User:Chandra R./Temp/REVIEW ARTICLE.doc
Diabetes mellitus, a current threat to world population health with its multiple disorders, is now one of the major diseases. Diabetes is very aged disease since 1550 B.C. It was documented by Egyptians on papyrus. Historical accounts reveal that as early as 700-200 B.C., Diabetes mellitus was a well recognized disease in India and was even distinguished as two types; a genetically based disorder and other one resulting from dietary indiscretion (Oubre et al., 1997).
The term diabetes, which is Greek word, means “to run through” or “a siphon” was coined by Aretaeus of Cappadocia (81-138 A.D.), who noted that a large amount of urine “run through” the kidneys in this disease. The Latin adjective, mellitus means ‘honey-sweet’, was added by Cullen (1710–1790) in order to distinguish diabetes mellitus or ‘sugar diabetes’ from diabetes insipidus. In the Sanskrit literatures of the 5th-6th century A.D., the Indian physician, Sušruta (A.D. 500) gave a recognizable description of diabetes mellitus as “Madhu-Meha” (or Ikshu-Meha) or Honey-urine and described the symptoms of thirst, foul breath, voracious appetite and languor.
The major breakthrough came in 1921 through isolation of blood sugar lowering hormone by Banting and Best. Earlier insulin was extracted from the pancreas of calf, porcine. After introduction of recombinant DNA technology, the synthetic genes for the A and B chains were cloned into bacteria (Eli Lilly, Indianapolis) and the resultant peptide products were combined to form human insulin.
Besides the use of insulin for the treatment of diabetes, other therapeutic approaches for the control of hyperglycemia include the use of α- glucosidases, sulphonylureas, biguanides, and thioazolidinediones etc. However, these drugs have many adverse effects such as causing hypoglycaemia, liver problems, lactic acidosis, weight gain and diarrhea. Since the currently available treatment is expensive and far from satisfactory, alternate therapeutic approaches like the use of medicinal plants for controlling diabetes are gaining popularity among the scientific community.
For centuries, plants with medicinal properties have been employed by traditional systems of medicine like Ayurveda, Siddha, Unani, Traditional Chinese Medicine, Native American Medicine, and Latin American folk systems for the treatment of various diseases including diabetes mellitus. They are considered to be effective and non-toxic. They have a vast potential which has only partly
been explored by modern methods. Traditional plant remedies have provided modern medicine with numerous pharmaceutical preparations. During the last two decades, there has been a sudden resurgence of interest in medicinal plants used in traditional systems of medicine. The use of herbal medicine as an alternative therapy is gaining considerable recognition and popularity worldwide. In fact, the use of herbal remedies has increased approximately 380% during the last 7 years in the United States. So there is a great need to emphasize on the use of these traditional medicines for the cure of diabetes and other diseases.
Changes in human behaviour and lifestyle over the last century have resulted in a dramatic increase in the incidence of diabetes worldwide. Diabetes mellitus is now a major threat to human health in the 21st century. In the past two decades there is an explosive increase in the number of people affected with diabetes. The global prevalence of diabetes for all age group worldwide was estimated to be 2.8% in 2000 and 4.4% in 2030. The total number of people with diabetes is projected to rise from 171 million in 2000 to 366 million in 2030. The prevalence of diabetes is higher in men than women, but there are more women with diabetes than men. The urban population in developing countries is projected to double between 2000 and 2030. The most important demographic change to diabetes prevalence across the world appears to be the increase in the proportion of people >65 years of age (Sarah et al., 2004). The Asia Pacific region is at the vanguard of the current epidemic of diabetes (Cockram, 2000). The Indian scenario is equally alarming, with the age and gender standardized prevalence rate of 4.3% (Sadikot et al., 2004), clearly shows that the WHO estimate of the Indian diabetes burden of 35 million people by 2025 (King et al., 1998) has been reached more than two decades earlier. In figure 1 you can compare the number of people at the age group of 20-79 in 2007 and 2025. Figure 2 is covering the statistics of diabetic people country wise in 2007 and in 2025. This increase in incidence of diabetes in developing countries is due to the rapid increase in population, increased longevity and high ethnic susceptibility to diabetes coupled with rapid urbanization and lifestyle changes.
The frequency of type 1 diabetes is low, relative to type 2 diabetes, which accounts for over 90% of cases globally. The diabetes epidemic is affecting particularly to people with type 2 diabetes, and is taking place both in developed and developing nations, which is strongly associated with a sedentary lifestyle and obesity (Zimmet, 1999). This trend of increasing prevalence of diabetes and obesity has already imposed a huge burden on health-care systems and this will continue to increase in the future (Zimmet, 2000; American Diabetes Association, 1998). Although type 2 diabetes is numerically more prevalent in the general population, type 1 diabetes is the most common chronic disease of children. But with the increasing prevalence of type 2 diabetes in children and adolescents, the order may be reversed within one to two decades (Fagot-Campagna et. al., 2000; Fagot-Campagna and Narayan, 2001). Epidemiological studies among migrant Asian Indians in many countries showed higher prevalence of type 2 diabetes compared with the host populations and other migrant ethnic groups (Zimmet, 1999). Studies conducted in India in the last decade have highlighted that not only is the prevalence of type 2 diabetes high, but also that it is increasing rapidly in the urban population (Mohan et al., 2001; Misra et al., 2001).
Fig. 2. Country wise frequency of diabetic people in world (Source: Diabetes Atlas Third Edition, © Internaitonal Diabetes Federation 2006)
The classification and diagnostic criteria used for the diagnosis of diabetes and disorders of glucose homeostasis has been the subject of much debate (Albert and Zimmet, 1998; Expert Committee, 1997). Currently, there are five major clinical categories of disordered glucose homeostasis:
- Type 1 Diabetes
- Type 2 Diabetes
- Impaired glucose tolerance/impaired fasting glucose
- Gestational Diabetes
- Other rare form include maturity-onset diabetes of the young (MODY), pancreatic diabetes.
Several types of diabetes have been reported and are enlisted below. Of these, Type 1 diabetes mellitus (T1DM) and Type 2 diabetes mellitus (T2DM) are the two major types of diabetes that affect majority of the population.
- 1 OTHER TYPES OF DIABETES MELLITUS
- 2 ALTERNATIVE THERAPY: USE OF PLANT PRODUCTS AS POTENTIAL ANTI- DIABETIC AGENTS
- 2.1 Butler, A. E., Janson, J., Bonner-Weir, S., Ritzel, R. A., and Butler, P. C. (2003) Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes, Jan;52(1):102-110.
- 2.2 Kahn, S. E. (2001) Importance of ß-Cell Failure in the Development and Progression of Type 2 Diabetes. The Journal of Clinical Endocrinology & Metabolism, Vol. 86, No. 9, 4047-4058.
OTHER TYPES OF DIABETES MELLITUS
1.Diabetes due to pancreatic disease
-Chronic or recurrent pancreatitis
2.Diabetes due to other endocrine disease
3.Diabetes due to drugs and toxins
-Glucocorticoids and ACTH
4.Diabetes due to abnormalities of insulin or its receptor
-Circulating antireceptor antibodies
5.Diabetes associated with genetic syndromes
-DIDMOAD (Diabetes Insipidus, Diabetes mellitus, Optic Atrophy, and Deafness) syndrome
-Myotonic dystrophy and other muscle disorders
-Type 1 glycogen storage disease
Type 1 indicates the processes of beta–cell destruction that may ultimately lead to diabetes mellitus in which “insulin is required for survival” to prevent the development of ketoacidosis, coma and death. An individual with a Type 1 process may be metabolically normal before the disease is clinically manifest, but the process of beta–cell destruction can be detected (fig. 3) Type 1 is usually characterized by the presence of anti–GAD (Glutamic acid decarboxylase), islet cell or insulin antibodies which identify the autoimmune processes that lead to beta–cell destruction. In some subjects with this clinical form of diabetes, particularly non–Caucasians, no evidence of an autoimmune disorder is demonstrable and these are classified as “Type 1 idiopathic”. Aetiological classification may be possible in some circumstances and not in others. Thus, the aetiological Type 1 process can be identified and sub–categorized if appropriate antibody determinations are performed. It is recognized that such measurements may be available only in certain centres at the present time. If these measurements are performed, then the classification of individual patients should reflect this. Type 1 Diabetes is autoimmune disease that affects 0.3% on average. Researchers believe that some of the Etiology and Risk factors which may trigger type 1 diabetes may be genetic, poor diet (malnutrition) and environment (virus affecting pancreas). Secondly, in most of the cases diabetes occurs because there is abnormal secretion of some hormones in blood which act as antagonists to insulin. Example- Adrenocortical hormone, Adrenaline hormone and Thyroid hormone.
Concurrent with obesity epidemic, the incidence of type 2 diabetes is increasing at an alarming rate.
Type 2 diabetes arises when the endocrine pancreas fails to secrete sufficient insulin to cope with the metabolic demand (Donath and Halban, 2004), because of acquired β-cell secretory dysfunction and/or decreased β -cell mass. Insulin secretory dysfunction in type 2 diabetes is well documented and has been reviewed elsewhere (Kahn, 2001). Whether insulin secretory dysfunction is a cause or consequence of the disease is still debated, but there is mounting evidence that it may be symptomatic of changes in β -cell mass. Although proposed nearly 50 years ago, the hypothesis that β -cell loss plays an important role in the pathogenesis of type 2 diabetes has only recently come to the fore. β -cell mass in the adult is plastic, and adjustments in β -cell growth and survival maintain a balance between insulin supply and metabolic demand. For example, obese individuals who do not develop diabetes exhibit an increase in β -cell mass that appears to compensate for the increased metabolic load and obesity-associated insulin resistance. However, this β -cell adaptation eventually fails in the subset of obese individuals who develop type 2 diabetes (Weir et al., 2004). Indeed, most individuals with type 2 diabetes, whether obese or lean, show a net decrease in β -cell mass (Butler et al., 2003). Thus, type 2 diabetes is a disease of relative insulin deficiency.
The term diabetes mellitus describes a metabolic disorder of multiple aetiology characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. The effects of diabetes mellitus include long–term damage, dysfunction and failure of various organs. Diabetes mellitus may present with characteristic symptoms such as polydipsia (thrist), polyuria (excretion), polyphagy (eating), blurring of vision, and weight loss. In its most severe forms, ketoacidosis or a non–ketotic hyperosmolar state may develop and lead to stupor, coma and, in absence of effective treatment, death. Often symptoms are not severe, or may be absent, and consequently hyperglycaemia sufficient to cause pathological and functional changes may be present for a long time before the diagnosis is made. The long–term effects of diabetes mellitus include progressive development of the specific complications of retinopathy with potential blindness, nephropathy that may lead to renal failure, and/or neuropathy with risk of foot ulcers, amputation, Charcot joints, and features of autonomic dysfunction, including sexual dysfunction. People with diabetes are at increased risk of cardiovascular, peripheral vascular and cerebrovascular disease (WHO report, 1999).
Apart from all these symptoms there are major skin and other complications as cataract and glaucoma. Diabetes affects different body parts of a person including skin. The skin disorders can be seen in normal individual too, but diabetics are more frequently prone to it. Some of the specific skin infections frequently seen in the diabetes patients are bacterial and fungal infections, dermopathy, necrobiosis lipoidica, diabeticorum, xanthomatosis, disseminated granuloma annulare and blisters and others as albuminiuria, Diabetes myonecrosis, diabetic mastopathy (http://diabetesinformationhub.com).
Several pathogenetic processes are involved in the development of diabetes. These include processes which destroy the beta cells of the pancreas with consequent insulin deficiency, and others that result in resistance to insulin action. The abnormalities of carbohydrate, fat and protein metabolism
are due to deficient action of insulin on target tissues resulting from insensitivity or lack of insulin.
If a diagnosis of diabetes is made, the clinician must feel confident that the diagnosis is fully established since the consequences for the individual are considerable and lifelong. The requirements for diagnostic confirmation for a person presenting with severe symptoms and gross hyperglycaemia differ from those for the asymptomatic person with blood glucose values found to be just above the diagnostic cut–off value. Severe hyperglycaemia detected under conditions of acute infective, traumatic, circulatory or other stress may be transitory and should not in itself be regarded as diagnostic of diabetes. The diagnosis of diabetes in an asymptomatic subject should never be made on the basis of a single abnormal blood glucose value. For the asymptomatic person, at least one additional plasma/blood glucose test result with a value in the diabetic range is essential, either fasting, from a random (casual) sample, or from the oral glucose tolerance test (OGTT). If such samples fail to confirm the diagnosis of diabetes mellitus, it will usually be advisable to maintain surveillance with periodic re–testing until the diagnostic situation becomes clear. In these circumstances, the clinician should take into consideration such additional factors as ethnicity, family history, age, adiposity, and concomitant disorders, before deciding on a diagnostic or therapeutic course of action. An alternative to blood glucose estimation or the OGTT has long been sought to simplify the diagnosis of diabetes. Glycated haemoglobin, reflecting average glycaemia over a period of weeks, was thought to provide such a test. Although in certain cases it gives equal or almost equal sensitivity and specificity to glucose measurement (McCance et al., 1994), it is not available in many parts of the world and is not well enough standardized for its use to be recommended at this time. Another criterion for the diagnosis is the glycosylated haemoglobin (HbA1c). If the HbA1c level is >6%, the person will be diabetic.
The clinical diagnosis of diabetes is often prompted by symptoms such as increased thirst and urine volume, recurrent infections, unexplained weight loss and, in severe cases, drowsiness and coma; high levels of glycosuria are usually present.
A fasting blood sugar level less than 100 milligrams of glucose per deciliter of blood (mg/dL) is considered normal. If your blood sugar level is 100 to 125mg/dL, you have prediabetes - also called impaired fasting glucose (IFG). If you are suffering from prediabetes then the fasting blood sugar as well as post postprandial blood sugar will fluctuate easily. After fasting for at least eight hours, FBS (fasting blood sugar) is checked and then an oral dose of 75 g glucose (Oral glucose tolerance test OGTT) is administered. For children the oral glucose load is related to body weight: 1.75 g per kg. The blood glucose level is checked after one hour and if it reaches 144-199 mg/dl after two hours, you have impaired glucose tolerance. Currently, type 2 diabetes mellitus is diagnosed when the underlying metabolic abnormalities consisting of insulin resistance and decreased β-cell function cause elevation of plasma glucose above 126 mg/dl (7 mmol/liter) in the fasting state and/or above 200 mg/dl (11.1 mmol/liter) 120 min after a 75-g glucose load (Report of the Expert Committee, 1999). The requirements for individual diagnosis differ from those of population studies. The diagnosis should not be based on a single glucose determination but requires confirmatory symptoms or blood/plasma determination. Diagnosis requires the identification of people at risk for development of complications in whom early preventive strategies are indicated. Ideally therefore both the 2–h and the fasting value should be used. However, the fact that many newly diagnosed type 2 diabetic subjects already suffer from so called “late complications of diabetes” at the time of diagnosis (Beck et al., 1994) indicates that the diagnosis may have been delayed and, in addition, that the prediabetic condition is harmful to human health and requires increased awareness by physicians and the general public. Thus, type 2 diabetes mellitus represents only the “tip of the iceberg” (Fig. 4) of long existing metabolic disturbances with deleterious effects on the vascular system, tissues, and organs.
Type 1 Diabetes is treated with insulin and diet and has no place for the use of oral hypoglycemic agents.
The selection of right type of food is extremely important at this stage. One should restrict to food with low fat and low calories, and on the other side, fresh fruits and vegetables with lots of antioxidant should be the preferred choice.
Insulin is synthesized as a preprohormone in the beta cells of the islets of Langerhans. In normal individual, insulin is produced by the body in response to the rise in blood glucose level. Apart from it, spurts of insulin are produced throughout the day and night, to look after the body's resting needs for insulin and ensure that cells can take up glucose. In other words function of insulin is to counter the concerted action of a number of hyperglycemia generating hormones, and to sustain low blood glucose levels. In people with type 1 diabetes, the pancreas no longer makes insulin as the beta cells have been destroyed and they need insulin shots to use glucose from meals.
Insulin cannot be taken as a pill as it will be break down during digestion just like the protein in food. Insulin must be injected into the fat under your skin, to make it get into your blood. By reducing the concentration of glucose in the blood, insulin is thought to prevent or reduce the long-term complications of diabetes, including damage to the blood vessels, eyes, kidneys, and nerves. In general, the insulins in common use can be considered in four groups based on their action profiles.
|Types of Insulin||Examples||Onset of action||Peak of action||Duration of action|
|Rapid Acting||Humalog (lispro)(Eli Lilly)||15 minutes||30-90 minutes||3-5 hours|
|NovoLog (aspart)(Novo Nordisk)||15 minutes||40-50 minutes||3-5 hours|
| Short Acting
|Humulin R (Eli Lilly)Novolin R(Novo Nordisk)||30-60 minutes||50-120 minutes||5-8 hours|
|Humulin N (Eli Lilly)Novolin N (Novo Nordisk)||1-3 hours||8 hours||20 hours|
|Intermediate Acting||Humulin L (Eli Lilly)Novolin L (Novo Nordisk)||1-2.5 hours||7-15 hours||18-24 hours|
|Mixed Acting||Humulin 50/50, 70/30 Humalog Mix 75/25Humalog Mix 50/50(Eli Lilly)Novolin 70/30Novolog Mix 70/30(Novo Nordisk)||The onset, peak, and duration of action of these mixtures would reflect a composite of the intermediate and short- or rapid-acting components, with one peak of action.|
|Long Acting||Ultralente (Eli Lilly)||4-8 hours||8-12 hours||36 hours|
|Lantus (glargine) (Aventis)||1 hour||None||24 hours|
Endurance exercise increases the rate of utilization of all metabolic fuels. Hence, it decreases the glycogen content in muscle. The latter may result in an increase in the activity of glycogen synthase and, consequently, may decrease the requirement for insulin in the stimulation of glycogen synthesis after a carbohydrate meal. In addition, it has been shown that, in normal subjects, endurance training markedly increase insulin sensitivity, so that very much lower concentrations of insulin are required to control blood glucose concentration after an oral glucose load. It has also been shown that, in diabetic subjects who were exercised to deplete muscle glycogen stores (by 80%), the rate of glycogen synthesis in the muscles for 4-hour post -exercise, after a carbohydrate-rich meal, was the same whether the subjects took their normal insulin or were deprived of it.
ORAL HYPOGLYCEMIC AGENTS
Current therapeutic approaches were largely developed in the absence of defined molecular targets or even a solid understanding of disease pathogenesis. Within the past few years, our understanding of biochemical pathways related to the development of metabolic syndrome has expanded. There is an unprecedented range of molecular drug targets within these pathways. They have been identified on the basis of predicted roles in modulating one or more key aspects of the pathogenesis of diabetes and metabolic syndrome. Several mechanistic categories for new therapeutic approaches can be considered. First are approaches aimed at reducing excessive glucose production by the liver; second, mechanisms to augment glucose-stimulated insulin secretion; third, specific molecular targets in the insulin signalling pathway; and fourth, new approaches to obesity and altered lipid metabolism, which offer the prospect of net improvements in insulin action (or secretion) (Fig. 5) (David, 2001).
Fig. 5. A better understanding of defects involving several key organ systems has led to new drug targets for type 2
When diet, exercise and ideal body weight aren’t enough to maintain normal blood sugar level, there may be need to start medication. Medications used to treat diabetes include insulin too. Usually, people with Type 1 diabetes don't use oral medications. Diabetes Medications work best in people with Type 2 diabetes who have had high blood sugar for less than ten years with normal weight or obesity. Some people who begin treatment with oral medications eventually need to take insulin.
Insulin and oral diabetes medications deliberately work to lower your blood sugar. In certain cases medications taken for other conditions may affect glucose levels. Number of drug options exists in market for treating type 2 diabetes (Table 1), includes:
Since 1994, sulfonylureas were the only drug used for diabetes in United States. It stimulates your pancreas for the production of more insulin to lower down your blood sugar. It can be effective when your pancreas can make some insulin of its own. Sulfonylureas such as glipizide (Glucotrol, Glucotrol XL), glyburide (DiaBeta, Glynase PresTab, Micronase) and glimepiride (Amaryl) are prescribed more often. If your body is sensitive to sulfa drug then you must avoid sulfonylureas.
- Low blood sugar.
- Stomach upset.
- Skin rash and itching.
- Weight gain.
Metformin (Glucophage, Glucophage XR) is the generic name of this drug. It works by inhibiting, the production and release of glucose from your liver. It also lowers down the insulin secretion. One good thing about biguanides drug is that it tends to slow down weight gain than do others. It can also improve blood cholesterol level, which is generally high if you are type 2 diabetic.
- If you already have a kidney problem, metformin may build up in your body. Inform your doctor when you are placed on this medication regarding your kidney problem.
- If you are vomiting, have diarrhea, and can't drink enough fluids, you may need to stop taking this diabetes medication for a few days.
- You may feel metallic taste.
- If you are going for medical test using dye, or planning to opt for any surgery, then inform your doctor about your metformin intake. He will instruct you to stop taking metformin for some specific period.
α -glucosidase Inhibitors
α -glucosidase inhibitors are of two types, acarbose and miglitol. They block the enzymes of digestive system which are responsible to break down the starches you eat. The sugar produced is absorbed slowly and helps prevent the rise of blood sugar level throughout the day, but usually right after meals. Drugs under this class are acarbose (Precose) and miglitol (Glyset).
- Stomach problems such as gas, bloating and diarrhea, that is temporary.
- High dosages may cause permanent changes in liver.
The generic names for these drugs are pioglitazone (Actos) and Troglitazone (Rezulin), Rosiglitazone (Avandia). Troglitzeone (Rezulin) was banned in March 2000 as it causes liver failure. Thiazolidinediones drug makes your body tissue more sensitive to insulin. The insulin can then move glucose from your blood into your cells for the production of energy.Side Effects:
- It may affect your liver function and lead to nausea, vomiting, stomach pain, lack of appetite, tiredness, yellowing of the skin or whiteness in the eyes, or dark-colored urine.
- If you take birth control pills, this drug may decrease its effectiveness in preventing pregnancy.
- Unusual weight gain.
- Loss of appetite may develop risk of anemia which will make you feel tired.
- Swelling in the legs or ankles.
Meglitinides is available with the generic name Repaglinide (Prandin). It helps your pancreas make more insulin right after meals which lowers blood sugar. This effect is much similar to short acting sulfonylureas. Meglitinides works quickly, and the results fade rapidly, so your doctor might prescribe Repaglinide only or with Metformin.
- weight gain
- low blood sugar
|Insulin||Insulin receptor||Liver, fat, muscle||Hypoglycemia, weight gain|
|Sulhponylureas (e.g. glibenclamide plus nateglinide and repagnilide)||SU receptor/K+ ATP channel||Pancreatic β-cell||Hypoglycemia, weight gain|
|Metformin-biguanides||Unknown||Liver (muscle)||Gastrointestinal disturbances, lactic acidosis|
|Acarbose||α- glucosidase||Intestine||Gastrointestinal disturbances|
|Pioglitazone, rosaglitazone (thioazolidinediones)||PPARγ||Fat, muscle, liver||Weight gain, Oedema, Anaemia|
Insulin resistance is routinely present; a treatment that improves insulin sensitivity of muscle, adipose tissue, liver, or a combination of these should also benefit nearly all patients. Also, neither insulin secretion nor insulin action is a simple process, and single-agent regimens may not adequately restore either of these two functions. Moreover, changes of insulin resistance at various sites may not always be the same and a treatment targeting hepatic sensitivity may have more effect on fasting hyperglycemia.
Given these complexities, therapy of Type 2 diabetes should strive to do several things at once. Both insulin deficiency and insulin resistance should be treated, and both basal and postprandial hyperglycemia should be addressed. Since no single agent can do all this, combinations will routinely be needed.
Evidence is accumulating that the longer-acting agents have less tendency to cause hypoglycemia than the others, especially glibenclamide, Repaglinide and nateglinide are insulin secretagogues which, like sulfonylureas, act by binding to the KATP –channel complex on beta cells, but they have more rapid onset and shorter duration of action than the sulfonyl ureas. Due to this difference, they may have slightly more effect on postprandial hyperglycemia than sulfonylureas.
The α-glucosidase inhibitors acarbose and miglitol delay absorption of dietary carbohydrate by blocking digestion of starches in the upper small intestine, and thereby reduce the postprandial glycemic peaks.
ALTERNATIVE THERAPY: USE OF PLANT PRODUCTS AS POTENTIAL ANTI- DIABETIC AGENTS
Type 2 diabetes has become a global epidemic. Modern medicines, despite offering a variety of effective treatment options, can have several adverse effects. Ayurveda, a science that uses herbal medicines extensively, originated in India. Of considerable interest is the adoption of Ayurveda by the mainstream medical system in some European countries (e.g., Hungary), emphasizing this modality is increasing worldwide recognition. From ancient times, some of these herbal preparations have been used in the treatment of diabetes (Saxena et al., 2004). World Health Organization (WHO) recommendations (WHO, 1980) on the use of alternative medicines for treating diabetes mellitus provide an impetus for research in this area. Currently, the focus of research in diabetes includes discovering newer antidiabetic agents as well as isolating the active compounds from herbal sources that have been documented to have antidiabetic properties as have been described in ancient texts (Tripathi, 1998).
More than 800 plants are used as traditional remedies in some form or another for the treatment of diabetes according to ethnobotanical information (Ajgaonkar, 1979; Alarcon- Aguilara et al., 1998). However, only a few herbs have been evaluated scientifically.
Azadirachta indica, Aloe vera, Eucalyptus globulus, Phaseolus vulgaris, Salvia lavandufolia, Syzygium jambolana, Lavandula stoechas, Cuminum nigrum, Coriandrum sativum, Melia azadirachta, Amanita phalloides, Opuntia streptacantha are some of the traditional anti-diabetic plants with scientific and/or medical support for the hypoglycemic effect, although the active principles are unestablished.
A wide array of active principles from plants, particularly disulfides, alkaloids, glycosides, and polysaccharides, peptidoglycans and diguanides have demonstrated hypoglycemic activity consistent with their possible use in the treatment of diabetes mellitus. Raw onion bulbs (Allium cepa) and garlic cloves (Allium sativum) have long been used as dietary supplements for the traditional treatment of diabetes in Asia, Europe, and the Middle East. Several plants are deemed to contain hypoglycemic alkaloids. Leaf infusions and decoctions of Catharanthus roseus (periwinkle) are widely used as a traditional treatment for NIDDM (Non insulin dependent diabetes mellitus). The seeds of Trigonella foenumgraecum (fenugreek) are more widely recommended for NIDDM patients. Various glycoside containing fractions have been implicated as hypoglycemic constituents of traditional antidiabetic plants. Gymnema sylvestre (gurmar) is used extensively as a treatment for NIDDM patients, in Asia and has been studied in healthy and alloxan-induced diabetic rabbits (Ajgaonkar et al., 1979). Leaves of Vaccinium myrtillus (bilberry) were widely used as a treatment for diabetes before the availability of insulin, and an active glycoside principle, neomyrtillin was extracted. Cyamopsis tetragonolobus (Indian cluster bean) is recognized in Asian folklore as a useful aid for the diabetic subject. Another group of hypoglycemic principles is the hypoglycins (aminopropylpropionic acid derivatives isolated from the unripe fruits of Blighia sapida (ackee fruit), a traditional treatment for diabetes in Central America and Africa.
Of all these plants described earlier for the treatment of diabetes Momordica charantia (Fig. 6) has great importance in current scenario for the same. M. charantia, a climber belonging to family Cucurbitaceae, is commonly known as bitter gourd, bitter melon and karela has shown promising effects in prevention as well as delay in progression of diabetic complications (nephropathy, neuropathy, gastro- paresis, cataract and insulin resistance) in experimental animals. The hypoglycemic chemicals of M. charantia are a mixture of steroidal saponins known as charantins, insulin-like peptides and alkaloids and these chemicals are concentrated in fruits of M. charantia (Grover et al., 2004). The mechanisms proposed for the hypoglycemic effect of M. charantia have been attributed to an inhibitory effect on glucose absorption in the intestine (Meir and Yaniv, 1985), enhanced insulin release from beta cells (Higashino et al.,1992), an extra pancreatic effect via increased glucose uptake by tissues in vitro (Welihinda et al., 1986), and due to inhibition of glucose-6-phosphatase and fructose-1,6-bisphosphatase in the liver and stimulation of red-cell and hepatic glucose-6-phosphate dehydrogenase activities ( Shibib et al., 1993).
Due to economic constraints, providing modern medical healthcare in developing countries such as India is still a far-reaching goal. Despite the choice of pharmacologic agents, physicians must stress the non-pharmacologic approaches of diet modification, weight control and regular exercise. Pharmacologic approaches must be based on patient characteristics, level of glucose control and cost considerations. Combinations of different oral agents may be useful for controlling hyperglycemia before insulin therapy becomes necessary. Apart from all these therapies for the treatment of diabetes discussed above, in present world, people are looking forward for herbal medicines with very less side effects. Plants like Momordica charantia, Trigonella foenum-graecum, Curcuma longa, Tinospora cordifolia, and Azadirechta indica getting a great attention for the treatment of this incurable and worldwide disease.
Alarcon-Aguilara, F. J., Roman-Ramos, R., Perez-Gutierrez, S., Aguilar-Contreras, A., Contreras-Weber, C.C., Flores-Saenz, J.L. (1998) Study of the anti-hyperglycemic effect of plants used as antidiabetics. J. Ethnopharmacol., 61:101–110.
Albert, K.G. and Zimmet, P. Z. (1998) New diagnostic criteria and classification of diabetes – again? Diabetic Medicine, 15: 535-6.
Ajgaonkar, S. S. (1979) Herbal drugs in treatment of diabetes; A review. IDF Bull., 24:10–17.
Beck, N. H. and Groop, L. C. (1994) Metabolic and genetic characterization of prediabetic states. Sequence of events leading to noninsulin-dependent diabetes mellitus. J. Clin. Invest., 94: 1714–1721.
Butler, A. E., Janson, J., Bonner-Weir, S., Ritzel, R. A., and Butler, P. C. (2003) Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes, Jan;52(1):102-110.
Cockram, C. S. (2000) Diabetes mellitus: perspective from the Asia-Pacific region. Diabetes Research and Clinical Practice, 50: Suppl. 2: S3–S7.
David, E. M. (2001) New drug targets for type 2 diabetes and the metabolic syndrome. Nature, 414: 821-827.
Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications. WHO report. (1999)
Donath, M.Y., and Halban, P. A. (2004) Decreased beta-cell mass in diabetes: significance, mechanisms and therapeutic implications. Mar;47(3): 581-589.
Expert committee (1997) Expert committee on the diagnosis and classification of diabetes mellitus: report sof the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care, 20: 1183-97.
Fagot-Campagna, A. Narayan, K. (2001) Type 2 diabetes in children. Br. Med. J., 322: 377-387.
Fagot-Campagna, A. (2000) Type 2 diabetes among North American children and adolescent: an epidemiologic review and a public health perspective. J. Pediatr., 136: 664-672.
Grover, J. K. and Yadav, S. P. (2004) Pharmacological actions and potential uses of Momordica charantia: a review. J. Ethnopharmacol., 93: 123–132.
Higashino, H., Suzuki, A., Tanaka, Y. and Pootakham, K. (1992) Hypoglycemic effects of siamese Momordica charantia and Phyllanthus urinaria extracts in streptozotocin-induced diabetic rats. Nippon Yakurigaku Zasshi, 100: 415–421.
Kahn, S. E. (2001) Importance of ß-Cell Failure in the Development and Progression of Type 2 Diabetes. The Journal of Clinical Endocrinology & Metabolism, Vol. 86, No. 9, 4047-4058.
King, H. R., Aubert, R. and Herman, W. (1998) Global burden of diabetes, 1995-2025. Prevalence, numerical estimates and projections. Diabetes Care, 21: 1414-1431.
McCance, D. R., Hanson, R. L., Charles, M. A., Jacobsson, L.T.H., Pettitt, D.J. and Bennett, P. H. (1994) Comparison of tests for glycated haemoglobin and fasting and two hour plasma glucose concentrations as diagnostic methods for diabetes. Br. Med. J., 308: 1323–28.
Meir, P. and Yaniv, Z. (1985) An in vitro study on the effect of Momordica charantia on glucose uptake and glucose metabolism in rats. Planta Med, 33:12–16.
Misra, A., Pandey, R. M., Rama D. J., Sharma, R., Vikram, N. K. and Khanna, N. (2001) Int. J. Obesity, 25: 1–8.
Mohan, V., Shanthirani, S., Deepa, R., Premalatha, G., Sastry, N. G. and Saroja, R. (2001) Diab. Med., 18: 280–287.
Oubre, A.Y., Carlson, T.J., King, S.R., Reaven, G.M. (1997) From plant to patient: an ethnomedical approach to the identification of new drugs for the treatment of NIDDM. Diabetologia, 40 (5), 614-617.
Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (1999) Diabetes Care, 22[Suppl 1]:S5–S19.
Sadikot, S. M., Nigam, A., Das, S., Bajaj, S., Zargar, A. H. and Prasannakumar, K. M. (2004) The burden of diabetes and impaired glucose tolerance in India using the WHO 1999 citeria: prevalence of diabetes in India study (PODIS). Diabetes Research and Clinical Practice, 66: 301-307.
Sarah, W., Gojka, R., Anders, G., Richard, S. and Hilary, K. (2004) Global Prevalence of Diabetes: Estimates for the year 2000 and projections for 2030. Diabetes Care, 27: 1047–1053.
Saxena, A. and Vikram, N. K. (2004) Role of Selected Indian Plants in Management of Type 2 Diabetes: A Review. The Journal of Alternative and Complementary Medicine, 10(2): 369–378.
Shibib, B. A., Khan, L. A. and Rahman, R. (1993) Hypoglycemic Activity of Coccinia indica and Momordica charantia in diabetic rats. Biochem. J., 292: 267-270.
Tripathi B. (1998) Charak Samhinta, 5th ed., Vol. 2. Varanasi, India: Chaukhamba Surbharti Prakashan.
Welihinda, J. and Karunanayake, E. H. (1986) Extrapancreatic effects of Momordica charantia in rats. J. Ethnopharmacol., 17: 247–255.
Weir, G. C., Bonner-Weir, S. (2004) Five stages of evolving beta-cell dysfunction during progression to diabetes. Diabetes, 53(suppl 3):S16-S21.
Zimmet, P. (1999) Diabetes epidemiology as a tool to trigger diabetes research and care. Diabetologia, 42: 499-518.
Zimmet, P. (2000) Globalization, coca-colonization and the chronic disease epidemic: can the doomsay scenario be averted? J. Intern. Med., 247: 301-310.