Despite the discovery of insulin in 1921 by Dr. Frederick Banting and Charles Best, diabetes is still the third highest killer diseases in the world marginally out numbered by Cancer and Heart Attack. Type 2 diabetes[1], formerly referred to as non-insulin-dependent diabetes mellitus, or NIDDM, is the most common type of diabetes, accounting for 90% to 95% of all cases. Type 2 diabetes is characterized by a resistance to insulin action in many different tissues in the body coupled with an inability of the pancreas to deliver insulin in a precisely regulated pattern and quantity to control glucose metabolism. Although insulin is considered a life saving drug, followup studies indicate that 80% of the type 2 diabetics patients develop retinopathy (blindness) after about 15 years of insulin intake. It was argued that the traditional method of periodic administration of insulin (once or twice a day) instead of a more tight control (as in the case of normal human body) is the cause of these complications. Both the Diabetes Control and Complications Trial (DCCT) for type 1 diabetes patients and the United Kingdom Prospective Diabetes Study (UKPDS)[2] for type 2 diabetes patients on tight glucose control showed a remarkable improvement in blood glucose control and reduction in microvascular complications in the initial years. DCCT, however, pointed out that tight glucose control is impractical and that patients administered with tight control of glucose turned out to be three times more likely to succumb to complications in the long run. For type 2 diabetes patients, UKPDS showed that although there was a marked control of blood glucose in the first year, it degraded gradually in the following 15 years (causing diabetes related complications) for both tight as well as traditional treatment groups. As a result, it is now generally understood that some better therapy (other than insulin) has to be developed for the effective treatment of type 2 diabetes. Researchers in the west look forward to evolving techniques such as gene therapy to identify and rectify the possible genetic causes for insulin resistance in the peripheral tissues, leading to type 2 diabetes. So far, no signs of any immediate answers are reported in this newly developing field. Recent findings that diabetes is not caused by a single gene disorder nor due to the misbehaviour of any single organ further limits the hope for simple solutions.
Abnormally high levels of blood glucose, as well as other metabolites, damage both the small and large blood vessels, producing what are known, respectively, as microvascular and macrovascular complications in both Type 1 and Type 2 diabetes. These affect almost every organ of the body, and thus diabetes is a true multi-system disease. Microvascular complications is the term applied collectively to the effect of diabetes on the small blood vessels throughout the body that causes severe damage to the eye, kidney, and nervous system. Macrovascular complications refers to damages to larger blood vessels such as heart diseases or blocks in the major blood carriers due to the deposition of fatty substances (atherosclerosis), impairing the supply of nutrients and oxygen to vital tissues in the body.
Diabetes is a slow killer accounting for a host of related diseases. The most common of these are the cardiovascular diseases accounting for about 80% of deaths[11] with approximately 75% of these deaths occurring as a result of ischemic heart disease. Studies show that although angioplasty and coronary artery bypass can improve conditions, they do not produce lasting results in diabetes related heart diseases. Diabetes is known to be directly related to the following cardiac risk factors:
values just
above normal[12]. However, most diabetes experts are of the view
that it is the insulin resistance rather than hyperinsulinemia that confers
cardiovascular risk. This view is not contradicting to the epidemiological
studies since insulin resistance and fasting glucose levels are all related
phenomena4. Moreover, many related studies also are consistent
with this view[2,13]. This suggests the use of drugs that can
improve on the impaired insulin resistance of the peripheral tissues as the
best treatment methodology for diabetes related
complications[14,15].
It is now generally recognised that insulin resistance is often associated with low levels of HDL (good cholesterol) and elevated levels of triglycerides. The possibility that herbal medicines may help sustaining or supporting these cholesterol levels cannot be ruled out without systematic investigations.
The second most common phenomena associated with diabetes is retinopathy or blindness[16]. Recent studies indicate that in most patients, the onset of retinopathy generally predates the diagnosis of diabetes by about 6 years. Retinopathy is the damage of the retina, the layer of cells at the back of the eye that contains the photoreceptors that produce the electrical and chemical signals that allow us to see. Retinopathy develops when damage occurs to the small blood vessels that supply the retina with oxygen and other nutrients. This damage changes the flow of blood, weakens blood vessel walls, and stimulates the growth of harmful blood vessel components. The damage may be mild (background retinopathy) or it may become severe (proliferative retinopathy). In proliferative retinopathy, new blood vessels form and may rupture and bleed into the retina, threatening sight. Another condition, macular edema, can develop when the fluid leaking from the blood vessels pools in the center of the retina and impairs the area of most precise, central vision. Vascular Endothelial Growth Factor (VEGF), a kind of protein molecule that stimulate the growth of specific type of cells appears to be a major cause of new blood vessel growth that occurs in patients with proliferative diabetic eye disease. No effective therapies to prevent this are yet known. Laser photocoagulation and vitrectomy surgery, both of which can help preserve vision are the only effective treatments for retinopathy. Tight control of glucose level and hypertension are the only known preventives.
Diabetes causes irreparable damages to the kidney. Diabetic kidney disease is called nephropathy. The seriousness of nephropathy is that it might not become noticeable until more than 75% of the kidney is damaged. Microalbuminuria is an early symptom of diabetes related kidney damage. It shows up even before proteinuria (protein in the urine), the decisive manifestation of kidney damage is observed. Certain classes of antihypertensive drugs, the angiotensin-converting enzyme inhibitors (ACE inhibitors), slow progression of renal diseases. Once affected, dialysis and transplantation are the only known solutions to nephropathy. Even in such cases, five year survival chance for the patient is estimated to be less than 21%, far below that of even cancer patients. Tight glucose and hypertension control and prevention of any urinary tract infection are important to prevent nephropathy.
Neuropathy or damage to nerve cells is also common in diabetic patients. Both the peripheral nerves, which are involved in sensation and movement, and the autonomic nerves, which control many internal functions, such as heart rate, gastric motility, bladder function, and ability to have a normal sexual response are affected. Peripheral neuropathy causes pain and loss of sensation, contributing to the increased risk for limb infection, ulceration, and amputation. Autonomic neuropathy may lead to heart arrythmias, poor control of blood pressure, and digestive and sexual dysfunction.
The Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR)
examined the natural history of diabetic retinopathy[17] in both type
1 and type 2 diabetes. This study reported that even a single measurement of
could predict the risk of any retinopathy 4 years later, and the
risk of proliferative retinopathy some 10 years later. The data demonstrated a
strong and consistent relationship between glycemia and the incidence and
progression of microvascular disease in both type 1 and type 2 diabetes.
Additionally, other studies have suggested that duration of hyperglycemia
also influences the risk of retinopathy. For example, it is estimated that nine
years' exposure to a level of 8% (normal 
) yields
approximately the same risk of retinopathy as 2 1/2 years' exposure to a
level of 11%. The United Kingdom Prospective Diabetes Study
(UKPDS)[2,18] did followup studies on patients for a mean of 10
years to determine whether intensive glucose control therapy would result in
reduced micro- and/or macrovascular complications. They found that for
every percentage point decrease in , there is a 35% reduction
in risk of complications. These observations lay the rational in
considering measure as the primary observation in evaluating
various treatment methodologies.