Diabetes mellitus is a chronic disease which affects an estimated 175 million people worldwide and which causes serious health complications including renal (kidney) failure, heart disease, stroke and blindness. It is a leading cause of adult blindness and end stage renal disease.

     Approximately, 60-70% of diabetics develop some form of peripheral nerve damage which can lead to amputation. Additionally, diabetics are two to four times more likely to have heart disease or to suffer stroke. It has been projected that by the year 2010, the number of diabetics worldwide will increase from 175 million to 240 million. Diabetes is therefore, identified as one of the major public health challenges of the 21st century.

Type 1

This type of diabetes develops when the body’s immune system destroys pancreatic beta-cells, the cells responsible for making the hormone insulin that regulates blood glucose. The result is a pancreas that produces little or no insulin. The mechanism of attack on the beta-cells is unknown but genetic, autoimmune, environmental and viral factors have been implicated.

The classical symptoms include thirst, polyuria, wasting / or keto-acidosis. This form of diabetes has been reported among children and young adults. They need several injections of insulin a day or an insulin pump to survive. This condition has been reported in 5-10% of all diagnosed diabetic cases.

Type 2

Type 2 diabetes can further be divided into non-obese, obese and maturity-onset diabetes of the young. This accounts for 90-95% of all diabetic cases. This is the most common form of diabetes.

Patients with Type 2 have two defects:

a. abnormal insulin secretion [leading to insufficient insulin]

b. resistance to insulin action in target tissues [inability to utilize the insulin that is produced]

In insulin deficient diabetes, the secretion of the hormone is either totally defective or severely impaired. The failure of the pancreatic beta-cells to secrete insulin probably involves genetic, viral and auto-immune processes among others. Viral infections are capable of damaging the pancreas. To become diabetic, an individual must not only be affected by viruses but must also develop antibodies to islets cells.

Type-2 diabetes is associated with obesity, older age (> 40 years), family history, physical inactivity, impaired glucose tolerance, prior history of gestational diabetes and certain races. It may present with classical symptoms but often is asymptomatic. Despite the presence of hyperglycemia, the concentration of ketone bodies in the blood and urine are low. Today this condition is increasingly being reported among children and adolescents. [Individuals who are at high risk of developing Type 2 diabetes].

Gestational diabetes

This condition has been reported among pregnant women and treated with insulin. It can have deleterious consequences for both the mother and the fetus. This condition is temporary and disappears after birth. However, women with this form of diabetes have a higher incidence of developing Type 2 diabetes later.

Insulin resistance

Every cell in our body requires energy in order to function. The body’s primary energy is derived when our body breaks down carbohydrates into glucose in the blood stream. The more carbohydrates are consumed, the higher the blood glucose levels. The glucose from the digested food circulates in the blood as a ready source of energy. The beta-cells of the pancreas produce a hormone called insulin whose function is to push the blood glucose into the various cells of the body.

On each cell surface are insulin receptors whose function is to regulate the inflow of glucose to provide the cells with energy. The insulin binds to the receptor site on the outside of cells and acts as a key to open into the cell through which glucose can enter. In a healthy individual, the pancreatic beta-cells produce exact amount of insulin needed to match the amount of food ingested. The controlled system of the body maintains and regulates the blood glucose. Blood glucose has to remain within normal limits i.e. between 70 to 120 mg / dl (milligrams per deciliter) after a heavy meal. In diabetes mellitus, this metabolic process is altered.

Due to factors identified (that includes life-style changes and high carbohydrate diet] and with so much insulin [consequences of high insulin elevation and resistance], these receptors begin to malfunction. Blood glucose builds up in the blood stream and the cells starve. With defects on the receptors, the body needs to produce more insulin to push the glucose into the cells. This process continues and eventually type 2 diabetes sets in. Once the blood glucose reaches a certain level, unused glucose naturally spills into the urine as the body’s natural response is to get rid of excess glucose. This results in frequent urination (polyuria) and unquenchable thirst (polydipsia) because of the continued removal of fluids to transport the extra glucose into the urinary bladder. The body then is forced to turn to other sources of energy in the body (polyphagia). It breaks down the stored fats for its glucose. A by-product of this is the ketone-bodies which builds up in the blood and may result in dangerous events. Keto-acidosis has been reported in 10% of diabetic deaths. [warning signs and symptoms of diabetes].

Long term complications of this disease affecting the vasculature, eyes, kidneys, nervous system and the probable developments of drug dependency in a large number of patients are the two major sets of problems that are confronted all around the world.

The classical triad of diabetes is:

Polydipsia - The increased level of glucose in the blood leads to hyper-osmolarity and depletion of intra-cellular water. This triggers thirst centers in the brain leading to thirst.

Polyphagia - Insulin deficiency leads to catabolism of proteins and fat leading to a negative energy balance and increased appetite.

Polyuria - Increased blood glucose spills over into the kidney as well as promoting an osmotic diuresis leading to increased urination.

Consequences of high insulin elevation and insulin resistance

• Weight gain
• Fat accumulation and storage leading to obesity
• Heart diseases
• Hardening of the arteries
• Increased blood cholesterol and triglyceride levels
• Kidney diseases
• Mineral and vitamin deficiencies

Warning signs and symptoms

• Frequent thirst
• Frequent urination and urine is foamy
• Unexplained weight loss
• Increased hunger
• Lethargy and tiredness
• Weakness
• Frequent or recurring skin infections
• Extreme fatigue
• Wounds that don’t heal
  

Long-term complications

• Impotence and loss of libido
• Numbness and pain in the extremities
• Blurry vision leading to blindness
• Sweet-smelling breath (ketoacidosis –effect of fat metabolism)
• Amputations f the lower limbs
• Kidneys have repeated episodes of infections leading to a non-functioning kidney.
• Skin may show rare changes –an unusual degenerative change occurring within the dermis.
• Cardiovascular diseases and stroke
• Peripheral neuropathy –pain and numbness in the extremities usually in the legs and feet

Individuals who are at high risk of developing Type 2 diabetes

• People who are obese (more than 20% above their ideal weight)
• Family history of diabetes
• Have a blood pressure above 140/90 mm Hg or above
• Have a high density lipoprotein cholesterol less than or equal to 35 mg/dL and /or a triglyceride level greater than or equal to 250 mg/dL
• Have impaired glucose tolerance or impaired fasting glucose on previous testing
• Females who have been diagnosed with gestational diabetes or have delivered a baby weighing more than 4 kg
• High-risk ethnic population [Indians, Hispanic, native American, African-American]
• People on some medications [e.g. cardiac drugs, hormones, anti-inflammatory drugs, anti-depressants, adrenergic agonists drugs etc.] can impair body’s use of insulin, impair glucose absorption etc.

Screening methods and Diagnosis

1. Glucose measurement in blood plasma
2. Venous plasma glucose measured one hour later
3. In pregnant women at 24th and 28th week – administering 50 g oral glucose load –identify glucose intolerance
at week 24
4. A value of >= 140 mg/dL (7.8 mmol/L) in venous blood glucose –do GTT (Glucose Tolerance Test)

Diagnosis

1. Fasting over-night for at least 8 hours but not more than 14 hours
2. dminister 100 g oral glucose
3. Plasma glucose is measured fasting and at 1, 2 and 3 hours after oral glucose load
4. Meeting the following venous glucose concentrations for positive diagnosis;

Fasting 1 hour 2 hours 3 hours

= 105 mg/dL = 190 mg/dL = 165 mg/dL = 145 mg/dL

[5.8 mmol/L] 10.6 mmol/L] [9.2 mmol/L] [8.1 mmol/L]

5. Hemoglobin A1C (HBA1C) This is based on the level of glycosylated hemoglobin, a substance that accumulates over time in the blood. In poorly controlled diabetics, the figure is usually high. Because it is a test of an accumulated substance rather than an indicator of a momentary blood glucose level, the HBA1C indicates the level of glucose control in the last two to three months.

GOALS FOR BLOOD GLUCOSE IN THE CONTROL OF DIABETES

Goal	Acceptable		Ideal
	mmol/L	mg/dL	mmol/L	Mg/dL
Fasting	3.3-7.2	60-130	3.9-5.6	70-100
Preprandial	3.3-7.2	60-130	3.9-5.6	70-100
Postprandial (1hr)	<11.1	<200	<8.9	<160
3 A.M.	>3.6	>65	>3.6	>65

Acceptable refers to goals for conventional therapy, while ideal indicates goals with intensive insulin therapy Adapted from: Harrison’s Principles of Internal Medicine -13th Edition

GLYCOSYLATED HEMOGLOBIN HBA1C

Every person, whether or not he or she has diabetes, has a certain amount of glycosylation present. Because of more glucose in their blood, people with diabetes have a greater amount of glycosylation present. A low result on the glycosylated hemoglobin test is a good result. If your test is in the good control category, you can be satisfied that your diabetes management plan is working well. If the results are in the marginal category, some fine tuning of your treatment plan may be needed. A poor result can be improved. This test gives you valuable feedback of how well you are controlling your diabetes. Ask your doctor to help you in improving your diabetes management. Your physician will help you determine your goal range for glycosylated hemoglobin. If you are Type 1 or Type 2 diabetic, you should be having this test done every 90 days (3 months); there is no reason that you should not.

Preventing diabetic complications*

Glucose control - Clinical studies carried out in various parts of the world have shown that improved glycemic control benefits people with either type 1 or type 2 diabetes. It has been found that for every1% reduction in the results of HBA1C blood tests, the risk of developing micro-vascular diabetic complications (retinopathy –eye diseases), nephropathy (kidney diseases) and neuropathy (nerve diseases) reduced by 40%.

Blood pressure control - Blood pressure control reduces cardiovascular disease (heart disease and stroke) by approximately 33-50% and also reduces micro-vascular disease (eye, kidney and nerve disease) by approximately 33%.

For every 10 millimeter drop of mercury (mm Hg) in systolic pressure, the risk for any complication related to diabetes is reduced by 12%.

Blood lipids control - Improved control of cholesterol and lipids (such as HDL, LDL and triglycerides) can reduce cardiovascular complication by 20 to 50%.

Eye diseases - Detecting and treating diabetic eye disease early can reduce the development of vision loss by 50 to 60%.

Foot care - Comprehensive foot care can reduce amputation rate by 45 to 85%.

Kidney disease - Detecting and treating early kidney disease can reduce development of kidney failure by 30 to 70%.

*Source: Center for Disease control and prevention –Diabetes Fact Sheet

Treatment for diabetes –allopathic drugs

Traditionally, type-2 diabetes mellitus has been controlled with dietary restriction, exercise, oral hypoglycemic drugs such as insulin-sensitizers, a-glucosidase inhibitors, glucagons-like peptide 1, sulphonylureas and biguanides. They have remained the main stay of oral hypoglycemic treatment for more than 30 years. However, maintaining glucose control in these patients remains a difficult task. Most of the modern diabetic drugs have succeeded in treating symptoms of diabetes but have failed to suppress the progression of diabetes and diabetic complications.

In the last decade, with increasing morbidity and mortality and severe side effects attributed to drugs and drug interactions there has been a growing trend among those ill to seek alternative remedy of their ailing conditions.

The ultimate aim of treatment would be to find a way to increase insulin sensitivity and help to get the glucose out of the blood and into the cells for metabolism and convert it into energy. One ancient field of medicine that has been successful in providing alternative drugs and addresses the main issues in diabetes in the field of diabetes is Ayurveda.

What is Ayurveda medicine?

Ayurveda, the science of life, prevention and longevity is the oldest and most holistic medical system in the world. This medical system originated in India about 5000 years ago. Ayurveda is derived from a Sanskrit word made of the words “ayus” and “veda”. “Ayus” means life and “veda” means knowledge or science. Thus the term “ayurveda” means ‘the knowledge of life’ or the ‘science of life’. In principle, “ayu” comprises of the mind, body, senses and the soul.

The aim of this holistic system is to prevent illness, heal the sick and preserve life. This includes protecting health and prolonging life and eliminating diseases and dysfunctions of the body.

Ayurveda is based on the fact that the universe is made up of five elements: air, water, fire, earth and ether. These are represented in humans by three bodily humors or ‘doshas’ called ‘vata’, ‘pitta’ and ‘kapha’. They govern all metabolic activity – anabolism (kapha), catabolism (vata) and metabolism (pitta). When any of the doshas accumulate in the body beyond undesirable levels, the body losses its balance and the state of disease sets in. When the three doshas are balanced one is in good health. This form of medicine suggests specific life-style and nutritional guidelines to help individuals to reduce the excess doshas.

Ayurvedic therapy

Therapies used in Ayurvedic medicine may include herbal supplements, mineral and fruit / vegetable preparations plus cleansing processes and dietary modifications. The principle of Ayurvedic remedies is to act on the total body, strengthen the power of resistance and promote healing. Thus, this system provides new vital energy, prevents and corrects the ageing process. It also helps to combat illnesses and frees one of psychological burdens.

Ayurvedic treatment of diabetes

Diabetes in Sanskrit is “madhumeha”, ‘madhu’ meaning sweetness and ‘meha’ excessive urination. Indian physicians have known this disease for several thousand years. The earliest description of ‘madhumeha’ is found in one of the sacred Vedas, the Atharvaveda that dates back to around 1500 to 1000 B.C. The great physician Caraka in Caraka Samhita (a medical treatise) described the etiology, symptomatology, pathology, prognosis and management principle of diabetes. He defined ‘madhumeha’ as a disease where the patient passes urine which is characteristically sweet, astringent and rough. He described twenty variations or presentations of diabetes. Another Physician, Vagbhata, who wrote the third of the three most important treatises added sweetness to be present in the whole body. The great physician Susruta who wrote the major surgical text in Ayurveda used the term ‘kshaudrameha’, which means the urine resembles honey and acquires the sweet taste. Another term ‘dhatupaka janya vikruti’ was used where ‘dhatupaka’ means metabolism. When the full term is expressed it means derangements in body tissues takes place due to discrepancies in metabolism.

Principle of treatment

Physician Caraka classified patients with ‘madhumeha’ into 2 groups according to their vitality, constitution and disease etiology. Patients were either obese and strong or lean and weak. Treatment protocols were different for each type. While cleansing processes was part of the treatment, herbal therapy and diet was used.

Ayurveda Pharmacopoeia

The pharmacopoeia of India is very rich in herbal treatment for diabetes. Eighty five percent of the 20 anti-diabetic plants widely used around the world has been prescribed in India. The Ayurvedic herbal supplements for diabetes have been selected on the principles of rasa (taste), guna (physicochemical properties), veerya (potency), vipaka (post-digestive effect) and prabhava (unique effect of the supplement). Each of the principles in the supplement is believed to have specific effect on the doshas and functions of the body, which is how they exert their therapeutic effects. These medicinal substances bring about a balance of three bodily doshas.

Herbs and vegetable products comprise the most extensive portion of the Ayurvedic Materia medica. Any part of the plant could be used medicinally. Traditionally, the entire herb or whole plant extract are used rather than just isolated ingredient as used in allopathic drugs. In earlier Ayurvedic texts, 600 herbs have been mentioned to have anti-diabetic potency. Today modern Ayurveda has identified more than 1200 plants.

Briefs of individual herbs

Azadirachta indica (Margosa or Neem) Parts used: bark Description Available throughout India in deciduous forests and is also widely cultivated. It is a medium large sized tree 10-15 m in height with a clear bole of grayish to dark tuberculated bark; compound leaves, imparipinnate leaflets, sub-opposite, serrate and very obliques at base; flowers, cream or yellowish-white in auxillary panicles, staminal tubes, conspicuous, cylindrical, widening above, lobed at the apex. Fruits are one seeded drupes with woody endocarp, cotyledons thick, fleshy and oily. It is hardy, quick growing, ever green showy tree.

The herb has anti-septic, anti-inflammatory, anti-bacterial and anti-hyperglycemic [insulinotropic action] properties. It is used in healing chronic wounds, diabetic foot and gangrene developing conditions. The hepato-renal protective activity and hypo-lipidemic effect has been recently published. It is a blood purifying agent and a prophylactic in micro-angiopathy.

Phyllanthus emblica (Indian gooseberry) Parts used: dry fruit, leaves, bark and root bark. Description It is found growing throughout India in the deciduous forests and on hill slopes and cultivated in the plains. This is a small to medium sized deciduous tree, 8-18 m in height with thin light grey bark exfoliating in small thin irregular flakes. The leaves are simple, very many sub-sessile, closely set along the branchlets, districhous, light green having the appearance of pinnate leaves. The flowers are greenish yellow in axillary fascicles, unisexual, males numerous on short tender pedicles, females few, sub-sessile, ovary three celled. The fruits are globose, fleshy, plae-yellow with six obscure vertical furrows, enclosing 6 trigonous seeds in 2 seeded, 3 crustaceous cocci. The small leaves are set in pinnate fashion, very closely. Fruits are 1.5-2.5 cm in diameter.

Besides being a rich source of vitamin C, the herb is considered one of the best cardiac, neuro-hormonal and liver-tonic [hepato-protective]. It has been scientifically proven that it modifies hepato-toxic and reno-toxic effects. In Ayurveda, based on its anti-bacterial and anti-inflammatory activity it has been accredited as a prophylactic medicine for preventing ophthalmic problems (that includes retinopathy) and different diabetic conditions. It also has anti-ageing and rejuvenation properties. The herb has gained scientific acceptance that it supports the blood vessels, nerves at the cellular levels for improving the immunologic barrier as well as smooth maintenance of circulation and conduction of impulses.

Curcuma longa (Turmeric) Parts used: dry rhizome Description: It is available throughout India and cultivated. It is a perennial herb, 60-90 cm in height with a short stem and tufts of erect leaves. The rhizome is cyclindrical, ovoid, orange-colored and branched. The leaves are very large, petioles as long as the blade, oblong, lanceolate, tapering to the base up to 45 cm long. The flowers are pale yellow in spikes concealed by the sheathing petioles. The flowering bracts are pale green. It is a fleshy rooted herbaceous plant.

It has antiseptic, anti-bacterial activity and anti-inflammatory properties. It is well-known as a powerful blood purifier. Helps in healing chronic wounds quickly particularly corneal wound healing. Recent research shows that it has atherogenesis prevention property [anti-atherosclerotic effect], is a good antioxidant, possesses immuno-modulatory and cytotoxic, activity, inhibits aggregation and alters eicosanoid metabolism in human blood platelets and also has hypolipidemic action. It is vascular supportive and useful in conditions where gangrene development is a possibility as in diabetic foot. Has a protective effect on liver damage. It has been prescribed since time immemorial in Ayurvedic mewdicine for controlling diabetic complications, Experimental evidence in rats show that it inhibits LDL oxidation and has hypocholesterolemic effect.

Trigonella foenum-graceum (Fenugreek) It grows wildly in Kashmir, Punjab and upper Gangetic plains. It is also cultivated in many other parts of India as a pot-herb. It is an aromatic, erect, annual plant 30-60 cm in height. The leaves are pinnate, 3-6 folister while the leaflets are toothed. The flowers are white or yellowish white. The fruit pods are 5-7.5 cm long with long persistent beak, 10-20 per pod, greenish-brown along with a deep groove across one corner.

Trigonella has been known in Ayurveda to be the best known anti-hyperglycemic herb and has been in use for more than 2000 years. It has been recently proven that this herb possesses anti-hyperglycemic property. It is also a powerful anti-inflammatory herb with anti-bacterial activity. It is good in toxic conditions and disorders of the liver. It prevents tissue resistance and enhances intra-extra cellular transportation.

Rotula aquatica (Country borage) Parts used: Root Description: It is available throughout India especially in the sandy and rocky beds of streams. It is a small shrub, much branched, 60-180 cm in height having numerous lateral, short and arrested branchlets, which often root. The leaves are simple, nearly rounded at the apex, more or less hairy, sessile and spatulate, crowded at the branches. The flowers are pink, having short pedicellate, single or couple together on short branches which s lateral. The fruits are sub-globose, orange and drupes which is tipped with the remains of the style.

Diabetic nephropathy is one of the commonest complications of tissue damage caused by diabetes. This herb is specially used for treating renal pathology such as diabetic nephropathy. The herb is also a powerful laxative and diuretic.

Syzygium cumini (black plum) Parts used: bark, fruit, seeds and leaves. Description It is available throughout India. It is mostly seen in forests up to 1800 meters, usually on river banks and moist areas and also cultivated as shade trees. It is a medium to large sized tree, 20-30 cm in height, having smooth light grey bark with dark patches, simple leaves, opposite, variable in shape, 3cm broad, 10-15 cm long. The flowers are greenish-white or dull white, while the fruits are oblong or ovoid-oblong, dark purple with pinkish juicy pulp and one seeded. These seeds are round and strong. This is a tall and evergreen tree. The leaves are smooth, shining and long.

It is a powerful anti-inflammatory herb and good in toxic conditions and disorders especially affecting the liver. It has been used as an anti-microbial prophylactic in alleviating infections associated with chronic diabetes. It also exhibits hypolipidemic effect. It diminishes tissue resistance and improves intra-extra-cellular transportation.

Terminalia bellerica (Belleric myrobalan) Parts used: bark and fruits Description: This is a genus of 250 species from tropical regions of which 12 are native in India. It is seen throughout India in deciduous forests up to an elevation of 900 meters. These are large trees.. It is a large buttressed, deciduous tree with thick, brownish grey-bark having shallow longitudinal fissures, simple leaves, alternate, long petioles, crowded at the extremities of the branches, broadly elliptic, margins entire, prominent mid-rib on both surfaces. Leaves are alternate or sub-opposite, often with glands on the petiole or on the lower part of the midrib beneath. The flowers are in axillary spikes, longer than petioles. The fruits are ovoid, grey drupes, obscurely s-angled, narrowed into a very short stalk. Plants are propagated by seeds.

This herb provides symptomatic relief of polydipsia and works as a prophylactic in diabetic retinopathy. It also arrests general debility. It possesses rejuvenating property particularly in arresting necrosis.

Terminalia chebula (Chebula myrobalan) Parts used: Dry fruit Description: It is available throughout India in deciduous forests on dry slopes up to 900 meters. It is a moderate to a large sized tree, deciduous, rounded crown and spreading branches with ovate leaves. The flowers are elliptic or obovate and yellowish found in terminal spikes or short panicles. The fruits are glabrous, shining, ellipsoidal, the drupes are ovoid or obovoid, yellow to orange-brown in color, faintly angled, up to 4 cm long. The seeds are hard and yellow while the leaves are covered with hairs. The fruit have specific segments.

It is a prophylactic for diabetic neuropathy and retinopathy. It is an effective antidote for internal inflammatory conditions such as pancreatitis. It is considered rejuvenative and also reverses necrosis. Recent evidence shows that it has anti-oxidant, anti-bacterial, hypolipidemic and cardio-tonic activity. It has been demonstrated that it has anti-mutagenic activity in Salmonella typhimurium and reduces cholesterol induced atherosclerosis in rabbits.

Tribulus terrestris (land caltrop) Parts used: dry whole plant Description: It is a trailing and spreading herb, densely covered with minute hair, compound leaves, in opposite pairs, 3-6 leaflets up to 8 cm long, usually silky flower, white or yellow, solitary, arising from the axils of leaves. The ovary is bristle, style short and stout. The fruits are globose, spinous or tuberculate and often cling to the bodies of animals. The trailing plant is common in sandy soil. The carpels of the fruits resemble a cloven hoof of the cow. It is an annual or perennial prostrate herb with many slender spreading branches.

It is a powerful diuretic, tonic and aphrodisiac. It reduces inflammations, edema, urinary complaints, impotence and painful micturition. It serves as a prophylactic for diabetic nephropathy and is supplementary in healing diabetes induced impotence.

A number of animal experimentation studies (unpublished and published) and human clinical trials (unpublished and published) have been carried out at various medical institutions in India and other parts of the world (in Malaysia, Sudan etc). Most of the toxicological and teratogenicity studies were conducted at the Department of Toxicology, The Frederick Institute of Plant Protection and Toxicology, Padappai, Kanchepuram District, Tamil Nadu, India. The list of studies conducted by this Institute is as follows:

Animal Experimentation - Unpublished data (Reports)

Kandasamy R, Ramachandran PV & Murthy PB. Acute oral toxicity study into a herbal preparation in Wistar Rats.. Kandasamy R, Ramachandran PV & Murthy. A 14 day repeated oral toxicity study with a herbal preparation in Wistar Rat. One animal study (Clinical aspects) was conducted at the National Institute of Nutrition, Indian Council of Medical Research, Hyderabad, India.Giridharan NV. Effect of Cogent db+ on mutant obese rats with impaired glucose tolerance (WNIN/GR-Ob). 2000.

Summary of the animal studies

• The LD50 for Wistar rat of Cogent db+ was considered as greater than 6000 mg/kg body weight.
• The herbal preparation even at the dose of 1000 mg/kg body weight was considered safe in Wistar rats.
• Cogent db+ was not teratogenic in Wistar rats.
• Cogent db+ had exhibited hypoglycemic and hypocholesterolemic effect.
• The general well-being in terms of increased activity was observed in treated animals.

Unpublished human clinical trials are as follows

1. Kuttan R. Clinical evaluation in ten patients taking anti-diabetic herbal preparation (Cogent db+) – first preliminary
study – 1998.
2. Kamath S, Sharat Kumar W, Singh RG, Usha K. Effect of Cogent db+ (a herbal formulation) in the treatment of Diabetes mellitus. Banaras Hindu University, Medical College, Department’s of Pediatrics, Nephrology and Pathology. 2000.**
3. Jayakumar RV. Clinical evaluation of herbal preparation in non-insulin dependent Diabetes mellitus – a double blind placebo controlled trial. Department of Medicine, Medical College Trivandrum, Kerala, India.2000.
4. El-Toum MA. Anti-diabetic activity of Cogent db+ tablets on 30 patients in Khartoum, Sudan. 2000.
5. Cyebele. A randomized clinical trial on 100 diabetic patients with Cogent db+. 2000.
6. Cybele. The utilization of Cogent db+ on the treatment of 80 diabetic patients.

The results of all the unpublished studies can be summarized as follows: In diabetic patients taking the supplement:

• Blood glucose (fasting & post-prandial) was lowered.
• Glycated hemoglobin which was elevated was found to be lowered at the end of three months (HbA1c)
• Consistent decrease in urinary glucose in cases where it was elevated
• Increased tolerance to glucose
• The supplement produced a lowered fasting blood glucose which did not alter even after withdrawing the supplement
• No change in hepatic, kidney or hematological parameters was observed, concluding that the drug did not produce toxicity.
• Patients who were on insulin therapy also showed response and the subsequent insulin requirement decreased at the end of 4 months.**

Published papers

Three animal studies and one human clinical trial papers have been published in reputed International journals.

Animal studies

1. Joy KL, Kuttan R. Anti-diabetic effect of Cogent db+ -a herbal preparation. Amala Research Bulletin 1998; 18: 109-114.

2. Pari L, Saravanan L. Anti-diabetic effect of Cogent db+, a herbal supplement in alloxan-induced diabetes mellitus. Comparative Biochemistry and Physiology 2000; Part C 131: 19-25.

3. Saravanan G, Pari L. Effect of Cogent db+, a herbal supplement on serum and tissue lipid metabolism in experimental hyperglycemic rats. Diabetes, Obesity and Metabolim 2003; 5:

4. Saravanan G, Pari L, Venkateswaran S. Effect of Cogent db+, a herbal supplement, on plasma insulin and hepatic enzymes of glucose metabolism in experimental diabetes. Diabetes, Obesity and Metabolism 2002; 4:

Human Clinical Trial

Shekhar KC, Achike FI, Gurpreet Kaur, Kumar P, Hashim R. A preliminary evaluation of the efficacy and safety of Cogent db+ (An Ayurvedic supplement) in the Glycemic control of patients with Type-2 diabetes. The Journal of Alternative and Complementary Medicine 2002; Volume 8, Number 4; 445-457.

1.Joy KL, Kuttan R. Anti-diabetic effect of Cogent db+ -a herbal preparation.

Summary

Herbal preparation made available by Cybele Laboratories, Cochin was tested for anti-diabetic activity in rats made hyperglycemic by alloxan injection. Oral administration of an extract of the preparation was found to reduce blood glucose in normal rats, rats made diabetic by alloxan injection and rats made diabetic by alloxan injection and in rats loaded with glucose. Effect could be seen within 12 hours at concentration of 100 mg/kg body weight.

Continued administration of the supplement was found to produce further lowering of the blood glucose. There was also a normalization of glycated hemoglobin. The extract was found to improve the body weight and the total WBC. The hepatic function, as seen from the serum glutamate pyruvate transaminase, serum bilirubin and serum lipid peroxidase was found to be normal after the administration of the extract. Similarly, kidney function test showed a positive improvement as seen from the serum creatinine and blood urea nitrogen.

Histopathological analysis indicated that inflammation and necrosis produced by alloxan was reversed by simultaneous administration of this herbal preparation. [Figures 1, 2 and 3]. Comparison with Daonil (a Glibenclamide preparation) indicated that the extract produced more satisfactory performance as seen from the reduction in blood glucose when given orally. The extract did not produce any toxicity even at concentrations of 500 mg/kg body weight, in rats tested. 75% alcoholic extract gave most satisfactory effects followed by water extract.

Figure 1	Figure 2	Figure 3
Normal Tissue	Alloxan treated (infiltration of lymphocytes, plasma cells and polymorphs indicating inflammation and necrosis)	Alloxan and Cogent db treated - normal tissue

2.Pari L, Saravanan L. Anti-diabetic effect of Cogent db+, a herbal supplement in alloxan-induced diabetes mellitus. Comparative Biochemistry and Physiology 2000; Part C 131: 19-25.

Abstract

Cogent db+, a compound herbal supplement was investigated for its possible anti-diabetic effect in alloxan-induced diabetic rats. Oral administration of 0.15, 0.30 and 0.45 g/kg body weight of the aqueous solution of Cogent db+ for 40 days exhibited a significant reduction in blood glucose, glycosylated hemoglobin and increased plasma insulin, total hemoglobin along with anti-hyperlipidemic effects in diabetic rats. The effective dose was found to be 0.45 g/kg body weight. It also prevents body weight loss in diabetic rats. An oral glucose tolerance test (OGTT) was also performed in experimental diabetic rats in which there was a significant improvement in glucose tolerance in rats treated with Cogent db+. A comparison was made between the action of Cogent db+ and a known ant diabetic drug-glibenclamide (600 µg/kg body weight). The ant diabetic effect of Cogent db+ was more effective that that observed with glibenclamide.

3.Saravanan G, Pari L. Effect of Cogent db+, a herbal supplement on serum and tissue lipid metabolism in experimental hyperglycemic rats. Diabetes, Obesity and Metabolim 2003; 5:

Abstract

Aims: We have previously reported the anti-iabetic effect of Cogent db+. The present study with alloxan-induced hyperglycaemic rats is focused on the mechanism of action, specifically on the activity of hepatic lipogenic enzymes, serum and tissue lipids.

Methods: Male Wistar rats body weight of 180-200 g (six normal and 18 diabetic rats) were used in this study. The rats were divided into four groups after the induction of alloxan diabetes: normal rats; diabetic control; diabetic rats given Cogent db+ (0.45 g/body kg weight); diabetic rats given glibenclamide (600 µg/kg body weight). After 40 days treatment, fasting blood glucose, plasma insulin, activities of hepatic lipogenic enzymes, serum and tissue lipids were determined in normal and experimental animals.

Results: Oral administration of Cogent db+ for 40 days resulted in significant reduction in blood glucose, serum and tissue (liver and kidney) lipids, whereas the levels of plasma insulin and the activity of hepatic lipogenic enzymes were significantly increased in alloxan diabetic rats. Similar studies using glibenclamide have been conducted to compare the mode of action of these two drugs.

Conclusions: Thus our study shows that Cogent db+ exhibits a strong antihyperlipidaemic effect which could exert a beneficial action against macrovascular complications (cardiovascular diseases) associated with diabetes mellitus.

4.Saravanan G, Pari L, Venkateswaran S. Effect of Cogent db+, a herbal supplement, on plasma insulin and hepatic enzymes of glucose metabolism in experimental diabetes. Diabetes, Obesity and Metabolism 2002; 4:

Abstract

Aims: The present study was designed to investigate the effect of Cogent db+, a polyherbal drug on blood glucose, plasma insulin and the activities of hepatic glucose metabolic enzymes in alloxan-induced diabetic rats.

Methods: Male Wistar rats body weight of 180-200 g (six normal and 18 diabetic rats) were used in this study. The rats were divided into four groups after the induction of alloxan diabetes. In the experiment, six rats were used in each group. Group 1, normal rats given 2 ml of saline; Group 2, diabetic control rats given 2 ml of saline; Group 3, diabetic rats given aqueous solution of Cogent db+ (0.45 g/kg body weight);; and Group 4, diabetic rats given aqueous solution of glibenclamide (600 µg/kg body weight). The treatment was given for 40 days. After the treatment, fasting blood glucose, plasma insulin, urine sugar and the activities of hepatic glucose metabolic enzymes were determined in normal and experimental animals.

Results: Treatment with Cogent db+ resulted in a significant reduction in blood glucose and the activities of glucose-6-phosphatase and fructose-1,6-bisphosphatase in the liver, whereas the level of plasma insulin and hepatic hexokinase activity were significantly increased in alloxan-diabetic rats.

Conclusions: The present investigation suggests that Cogent db+ controls the blood glucose level by increasing glycolysis and decreasing gluconeogenesis with a lower demand of pancreatic insulin than in untreated rats. This is possible because it regulates the acitivities of hepatic glucose metabolic enzymes.

Shekhar KC, Achike FI, Gurpreet Kaur, Kumar P, Hashim R. A preliminary evaluation of the efficacy and safety of Cogent db+ (An Ayurvedic supplement) in the Glycemic control of patients with Type-2 diabetes. The Journal of Alternative and Complementary Medicine 2002; Volume 8, Number 4; 445-457.

Abstract

Objectives and study design: A non-randomized, non-placebo-controlled trial to evaluate the efficacy of Cogent db+ (an herbal preparation; Cybele Herbal laboratories [PVT] Ltd. Kochi, Kerala State, India) as an adjuvant in the treatment of patients with type 2 diabetes was carried out during a 3-month period.

Settings/location: This study was conducted in two major peripheral clinics of Kuala Lumpur in the Klang Valley, Malaysia.

Subjects

A total of 39 Cogent db+ -treated cases and 40 age-matched controls were recruited for this preliminary study. Nineteen (19) subjects (10 and 9 from control and treatment groups, respectively) dropped out of the study leaving a total of 60 subjects (30 each for control and treatment groups) who completed the study.

Interventions: All subjects in the treatment group were given Cogent db+ (2 tablets three times daily after each meal) in addition to the regular allopathic drugs (Daonil [Aventis Farma, SA Petaling Jaya, Selangor State, Malaysia] and Diamicron [Sevier, Bangkok, Thailand] with or without Metformin [Upha Corporation, Bangi, Selangor State, Malaysia] that they took in common with the control group.

Outcome measures: Thirty-two (32) clinical variables were investigated, including liver enzymes, kidney function tests, hematologic parameters, blood glucose, insulin and C-peptide assays.

Results: At the end of three months it was found that there was a significant decrease in the levels of fasting and postprandial blood glucose, cholesterol, triglycerides, glycated hemoglobin (HBA1c) and fasting insulin in the treatment group compared to the controls. Cogent db+ did not alter the liver function tests, hematologic parameters or the kidney function tests.

Conclusions: These results concur with earlier animal studies that indicate that Cogent db+ is safe, reliable, tolerable and efficacious in the control of type 2 diabetes mellitus.

Is a potent anti-diabetic supplement as revealed by its blood and urinary glucose lowering effect, significant reduction in HBA1c, glycated hemoglobin and proteinuria0

Cogent db+ USED AS AN ADJUVANT THERAPY MAY HELP: Enhance beta-cells response to insulin Normalize blood glucose Sustain energy by promoting effective utilization of glucose Improve liver functions and restore liver enzymes Improve kidney functions Prevent diabetic complications Reduce the risk of diabetic gangrene Improve libido and general vitality Rejuvenate the pancreas Reduce cholesterol and triglycerides

MANAGEMENT OF DIABETES USING COGENT Db+

• Visit your personal Physician to determine whether you are diabetic·
• If you are already a confirmed diabetic check your glycosylated or glycated hemoglobin and blood glucose levels (base-line data)
• Take two tablets of Cogent db+ after breakfast and 2 tablets of Cogent db+ after dinner (for those who are on oral diabetic tablets or even insulin – they need to be taken half an hour before meals)
• Exercise and diet are very important – approach your dietician for a diet for you and recommended exercise by your Physician
• Check your glycosylated hemoglobin at the end of three months
• Your physician will guide you through a good control of your condition.