So, what is cough? It is the spasmodic expulsion of air from the inside of our lungs to the exterior. The air is expelled due to a sudden contraction of the chest wall muscles in response to a stimulus. The purpose is to dislodge and expel any matter trapped inside the airways. Trapped material may be mucous, blood, or a foreign body. Thus cough is a protective phenomenon helping to keep our airways free of obstruction thus allowing better oxygenation of blood. But sometimes there may be no material to expel from the airways. In such cases the cough is a result of irritation of the airway wall and may serve the only purpose of being a nuisance to the person coughing.

Cough may be caused by many mechanisms like:
1. Direct irritation of the airway wall by material introduced from the outside environment or material abnormally produced from within our lungs such as pus, mucous or blood. Such abnormal material is produced during disease states like pneumonia, abscess to name a few.
2. Allergic mechanisms in which the airway becomes hypersensitive to otherwise normal stimuli like dust, cold air, or drugs. One common disease causing such hypersensitivity is bronchial asthma. It is common for asthma to run in families, usually affecting people from childhood and sometimes presenting only cough.
3. Drugs like ACE inhibitors are another common cause for cough in which case the cough subsides if the drug is withdrawn. Ace inhibitors like Ramipril are commonly used as antihypertensives and cardiac medication.
4. After many viral infections involving the upper airways like throat in which the the airways are irritated producing a cough.
5. Smokers tend to have a chronic (longstanding) cough which is mostly irritating to others than themselves. This is because they themselves get habituated to the cough.

The importance and the treatment of cough would obviously depend on the cause of cough. A discussion of the various treatments available depending upon the diagnosis (establishing the disease process responsible for the cough) of the disease is outside the scope of this discussion.

So, where exactly does the cough syrup come into the picture. Traditionally the cough syrup used to be mixture of ingredients. Different ingredients have different actions with sometimes seeming opposite action.
1. Cough suppresants: Codeine is the prototype drug with cough suppressing action. It is useful for people with dry irritating cough which apparently serves no purpose in clearing the airway. It is particularly useful when there is coughing up of blood which needs to be stopped. Codeine is an opioid which is a derivative of opium the well known narcotic which is traded in the illicit drug market. This is why cough syrups containing codeine or its congeners are prone to misuse by addicts, especially so because it is easily available over the counter. Teenagers are particularly prone to this form of addiction.
2. Expectorant: This supposedly is to facilitate the cough in expelling the abnormal produce of the lungs. Guaifenesin is an example.
3. Mucolytic: A substance which reduces the viscosity of mucous to ease the expectoration (expulsion of mucous). Bromhexine is an example drug. Utility is doubtful.
4. Antihistaminic: Apparently reduces the allergic or hypersensitive reaction of the airway thus alleviating the cough. Chlorpheniramine is an example of this group.
5. Decongestants: These are used to dry up the mucous membranes in cases of excessive secretion. Pseudoephedrine is an example.

Cough syrups available over the counter are different combinations of the above mentioned drugs. Hundreds of cough syrup brands are sold in India. And believe me, no two cough syrups are alike! A Times of India report says that cough syrups are the leading selling brands in India (1). A Cochrane Collaboration meta-analysis (an analysis of available literature) shows that there is no evidence either in favour of or against over-the-counter-cough medication for acute cough in children or adults (2). This of course is a generalized statement. A few special situations are given below:
1. Decongestants like pseudoephedrine are also known to cause hypertension.
2. Antihistamines cause sedation and are not suitable for people who need to remain alert like drivers or machinery operators.
3. The potential of opioids to be abused has already been discussed.
Recently the US Food and Drug Administration (FDA) has removed about 500 unapproved cough and anti allergy medications from the US market (3). This serves to prove that such medications have proliferated unnecessarily in the market and that the manufacturing companies target an unaware and cough syrup hungry population. The extent of advertisement is such that patients are unhappy if their doctor does not prescribe them the best cough syrup. This problem can be solved with patient education and strong legislation.

Resources:
1. http://articles.timesofindia.indiatimes.com/2007-01-24/india-business/27887089_1_cough-syrup-human-mixtard-brands
2. The Cochrane Collaboration Meta-analysis of over-the-counter- cough and cold medications in children and adults:
www.cfah.org/hbns/archives/viewSupportDoc.cfm?supportingDocID=524
3. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm245048.htm

Strangely, this phenomenon of “gas” is not discussed in standard textbooks of medicine, neither was it given much importance by our medical teachers. Of course there is reference to flatulence, bloating, and eructation. Flatulence is the excessive passage of gas through the anus. Bloating the sensation of distension of the abdomen. Eructation and belching is the expulsion of gas through the mouth.

Gas is normally present inside our intestines. Majority of the gas is produced by the resident intestinal bacteria. It is normal for the gas to be expelled through the mouth (burping or eructation) or anus (flatus). Daily about 500 ml (half a litre) of gas is expelled through the anus. It may vary depending upon our food habit. On an average healthy men pass flatus 14 times a day. The odour of flatus depends on the presence of sulphur containing gases.

Although gas is normally present in our intestines often it is attributed to be the cause of varous symptoms. Upper abdominal discomfort also referred to as dyspepsia is frequently attributed to “gas”. This manifestation may be due to various diseases like peptic ulcer, cholelithiasis, hepatitis, pancreatitis, or inflammatory bowel disease. Many times patients come complaining of “gas” which turns out to be a sensation of pressure over the upper abdomen due to ischaemia (reduced blood supply) of the heart muscle. From the above discussion we may be clear that “gas” is not a disease in itself. In fact this term is used as people are familiar with it. They find other people and medical personnel using this term with alacrity. It is a term that they themselves find easy to understand and for other people to understand. However, the broad and variegated use of the term obscures its definition. Different people use it to mean different things. Most often people use it to explain some abdominal discomfort which requires clarification. This particular abdominal symptom may range from anything in between pain in the abdomen to diarrhoea. In other instances “gas” may be used to denote the cause of distant symptoms such as headache, giddiness, and instability of gait to name a few.

Reasons for such inappropriate use of this term may be an inadequate vocabulary, inadequate knowledge of basic anatomy and physiology, and cultural and peer pressure. Whatever the reason, use of such ill defined terminology has a devastating effect on the medical practitioner who has to crawl through the maze of murky waters (or gases?) of the patient’s history to unravel the real problem. And that is only the beginning. The next difficult part is to convince the patient that possibly his disease is due to “XYZ” and is not due to “gas”. You can obviously see the patients lip tightening with the angle of the mouth drooping down in disapproval, “Oh, it’s nothing like that, Doctor. It’s only a spot of gas. I’m sure it doesn’t need all those investigations. Couldn’t I try an antacid for a few days?”.

It is not uncommon to find people who treat themselves with antacids for “gas” and to present to hospital later with intractable symptoms only to find that they have had a heart attack. By this time it is usually too late to treat the patient.

During a focussed search on the internet on this topic I found a study by Mridula Rai and Jugal Kishore from the Department of Community Medicine, Maulana Azad Medical College, New Delhi, India. The article was on the myths about diabetes in the North Indian population ¹. They had conducted a study in 2008 in New Delhi on the above topic. Some results are given in the table below:

The myths mentioned above must have been continuing for generations together and have deep rooted origins. They were found to be more prevalent in the less educated groups. Dissemination of scientific knowledge may not be sufficient to eradicate these long standing beliefs. However, it may be one step forward. It is more pertinent to define them as beliefs rather than myths as they are believed by a large segment of the population. Though these beliefs enjoy the the support of many people over many generations I have sufficient evidence to contest them which is exactly what I am going to do in my next paragraphs. I would like to discuss one by one about the beliefs stated above.

1. “Eating sugar causes diabetes”

This is perhaps one of the most quoted and misquoted statements regarding diabetes. Much of the trouble lies with the definitions of the words in the statement made. “Causes diabetes” here means produces diabetes in a person who was previously non-diabetic. Till date there is no evidence of any particular inciting event causing diabetes in an individual who does not have it. In other words we yet do not know the reason why diabetes occurs (What really happens in diabetes). We have a few bits and pieces of the puzzle. We know that insulin becomes deficient, that there is a lot of resistance to the action of insulin in the tissues so glucose cannot enter the cells, that there is overproduction of glucose from the liver. Still we do not know exactly how this state of affairs came about. Certainly eating sugar cannot cause insulin deficiency or resistance to the action of insulin. So eating sugar cannot produce diabetes in a normal person. Eating sugar cannot increase the blood level of glucose in a normal individual. But eating sugar would increase the blood glucose level in a person with diabetes. So what might be said reasonably is that eating sugar can worsen diabetes. This means sugar should be restricted in a person with diabetes. Does it mean that normal persons can eat as much sugar as they like? The answer is no. Sugar contains calories. Too much of it can be a cause of weight gain. If weight gain is not an issue even then sugar should be taken in the desired proportion in the diet. As discussed earlier (link to My doctor says I have diabetes. What do I eat?) carbohydrate should consist of about 50% of total caloric intake of the diet. Complex carbohydrates containing more fibre are considered to be more healthy than simple sugars. Either way too much of sugar in the diet could be deleterious and should be avoided.

2. “Soaking feet in water helps decrease blood sugar level”

Soaking feet in water is an important component of Chinese traditional medicine. Use of water is the prime component of hydrotherapy. Till date there is no evidence of benefit in diabetes by soaking feet in water.

3. “Diabetes occurs because of past sins and can be cured by spiritual treatment”

Past sins are attributed to be the cause of many adverse situations in our life including disease and death. We often take the help of spiritual healers to atone for our past sins. Many religions reinforce this belief. However it is not clear how past sins may be the cause for reduced insulin secretion and insulin resistance. Hence modern medical literature carries little support for this theory. Although there is no harm in pursuing religious enhancement it will be a sad thing if such pursuit results in delay in treatment of diabetes mellitus.

4. “There is no role of diet or lifestyle measures in the treatment of diabetes”

I found this statement counter intuitive. However, since it has been a response in this study it must be taken seriously. Ancient Indian healers like Sushruta stressed the importance of diet and exercise. It appears to be common sense that diet will have an effect on the sugar metabolism inside the body and that exercise will have a beneficial effect on the disease process. In modern medicine this theory has been validated time and again.

5. “Normal blood sugar level < 200 mg%”

If blood is drawn in the fasting state blood glucose should be less than 100 mg% and if drawn 2 hours after meal then the value should be less than 140 mg%. Fasting blood glucose greater than 126 mg% and 2 hr post meal blood glucose greater than 200 mg% is termed diabetes mellitus. Any values in between is called glucose intolerance or prediabetes.

6. “Once on drugs and insulin you can have anything”

The basic principles hold true always. Dietary modification and exercise do not have any substitute. If blood glucose or other adverse parameters are not controlled by these measures alone then drugs/insulin have to be added. That does not mean dieting and exercise can be stopped.

7. “Diabetes occurs only in old age”

Traditionally it used to be thought that type 2 diabetes mellitus affected people above the age of 40 years. However, over the years the occurrence of type 2 diabetes has increased in younger people specially in those who are overweight. Type 1 diabetes mellitus occurs typically in younger people. So diabetes is not just a disease of the elderly.

8. “Diabetes is contagious”

By contagious we mean that it can be spread from person to person contact. This happens in case of diseases transmitted by micro organisms. Though the reason behind the occurence of diabetes is exactly not known it is certainly not because of any micro organism. So there is no scope of transmission of diabetes by person to person contact.

9. “No complications can occur even if diabetes is uncontrolled”

Had this been the case I need not have written this blog at all! Where I work I have at least a hundred patients who are suffering from kidney related complication of diabetes. Out of them many are on haemodialysis which is a procedure carried out regularly in hospital. During this procedure a machine does the work of the kidney. It is expensive, painful and in the long run the patient’s life may be prolonged but it is not saved. And kidneys are not the only organs damaged. There are the eyes, the nerves and the heart to name a few. In fact most patients are detected to have diabetes when they consult a doctor for one of its complications.

References:

1. Int J Diabetes Dev Ctries. 2009 Jul-Aug; 29(3): 129–132. Myths about diabetes and its treatment in North Indian population: Mridula Rai and Jugal Kishore

A few days ago I had a 22 year old man admitted in the hospital. He had type 1 diabetes mellitus and mild mental retardation and was partially deaf. He had come to hospital with vomiting and a sense of breathlessness.

Type 1 diabetes mellitus

Till now we have been discussing type 2 diabetes as this disease is much more prevalent in our community. We know that it occurs due to resistance in the tissues to the action of insulin and the inability of the pancreatic beta cells to produce enough insulin to the overcome this resistance. However, in type 1 diabetes mellitus the pancreatic cells are unable to secrete insulin at all. This is why all other medications are futile in this condition and insulin has to be given from outside to keep the patient alive. Our patient was also on insulin but he had stopped it. Somehow he could never remember to take the insulin unless somebody supervised him. Even when he was taking the insulin sometimes he would inject a dose less than that had been prescribed. It was not practically feasible for his family members to supervise him four times a day at times when he was taking insulin. So whenever his insulin doses became too irregular or he stopped it altogether he would land up in hospital with complications of diabetes mellitus.

Diabetic ketoacidosis

This young man landed up in the intensive care unit of our hospital. A random blood glucose was found to be 550 mg/dl. His blood pH was 7.20 (Normal value 7.35-7.45) which indicated acidosis. The blood had became acidic because of accumulation of organic acids.

How diabetic ketoacidosis occurs

Treatment of diabetic ketoacidosis

He was given intravenous fluids and insulin as necessary to increase the metabolism of glucose to produce energy and reverse the breakdown of fatty acids which was responsible for the organic acids in the blood. As the patient had been brought to hospital at an early stage of the disease he recovered quickly and went home.

Why prescribing insulin only does not work

As the patient was deaf and mentally retarded it was difficult to explain to the patient anything. I explained to the father and the family members about the importance of taking insulin regularly and why they had to supervise him. Though they dutifully nodded their head however they know this already and they are tired of doing all they can every day. The patient’s father said that usually things went wrong when he went on a business trip. After all human beings cannot be expected to be machines. So we expect our patient back any day again!

How can diabetes harm me even when I feel OK?

The small vessels of the human body are one of the most common places which are damaged badly in diabetes.
As shown in the diagram the gaps in the endothelium enlarge allowing the vessel to become leaky. Proteins from the blood inside the lumen of the vessel migrate and deposit in the vessel wall. In addition increased matrix is produced by the pericyte, smooth muscle cells hypertrophy leading to increased thickness of the vessel wall and decreasing lumen. Finally aggregation of the cells in the blood to the vessel wall creating micro (small) thrombi (blood clots) lead to the occlusion of vessel lumen obstructing the flow of blood to the vital organs. This phenomenon occurs throughout the body and particularly damages the small vessels to the kidneys, retina (eyes) and nerves. Also the large vessels to the brain and heart are affected. In fact the large brunt of disease and death in persons with diabetes is due to the disease of the heart (heart attack) and brain (stroke) both of which occur due to the abnormality in the blood vessels described above. Just imagine what would happen if all the vessels in the eyeball shown below get clogged!

The inside of a human eyeball

Changes to the small vessels (like those in the retina, kidneys and nerves) happen long after the start of the disease process. But the damage to the larger blood vessels supplying the heart and the brain start much earlier and even before the onset of diabetes mellitus.

The above pictures show a normal and an obstructed blood vessel supplying the heart. The part of the cardiac muscle being supplied by the obstructed blood vessel has died due lack of oxygen. This is known as heart attack or myocardial infarction and is a serious condition. The risk of heart attack and stroke (jeoparidized blood supply to the brain) increases even in those people who do not have diabetes but the blood glucose is higher than normal (this condition is called glucose intolerance, nowadays, prediabetes).

In diabetes mellitus there may be a total or partial deficiency of insulin secretion from the beta cells of the pancreas. Hence a logical treatment of diabetes is replacement of insulin from external sources. This was first made possible by the work of Banting, Best and MacLeod who won the Nobel Prize for Physiology and Medicine in 1923 for their contribution. They extracted insulin from the pancreas of a dog and injected into a diabetic human being with dramatic result. They found that insulin could not be given orally as it was degraded in the gastrointestinal tract (the tube into which food goes and is processed for use by the body). Initially insulin used to be extracted from animal (bovine and porcine pancreas). With improvement in production technology pure animal insulin could be produced. Nowadays human insulin can be produced by recombinant DNA technology. But it is more expensive than animal insulin. Though use of human insulin is in vogue animal insulin can be used with similar effect at a cheaper price. It is definitely suitable for people in our country who have difficulty in purchasing insulin.

Why does my doctor prescribe me insulin?

Most patients prefer oral drugs to insulin which needs to be injected. Neverthless, insulin has to be prescribed to some individuals. Certain conditions where insulin is required are:

1. When blood glucose levels are very high

2. Pregnant women

3. Kidney, liver or heart disease

4. Associated infections like tuberculosis

5. During surgery

6. When a patient with diabetes is hospitalized due to serious illness.

7. When blood glucose cannot be controlled with oral drugs any more

8. Type 1 diabetes mellitus where the pancreas cannot secrete any insulin and oral medication has no effect.

The basic defect in type 2 diabetes mellitus is progressive failure of the beta cells of the pancreas to secrete insulin. In the earlier stages this defect can be overcome by drugs which help in the release of insulin or its action. However when the deficiency crosses a threshold insulin must be supplanted from external sources.

Do I have to keep on taking insulin once I start?

If insulin is started because of a condition which is temporary like pregnancy or tuberculosis then oral drugs may be restarted later on. However, if the condition is permanent like chronic kidney disease or pancreatic failure then it has to be continued lifelong.

It is a common perception that it is possible to be habituated to insulin. One cannot become habituated to insulin. Unlike smoking, sedatives (benzodiazepines like diazepam), alcohol or ganja insulin in not habit forming. The reason it has to be continued lifelong is totally different. It is because the body is unable to produce it in required quantity. Furthermore insulin is essential for the functions of the body without which disease and death is inevitable.

What is the technique of taking insulin?

Insulin is injected into the fat beneath the skin. This technique of injection is called a subcutaneous injection. It may be injected into areas like the abdomen, upper arm and thighs where there is plenty of fat. The skin is pinched up in a fold and the needle is introduced at 90 degrees to the skin and the requisite dose injected in. There are many types of devices to inject insulin like syringes, pen devices, pumps. Pen devices are most suitable for home use by the patient. But they come at higher price.

Human Mixed Insulin Regular/Long acting 100 iu/ml

Insulin Syringe 100 iu/ml

Insulin Syringe 40 iu/ml

Human Regular/Soluble Insulin 40 iu/ml

Why are there so many types of insulin available in the market?

In the human body there is only one type of insulin. But for patients we use different types of insulin. The main reason behind this is that we cannot mimic the sophisticated pattern of insulin secretion maintained by the human body. The human pancreatic beta cells secrete a basal amount of insulin and in addition secrete more or less according to necessity, such as after meals. The two basic forms of insulin available are short acting and long acting forms. The short acting insulin is clear or transparent and the long acting insulin is cloudy. The long acting insulin is prepared by mixing protamine with insulin which delays its passage of from the subcutaneous tissue (layer of fat beneath the skin) to the blood. Short acting insulin is given 15-30 minutes before meals so that it neutralizes the rise of blood glucose that occurs after a meal. Long acting insulin acts almost throughout the day and if given once daily maintains the basal or fasting blood glucose level at normal. It is usually given at bedtime and has no relation to meals. To complicate matters mixed insulins are available containing different proportions of short acting and long acting insulin. These mixed insulins are very popular and are used widely.

Recently tailor made insulins have arrived. These insulins are minor variations of the original insulin molecule. As we know insulin is a protein and comprises of amino acids. Even the change of a single amino acid will change its properties. This principle is exploited here and minor changes in the amino acid sequence has produced insulin lispro and insulin aspart which are very short acting and insulin glargine which is very long acting. The advantages of these formulations is that the ultra-short acting insulins may be given just before meals in which the patient need not wait before eating thus saving much inconvenience and the ultra-long acting insulins keep on acting for 24 hours fully (actually the long acting insulin mentioned earlier does not cover the full day). However these formulations are relatively expensive.

How should I keep the insulin?

Insulin vials may be kept in a cool dark place (25 degrees Centigrade) for 4-6 weeks. If kept in the refrigerator at 4 degrees Centigrade it may be used till its expiry date. Exposure of the insulin vial to heat or microwaves will cause its degradation.

What are the side effects of insulin?

The most dreaded side effect of insulin is too much lowering of blood glucose (hypoglycaemia). This phenomenon may lead to death in a very short time. Repeated episodes of hypoglycaemia in the elderly may lead to permanent brain damage.

Why does the doctor keep on changing my dose of insulin?

The appropriate dose of insulin in a patient is arrived at by trial and error. It takes time to do this and the patient has to come to the doctor many times before an optimum dose is achieved. Even after that the dose of insulin has to be regulated if the patient has additional illnesses like tuberculosis or is hospitalized. So patients on insulin treatment require frequent blood tests (more needle pricks!) specially so during the period of titration of dose of insulin. During this period it may be useful for the patient to test his own blood glucose at home with a glucometer. This is known as self monitoring of blood glucose. These tests are costly and painful but certainly useful in the titration of insulin dose and certainly in the timely prevention of hypoglycaemia.

Gliptins and their mechanism of action

Gliptins are drugs which inhibit the enzyme dipeptidyl peptidase. This enzyme is responsible for the breakdown of incretins which increase the secretion of insulin from the pancreas. Incretins are hormones liberated from the intestine (a part of the canal joining the mouth and the anus in which the food we eat is processed) on eating food.  Examples of gliptins are sitagliptin and vildagliptin. These drugs are relatively new and expensive in the repertoire of antidiabetic agents. Apart from secreting insulin they also decrease the secretion of glucagon from the pancreas. Glucagon has the opposite effect of insulin and increases the blood glucose level. In addition gliptins delay the passage of food through the stomach and increase the sensation of fullness after eating. Due to these facts the drug reduces obesity. As the release of incretins is linked to meals the chance of dangerous reduction of blood glucose following gliptin administration is rare.

Gliptins are usually recommended when therapy with metformin or glitazones fail to control high blood glucose specially in obese patients. They are better avoided in pregnant patients and those with heart disease.

Alpha Glucosidase Inhibitors

Mechanism of action of alpha glucosidase inhibitors

These drugs delay the breakdown of carbohydrates taken in food and the absorption of glucose into the blood. So the abrupt rise of blood glucose after eating a meal is prevented. When we eat a meal the food is propelled into the stomach through the oesophagus. From the stomach it goes to the intestine. All along this tract the food is mashed and broken down into simpler small molecules. Mashing of the food occurs mechanically and breakdown into smaller molecules occurs by the help of enzymes present in the intestinal cells. Glucose is one such final breakdown product of carbohydrate. It enters the membrane of the intestinal cells and finally enter the blood stream. This process is known as absorption. Alpha glucosidase is one such enzyme present on the intestinal cell membrane helping in the conversion of complex carbohydrates into glucose. This enzyme is inactivated by this group of drugs called alpha glucosidase inhibitors.

Examples of alpha glucosidase inhibitors are acarbose and voglibose. They are to be taken just at mealtime. Carbohydrate must be present in the diet for these drugs to be useful. They are specially suitable for a subgroup of patients with diabetes who have normal fasting blood glucose levels but increased blood glucose after meals. An important side effect of such drugs is intestinal problems such as fullness, pain and diarrhoea. It is better not given in chronic intestinal illnesses.

Metformin

Metformin is the most widely used anti-diabetic drug in the world. It assists insulin in augmenting glucose uptake by the cells and reduces glucose production from the liver.

How metformin acts

The specialty of metformin is that it is the only anti-diabetic drug that reduces the chances of heart attack and stroke even in low doses. This action occurs exclusive of its blood glucose lowering action. Unlike many other anti-diabetic drugs it does not cause weight gain. Hence it is preferred in fat patients. It is usually the first drug to be given in all patients with diabetes. In some conditions, however, metformin is better avoided. Patients with kidney disease, liver disease, heart disease, those who consume too much alcohol are candidates in whom this drug should be avoided.

Metformin is started at a low dose and taken with meals and gradually the dose is increased to its maximum. That way patients tolerate the drug better. Common side effects of the drug are bloating, nausea and diarrhoea. It may be combined with other anti-diabetic agents like sulphonylureas or insulin. Metformin should be stopped before giving intravenous contrast drugs during x-rays and scans.

Meglitinides

Two drugs falling in this class are repaglinide and nateglinide. Meglitinides bind to a different part of the sulphonylurea receptor on the beta cells of the islets of Langerhans (See Diagram).  But their action is similar to that of sulphonylureas. They stimulate the early release of insulin from the beta cells. They suppress the immediate rise of blood glucose after a meal if given 15 minutes before the meal. It is useful for those patients who have a selective rise of blood glucose after food but normal fasting blood glucose levels. This condition is known as post prandial hyperglycaemia. As the drug is rapid acting it can be compared to insulin. It is specially suitable for persons with erratic meal patterns. The drug needs to be taken only before meals and may be skipped if no meal is taken.

Thiazolidinediones

Two drugs in this class also known as glitazones are pioglitazone and rosiglitazone. They act on nuclear receptors present inside the cell. As shown in the diagram there can be receptors for external molecules on the cell membrane. Similarly there exist receptors on the nuclear membrane. Thiazolidinediones bind to these nuclear receptors called PPARγ and activate a certain portion of the genome. Activation of this part of the genome causes production of proteins which increase the uptake of glucose and fatty acids into the cell. Thus basically they assist in the action of insulin. They are useful as combination therapy with other antidiabetic drugs like sulphonylureas. They should be used cautiously in combination with insulin because of their propensity to retain water in the body and thereby cause swelling. They should be avoided in patients with heart failure and liver disease. These drugs produce their blood glucose lowering effect slowly which may be apparent after 2 to 3 months. Very recently the European Medicines Agency has recommended suspension of Rosiglitazone considering the risk posed to the heart. The Food and Drug Administration, USA has also restricted the use of Rosiglitazone.

People often find names of drugs quite intimidating. Many people have asked me how doctors remember the names of so many drugs. Actually they do not. There are thousands of drugs with different names available in the market. It is important to understand that these are brand names. Different manufacturers of drugs give different names to the same drug and sell them. For example Paracetamol (the drug used to treat fever or pain) is marketed by Wellcome Burroughs as Calpol and Glaxo as Crocin and by other companies by other names. But the basic drug is Paracetamol which is the same in all the products manufactured by different companies under different names. Hence to prescribe the doctor needs to know only the name “Paracetamol” and not all the names given by companies to their particular brand of Paracetamol. The essential list of drugs provided by World Health Organization consists of about 130 drugs in total.

Let us come to the main topic of anti-diabetic drugs. These drugs can be grouped into a few classes. A diagram of the main groups of drugs are given with the areas in the body where they act:

Sulphonylureas

These drugs bind to the sulphonylurea receptor on the beta cells of the islets of Langerhans in the pancreas. This leads to a chain of events that ultimately induce the release of insulin from the beta cells. Attachment of the sulphonylurea to its receptor on the beta cell membrane closes the adjacent potassium (K) channel which in turn causes the calcium (Ca) channel to open. The calcium stimulates insulin release from the beta cell. Glucose generates ATP (adenosine triphosphate) due to its breakdown in the cell. Similar to the sulphonylurea the ATP causes the K channel to close and thus precipitate the same course of events leading to the secretion of insulin. The events are depicted in the diagram below.

Commonly given sulphonylureas are glipizide, gliclazide and glimepiride. This drug is effective as long as the beta cell of the pancreas has the capacity to secrete insulin. If there is complete beta cell failure then sulphonylureas are of no use. Hence these drugs are ideally used early in the disease when the beta cell has sufficient reserve. The commonest side effect is a fall in blood glucose. A fall in blood glucose can be dangerous as the brain ceases to function in the absence of glucose and the patient may die. Hence it is to be used with caution in the elderly and those with other grave diseases and alcoholics who are particularly vulnerable to suffer from a fall in blood glucose. Present guidelines suggest the use of sulphonylureas as a first agent if metformin cannot be used. With the use of only sulphonylureas blood glucose may be lowered up to 40 to 80 mg/dl. As mentioned the efficacy of these drugs are dependent on the capacity of the beta cells of the pancreas to secrete insulin. However with the progression of diabetes the function of the beta cell declines and ultimately sulphonylureas fail to stimulate the beta cell to secrete insulin. When this happens the drug has to be changed to insulin to control blood glucose. Many patients ask why their blood glucose became high though it had been under control earlier. This is one common situation causing rise in blood glucose despite continuing treatment. In such cases there is no use continuing the same drug any more.

 What drugs can my doctor prescribe for diabetes-2

The human body, organs and the pancreas

Our body is composed of cells grouped into tissues comprising of similar cells. These different tissues in turn form organs like heart, lungs and liver which perform different functions of our body. The pancreas is a similar organ situated in our abdomen. One part of the pancreas (exocrine) is responsible for the secretion of digestive juices which enter the intestine and are responsible for the digestion of the food we eat. And another part (endocrine) secretes various hormones of which insulin plays a major role in the metabolism of glucose. In the endocrine pancreas-the islets of Langerhans- consists of 1-1.5% of the total mass of the pancreas and have a 5-10 times supply of blood compared to the exocrine pancreas. Islets of Langerhans consist of A, B, D and PP cells. B cells secrete insulin and c-peptide in equal amounts and a small amount of proinsulin. Proinsulin has abut 7-8 % of the biologic activity of insulin. C-peptide is an biologically inactive molecule.

Insulin secretion

The human pancreas secretes about 40-50 units of insulin per day in normal adults. The increase of glucose in the blood stimulates insulin release. Certain substances amplify the glucose induced insulin secretion. Glucagon like peptide 1(GLP-1) is one of them. Substances similar to GLP-1 are used in the treatment of diabetes. In type 2 diabetes mellitus there is a defect in insulin secretion from the beta cells of the pancreas. The concentration of insulin in the blood of fasting humans averages 10 micro units/ml. After taking food insulin secretion rises and reaches a peak within 30-45 minutes and it seldom rises above 100 micro units/ml. This is followed by a rapid decline in concentration and return to baseline by 90-120 minutes. Insulin acts by binding to molecules on the cell surface called receptors.

Insulin action

The major role of insulin is to promote the storage of nutrients that we eat inside our body cells. Insulin promotes the entry of glucose into cells and the conversion of glucose to glycogen (a complex molecule serving as energy store). At the same time insulin prevents the breakdown of glycogen in the cells into glucose. Hence insulin acts to reduce the concentration of blood glucose which is stored inside the cells for either immediate or future use. The main cells which serve as energy stores are the liver, muscle cells and fat cells.

Defects in type 2 diabetes mellitus

In type 2 diabetes mellitus there is resistance to the action of insulin on the cells. It means that even though present in normal quantity insulin does not have the same effect on the cells. Thus entry of glucose and its storage as glycogen is diminished. With increasing number of fat cells in the abdomen insulin resistance increases. Thus in type 2 diabetes there is an insulin secretory defect and insulin action defect although no one knows exactly how this happens.