric electrical stimulation uses low energy, high
frequency stimulation with no substantial effect on gastric
emptying. The Enterra system, a low energy high frequency
gastric electric stimulation device, was approved by the
FDA under the humanitarian use device designation in
2000 for treatment of patients with refractory nausea and
vomiting due to gastroparesis. Gastric electrical stimulation
is invasive and there are surgical complications associated
with its use.
Pain management is often challenging in patients with
gastroparesis. While patients may respond to prokinetics
and other conventional treatments used to improve gastric
function, some patients require additional medications to
help control pain. Medications commonly used for chronic
abdominal pain such as tricyclic and tetracyclic
antidepressants, gabapentin and pregabalin can be used to
treat pain. Pain management is best undertaken using a
multidisciplinary approach targeting the underlying motility
disorder as well as peripheral and central circuits. Opiates
should be used very sparingly and only in refractory cases.
If needed, a weaker opiate such as tramadol or a agonist,
asimadoline, should be considered.
FUTURE DIRECTIONS
Future treatments will be guided by our increased
understanding of the pathophysiology of the disease and
we propose can be hastened by the following. 1.
Development of non-surgical approaches to full thickness
biopsies of the stomach. Recent reports have described
non-invasive endoscopic technique to obtain full-thickness
gastric biopsies. 2. New treatment based on our increased
understanding of the pathophysiology of the disease. 3.
New prokinetics. 4. Studies aimed at better understanding
the correlation between electrophysiology, global and
segmental gastric function and symptoms. 5. Prospective
follow-up studies to determine the long-term outcome of
diabetic gastroparesis as well as the long-term outcome of
treatments. 6. Development of predictors of which patients
will go on to develop diabetic gastroparesis. 7.
Development and validation of better animal models,
especially of type 2 diabetes. 8. Studies on the potential
use of stem cell-based treatments.
Ref: Diabetic gastroparesis: what we have learned years
and had to unlearn in the past 5 years. Purna Kashyap,
Gianrico Farrugia. Gut ;2010 59: 1716-1726.
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T T E R
 Vol. 9 No. 1, February - April 2011

Dr. Sheikh Marufuzzaman Dr. Ketaki Dewan

MBBS, MD (Cardiology) MBBS, CCD
Asst. Professor (Cardiology) Rangamati Diabetic Hospital,
Comilla Medical College, Comilla. Rangamati.

Dr. Md. Zahidul Hassan Dr. Nigar Sultana (Eti)

MBBS, CCD MBBS
Medical Officer Medinova Hospital Complex,
Khulna Diabetic Centre, Khulna. Sirajgonj.

Dr. Md. Shahriar Kabir Dear Doctor,

This issue of your diabetes newsletter
MBBS, MCPS, FCPS, MD is focused on "Diabetic gastroparesis:
Dinajpur Medical College, what we have learned and had to
unlearn in the past 5 years". We
Dinajpur. appreciate your comments and
queries. Please participate in quiz
competition & win prizes.

Editorial Board Executive Editor

Dr. Omar Akramur Rab, MBBS, FCGP, FIAGP Arindom Pal
Mohammad Hanif, M. Pharm, MBA Cell : 01730356325
A.H.M Rashidul Bari, M. Pharm, MBA arindom@squaregroup.com