Originally published in The Ottawa Citizen June 5, 2002
Original Title: Making the Medicine Go Down

Last week’s column outlined how type 2 diabetes develops and causes harm: the liver produces too much sugar, the muscle, liver and fat cells poorly absorb sugar because they are less responsive to insulin and the insulin producing beta-cells of the pancreas eventually burn out.

Type 2 diabetes can require strict adherence to a treatment plan. For some, it severely compromises their lifestyle. Compliance to a particular regimen can be difficult. Nonetheless, diabetes sufferers should have every opportunity to take control of their condition. Understanding the choice of medical therapy contributes to better compliance.

Treatment is individualized. Risk factors like obesity, smoking, heart disease and high cholesterol levels among others figure prominently in selecting a proper treatment regimen.

The first step to control blood sugar is to eat healthful foods and to exercise. The Ottawa Hospital Diabetic Clinic has the resources to develop specific diabetic diets in line with the patient’s lifestyle. Weight loss especially in overweight individuals will reduce blood sugar levels. Indeed a loss of ten pounds can have significant positive effects. If this step is not helpful then the addition of one or more of the five classes of diabetes medication is in order. Each has a specific mechanism of action but all work to lower blood sugar.

DiaBeta (glyburide) and Diamicron (gliclazide) are one of the mainstays of treatment. They increase insulin production and may provide better sugar absorption into fat and muscle tissue. They can cause weight gain thus may not be the best choice for obese patients. Blood sugar levels can become too low (hypoglycemia) if meals are skipped with use of the medication.

Gluconorm is a newer medication that acts like DiaBeta only faster. It is used immediately before a meal since sugar levels surge upwards after eating. People who may have difficulty maintaining a regular meal schedule use it.

Avandia and Actos are a new class of medication designed to increase insulin’s effect on muscle and fat tissue. The pancreas gets some needed rest. It does not have to produce as much insulin to maintain normal blood sugar levels. Lower insulin levels reduce the growth rate of arterial plaques or clots that can lead to heart attack or stroke. These medications do not cause low blood sugar levels.

Metformin works by reducing the liver’s sugar production and release into the bloodstream. It can increase insulin receptor sensitivity in the liver, muscle and fat cells. It does not cause low blood sugar levels nor weight gain. For this reason, it is usually the first choice of medication for obese or overweight patients.

Prandase prevents the small intestine from absorbing sugar by blocking a digestive sugar enzyme. Blood sugar levels do not increase as much after eating. The main side effects include flatulence, bloating and abdominal discomfort. These wane over time.

Combinations of these medications may be used to provide effective diabetes control. The addition of insulin injections may be required if there is severe disease, lack of efficacy of oral medications or non-compliance.

Type 2 diabetics often have other medical conditions such as high cholesterol, obesity, heart and kidney disease. Smoking must stop and alcohol consumption curtailed. Early diagnoses and intervention is key. It is much easier to prevent the complications of diabetes than to treat the end stages of the disease.

The big stumbling block is compliance. Facing a handful of pills everyday can be demoralizing. It can easily trigger a normal denial defense mechanism. Early stages of diabetes do not have many symptoms. People feel just fine thank you very much. Nevertheless the reaction, albeit understandable, is the wrong path to choose.

Newer once-a-day formulations like Diamicron MR, Actos and Avandia address this issue. They can reduce the daily dose of pills but provide equal if not better control because of better compliance. A once-a-day version of Metformin is available in the United States. Canadian availability usually follows.

Equally important is weight loss and exercise. In some cases, weight loss and exercise over time can reduce the dose of daily medication.

The incidence of diabetes continues to increase. It is no wonder that heart disease is the number one cause of death in Canada and the United States. You cannot feel or see diabetes in its early stages. It is responsible for terrible suffering: kidney failure, stroke, heart disease, loss of limbs, nerve damage and blindness.

If there is a family history or closing in on 40, a simple blood sugar test can aid in early diagnosis. Take the test. Save your life.

Related articles:

1. How frequently should we monitor blood sugar in diabetics?
2. Sitagliptin, a novel treatment for type II diabetes
3. Dealing with diabetes means understanding how it works

Originally published in The Ottawa Citizen May 28, 2002

Original Title: Just a Spoonful of Sugar

At Montreal’s Jewish General Hospital, the chief of emergency medicine, Dr. Marc Afilalo always emphasized the importance of knowing the pathophysiology of diseases. ‘Pathophysiology’ refers to the abnormal physical processes that cause disease: in short, how things work.

Patients face this conundrum daily. They take medications for conditions that they know are serious but are unaware of how the disease inflicts harm upon their body.

One such disease is type 2 diabetes formerly known as non-insulin dependent diabetes. Most people are aware that diabetes causes abnormally high blood sugar levels (hyperglycemia) but what is the reason? What happens if it remains poorly controlled or untreated?

Sugar (glucose) is the body’s main fuel source. The body has to be able to store, transport and deliver it depending upon the demands of the cells. Normally sugar is stored in the liver and muscles. The liver also produces glucose.

After a meal, sugar is absorbed from the intestine into the blood stream. In response, the pancreas secretes insulin produced by cells called beta-cells. Insulin helps the muscle, liver, fat and almost all other tissue cells absorb the sugar. It binds to an insulin receptor (like a key in a lock) on the cells’ surface opening the door for the sugar to enter.

There is evidence to suggest two mechanisms are responsible for the development of diabetes.

The first is a defect in the beta-cells ability to produce insulin. The second is the liver and muscle insulin receptors weakly respond to insulin. The liver releases more sugar because of this effect. More insulin is required to get the cells to absorb sugar. It is like having a rusty lock requiring several attempts inserting and turning the key until it finally opens.

The beta-cells try to compensate by producing more insulin to keep the sugar levels normal. However, the end result is that they burn out and insulin production fails.

Glucose is a sticky molecule. It binds to the body’s many cell types causing serious damage over time. Of particular importance are those found in the kidneys and arteries of the eye, brain, heart, kidneys and lower legs and feet.

The kidneys are responsible for filtering and removing toxins from the blood. They also maintain the body’s salt and water balance. Sugar will damage the filters like poking large holes into a sieve destroying kidney function. Salt, protein and water imbalances can cause swelling of the legs, hypertension and heart failure among others.

The inner lining of the artery is called the endothelium. Glucose can bind to this layer. This makes it easier for cholesterol and blood clotting factors to form a clot (thrombus) or plaque leading to eventual arterial blockages in the heart, brain, eyes and lower legs and feet. High insulin levels can also stimulate the growth of the endothelial cells, increase the stickiness of a blood clotting cell (platelets) and cause the arteries to constrict or narrow (vasoconstriction).

Heart attack and stroke risk increase. Areas of the retina can die causing partial to complete blindness. Oxygen delivery to the lower legs and feet is reduced. The nerves that provide information about the foot’s position and touch sensation malfunction (peripheral neuropathy) that can lead to foot injury and skin ulcers. The skin on the shins becomes smooth and shiny because of hair follicle death.

Other factors that complicate this process are elevated cholesterol levels, hypertension, obesity, smoking and family history of heart disease and stroke.

Hypertension increases the strain on the arterial walls and can cause a piece of the clot to break off (embolus) and travel to the brain causing a stroke. It can hasten the complete blockage of the main coronary arteries leading to heart attack.

Obesity will increase the demand for insulin. A larger body mass implies many more cells each with its own insulin receptors. More receptors mean more insulin is required to maintain normal sugar levels. Further these cells can be insulin resistant. The beta-cells cannot keep up with the increase in demand for insulin: hyperglycemia worsens.

The nicotine from cigarettes causes vasoconstriction increasing the risk of heart attack, stroke and loss of the lower limbs.

Many people have a combination of these risk factors. Diabetes is an insidious and destructive disease causing tremendous harm and incapacity (morbidity) and eventual death (mortality).

What if you were a researcher and you had the resources necessary to develop diabetes medications? Given the pathophysiology of diabetes, what strategies would you use to alter the various processes outlined above?

Next week’s column will focus upon treatment and demonstrate how scientific research propels the development of new and innovative strategies in the battle against diabetes.

Related articles:

1. Great variety of drugs helps treatment of diabetics
2. New understanding behind the mechanism of diabetes
3. Transplanting insulin producing cells or islet cells into people with type 1 diabetes