Canadian Health Awareness Society : Resources

Generally, there are 2 main types of diabetes: Type 1 and type 2.

Type 1 are seen in young peoples and is due to loss of the pancreatic function in producing insulin, which is required to bring glucose into the cells to be used as a fuel, much like gasoline for a car.

These patients will need insulin right away. With no insulin they will die. In 1922, Dr. Frederick Banting, a Canadian doctor from Toronto, successfully extracted insulin from dogs and purified it so that it can be given to patients. From then on, millions of lives have been saved. Dr. Banting was awarded the Nobel Prize.

Since 1983, with the improved technique of DNA engineering, insulin can be made in large quantities and inexpensively from a bacterium from our colon (E. Coli), by borrowing its DNA factory. So now we no longer need to extract from animals and the insulin is pure human insulin. The problem of allergy was solved.

In 1986, the insulin pen was born. Now patients don't need to carry large bottle of insulin solution, huge and frightening needles & syringes. The insulin pen is not much bigger than a ball pen and the needle is smaller than those used for taking blood tests. It can be given by children & adults with very little training.

There are 2 types of insulin - The short & the long acting.

The short one is used each time when the patient eats. In a normal person, each time he or she eats, the pancreas will automatically secrete up to 10 times more insulin to carry the glucose, absorbed from the gut, into the cells.

However the old short acting insulins are really not fast enough. The patient had to give the injection at least 1/2 hour before each meal. It becomes problematic in timing. If given too late, it is not fast enough and a higher dose is needed but then it stays too long in the blood, so that a few hours later when all the food is gone and there is still a lot of insulin left behind, the patient's blood glucose will drop to dangerous level .The patient may even pass out because our brain cells need glucose every minute & every second.

In the late 1900s, ultra fast insulin (Humulogo® & Novorapido®) became available. These insulins can be given at the time when the patient eats. So it is more convenient & safe. The patient may use less insulin.

We should always remember to use the least and effective amount of insulin. Because too much insulin not only can drop the blood glucose suddenly if eating is delayed or if the patient physically more active, it can also make the patient gain weight! Remember Insulin is a hormone not only for storage of food but also for growth as well. Insulin is required for growth by normal as well as abnormal cells such as cancer cells.

The 2nd type of insulin is the slow release form, given once a day and it lasts up to 24 hours. The old one is NPH® which is being gradually replaced by 2 new & better ones. (Lantus® and Detemir® ) Better because they are more stable and more predictable. So they are less likely to cause low blood sugar.

On the 15th Oct., 2007 inhaled short acting insulin was supposed to come to Canada. It had been available for a few years in US & Europe. This will be appealing to people who are afraid to use needles. It is also more convenient.

The idea of giving medication by inhalation is not new. Asthmatic use inhalers and some anaesthetic agents are given the same way. Our lung is made up of 300 millions of small air pockets for absorbing oxygen. It has a surface area of the size of a tennis court!

Besides, unlike the gut, where digestive enzymes and food interfere with drug absorption, the environment inside the lung is less hostile. Now technology is advance enough to deliver insulin down into the terminal end of our bronchial tree where there is no food & no enzymes to destroy it.

But like all new drugs, there are always some obstacles to overcome.

1. Patients with lung disease like asthma & emphysema will not be able to use. Smokers cannot use.

2. Since the dose of insulin used will be 3-5 times more than by injection, it will be more expensive.

3. So far the study on the use of this inhaled insulin is only short term (a few years). The result is very favourable. There is very little effect on the lung function and if there is any, it is reversible once the inhalation therapy stopped. But we don’t know the long term effect.

4. However, because the sale of this inhaled insulin was so low that the manufacturer withdrew the product from the market in late 2007.

In any case it is still very exciting that there is an alternative in giving insulin. It may help patients who are adamant that they will not, under any circumstance, use needles to inject themselves and as a result of this fear, by delaying in starting insulin, they allow the persistent high glucose to damage their organs. I am sure giving more time we will have more improved form of inhaled insulin. There will be smaller inhalers and safer insulin. And given time, will even be more affordable. As well, oral insulin may be a possibility.



Type 2 diabetes is more complicated than type 1. For various metabolic reasons, such as obesity, the insulin becomes ineffective. Just like inflation. We need more money to buy the same product. So the patient has to make and secrete more insulin to bring glucose into the cells. At first the pancreas was able to do that. In fact some patients, who are so called pre-diabetic, are actually secreting more insulin than a normal person. But eventually, the pancreas starts to fail, the demand not met, and blood glucose starts to rise and he or she becomes a full blown diabetic patient.

In a type 2 diabetic patient the pancreas is not all dead, except it is not secreting enough insulin both after meals & in between meals. So while the patient is fasting or when he or she is sleeping, there is not enough insulin to stop the liver from sending more sugar to the blood.

Our liver is a very important factory of our body. It makes many useful products such as bile for digestion of our food, cholesterol for our brain cells, clotting factors to stop bleeding. It also stores up glucose as glycogen. When we are fasting, the liver will break down glycogen and secretes small amount of glucose for our cells, especially our brain cells.

When the blood glucose goes down to below 4.0 mmol/L, we have a hypoglycemic reaction. The reaction is a warning to us that we should take immediate action to ingest sugar to bring the blood glucose back to normal. But if we don't do that and when blood glucose drops below 2 mmol/L, we will pass out and we may die.

In a type 2 diabetic patient, the liver is producing too much glucose during the night when the patient is sleeping and not eating food. That is why the blood glucose is higher in the morning upon wakening up than before going to sleep the night before. So the first pill that doctors give to a new diabetic patient is metformin. It is not a new pill. It came out in 1957. And is still the most frequently prescribed diabetic pill in the world.

Metformin works by stopping the liver from sending too much glucose into the blood. It is most effective when it is given at night or before going to bed. It does not work on the pancreas. I still consider this is the best pill. It is inexpensive. It will not drop the blood glucose too low because it does not stimulate the pancreas to secrete more insulin. It will help the patient to lose weight by burning more fat. After all, it has been used for more than 50 years and no serious side effects are seen.

However, it can cause stomach aches and diarrhea in some patients. But if we start the pill in low doses and take our time to increase the dose slowly, more patients can tolerate this cheap, and useful pill with very few side effects.

In 1953 the first pill came out that can stimulate the pancreas to secrete insulin so the type 2 diabetic patients don’t have to inject insulin. Of course this pill is no use for the type 1 patients.

These types of pills we use now are GLYBURIDE, DIAMICRON, AMARYL and GLUCONORM. All these pills help to lower the sugar after a meal. But they can drop the glucose down to dangerously low levels. Especially Glyburide, which is a very powerful stimulant of the islet cells of the pancreas. So if the patient eats less or exercises more than usual, blood sugar can drop to dangerous level. Old patients are particularly vulnerable. They also make the patients gain more weight. So they behave like insulin.

In the early 1900s, a third oral diabetic agent was born. ACARBOSE. It does not work on the pancreas or the liver. It is not even absorbed after it goes down the gut. It works by slowing down the absorption of the sugar in the food making it easier for patients to deal with the large influx of glucose after a meal.

In the late 1900s, a 4th pill came out. AVANDIA & ACTOS.

These pills work on the fat cells. It creates more storage space for fat. We all inherited from our ancestors to be able to store excessive food as fat in our abdomen. This fat can be sent to the liver to be converted into glucose as well as cholesterol. That is why if we don't eat for a few weeks, we still can maintain normal amount of glucose in the blood. So Avandia and Actos, by creating more storage space for the excess fat, less fat will be sent to the liver and less sugar will be made and sent back into the blood. Besides they also help the pancreas from dying too early in type 2 patients. When they are given to some obese type 2 patients, they can cut down the dose of insulin. But in early 2008, different doctors in the world are reporting 2 alarming side effects.

1. Patients with weak hearts can get more heart attacks and more heart failure, because the patients tend to retain more fluid which the weak heart cannot handle.

2. In ladies, but not men, there is a higher incidence of fracture of bones. Besides, these pills induce weight gain!

So in 2009, we are anxiously waiting for the arrival of the 5th pill. These are the INCRETINS.

INCRETIN is one type of hormones, much like the 2 hormones secreted by the pancreas - Insulin & Glucagon.

Let me explain what Glucagon is:

It is another hormone the pancreas secrete besides insulin. It has exactly the opposite effect of Insulin, i.e. it elevates the blood sugar by telling the liver to break down glycogen into glucose and send glucose into the blood. By doing so, it helps to prevent blood glucose from dropping to dangerous level while we are not eating. But if too much is secreted, then the blood glucose will be higher, making it more difficult for insulin to do the job.

Going back to INCRETIN, it is a hormone secreted by the gut whenever food comes in contact with the wall of the gut. Then it swims to the pancreas to do 2 things:

1. It stimulates the pancreas to secrete more insulin to move the glucose into cells.

2. It tells the pancreas to stop making GLUCAGON, so shuts down the liver from sending glucose into the blood.

INCRETIN can do 3 more things.

1. It swims to the stomach and tells the stomach to pump food into the gut more slowly, thereby slowing down the absorption of glucose and giving more time for the weak pancreas to deal with the influx of glucose following a meal.

2. It sends a message to our eating center in our brain so we don’t feel hungry too quickly. By eating less amount and less frequent, it helps the patient at least not to gain weight by over eating. And most type 2 patients are overweight if not outright obese!

3. In rodents, apparently INCRETIN can protect the pancreas by stopping the pancreatic cells from early death, as well as inducing growth of new cells. There is indirect evidence that this also happen in humans. So this is the very first time we have a drug that can do that, i.e. make more pancreatic cells.

INCRETIN COMES IN 2 FORMS – INJECTABLE & ORAL FORM.

The injectable form is extracted from the saliva of a lizard that lives in the desert of Mexico & Southern USA. This lizard only feeds 4 times a year. The INCRETIN hormone is found in its saliva. Unlike the human form, which only last a few minutes because as soon as secreted it is destroyed by an enzyme, the INCRETIN of this lizard last for 24 hours. Now a pharmaceutical company is able to extract this from the saliva of the lizard, purify it before it is given to humans. But it cannot be given by mouth.

This is Exenatide (Byetta), manufactured by Lily, It has been available in USA for a few years. But as of September 2009, is still not available in Canada. It is given by injection twice a day. And a long acting one given once a week will be available very soon. Not only it helps to control blood glucose, but it also induced significant weight loss. So it is a bonus to those obese diabetic patients.

Another pharmaceutical company (Novo Nordisk) will be launching a humanized form of incretin (Liraglutide) given once a day, in Canada at the end of 2009 or early 2010. Because it resembles more like the human form of incretin, there will be less allergic adverse effects compared with Exenatide.

The oral form is an inhibitor of the enzyme that destroys the INCRETIN. So the INCRETIN we make in our gut will last longer than a few minutes. In fact, we now believe that type 2 diabetic patients cannot make enough of this INCRETIN, so that when they eat, food passes into gut, there is not enough stimulation of the pancreas to secrete insulin as well as not enough suppression of the GLUCAGON. The liver not knowing that the patient has eaten already, still sends more glucose into the blood. This is the reason why the patient every day wakes up with blood glucose higher than before he or she went to sleep the night before.

In January 2008, the first oral incretin was launched in Canada. Januvia comes as a 100mg tablet given once a day. But it costs at least $3.00 a pill!

Beyond 2009, there will be 2 other medications with entirely different action.

1. An agent that can induce more glucose loss by passing it in the urine. Scientists have discovered blood glucose can be lowered by eliminating glucose via the kidneys without doing any harm to the kidneys. This will also induce more weight loss, another bonus for obese patients.

2. An agent that can induce our cells to burn more fat, to make more energy and heat to keep us warm instead of converting fat into glucose. So we can "eat all we can!" This is a class of drugs call AMP kinase activators. It probably will take a few years before it will become available to us.

So there is always hope in winning the battle against diabetes. The future looks very promising. As a physician who has seen many terminally ill diabetic patients in the intensive care unit for the last 30 years, I welcome any new method of preventing the complications of this dreadful disease. Diabetes is worse than some cancers. Now some cancers can be cured with modern treatment. Yet we still have no cure for diabetes. But we have many ways to detect it early and by changing our diet and lifestyle and using old & new medications carefully (not jumping into new ones too early without balancing the benefit & the risk) we can control diabetes and our patients will live a normal, healthy and happy live!

"The flame of hope" will continue to burn brilliantly outside Dr. Banting's house in Ontario.