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.

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© Dr. Barry Dworkin 2002