Canadian Health Awareness Society : Resources

Diabetes was found in the literature of the ancient world. It goes back to 1500 BC. In Egyptian, Greek, Persian and Chinese writings there were descriptions of patients inflicted with a disease that made them pass a lot of sweet urine which attracted ants and insects. For a long time diabetes was thought to be a disease of the kidney, a theory based on which several innovative treatments were invented. In the Middle Ages, Persian doctors recommended their patients ride horses, thinking that the jogging motion would massage the kidneys so they would not pass so much urine. In Europe, patients were given "kidney tonics" (alcohol, opium and aphrodisiacs) whereas the Chinese doctors forbade their patients alcohol and sex in order to purify their kidneys. In 1869, a German medical student, Paul Langerhans, discovered under his microscope that there were tiny islands of cells scattered in the pancreas. He didn't know what their function was and thought they were probably lymph nodes.

30 years later, another German physician, Dr. Oskar Minkowski, successfully removed the pancreas of a dog without killing it. That dog instantly became diabetic and passed large amounts of urine before it died soon after. Apparently he tasted the dog's urine and confirmed the presence of sugar. He concluded that "something "lacking in the pancreas drives the kidney to excrete excessive sweet urine. Now we know that this "something" is insulin. After all, the kidney is an innocent bystander.

There are 2 types of cells in these islets : - beta and alpha cells. Beta cells produce insulin. Insulin goes to different parts of our body to deliver glucose into our cells to be used for energy, just like gasoline for the car. The alpha cells secrete glucagon. Glucagon goes to the liver and instructs the liver to make glucose and secretes the glucose into the blood. This is important to maintain enough glucose for the brain 24 hours a day.

In a normal person, the islet cells secret insulin in a fed state and glucagon in the fasting state to ensure our blood glucose is also between 4 to 6. In a diabetic patient, there is not enough insulin either because the islet cells malfunction or die, or insulin becomes inefficient. This is what we call "insulin resistance". The common cause of insulin resistance is obesity. When there is too much fat accumulated in our abdomen, there is an over spill of fat to the liver. The liver uses fat to make more glucose and cholesterol, and the liver becomes a fatty liver. Too much fat in other parts of our body prevents insulin from getting to the cells which is the reason why insulin becomes ineffective. On the other hand, diabetic patients inappropriately produce too much glucagon even when blood glucose is high, especially during sleep, so that the patient wakes up with higher glucose than before going to bed.

Type 1 diabetes is commonly seen in young children and adults. Their beta cells are dead. They require insulin around the clock to stay alive. However, their alpha cells are still functioning and continue to make glucagon.

In type 2 diabetes, their beta cells are not totally dead but not enough to make sufficient insulin. Initially, they can take pills to stimulate the remaining beta cells to make more insulin or make insulin more effective. On the other hand, they have too many alpha cells, instructing the liver to make more glucose and send to the blood. 30 years ago, type 2 diabetes was seen in patients older than 50 years. Now it is seen in children and young adults.

This is the result of poor diet and lack of exercise leading to morbid obesity. Obesity leads to insulin resistance.

Diabetes is a disease of 2 hormones, not enough insulin and too much glucagon.

We have 2 kidneys. Each one has one million filters to excrete waste products. Glucose is a valuable molecule to us. The small glucose molecules after going through the large pores of the kidney filters are all reabsorbed back into the blood circulation from the kidney tubules by the ``SGLT transporter``. Otherwise, we will lose all our glucose in a matter of a few hours. But if our blood glucose goes up more than 10 ( normal 4-6), the reabsorbing capacity of the tubules will be exceeded. Glucose will then be found in the urine. In diabetic patients, by sensing that there is not enough glucose delivered into the cell because of the lack of insulin, the kidney tubules increase their reabsorbing capacity and glucose will not spill into the urine until at a much higher blood glucose level (14). This further raises the blood glucose level of the patient. Prolonged high blood glucose will damage our micro- and macro-circulations leading to blindness, kidney failure, stroke and heart attack.



Herbal medicine goes back to ancient times. Tree barks had been used for curing various diseases. Since the 19th century, chemical molecules have been extracted from plants and made into medications we are now still using.

• Aspirin is from a willow tree.
• Quinidine, a drug for irregular heartbeats, is from cinchona plant.
• Metformin, the most frequently used diabetic pill is from the beautiful French violet lilac flower.
• Vincristine which cures many childhood leukemia is extracted from a periwinkle plant.
• Taxol, used for various cancers like breast and lung comes from Pacific Yew tree.
• Artemisinin, the most potent drug for malaria comes from Chinese Herb Artemisia Annua青蒿.

Since June 2014, a new class of oral diabetic medication becomes available in Canada. This is the SGLT2 inhibitor. It comes from apple tree bark. Since 150 years ago, it has been known that an extract from apple tree bark (Phlorizin根皮苷) given to animal will make them pass a lot of sweet urine just like a diabetic patient.

Now, this molecule has been purified so it becomes safe to be given to a human. It blocks re-absorption of glucose after filtered by the kidneys. So it lowers blood glucose without the need for insulin. With no insulin involved, it will not induce hypoglycemia. As well, by excreting glucose in the urine, excessive calories will be lost and the body will compensate by burning fat, resulting in weight loss. High glucose creates glucose toxicity making the islet cells work inefficiently. Too much fat induces insulin resistance and devalues the function of insulin. So this new agent by lowering blood glucose can improve islet cell function as well as make insulin more powerful.

In a clinical trial, it was found that the SGLT2 inhibitors can lower blood pressure. This is a bonus as many diabetic patients have high blood pressure. It can also lower uric acid. High uric acid gives us gout and kidney stones and raises our blood pressure.

Like all medications, it has side effects. The most common side effect is bacterial and yeast infection of the urinary tract. However, this can be avoided if the patients practice immaculate toilette hygiene and keep themselves adequately hydrated by having a few more glasses of clear water a day.

There is a rare hereditary disease call "familial glycosuria". Members of this family inherited a defective SGLT receptor gene. So from the first day they were born, their kidney cannot retain glucose. Other than passing more urine, they lead a normal life without any urinary tract and kidney problems. In fact, they are protected from gaining weight and less likely become diabetic. This means that it is safe to use this new SGLT2 inhibitor pill taken once a day on a long-term basis.

In the last 60 years, we have several oral agents for the treatment of diabetes.

1. 1954. Sulphonylurea (Glyburide, Diamicron)  stimulates the islet cells to release insulin. But it can induce hypoglycemia and weight gain.。

2. 1957 Metformin (extracted from French lilac flower)  blocks the liver from over producing glucose. Normally it is a good thing for the liver to secrete glucose during fasting, to ensure sufficient glucose available for our brain. But in diabetic patients, the liver is over zealous in making too much glucose, especially during their sleep so that they wake up in the morning with glucose higher than before they slept.

3. Early 1990s Glucobay  slows down the absorption of glucose in the gut. It has only a mild effect in lowering glucose after meals.

4. Late 1990s Avandia and Actos  They are insulin sensitizers by making insulin more efficient. But they can induce weight gain, retain fluid and heart failure.

5. 2008 DDP4 inhibitors (Januvia, Onglyza Trajenta)  raise the GLP1, a gut hormone that helps the islet cells to produce more insulin, stores it and only secretes it when we eat. Unlike Glyburide and Diamicron, it will not induce hypoglycemia. It can also decrease glucagon. By slowing down the pumping action of our stomach, the DDP4 inhibitors can help to slow the rise of blood glucose after meals, making it easier for the insulin to handle the glucose load. These also come in a more powerful injectable form (Victoza, Byetta )

In treating patients with type 2 diabetes, we have to lower insulin resistance which is mostly related to obesity and at the same time preserve the function of the islet cells. If there is a "magic bullet" for Type 2 diabetic patients, it will be one pill that combines Metformin, DDP4 and SGLT2 inhibitors.

When this is available, type 2 diabetes will be better controlled with diet, exercise and this "pill"!