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We discussed oral medications for treating type 2 diabetes in previous articles. There will come a time in the lives of type 2 diabetics when they should consider adding insulin to treat their diabetes if the oral medications are not adequate to control their disease. In addition, type 1 diabetics cannot use oral medications to control their diabetes. For them insulin is the only choice. Let us consider the circumstances under which insulin therapy is indicated and the various forms of insulin available for different needs.
Type 1 diabetes: In this case the body (pancreas) fails to produce insulin which “unlocks” the cells of the body to permit glucose for energy production. Type 1 accounts for 5-10 per cent of all cases of diabetes. Young people are the main target for this type. It is caused by the attack of immune cells on the pancreas thereby destroying the insulin producing cells. Those who have type I diabetes must take daily insulin shots to survive.
Type 2 diabetes: This is the most common form which develops in adulthood gradually producing a condition in which the cells are unable to utilise insulin effectively (called insulin resistance). To compensate for this condition, the pancreas initially overproduces insulin to manage the situation. In due course, the pancreas loses its ability to produce insulin at which time patients require a combination of oral drugs and insulin to control glucose levels.
In general terms, people who have diabetes (either type 1 or 2) must lose weight if they are overweight or obese. An indication of overweight or obesity is the body mass index (BMI) which can be calculated as follows. Divide your weight (in kilograms) by the square of your height (in meters). If the value is less than 25 it is acceptable. If it is between 25 and 30 one is considered overweight and beyond 30 one is considered obese. The BMI has to be brought under 25 by proper diet and exercise. For example, a person who is 1.7 meters tall must weigh less than 72 kilograms to be considered normal (For BMI calculation visit
http://diabetes.niddk.nih.gov/dm/pubs/insulinresistance/#bmi and scroll down the page until you see the table of BMI)
In addition, the hemoglobin A1c level has to be less than 7. Blood pressure has to be kept at or below 130/80 mm of mercury. Total cholesterol has to be less than 200 mg/dL with LDL cholesterol below 100. Such a tight control is necessary to prevent cardiovascular problems, stroke and other diabetes-related illnesses such as retinopathy, neuropathy, and kidney diseases. If one is a smoker it is important to quit the habit.
While the haemoglobin A1c level has to be measured in a medical laboratory, the patient can monitor the blood glucose level with a meter at home. Fasting blood glucose level (preferably taken in the morning before breakfast) must be between 90 and 120 mg/dL while the post-prandial (2 hours after a meal) must be less than 180 mg/dL. These numbers must be tailored to suit the needs of the patient based on individual circumstances, on the advice of a physician. When diet, exercise, and/or oral medications fail to achieve the limits mentioned above, the physician may recommend the usage of insulin.
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| Native structure of insulin |
History: Insulin was first extracted at the University of Toronto in 1921 from dog pancreas and was shown to lower sugar level in the blood. Later it was extracted from ox pancreas, purified, and used to treat a 14-yr-old boy who was near death in 1922.
Eli Lilly purified insulin from beef pancreas in 1922. Bovine insulin and pig insulin were used for a long time to treat diabetes in humans. The animal insulins differ from the human version only slightly. However, they produced allergic reactions in some humans due to the impurities present in them. Novo-Nordisk even converted the bovine insulin to the human form enzymatically and marketed it. In 1978,
Genentech produced human insulin using human gene in the bacterium E.coli using recombinant DNA techniques and licensed the process to Eli Lilly. The product was approved for human usage by FDA in 1982 and Lilly started producing and selling it as Humulin in 1983. Although the animal insulins are still used in the rest of world, since 2006 only the recombinant version is sold in the US.
Besides Lilly (USA), Novo-Nordisk (Denmark), and
Sanofi-Aventis (France) are the other major manufacturers of recombinant insulin, selling it worldwide. There are several other minor manufacturers in various countries which sell the product in their own countries. In recent years
Wockhardt launched the first human recombinant insulin,
wozulin, in India. It appears that Shreya Life Sciences Private
Ltd. in India is in the process of selling its recombinant insulin,
recosulin. India reportedly tops the world in the number of diabetics, closely followed by China and the US.
Mechanism of action: If glucose does not enter the cell but stays in the bloodstream it can chemically react with the blood vessel walls and damage them leading to cardiovascular problems. Insulin functions by binding to its receptors on cell surfaces and starting a cascade of reactions which include transport of a protein called Glut-4 transporter to the surface to facilitate glucose influx into the cells which can then function in various cellular reactions. Regular insulin takes 30 minutes to start functioning, peaks at 2-4 hours, and continues to exert its action for 6-8 hours. Depending on the frequency of food intake it may be necessary to take insulin shots before each meal at prescribed doses. The dosage is usually determined by trial and error and measuring the glucose level before and after each meal and making necessary adjustments. Many patients who require insulin will need to have a base level of insulin for day-long effect and a short acting form to cover the meals.
Storage: Not too long ago patients used to go to the doctor to get insulin shots. Not anymore. Nowadays insulin is available in vials and cartridges which patients can use for self-administration. Insulin in vials must be stored in the refrigerator at 2-7 deg Celsius. However, they can also be kept at room temperature (15-30 deg Celsius) for up to a month. Pen insulins can be kept at room temperature for two weeks.
Side-effects: If insulin usage is not exactly tailored, it may cause some problems. Too much insulin may result in a situation called hypoglycemia (low blood sugar). In addition, if a sulfonylurea drug is used, or a meal is missed or delayed, or alcohol is consumed when taking insulin that will also result in hypoglycemia. Some symptoms of hypoglycemia include sweating, dizziness, tremor, blurred vision, light-headedness and tingling in the limbs. In such a situation one should immediately consume a candy, glucose tablets, or even some fruit juice. If left untreated it can cause seizures, unconsciousness and even death. Alcohol consumption will suppress glucose production by liver when needed thus accentuating the hypoglycemic effects of insulin. The other extreme, hyperglycemia (high blood sugar) can also result if too little insulin is used. Hyperglycemia symptoms include drowsiness, flushed face, thirst and frequent urination. It can result in drowsiness, flushed face, excessive thirst, frequent urination, fruity odor in breath, and ultimately even death.
Let us examine the different types of insulin that are available for specific needs of diabetic patients under different circumstances in the next article. For a background information on insulin please visit
http://www.fda.gov/diabetes/insulin.html#3
Sethuraman Subramanian
subramaniansethu@hotmail.com
Disclaimer: The information provided here is for information only and the readers are encouraged to contact their physicians for proper medical advice regarding insulin therapy.
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