Vol. 3 No. 2, April- June 2005
T Local Herbal Research
Diabetes mellitus is a major health problem worldwide but its therapeutic
management still suffers from major limitations. Plants have been used for the
treatment of diabetes for centuries. A systematic study of plant materials used for
treating diabetic patients has been undertaken by the Bangladesh Institute of
Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders
In these trials, the plant commonly known as fenugreek (Trigonella
foenumgraecum), which is native to southeast Europe and west Asia, was
scientifically tested for its well-known ability in traditional medicine to act as a
substitute for insulin among diabetic patients. Using the diabetic model rats,
fenugreek was found to have a partially mediated activity due to a soluble dietary
fiber (galactonmannan) present in the plant. Analysis of the data indicated the
possibility of delayed glucose absorption in the gut.
Additional results showed that the water extract of fenugreek can effectively
reduce the rise in plasma glucose during digestion without any elevation in serum
insulin levels. Preliminary findings indicate that the antihyperglycemic effect of the
fenugreek water extract might be related to the inhibition of disaccharidase activity
in the gut.
The therapeutic details of the extract (timing, dosage, etc.) have not been
determined through scientific experimentation. In addition, the animal models used
for the experiments have not simulated Type 2 diabetes and, consequently, were
not entirely suitable for additional scientific study in the majority of diabetic
subjects. The pungent smell and gastric upset in higher doses also adversely
affected the widespread use of the product. The components of the powder, which
in the past had produced a pungent smell and also gastric upset in larger doses,
were removed while preserving their antihyperglycemic benefits. Clinical trials
currently are taking place to identify the proper timing and dosage based on
information generated from the rat experiments.
The Department of Chemistry at the University of Dhaka, Bangladesh, has
assisted in the project's overall development. Scientific assistance in the form of
training and advice was available from the scientists of the Department of Medical
Cell Biology at Uppsala University, Sweden, and the Department of Chemistry at
Mahidol University of Bangkok, Thailand. Financial support was obtained from the
International Program in the Chemical Sciences (IPICS) and International
Foundation for Science (IFS).
Combination Therapy More Renoprotective for Diabetics Than Monotherapy
Combination therapy with an ACE inhibitor and an angiotensin-receptor blocker (ARB) appears to have a stronger
renoprotective effect than monotherapy with either drug, even when the two drugs are each given at half the normal dose,
Japanese researchers report.
Both ACE inhibitors and ARB have renoprotective effects in diabetic kidney disease, Dr. Hiroshi Ikegami of the Osaka
University Graduate School of Medicine and colleagues note in their report in the January issue of the American Journal
New research shows the two classes of drugs have different pathways of action beyond their effects on the renin-
angiotensin system. Specifically, ACE inhibitors target the kallikrein-kinin system involved in vasoconstriction, while
ARBs can block angiotensin II produced independently of ACE. The researchers determined whether combining a half-
dose of each drug would be more beneficial than monotherapy in patients with diabetic kidney disease.
27 patients with type 2 diabetes, all of whom had been on 10 mg imidapril or 8 mg candesartan for longer than 3 months,
were switched to 5 mg imidapril and 4 mg candesartan daily. The researchers measured urinary albumin index (UAI) and
blood pressure at baseline and after 3 months on the combination regimen.
While there was not a significant change in blood pressure, the researchers found, average UAI was reduced from 79.4
mg/g Cre to 52.5 mg/g Cre.
It is speculated that potentially more effective inhibition of the renin-angiotensin system by the combination has a
predominantly vasodilatory effect on efferent arterioles, leading to a reduction in intraglomerular pressure and thus to
The clinical effectiveness of combination therapy that we report here further warrants its application to diabetic kidney
disease and may contribute to amelioration of the
prognosis of the disease.
SOURCES:Am J Hypertens 2005;18:13-17.
Diabetic Patient Satisfaction With Physician Relationship Explored
Scientists report correlates of satisfaction for the relationship between type 2 diabetic patients and their physician in
a recent issue of Diabetes Research and Clinical Practice.
According to published research from Italy and the United States, in the context of an Italian nation-wide outcomes
research program on type 2 diabetes, researchers investigated the contribution of both patient and setting-related
factors to patient satisfaction with their relationship with their physicians. The level of patient satisfaction was
measured using the American Board of Internal Medicine (ABIM) 14 patient satisfaction questionnaire. The main
results were obtained using multilevel analysis, a statistical technique that takes into account the clustered nature of
Overall, 3,563 patients were recruited by 101 diabetologists and 103 general practitioners (GPs). Information on
patients' satisfaction was available for 2,515 patients (71 % of the whole sample). Patients' satisfaction was related
to patient characteristics and attitudes, but not with physician's sex, age, specialty, and setting of care. In particular,
patients who were less likely to delegate to physicians responsibility for diabetes management and those perceiving
a lower degree of involvement in disease management showed lower levels of satisfaction.
Lower satisfaction scores were also related to lower levels of school education, more severe clinical conditions, and
lower psychological adaptation to diabetes. However, patients reporting higher levels of diabetes related worries
and more frequent encounters with health care providers showed higher levels of satisfaction.
In conclusion, patient satisfaction with physicians' humanness and communication skills is strongly related to
personal characteristics, attitudes, expectations, and perceived health. In deciding the best decision-making
approach to adopt in individual patients, it is of primary importance to measure how the patient perceives and
engages in relationships.
Diabetes Res Clin Pract, 2004;66(3):277-286).
Gliclazide 80 mg tablet Glibenclamide 5 mg tablet Nateglinide 120 mg tablet
Metformin 500, 850 mg tablets & 500 mg extended release tablet
April - June.05 Page-2
Good oil in walnuts helps diabetes patients
People developing Type 2 Diabetes know they need more than an apple a day to keep the doctor away. But a handful of
walnuts might help.
Walnuts are rich in polyunsaturated fats, Omega oils and vitamins.
Researchers at the University of Wollongong's Smart Foods Centre released the results of a study that shows how to
harness the nutritional value of walnuts, especially the "good" oils, to help people manage their diet better in the early
stages of Type 2 Diabetes Mellitus.
The research showed that including walnuts in the diet improves the relative amounts of "good" cholesterol in this group
The research had demonstrated how a diet including 8-10 walnuts a day delivered the right kinds of fats and fatty acids
that might help the body address one of the problems associated with early stage Type 2 Diabetes - insulin resistance -
which hinders the absorption of glucose from the bloodstream into human cells.
The composition of walnuts can be useful in delivering the right kinds of fatty acids. For around 60 people with Type 2
Diabetes for the six-month study, individualised diets had been developed. The diets were based on the core food
groups of cereals and breads, fruit and vegetables, lean meat, fish, low-fat dairy products, oils, avocadoes, peanut butter
and nuts. Each diet in the treatment group included 30g of walnuts (equivalent to around 8-10 nuts) per day.
The diets were carefully modelled to balance all the other dietary factors such as carbohydrates, proteins, calories and
fats from the other foods to ensure the benefit was correctly attributed to the walnuts.
The study had been important because it confirmed the theoritical benefits of a certain food. This particular research
finding is also useful for doctors and
dietitians when they provide advice to
people on how to get good fatty acids
into their diets.
SOURCE:Diabetes Care, December, 2004
NEW PATCH TECHNOLOGY MAY SOON END DIABETES TEST MISERY
A Revolutionary new skin patch that checks glucose levels every 60 seconds could provide a completely pain-free way of
monitoring diabetes. The high-tech patch performs round the-clock measurements and beams the readings to a
handheld monitor, no bigger than a mobile phone. The device, which is expected to be available in the U.K. later this
year, does away with the daily routine of painful finger-prick tests to measure changes in glucose. It is also hoped it will
allow diabetics to control their glucose levels more easily, reducing the long-term risks of heart disease, blindness and
kidney dama ge.
Additionally, the patch is programmed to sound an alarm if blood glucose rises or falls to dangerous levels. Pain-free
glucose testing systems are something scientists have been striving to achieve for many years. One device already
available is a watch that tests blood sugar levels every 20 minutes over a 12-hour period. Called GlucoWatch, it uses a
tiny electric current to draw glucose out of the skin on to a special gel, before giving an instant reading. But while this
device is not intended to replace regular blood tests, the newest patch technology mentioned above is believed to be so
accurate it may replace finger-prick samples. Named as "Freestyle Navigator", it has been developed by U.S. firm Abbott
A miniature sensor is first implanted just under the skin on the upper arm or tummy by the patient, using a specially-
designed spring-loaded device. Over the top of this goes a patch that is about the same size as a sticking plaster,
containing a tiny transmitter. The sensor constantly detects glucose levels in the body's interstitial fluid which circulates
between cells - and the transmitter sends the information to the handheld monitor, which is small enough to be carried in
a pocket or purse.
Secrin 1 Secrin 2 Secrin 3 Zitrol XR 2.5 Zitrol XR 5 Zitrol XR 10
Glimepiride 1, 2 & 3 mg tablets Glipizide 2.5, 5 & 10 mg extended release tablets
Pioglitazone 15 mg tablet
April - June.05 Page-3
Diabetic neuropathy is a common complication of diabetes The importance of glycemic control
that can affect virtually every tissue of the body. Current The patient who presents with signs and symptoms of
understanding of the pathophysiology is complicated and diabetic neuropathy may well have poorly controlled
incomplete. The available treatments are modestly to diabetes. It has been showed that every 1% decrease in the
moderately effective in relieving symptoms but are limited glycosylated hemoglobin (A1C) level - which corresponds to
by adverse effects and drug interactions. The emphasis of a 20-22 mg/dL decrease in plasma glucose levels - yields a
management of diabetic neuropathy remains prevention by 25% reduction in the risk of diabetes complications.
glycemic control. Good glycemic control not only decreases the initial
incidence of diabetic neuropathy, but it can also slow the
Hyperglycemia & neuropathy progression of established neuropathy and it may even
A recognized link exists between persistent hyperglycemia allow for reversal of nerve damage in early-stage disease.
and diabetic neuropathy. The incidence of neuropathy
correlates with the duration of diabetes, and tight glycemic Classification:
control can reduce the risk. Nevertheless, the mechanisms Diabetic neuropathy is a term commonly used to
that underlie neuropathy are poorly understood. characterize a group of
syndromes, which can be
Hyperglycemia Microvascular vasoconstriction,
capillary basement membrane classified as follows:
Increased extracellular thickening, endothelial hyperplasia,
protein glycation hemologic abnormalities Sensorimotor Neuropathy
Increased intracellular glucose in
AGE formation nerve and vascular tissue or Distal Symmetrical
RAGE activation Neural hypoperfusion and ischemia Diabetic mononeuropathy,
Sugar + ROSs carbonyls Increased glycolysis
and TCA cycle activity
Increased redox reaction: glucose which includes cranial
diacylglycerol sorbitol fructose
Carbonyls + protein or Mitochondrial n e u r o p a t h y ,
lipids glycoxidation or dysfunction
lipoxidation products Reduced NADPH + glutathione, radiculopathy/plexopathy,
Increased Protein + glucose entrapment neuropathy, and
Oxidative stress Polyol pathway flux asymmetric lower limb motor
Protein kinase C
neuropathy, which includes
nerve dysfunction and death cardiovascular abnormalities
(orthostatic hypotension), GI
disturbances (gastroparesis and diabetic
One proposed metabolic cause is the accumulation of diarrhea), and GU problems (including sexual dysfunction
sorbitol secondary to hyperglycemia. Another theory and bladder abnormalities).
suggests that increased sorbitol levels do not directly cause
neuropathy; rather increased oxidation of sorbitol to Importance of early diagnosis:
fructose catalyzed by sorbitol dehydrogenase might Early diagnosis of diabetic neuropathy is important for
mediate impaired nerve function early in the disease. several reasons:
Metabolic abnormalities being evaluated include imbalance Neuropathic signs may be a warning that glucose levels
between NADP and its reduced form, NADPH. have been poorly controlled, so finding them can trigger
The auto-oxidation of glucose is another mechanism that more intensive monitoring & changes in treatment regimen
can promote the production of reactive oxygen species and Improving glycemic control decreases the risk that
damaging oxidative stress. Elevated glucose levels diabetic sequelae
resulting in glycation of proteins, ultimately lead to formation Early signs of peripheral sensory neuropathy should
of advanced glycation end products which in turn increase reinforce the urgent need to follow the patient closely, in
the amount of reactive oxygen species & can result in particular with regular and careful foot examinations, for
impaired blood flow to nerves and ischemia. Alterations in progressive loss of sensorimotor function and the
metabolism of essential fatty acids in diabetes might also development of foot ulcers or deformities.
have effect on nerve function. Autonomic neuropathies can have disabling and
April - June.05 Page-4
N E W S L E T T E R
potentially life-threatening consequences. neuropathy. This weakness can alter the weight-bearing
Although signs of neuropathy may be present early in the capacity of the foot and lead to deformities in foot structure
course of the disease, most patients will be asymptomatic and shape, further predisposing the patient to ulcer and
and the disorder will not be detected until after symptoms callus formation. Diabetes is a leading cause of Charcot's
appear and irreversible nerve damage has occurred. joint, in which the loss of sensation causes the patient to
Screening for sensory loss in the feet of patients with overuse the joint, grinding it down and ultimately altering
diabetes currently offers the best chance for early detection the shape of the foot.
of sensorimotor neuropathy. No formal, quantitative tests
for autonomic neuropathy or mononeuropathy are currently Early detection
recommended because of the invasive nature of such The routine foot examination should include a check for
procedures. Simple tests are advised, such as checking for pulses, assessment of reflexes, visual inspection for injuries
orthostatic changes by measuring BP and pulse rate while or damage to the skin, a careful examination of the areas
the patient is lying down and then standing. Even if no tests between the toes, a sensory examination, and a review of
are done, patients should be questioned carefully for symptoms. The sensory examination can include a
evidence of autonomic symptoms. In addition, all diabetic monofilament test (a quick, inexpensive method for testing
patients require periodic foot examinations, should inspect the patient's ability to detect 10 g of pressure, which has a
their feet daily, and must take great care in selecting their positive correlation with a propensity for ulcer formation), a
footwear. test to discriminate pain from pressure (using a pin, for
example), and a test for vibratory sensation (using a tuning
Sensorimotor Neuropathy fork).
Sensorimotor Neuropathy is the most common form of
diabetic neuropathy, and its prevalence and severity appear Diagnostic approaches
to parallel the duration of the diabetes. It affects more than Nerve conduction studies (NCS) is the electrophysiologic
50% of patients who have had diabetes for 25 years or methods that measure conduction velocity but may not be
longer. Based on the number of patients who present with very helpful in early stages. In more advanced neuropathy,
symptoms, the prevalence of sensory neuropathy is electrophysiologic measurements strongly correlate with
estimated to be 20%; however, with routine testing to detect clinical end points.
early signs of neuropathy, that figure would likely increase Quantitative sensory testing (QST) to assess sensory
to about 40%. thresholds requires the use of a standardized instrument to
Sensorimotor neuropathy affects the sensory neurons, with deliver painful, vibratory, or thermal stimuli. QST testing
small-fiber sensory loss resulting initially in loss of pain, requires only about 10 minutes to perform and is
light touch, and temperature sensation, followed by loss of noninvasive. This approach is promising, but its clinical role
vibratory sensation as degeneration of the large myelinated compared with standard pin and pressure testing has not
fibers advances. Sensorimotor neuropathy typically begins been defined. Both NCS and QST provide quantitative
in the feet and predisposes patients to foot ulcers (most measures of peripheral nerve activity.
commonly due to abrasion from poorly fitting shoes), which Recently, different clinical scoring systems were developed
can progress to cellulitis, osteomyelitis, and gangrene, as quantitative instruments to document the presence and
ultimately requiring amputation of the affected toes or foot. severity of sensorimotor neuropathy. The Toronto Clinical
Proximal progression of the nerve degeneration can lead to Scoring System (Table-1) is a simple screening methods to
diminished ankle reflexes, which are among the early signs stratify patients into severity categories and correlated well
of Sensorimotor neuropathy. The majority of affected with NCS findings and complications in subjects with
patients will experience no symptoms as they progressively nensorimotor neuropathy.
lose feeling in their feet, which is why periodic foot The use of whole nerve biopsy to examine nerve
inspection and sensory assessment, even in the absence of morphology is too aggressive an approach for routine
symptoms, is so critical for detecting
Table-1 - Toronto Clinical Neuropathy Scoring System
Sensorimotor neuropathy and preventing
Symptom Scores Reflex Scores Sensory test Scores
Proper foot care and regular examinations Foot Knee reflexes Pinprick
Pain Ankle reflexes Temperature
should begin at the time of diagnosis of Numbness Light touch
type 2 diabetes because as many as 5% to tingling Vibration
10% of patients may already have early Ataxia
neuropathy. Loss of motor function and Upper-limb symptoms
resulting weakness will follow sensory loss Sensory testing was performed in the first toe. Symtom scores: present = 1, absent = 0
Reflex scores: absent = 2, reduced = 1, normal = 0. Sensory test score: abnormal = 1,
in a minority of patients with Sensorimotor normal = 0. Total scores range from normal = 0 to maximum of 19.
April - June.05 Page-5
N E W S L E T T E R
evaluation. A newer, less invasive approach involves skin- should be reassured that in many cases diabetic
punch biopsy & immunohistochemical staining of peripheral neuropathic pain is of limited duration and will often subside
nerve axons. over a period of 6 months to 2 years. Effective pain
Use of peripheral nerve imaging is based on evidence that treatment is important not only to alleviate a patient's
MRI can detect increased nerve hydration in diabetic suffering; if patients feel better, they may be more
patients with symptomatic or asymptomatic neuropathy. physically active, which helps with glycemic control.
Despite its advantages-it is not invasive and is easily The therapeutic approach should target improved glycemic
repeated for serial evaluations-MRI is costly and its control and pain relief. Symptomatic relief will not reverse
diagnostic sensitivity has not yet been proven. the neuropathy, nor will it restore sensation or nerve
function. Better glycemic control, however, especially early
Treatment in the course, can improve peripheral nerve function if
In some patients, pain will be a prominent symptom of substantial nerve degeneration has not already occurred.
progressive neuropathy and can range from an For painful neuropathy that does not respond to OTC
uncomfortable tingling or burning sensation to disabling analgesics, TCAs such as amitriptyline and anticonvulsants
pain in the legs and feet. Some patients complain of a such as carbamazepine have proven effective. For many
feeling of tightness or constriction in their feet. Presentation experts, low dose amitriptyline is the drug of first choice
may be atypical, such as asymmetric symptomatology or because it is both effective and inexpensive. Sedation is a
neuropathic involvement of the fingers, hands, or arms. In primary drawback, however. If this is a problem,
addition to prescribing medication for pain relief, the patient nortriptyline is also effective and can be tried instead.
Table 2. Dosage Adjustment, Targeted Dosages, Interactions, and Adverse Effects of Medications Commonly
Used to Treat Diabetic Neuropathy a,b,c
Targeted Dosage Dosage- Drug
Medication (mg/day) Adjustment Schedule Adverse Effects
Desipramine 75-200 25 mg h.s., increase by MAOIs Dry mouth, sedation, dizziness, confusion, orthostatic hypotension,
25 mg/wk constipation, urinary retention, confusion, blurred vision
Nortriptyline 75-150 10 mg/day, increase by MAOIs Dry mouth, sedation, dizziness, confusion, orthostatic hypotension,
10 mg/wk constipation, urinary retention, confusion, blurred vision
Amitriptyline 75-150 10 mg/day, increase by MAOIs Dry mouth, sedation, dizziness, confusion, orthostatic hypotension,
10 mg/wk constipation, urinary retention, confusion, blurred vision
Paroxetine 20-60 10 mg/day, increase by MAOIs, codeine, hydrocodone, Dry mouth, constipation, dizziness, sedation, insomnia,
10 mg/wk phenytoin, TCAs, SSRIs, sexual dysfunction, diarrhea
Citalopram 20-60 10 mg/day, increase by MAOIs, codeine, hydrocodone, Dry mouth, constipation, dizziness, sedation, insomnia, sexual
10 mg/wk phenytoin, TCAs, SSRIs, dysfunction, diarrhea
Venlafaxine 150-375 37.5 mg/day, increase by MAOIs, SSRIs, TCAs, tramadol Headache, nausea, sedation, constipation, diarrhea, dizziness,
37.5 mg/wk dry mouth, sexual dysfunction, hypertension, seizures
Bupropion 200-400 100 mg/day, increase by MAOIs, SSRIs, TCAs, phenytoin Agitation, dry mouth, sedation, insomnia, headache, N/V,
100 mg/wk constipation, anorexia, seizures
Carbamazepine 1000-1600 200 mg/day, increase by MAOIs, phenytoin, lamotrigine, Agitation, dry mouth, sedation, ataxia, N/V, blurred vision,
200 mg/wk methadone, tramadol, TCAs, confusion, fatigue, nystagmus, aplastic anemia
Oxcarbazepine 1200-2400 300 mg/day, increase by Carbamazepine, phenytoin, Sedation, dizziness, confusion, N/V, ataxia, tremor, dyspepsia,
300 mg/wk lamotrigine, TCAs nystagmus, hyponatremia, leukopenia, thrombocytopenia
Phenytoin 300-500 100 mg/day, increase by Bupropion, carbamazepine, N/V, nystagmus, ataxia, dizziness, confusion, blurred vision,
100 mg/wk fentanyl, lamotrigine, sedation, constipation, headache, insomnia, gum hypertrophy,
tramadol, TCAs, SSRIs, osteomalacia, blood dyscrasias, hypertrchosis
Gabapentin 1800-3600 900 mg/day, increase by Antacids, CNS depressants Sedation, dizziness, ataxia, N/V, dry mouth, constipation,
300 mg/wk nystagmus, leukopenia
Lamotrigine 200-600 50 mg/day, increase by Carbamzepine, Dizziness, ataxia, sedation, headache, blurred vision, diplopia, N/V,
100 mg biweekly - do not oxcarbazepine, phenytoin confusion, nystagmus, aplastic anemia, toxic epidermal necrolysis
ramps up or load dose
Mexiletine 600-1200 150 mg/day, increase by Lidocaine, phenobarbitol, Dyspepsia, dizziness, tremor, ataxia, insomnia, diarrhea, constipation,
150 mg/wk phenytoin, theophytoin, headache, nervouseness, hepatotoxicity, arrhythmia
Tramadol 200-400 150 mg/day, increase by MAOIs, TCAs,SSRIs, phenytoin, Nausea, sedation, constipation, headache, dry mouth, urinary
50 mg/wk carbamazepine, opioid retention, confusion, tremor, seizures
Oxycodone 40-160 20 mg every 12 hr, CNS depressants, tramadol, Sedation, dizziness, N/V, dry mouth, constipation, urinary
increase by 10 mg/wk TCAs retention, respiratory depression
Capsaicin Apply to affected ...................................... None reported Burning, itching, stinging, cough
area 3-4 times daily
McEvoy GK, ed. AHFS drug information 2002. bethesda, MD: American Society of Health-System Pharmacists; 2002.
this tableoutlines only suggested dosage schedules and is by no means a comprehensive source of adverse effects and drug interactions. MAOIs= monoamine oxidase
inhibitors, TCAs= tricyclic antidepressants, SSRIs=selective serotonin- reuptake inhibitors, N/V=nausea and vomiting, CNS= central- nervous- system.
April - June.05 Page-6
N E W S L E T T E R
Alternative therapies can include carbamazepine; Nevertheless, the condition need not be ignored.
mexiletine, an antiarrhythmic agent and local anesthetic; or Mechanical devices such as antiembolism stockings can be
imipramine. used to prevent blood from pooling in the legs.
The anticonvulsant drug gabapentin is also effective at Hypertension can be treated with drugs, particularly ACE
relieving neuropathic pain and it is less sedating at lower inhibitors, which may have a direct benefit in neuropathy.
dosages than amitriptyline or carbamazepine. Gabapentin Fludrocortisone acetate, 0.4 mg/d, and midodrine, 10 mg
is expensive, though, and its effectiveness may diminish bid or tid, may be helpful to counteract hypotension,
over time. although these drugs must be used with caution.
The high-potency cream formulation of capsaicin may offer Gastroparesis should be considered in patients who has
relief in some cases of severe neuropathic pain. For a few wide swings in blood glucose levels. Common symptoms
patients, only narcotic analgesics will produce adequate include early satiety, chronic nausea, and vomiting of food
relief. ingested hours before. Once the diagnosis of gastroparesis
Neurotrophic factors in development are generating a great is established, the clinician's attention should immediately
deal of excitement. While studies of neurotrophic factors focus on restoring nutritional status, providing symptomatic
continue, research is also focusing on the development of relief from nausea and vomiting, and improving gastric
orally administered small molecule drugs that induce the motility.
natural expression of nerve growth factors. Most patients require multiple prokinetic and antiemetic
For neuropathic pain that does not respond to medication, modalities for adequate symptom relief. Smaller, more
therapeutic alternatives include acupuncture and frequent meals offer benefit. Metoclopramide (10 mg/d for
electroanalgesic therapies such as transcutaneous mild gastroparesis) has been used to improve stomach
electrical nerve stimulation and percutaneous electrical emptying. Neurologic side effects can occur with long-term
nerve stimulation. Nonpharmacologic treatments for severe use. Erythromycin is another option. No dosage of
sensorimotor neuropathy include surgical revascularization, erythromycin as a promotility agent has been well-studied.
but this highly individualized and invasive option is Regimens used include 250 mg once or twice daily or 500
appropriate for a limited patient population. mg tid or qid.
The name, dose and side effects of the drugs is given in Diabetic diarrhea is usually due to sluggish intestinal
table 2. movements that allow bacteria to infect the upper
intestines; the bacteria release acids, which cause the
Autonomic neuropathies diarrhea. Diabetic diarrhea will sometimes respond to
Although more than 25% of patients with type 1 diabetes cyclical antibiotic therapy with tetracycline, amoxicillin, or
may have evidence of autonomic dysfunction at the time of metronidazole. Dosages are 250 mg bid or tid for
diagnosis and the consequences of autonomic neuropathy tetracycline and 500 mg bid or tid for amoxicillin or
can be quite serious. No routine screening tests are metronidazole. Bulking agents may be helpful in avoiding
recommended. Autonomic abnormalities may precede the cycles of constipation and diarrhea.
onset of sensory symptoms. Available treatments for Erectile dysfunction (ED) is caused primarily by autonomic
autonomic neuropathies address the symptoms of the neuropathy, and men with diabetes have a 3-fold increased
disease and not the underlying pathology. risk. The phosphodiesterase type-5 inhibitors (sildenafil,
tadalafil, and vardenafil) are effective for ED. When these
Cardiovascular autonomic neuropathy is the most
agents do not work, other treatments for ED, including
injections, implants, and suction devices, can be tried.
Clinical presentation may be
Intraoperative cardiovascular lability.
Postural hypotension Diabetic neuropathy is a many-faceted complication of
Silent myocardial ischemia/cardiac denervation diabetes that can be managed symptomatically with an
syndrome. array of drugs.
Patients typically present with postural hypotension. Those References:
with diabetes who have a resting heart rate of 90 beats per 1.AARON I. VINIK, MD, PHD, RAELENE E. MASER, PHD, BRAXTON D. MITCHELL, PHD,
minute or higher probably have cardiac autonomic ROY FREEMAN, MD. Diabetic Autonomic Neuropathy. Diabetes Care 26:1553–1579, 2003
2.BRUCE A. PERKINS, FRCPC, DAVID OLALEYE, PHD, BERNARD ZINMAN, FRCPC,
neuropathy. Postural hypotension combined with reduced VERA BRIL, FRCPC.Simple Screening Tests for Peripheral Neuropathy in the Diabetes
heart rate variability confers an increased risk of mortality. Clinic. Diabetes Care 24:250–256, 2001
These patients have a poor prognosis, and the use of 3. VERA BRIL, MD, FRCPC,BRUCE A. PERKINS, MD, FRCPC. Validation of the Toronto
Clinical Scoring System for Diabetic Polyneuropathy. Diabetes Care 25:2048–2052, 2002
medications to slow down the heart does not appear to
4.Jeremiah John Duby; R. Keith Campbell; Stephen M. Setter; John Raymond White; Kristin
affect the prognosis. A. Rasmussen. Diabetic Neuropathy: An Intensive Review. Am J Health-Syst Pharm
Postural hypotension can be very difficult to treat. 61(2):160-176, 2004.
April - June.05 Page-7
N E W S L E T T E R
For Medical Professional Only. This is circulated with prior approval of Licensing Authority ( Drugs).
Link Between Diabetes and Osteoporosis
Adult women with type 1 diabetes have relatively decreased bone mass, increased fracture
risk, and delayed fracture healing compared with healthy women without diabetes.
Researchers have show that the biomechanical integrity of diabetic bone may be impaired.
However, patients with type 2 diabetes usually do not have a decreased bone mass and, in
fact, may be relatively protected from osteoporosis.
Early onset of diabetes, in particular, is associated with reduced bone density, and patients
The trusted and tested Gliclazide
with type 1 diabetes show evidence of low bone mass following adolescence. This finding
may explain the higher incidence of hip fracture reported for postmenopausal women with
type 1 diabetes. The osteopenia associated with diabetes appears to be associated with a
decreased bone turnover associated with impaired osteoblastic maturation and function.
The rate of bone resorption in diabetes is normal and therefore elevated relative to the
decreased rate of bone formation. Studies in diabetic animals show that there is enhanced
apoptosis of osteoblastic cells and, although there is sufficient production of immature
mesenchymal tissue, there is failure to adequately express genes that regulate osteoblast
In contrast to findings in type 1 diabetes, patients with type 2 diabetes do not have low
bone mass and may be relatively protected from osteoporosis. It is not known whether
adolescents with type 2 diabetes will demonstrate a low bone mass. However, it is
hypothesized that this is unlikely since most of these children are also obese. Bone
turnover is suppressed in patients in poor glycemic control, bone metabolism returns to
normal with normalization of glycemia. Recent studies suggest that a negative correlation
may exist between levels of osteocalcin and glycemic control.
The difference in bone loss between the 2 forms of diabetes is often attributed to the
degree of adiposity. Increased body weight has been associated with an increased bone
mass in both normal and diabetic individuals, and may account for the relative protection
seen in patients with type 2 disease. In addition to the mechanical effects of increased
weight bearing, many women who are obese and relatively insulin-resistant have elevated
levels of androgens, which may contribute to bone maintenance. It should be noted that
there is some evidence of higher fracture risk in type 2 patients despite normal bone mass.
Type 1 diabetes does appear to be a significant risk factor for osteoporosis. Patients with
type 1 diabetes be monitored more carefully than persons without diabetes or those with
type 2 disease, and should be encouraged to consume a diet high in both calcium (at least
1200 mg/day) and vitamin D (400-600 IU/day). It appears that intensive insulin therapy and
a stable body weight in patients with type 1 diabetes is important in preventing bone loss.
Patients with diabetes and osteopenia or osteoporosis have successfully been treated with
bisphosphonates, with similar bone density results as patients without diabetes. Due to
impaired osteoblast function, patients with diabetes might be expected to benefit more from
bone anabolic (rather than anti-resorptive) medications, but this has yet to be demonstrated
in a clinical trial.
References: 1. Reddy GK, Stehno-Bittel L, Hamade S, Enwemeka CS. The biomechanical integrity of bone in experimental diabetes. Diabetes Res Clin
Pract. 2001; 54:1-8. Abstract . 2. Liu EY, Wactawski-Wende J, Donahue RP, Dmochowski J, Hovey KM, Quattrin T. Does low bone mineral density start in post-teenage
years in women with type 1 diabetes? Diabetes Care. 2003;26:2365-2369. 3. Bouillon R, Bex M, Van Herck E, et al. Influence of age, sex, and insulin on osteoblast
function: osteoblast dysfunction in diabetes mellitus. J Clin Endocrinol Metab. 1995;80:1194-1202. Abstract .4. He H, Liu R, Desta T, Leone C, Gerstenfeld LC, Graves
DT. Diabetes causes decreased osteoclastogenesis, reduced bone formation and enhanced apoptosis of osteoblastic cells in bacteria stimulated bone loss.
Endocrinology. 2003;Oct 2 [Epub ahead of print]. 5. Lu H, Kraut D, Gerstenfeld LC, Graves DT. Diabetes interferes with the bone formation by affecting the expression
of transcription factors that regulate osteoblast differentiation. Endocrinology. 2003;144:346-352. Abstract .6. Christensen JO, Svendsen OL. Bone mineral in pre- and
postmenopausal women with insulin-dependent and non-insulin-dependent diabetes mellitus. Osteoporos Int. 1999;10:307-311. Abstract .7. el Miedany YM, el Gaafary
This issue of your diabetes newsletter is
S, el Baddini MA. Osteoporosis in older adults with non-insulin-dependent diabetes mellitus: is it sex related? Clin Exp Rheumatol. 1999;17:561-567. Califc Tissue
focused on "Diabetic Neuropathy". We
appreciate your comments and queries.
Editorial Board Executive Editor
Dr. Omar Akramur Rab, MBBS, FCGP, FIAGP A.H.M. Rashidul Bari, M. Pharm
Ahmed Kamrul Alam, M. Pharm, MBA e-mail: firstname.lastname@example.org
Dr. Sayedul Islam, MBBS, MBA