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

Originally published in The Ottawa Citizen April 16, 2002
Original Title: Cholesterol Secrets

Many people are aware of the effects of elevated cholesterol upon their health. Indeed, the rates of heart disease and stroke continue to rise. Concomitant risk factors for heart disease like diabetes, hypertension, obesity, smoking and family history of heart disease and stroke complicate the picture.

Those with some or all these conditions use cholesterol-lowering agents as one means to reduce their risk of heart disease and stroke.

The medical terms reflecting the various cholesterol factors and lab measurements sometimes have a numbing effect as the patient tries to synthesize the results.

A lipid profile, the test used to diagnose hypercholesterolemia or a combination of elevated cholesterol and triglycerides, provides results for several lipid components; total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL) and triglycerides.

LDL and HDL are proteins that carry cholesterol to specific destinations. They act as transport trucks. They are respectively known as “bad” and “good” cholesterol.

LDL’s function is to transport the cholesterol produced in the liver and deliver it to the cells in the body. Cholesterol is necessary to maintain the integrity of the cell walls and for the synthesis of certain hormones.

The majority of cholesterol is produced in the liver from a variety of foods laden with saturated fat. It is the reason why healthy diets are low in saturated fat.

Consistent consumption of foods containing saturated fat stimulates the liver to produce more LDL. An elevated LDL means that the liver is producing too much cholesterol.

The LDL is sent out into the body with too much cargo. This results in deposition of the extra cholesterol into the arterial walls causing blockages or plaques; hence LDL is the bad guy.

HDL picks up and transports cholesterol from the cells and bloodstream back to the liver to be destroyed thus its good-guy image.

Triglycerides are molecules that act as a storage reservoir for fatty acids. Fatty acids are used as an energy source for various metabolic processes. Elevated triglycerides contribute to the problems associated with elevated cholesterol levels.

Initial treatment for people who do not have risk factors for heart disease nor have had a heart attack is diet (foods containing polyunsaturated fats do not promote cholesterol synthesis thereby reducing LDL levels), exercise (to increase HDL levels), smoking cessation and lifestyle modification. After three to six months, medical therapy is indicated if the initial treatment is unsuccessful.

The recommendation for people who have a genetic predisposition to high levels of triglycerides is to use medication because lifestyle modifications other than smoking cessation have little effect.

The risk of heart disease is related to the tug of war between LDL and HDL. A measure of the risk of heart disease is calculated from the total cholesterol divided by the HDL (TC/HDL ratio). The lower the ratio, the better.

Ideally the net effect should be efficient removal of extra cholesterol from the bloodstream and the arteries. The goal is to reduce LDL and total cholesterol and increase HDL.

The results of the Heart Protection Study released in November 2001 may possibly change the treatment approach for heart disease and stoke prevention.

This five-year study had 20,000 volunteers between 40 and 80 years of age at high risk of coronary heart disease. The study wanted to know if cholesterol-lowering therapy was of use in specific groups of individuals where there was a lack of evidence of the benefits of drug treatment.

These groups were women, diabetics, people over 70 years of age, those with arterial disease not involving the heart, and those with average or below-average cholesterol levels.

Volunteers used either 40 milligrams of simvastatin per day as cholesterol-lowering therapy, or matching placebos. The study’s major findings include:

A one-third risk-reduction of heart attack and stroke with statin use reducing the need for arterial surgery, angioplasty (dilation of the coronary arteries) and amputations.
High-risk patients with normal cholesterol levels, women and men over 70 benefited from treatment.
About five years of simvastatin treatment typically prevents heart attacks, strokes or other major vascular events in:

• 100 of every 1,000 people who’ve previously had a heart attack
• 80 of every 1,000 people with angina or some other evidence of coronary heart disease
• 70 of every 1000 patients who’ve previously had a stroke
• 70 of every 1000 people with occlusive disease in leg or other arteries
• 70 of every 1000 people with diabetes
• A reduction of hospitalization risk because of worsening angina by about 30 fewer admissions per 1,000 treated for five years.
• Like high blood pressure, it takes time for elevated cholesterol levels to cause harm. Talk to your doctor about whether you need to be tested.

There is now evidence to expand treatment options for people who fall into one of the high-risk groups to prevent much hardship. That is what it is all about.

Related articles:

1. Stroke out the numbers
2. Nuts lower blood cholesterol levels
3. Lifetime risk of stroke and heart disease far greater than any other condition but signs of illness not recognized

Originally published in The Ottawa Citizen March 26, 2002

Every man desires to live long; but no man
would be old. – Jonathan Swift (1667-1745)

Many men in their forties and early fifties begin to re-evaluate their lives. Physiologic changes and lifestyle choices can affect their physical, spiritual and emotional health.

One physiologic change starts at age 30 is a gradual decrease in testosterone levels. By age 70 levels are ten percent of what they originally were at age 30.

The testes (testicles) produce testosterone. Testosterone can be bound to a protein called Sex Hormone Binding Globulin (SHBG) or float freely within the bloodstream. The latter is free to exert its effect on the body and is called Bioavailable Testosterone (BT). As men age, SHBG levels increase whilst testosterone production levels decrease. The net effect is more testosterone remains bound to SHBG and thus BT levels decrease.

This condition is called Andropause. It is slowly becoming recognized as a cause of some of the problems seen in men as they age. About 30 percent of men in their fifties will have low testosterone levels low enough to cause symptoms.

Testosterone levels vary in men. Patients with normal levels may have symptoms of deficiency while others do not.. The clinical picture of Andropause varies. It can include depression, fatigue, irritability, reduced sex drive (libido), aches and pains, sweating and flushing, decreased sexual performance, reduction in muscle strength and mass, increased upper and central body fat, osteoporosis (calcium loss from bone) and a possible increased risk of cardiovascular disease.

Excess alcohol intake, psychological stress, infections, medications, surgery, excess weight and lack of exercise can contribute to its onset. Other diseases such as diabetes, depression and thyroid disease among others can cause similar symptoms and must be considered. A full diagnostic evaluation is essential to determine the cause.

The ADAM (Androgen Deficiency in Aging Males) screening questionnaire is used if a patient presents with the aforementioned symptoms.

• Do you have a decrease in libido (sex drive)?
• Do you have lack of energy?
• Do you have a decrease in strength and/or endurance?
• Have you lost height?
• Have you noticed a decreased “enjoyment of life”?
• Are you sad or grumpy?
• Are your erections less strong?
• Have you had a recent deterioration in your ability to play sports?
• Are you falling asleep after dinner?
• Has there been a recent deterioration in your work performance?
• A “yes” answer to either question one or seven or to any three questions increases the clinical suspicion for Andropause. The next step is a blood test to check the level of BT. This test is not covered by OHIP and costs about $75. (What would people say if estrogen and progesterone blood tests were not covered?)

If the BT level is low, testosterone replacement (TR) is suggested not unlike hormonal replacement therapy for menopausal women. Testosterone comes in many forms: gels, injectables, and pills. The pill form is the usual method used for testosterone replacement therapy. The dose is individualized for each patient. BT levels are checked three months after therapy begins.

A reversal of many of the symptoms occurs within the first six weeks of treatment. The patient’s mood and sense of well being improves, they have increases in physical and emotional energy, libido and sexual function, muscle strength, lean body mass and improved quality of sleep. Over the longer term, bone mass and integrity is preserved which helps combat osteoporosis.

Men who suffer from prostate or breast cancer should never use testosterone since it can worsen these conditions. For those who may have liver or heart disease, swelling of the feet, face or hands, enlarged prostate, diabetes or kidney disease, TR may not be indicated.

Your doctor will closely follow your progress repeating several blood tests that measure the effect of testosterone upon cholesterol, triglyceride and PSA (prostatic specific antigen) levels, periodic liver function tests and red blood cell production. The size of the prostate must be evaluated because testosterone can cause enlargement of the prostate.

These effects are not commonly seen since the amount of testosterone used is just enough to replace what was missing. Muscle mass does not increase to body builder size because of the low replacement dose. However, there are practice recommendations to be followed in order to maximize safety and efficacy of the treatment.

The biggest hurdle for men tends to be feeling ashamed or embarrassed by their symptoms. It is not a sign of weakness to suffer from this condition. It can be easily corrected and improve quality of life. Consult your doctor if you suspect that you may have this condition.

Related articles:

1. Testosterone deficiency in males can mimic many other conditions
2. Menopause survey
3. Reversing vasectomy