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Glucose is the source of energy as it is converted into ATP, which allows our body to function at an extracellular and intracellular level. Insulin regulates blood glucose levels when the concentration gets too high in the blood by lowering the glucose concentration. Insulin is produced in the beta cells of the Islet of Langerhans in the pancreas and is released when high blood glucose levels is detected. The hormone binds to specific receptors on the surface of muscle, fat and liver cells, triggering a signal for GLUT4 glucose transporters to move to the edge of the cells, allowing uptake of glucose from the blood into the cells. Insulin allows storage of glucose in the liver as glycogen via glycogenesis and is released when blood glucose is low. Type 2 Diabetes Mellitus (T2DM) is a disease whereby the target cells don’t respond efficiently to the insulin – insulin resistance. This means less glucose can be taken up into cells leaving more glucose in the bloodstream, increasing the amount of insulin produced. Over time, the pancreas producing insulin can be worn out until it can no longer produce enough to regulate glucose levels. Glucose levels remain high in the blood, known as hyperglycemia. Symptoms include increased thirst and urination which occurs due to water moving out of cells and into the blood due to a higher concentration of glucose in the blood than in the cells. This leads to cells being dehydrated, therefore increasing the level of thirst. Water in the blood is then filtered out as urine by the kidneys, therefore increasing the frequency of urination. As most glucose remains in the blood, cells are deprived of glucose and therefore the person may feel fatigued. Another symptom is blurred vision. This occurs due to high blood glucose levels causing fluid to move into and out of the retina of the eyes, causing the lens to swell.
There are many treatments for T2DM. Eastern styled treatments include herbal medicines which target the internal defensive power of the person against the environment. The main aim is to maintain equilibrium between humans and the environment. This is a holistic approach – focuses on the body and mind as one. Whereas western styled treatments tend to change the environment to suit to diseased. Medicines are formed from chemicals to target the effected cells from the diseases. This is a reductionist approach – physical solutions are given as treatments.
Western Treatment – Biguanide
Metformin is usually the first prescribed medicine to treat T2DM. It works by increasing glucose uptake in skeletal muscles and reducing hepatic gluconeogenesis through an inhibition of complex I in the mitochondrial respiratory chain. Organic cation transporters (OCT-1) catalyse and facilitate metformin uptake in hepatocytes and into mitochondria due to metformin’s positive charge, allowing it to travel down the membrane potential. This causes changes in ADP:ATP and AMP:ATP ratios which further activates AMP-activated protein kinase (AMPK). AMPK regulates cellular homeostasis and metabolism in our bodies; acting as a master switch to many metabolic reactions. In this case, AMPK switches on catabolic pathways which generate ATP, whilst switching off processes which consume ATP. Gluconeogenesis requires ATP to form glucose in the liver, thus AMPK reduces glucose production, lowering the concentration of glucose in the blood.
In an in-vitro study, the effects of metformin on complex I activity were investigated in cultured cells from intact and permeabilized human carcinoma cells (KB cells). Results show respiration in intact KB cells was reduced by 53% and 33% in permeabilized KB cells with metformin due to specific inhibition of action to complex I. However there was no effect when metformin was in the presence of TMPD and ascorbate. TMPD is an electron carrier reduced by ascorbate at cytochrome c oxidase – complex IV. This shows that metformin has no effect on complex IV, thus further supporting its effect on complex I activity. In a clinical trial, 3234 adults who were at high risk of developing diabetes were either assigned 850mg metformin twice a day, a placebo or lifestyle intervention. This trial lasted 3.2 years, with follow up lifestyle intervention training. Metformin reduced diabetes occurrence by 31%, compared to placebo (Figure 1). Effectiveness was greater for the obese, had a higher fasting glucose or had a history of gestational diabetes, thus supporting the inhibition of complex I due to reduced gluconeogenesis, leading to less blood glucose concentrations.
Common side effects of metformin include nausea, vomiting, loss of appetite and diarrhoea. More rare side effects include lactic acidosis – increased levels of lactic acid in the blood. Long term use may lead to decreased absorption of vitamin B12.
Figure 1 – Placebo = red line. Metformin = blue line
Glipizide stimulates insulin production by blockage of potassium channels in the beta cells in the pancreas. This leads to the cell becoming depolarised which opens up voltage-gated calcium channels, activating the secretion of insulin, thus lowering blood glucose levels. However, prolonged use of sulfonylureas can increase risk of cardiovascular disease, due to prolonged blockage of potassium channels. Side effects of glipizide include increased appetite, leading to weight gain, allergy rashes and bone marrow toxicity, which is rare but serious.
Eastern treatment – Herbal Medicine
Gymnema slyvestre is a woody climbing shrub which can treat diabetes due to gymnemic acids having anti-diabetic properties. The arrangement of gymnemic acid molecules are similar to that of glucose, allowing the gymnemic acids to become a competitive inhibitor to fill the receptors first. This leads to a prevention of absorption of glucose by the intestine, leading to hypoglycemia, thus lowering blood glucose levels. In clinical trials, the diabetic patient shows signs of stimulation of the pancreas, increasing the secretion of insulin. Sugar cravings are also prevented due to the similar shape, decreasing glucose and fatty acid assimilation.Pancreatic islet cells are regenerated, increasing the enzyme-mediated uptake of glucose.
A study on the activity of antioxidants present in Gymnema slyvestre on diabetic rats by Kang et al used ethanol extracts. Results showed gymnemic acid decreased levels of blood glucose by 14-60% within 6 hours of administration and levels of lipid peroxidation also decreased.
Acupuncture involves inserting needles to stimulate specific healing points in the body to help recovery and balance out the imbalances in the body, which is believed to cause the disease. In T2DM there are supporting studies whereby electro-acupuncture increases insulin levels and decreases blood glucose levels. Electro-acupuncture involves applying a low electrical current to the needles before inserting them into the healing points. Acupuncture helps to down-regulate cortisol, a hormone that stimulates gluconeogenesis in the liver and decreases fatty acid in the blood, thus resulting in a decrease in blood glucose. Herbal acupuncture involves inserting herbs and biological substances into specific healing points. Studies show herbal acupuncture has a greater effect on lowering blood glucose than control groups who had a placebo alongside an anti-hyperglycemia therapy, with a mean difference of 1.48. However there was no significant difference in reducing cholesterol levels. Side effects of acupuncture involve bruising, mild soreness and minor bleeding.
It is difficult to determine which approach, eastern or western, is more effective in treating T2DM. The western approach is fully science based, relying on scientific theorem for the medicine to work. This in itself is a strong positive, as there is much evidence supporting the effectiveness of the drug due to many tests and clinical trials taken before marketed. However, some may say that it is too scientifically based, as this can reduce the potential of the best care for the patient, if a treatment is not scientifically proven. Western medicine is precise as it has that specific purpose. It is developed to target the specific symptom, giving quick effectiveness in the body. For example, metformin targets complex I in the mitochondrial chain, which leads to reduction in hepatic gluconeogenesis and increasing of glucose uptake in cells. However it only focuses on the specific problem – it does not take into account of other body systems which could be contributing. This means the root of the problem is not solved. The eastern approach has a symbiotic relationship – sees all the body systems integrated as one. Therefore if one system is not working properly, the other systems must have contributing factors. This leads to balancing the imbalances of the whole body, aiming to restore the health of the whole body. Although eastern medicine has a good approach, there is very little medical research to support its effectiveness. It is unclear on how eastern medicine works in the body; it relies on observations and results, leading to a further problem of whether it could be the placebo effect. Eastern treatments occur to prevent T2DM before it comes, or slows down the development due to treating the whole body and mind, leading to an overall healthier body. Whereas western treatment only occurs after diagnosis of T2DM. Although effective, T2DM is a lifelong disease, so prevention is better than treating. Furthermore, western medicine has inevitable side effects. Metformin has side effects including nausea and diarrhoea, which both can affect the quality of life of the patient until they get used to the drug. On the other hand, eastern medicine has very little side effects. Side effects of acupuncture may include some bruising and bleeding, however very little infections due to sterile needles being used once each. A main positive of western medicine is that it is effective in urgent situations, whereas eastern medicine is a long process, therefore not suited for urgent situations. For example, a patient with T2DM may experience blurred vision due to damage to blood vessels in the retina caused by high blood glucose. Scatter laser surgery is used to treat this, where laser burns cause abnormal blood vessels to shrink. This method is effective and relatively quick, although more than one session may be required. However eastern medicine may take months to treat this, due to not having a specific treatment for this. Both approaches are effective in their own ways and are at their best when used together. Western medicine can target and treat the hyperglycaemia quickly and eastern medicine can treat the stress of the mind and hyperglycemia at a slower pace. Overall the two approaches are very different but complement each other in the treatment of T2DM.
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