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Thursday, March 3, 2011

A Primer on Diabetes

A Primer on Diabetes 
In Hindi, P. marsupium is known as Bibla (Vijayasar or Bijasar), while in English it is called Indian Kino because it was primarily cultivated as a source of kino. Kino is the dried exudation obtained by incising the trunk.

Kino has been used as an astringent, administered in diarrhea. The gum has been used for toothache; the bark has been used for diarrhea, heartburn, and in the management of diabetes; and the leaves have been used for boils, sores, and skin diseases.

The heartwood, a durable and termite resistant material, has been used in the management of diabetes and hyperlipidemia.
 

Diabetes mellitus, commonly known as diabetes, is one of the world’s oldest known diseases. A recent news report cites that "researchers at the Atlanta-based Centers for Disease Control and Prevention (CDC) said the prevalence of diagnosed diabetes in the U.S. rose rapidly across all regions, demographic groups and in almost every state during the past decade. Diabetes is the nation’s seventh leading cause of death, accounting for more than 300,000 premature deaths every year, the CDC said. About 800,000 new diabetes cases are diagnosed annually".

Diabetes mellitus is caused either by a lack of the hormone insulin (Type I diabetes) or the body's inability to use insulin (Type II diabetes also known as maturity-onset diabetes). Type II diabetes is often triggered by obesity, stress and a sedentary lifestyle. The CDC attributes the phenomenal increase in diabetes cases to the growing prevalence of obesity and decline in physical activity. Increase in diabetes cases between 1990 - 1998 was 33%
For people between 30-39 years of age the increase was 70%
For people between 40-49 years of age the increase was 40%




DIABETES PREVALENCE BY AGE




Type I, also called juvenile onset diabetes or insulin dependent diabetes mellitus (IDDM) accounts for about 10% of the total cases of the disease and afflicts the sufferers quite early in life. IDDM is caused by an individual’s inability to make insulin. Type II or maturity onset diabetes, also called non-insulin dependent diabetes mellitus (NIDDM), accounts for almost 90% of the diabetes cases. It is associated with a defect in insulin secretion as well as insulin resistance. Individuals who are abdominally obese (central obesity) tend to have diminished capacity to utilize glucose. They also have high levels of circulating free fatty acids (which impairs glucose metabolism) and a low number of insulin receptor sites.

Depending upon the nature of the disease, insulin and certain synthetic drugs like sulphonylureas, biguanidines and acarbose are widely used in its treatment. Before the discovery of insulin by Frederick Banting and Charles Best in 1921, patients with severe cases of diabetes did not survive. Today, although seldom fatal, diabetes is a dreaded disease on account of the related complications. Careful management of diabetes, including control of high blood pressure, can delay some of the serious complications associated with the condition, which include eye diseases, disease of the peripheral blood vessels and kidney failure. In recent years, evidence of cases of "insulin resistance" and the occurrence of side effects from prolonged administration of conventional drugs have triggered the search for safe and effective alternatives. Several plant extracts and isolated phytochemicals have been examined for antidiabetic activity with a view to identify alternative treatment strategies for diabetes. It has been observed that certain resistant cases of diabetes that do not respond well to conventional drugs often respond well to supplementation with natural remedies.

Diabetes is a chronic disorder characterized by high blood sugar levels and abnormal metabolism of carbohydrate, protein and fat. The disease is a result of the failure of the body to control blood sugar levels adequately. The normal fasting blood sugar levels are in the range of 75-115 mg/dl (milligrams per deciliter of blood). After a meal, the body tightly regulates increases in blood sugar to a level not exceeding 180 mg/dl in people without diabetes.

In a normal person, food which is made up of protein, carbohydrate and fat is digested by the enzymes in the digestive tract. Glucose, a simple sugar is an important end product of digestion. It is absorbed into the bloodstream and transported to the various cells in the body where it is utilized as a fuel to provide energy for the various life activities. Insulin is a hormone which acts as a key that opens the doors of the cells to allow glucose to enter. Insulin is produced in the body by beta cells, specialized cells located in the islets of langerhans of the pancreas.

The islets of langerhans are little islands of cells, named after their discoverer, Paul Langerhans. The islets of Langerhans contain three types of cells that help in glucose metabolism: alpha cells which make glucagon; beta cells which produce insulin; and delta cells which secrete somatostatin, a hormone which regulates the production of insulin and glucagon.


Normally, insulin and glucagon regulate blood glucose levels, causing almost all carbohydrate and about 50 to 60 percent of protein to be converted into glucose. Glucose is consumed as fuel by almost every type of body cell. In a person suffering from type I diabetes, there is an insufficient or no supply of insulin. In type II diabetes, insulin may be present in sufficient quantities, but it is unable to unlock the doors of the cells. In the normal case, insulin "fits" on to specific sites called insulin receptors located on the surface of the cell (the key holes) and unlocks the "doors" to let glucose enter. If the insulin cannot fit in properly due to lack of insulin receptors on the cell surface, the "doors" remain locked, causing a condition called insulin resistance. In such cases of diabetes, administration of insulin does not help because there are few receptor sites. If the doors of the cells remain unopened, due to lack of insulin or difficulty in utilizing insulin, glucose cannot enter the cells and remains in the blood. This causes increases in blood sugar levels even if no food is eaten.

Urine sugar levels increase when some of the excess blood sugar is excreted. The body begins to use alternative fuel souces (e.g. body fat and protein) for energy. The patient therefore loses weight, tires easily and has an increased appetite (polyphagia).

Excess glucose in the blood is harmful too. Sugar accumulation in the blood results in increased work load on the kidneys and increased sugar levels in the urine. The sugar enters the urine in solution form, draining water from the cells. This causes an increase in the volume of urine which triggers frequent urination (polyuria), and induces thirst (polydipsia) in the patient. High blood sugar levels over protracted periods of time causes "glycation" of key body proteins inducing secondary symptoms such as retinopathy which may lead to blindness, neuropathy (nerve degeneration) which may lead to gangrene, and nephropathy which may lead to kidney malfunctions.

Pterocarpus marsupium, the source of Silbinolâ




Pterocarpus marsupium Roxb. (from the family Leguminoceae) is a large tree that commonly grows in the central, western, and southern parts of India and in Sri Lanka.


In Hindi, P. marsupium is known as Bibla (Vijayasar or Bijasar), while in English it is called Indian Kino because it was primarily cultivated as a source of kino. Kino is the dried exudation obtained by incising the trunk.


Kino has been used as an astringent, administered in diarrhea. The gum has been used for toothache; the bark has been used for diarrhea, heartburn, and in the management of diabetes; and the leaves have been used for boils, sores, and skin diseases.

The heartwood, a durable and termite resistant material, has been used in the management of diabetes and hyperlipidemia.

 Clinical Studies

The results of the clinical studies mirror those of the preclinical studies.
The Indian Council of Medical Research undertook an antidiabetic Phase II open trial at four centers across India using Vijayasar (P. marsupium). Vijayasar was tested in newly-diagnosed non-insulin dependent diabetes mellitus (NIDDM) patients between 35 and 60 years of age for 12 weeks. Ninety-three of 223 patients admitted for the therapy were evaluated for 12 weeks. The parameters used for evaluation were blood glucose levels and glycosylated hemoglobin (HbA1c). The main findings for the study are summarized below and in Figure 1:


Figure 1. Mean blood glucose and HbA1c levels of patients during 12- week Vijayasar treatment. (No. of patients : Fasting blood glucose = 93, Postprandial blood glucose = 93, & HbA1C = 67)



Of the three cardinal symptoms for diabetes, a marked reduction was observed for polyuria (the production of large volumes of urine). The other two symptoms, symptomspolyphagia (gluttonous excessive eating) and polydipsia (abnormally intense thirst), initially observed in 21 and 7 patients respectively, disappeared in 14 and 7 patients, respectively by 12 weeks.

Control of both fasting and postprandial blood glucose was achieved in 67 of 93 newly diagnosed or untreated NIDDM patients. Approximately 73% of these patients required a daily dose of 2 g of Vijayasar. Only 10% of the patients required a higher dose of 4 g per day, and this dose was well tolerated.

No relationship was found between the dose of Vijayasar and the changes observed in the HbA1c levels. Only 7% of the patients attained control of HbA1c by week 12.

None of the patients reported any side effects.

The Indian Council of Medical Research concluded that Vijayasar (P. marsupium) be used in the treatment of newly diagnosed or untreated NIDDM patients. In addition they suggested that the treatment be restricted to mild diabetics (those that have blood glucose levels between 120 and 180 mg/dL and postprandial blood glucose levels between 180 and 250 mg/dL).

Another study on 20 patients with maturity onset diabetes mellitus was performed. The patients were divided into two groups- Group A and Group B. Group A consisted of 10 patients who received Vijayasar (P. marsupium heartwood) granules (5 g tid after breakfast, lunch, and dinner). Group B consisted of 10 patients who had received conventional drugs such as chlorpropamide, tolbutamide, and phenformin before receiving the Vijayasar granules. The study was conducted for 3 weeks. Significant reductions in the fasting and postprandial blood sugar levels were observed after treatment with Vijayasar that were comparable with the conventional drug therapies. Subjective improvements concerning reduction of appetite, polyurea, polydipsia, burning pains in limbs and general weakness were observed in a majority of cases within an 8-10 day period, and blood sugar levels were controlled at the end of 2 weeks.




Figure 2. Reduction of Fasting and Post Prandial Blood Sugar Level of diabetic patients during a 3 week treatment
Group A: Vijaysar (Aqueous extract) granules treated
Group B: Vijaysar treated after withdrawal of oral hypoglycemics



Two other studies determined the blood sugar lowering effects of formulations containing P. marsupium. in diabetic patients.

Efficacy of D-400, a herbal preparation consisting of Eugenia jambulana, Tinospora, cordifolia, P. marsupium, Ficus glomerulata, Momoradica charantia and Ocimum sanctum were conducted. 20 cases of persistent post prandial hyperglycaemia were selected for the study. Initial reduction in body weight. blood glucose was observed. After 12 weeks of treatment, rise in fasting and post prandial blood sugar was noticed in placebo treated groups. While D-400 treated groups showed a persistent fall in fasting and post prandial blood glucose level till the end of the trial. D-400 exibits benefical effects in treating pontial diabetic cases and during trial period no adverse effects were observed.




Figure 3. Effect of D 400 and Placebo on fasting blood glucose levels in early diabetic patients




Figure 4. Effect of D 400 and Placebo on Post Prandial Blood Sugar Level in early Diabetic Patients



Both studies concluded that the formulations were beneficial in treating diabetic patients.

Yajnik and coworkers evaluated the hypoglycemic activity of D-400 in 43 patients with maturity onset diabetes for 12 weeks. Of the 43 patients, 20 were newly diagnosed diabetics and 23 were diabetics already receiving oral and/or insulin treatment along with other forms of treatment.

After the 12 week treatment, significant reductions in both the fasting and postprandial blood sugar levels were observed in diabetics taking oral hypoglycemics as well as newly diagnosed diabetics. (Figures 2 and 3)
The treatment satisfactorily controlled 90% of the newly diagnosed diabetics.
Approximately and 80% and 20% of diabetics taking oral hypoglycemics were able to reduce the dosage of their medications or cease taking their medication, respectively.
The treatment was well tolerated by all patients, and no harmful effects were reported.




Figure 5. Effect of D-400 on fasting and post-prandial blood sugar levels in newly diagnosed diabetics. (week (-2) to week 0 placebo treatment,
week 0 and week 12 D-400 treatment) N=20





Figure 6: Effect of D-400 on fasting and post-prandial blood sugar levels in newly diagnosed diabetics. (week (-2) to week 0 placebo treatment, week 0 and week 12 D-400 treatment) N=23



Another research group compared the antidiabetic effects of two ayurvedic preparations- Gurmur, (a combination of the leaves of Gymnema sylvestre, Aegle marmelos, and Azadirachta indica) and Bija wood water (Pterocarpus marsupium water), in 30 diabetic patients aged 40-65. The Gurmur preparation significantly reduced the post meal blood sugar levels to normal levels. P. marsupium exerted an antidiabetic effect, but unlike the Gurmur preparation, the P. marsupium water exhibited a slow and steady hypoglycemic activity as shown in fig. 7.



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