The treatment of diabetes
has gone through revolutionary changes. Most Type
2 diabetics can now avoid ending up on insulin
injections. Most do very well with new oral medications.
“Mark” came to see me for his diabetes,
after suffering three angioplasties in two years.
Mark, like 95% of diabetics, had Type 2 diabetes.
Despite following his doctor’s advice and
following his anti-diabetic regimen, including
diet, exercise and insulin injections, he developed
severe coronary artery disease. He was quite demoralized.
Heart disease is the number one killer of diabetics.
Compared to non-diabetics, patients with diabetes
have a six fold increased risk for a heart attack.
The reason for this increased risk is a phenomenon
called Insulin Resistance, the root cause for
Type 2 diabetes, as well as heart attacks and
Therefore, now we treat diabetes by treating insulin
resistance.What is insulin resistance and how
does it cause heart attacks and strokes? Insulin
is a chemical produced by the pancreas in our
body. One of the main functions of insulin is
to drive glucose from the blood into the cells,
especially muscle cells, where it is used as a
fuel to produce energy.
Think of insulin as the doorman
who opens the door for glucose to get into the
cell. In individuals prone to Type 2 diabetes,
the hinges on the door of the cell are rusty.
Consequently, insulin cannot easily open the doors.
Now instead of one doorman, you need three or
four doorman to pry the door open. This is called
insulin resistance. In response to insulin resistance,
the pancreas produces more and more insulin, which
keeps blood sugar normal for some time. If insulin
resistance is not treated, the pancreas eventually
becomes exhausted and insulin production starts
This causes blood sugar to
start rising and eventually, a person becomes
It takes about one to two decades of insulin resistance
before a person becomes diabetic. During this
time, insulin resistance causes many other changes
in our body which are quite harmful. For example,
insulin resistance increases serum triglycerides
(the fat in the blood), lowers HDL cholesterol
(the good cholesterol) and changes LDL cholesterol
(the bad cholesterol) from type A (less dangerous)
to Type B (more dangerous). Insulin also increases
blood pressure in these patients. In addition,
Insulin resistance makes it easier for blood to
clot and impairs our body’s natural ability
to break down any clots.
All of these abnormalities set the stage for a
heart attack and stroke.Why is the old fashioned
treatment of diabetes flawed?When I first saw
Mark, his diabetes was out of control, because
his diabetes was being managed by an old fashioned,
outdated treatment plan. For years, he was taking
Glyburide, which initially controlled his diabetes.
However, after a few years, he had to go on insulin
shots to control his blood sugar. Glyburide is
an old drug and belongs to the class of drugs
known as sulfonylurea drugs. (Other drugs in this
class include Glipizide, Glimepiride and Chlorpropamide.
In the US, these drugs are available under the
brand names of Diabeta, Micronase and Glynase
for glyburide, Glucotrol for glipizide, Amaryl
for glimepiride and Diabenes for chlorpropamide).
Before 1994, these were the
only oral drugs available in the US for the treatment
of Type 2 diabetes. These sulfonylurea drugs act
by stimulating the pancreas to produce more insulin,
but do not treat insulin resistance. It’s
like flocking a tired horse to keep going. Eventually
it slows down, stumbles and drops dead.
“Mark’s” exhausted pancreas,
like a tired horse, could not produce enough insulin
despite stimulation from sulfonylurea drugs. Eventually,
he was placed on insulin shots to control his
diabetes. However, once again, it was a poor strategy
for controlling his diabetes. The reason? Sulfonylurea
drugs and insulin shots do not treat insulin resistance.
Consequently, most diabetic patients, including
Mark, develop coronary heart disease requiring
angioplasties or even heart bypass surgery. They
are also at high risk for stroke. The new treatment
of diabetesDoctors involved in research for treatment
of diabetes eventually realized that to effectively
treat Type 2 diabetics, insulin resistance must
be treated. The treatment for diabetes started
to change in 1994 with the release of Glucophage
(metformin), which treats insulin resistance at
the level of the liver.
However, in a diabetic, insulin
resistance develops at three levels: muscle, fat
and the liver. Therefore, metformin alone is not
enough to adequately treat
In 1997, Rezulin (troglitazone) and then in 1999,
Actos (pioglitazone) and Avandia (rosiglitazone)
were released. These drugs treat insulin resistance
at the level of muscle and fat. Rezulin was later
taken off the US market because of its association
with some cases of liver toxicity. However, Actos
and Avandia have proven to be safe and do not
cause liver toxicity.
By combining metformin (Glucophage) with Actos
or Avandia, we can effectively treat insulin resistance
at all three levels. Besides controlling blood
glucose, Actos and Avandia also reduce triglycerides,
increase HDL cholesterol and re-establish the
body’s ability to break clots and therefore,
reduce the risk for heart attack and stroke.
Diabetics who undergo balloon angioplasty of narrowed
coronary arteries frequently develop another blockage
after just a few months. This occurs due to the
formation of a new layer of lining in the coronary
blood vessel wall, known as neo-intima. Actos
and Avandia reduce neo-intima formation and therefore,
have the potential to decrease the need for repeated
angioplasties. In a recently published study,
Avandia was shown to significantly reduce the
need for repeated coronary angioplasties.
In another study, Actos was shown to reduce narrowing
of carotid arteries in the neck. This is a significant
finding, as people with narrowed carotid arteries
are at a high risk for stroke. By reducing insulin
resistance, Actos and Avandia reduce the burden
of excessive insulin production by the pancreas.
Relieved of the stress of overproduction of insulin,
the pancreas begins to work efficiently once again.
As a result, these patients usually do not have
to resort to insulin injections.
This certainly has been our experience at the
Jamila Diabetes and Endocrine Medical Center.
By using these new drugs, we have been able to
take most of our
patients off insulin injections. Mark was one
of those patients. With the new combination therapy
of treating insulin resistance with Glucophage
and Actos, his diabetes came under much better
control. We gradually took him off his insulin
injections. Naturally, he was quite thrilled that
he no longer had to endure insulin injections.
More impressively, he hasn’t had any more
coronary angioplasties in the last seven years.
There is another new class of drugs that specifically
target blood glucose rise after meals. These drugs
are Repaglinide (Prandin) and Nateglinide (Starlix).
These drugs work by increasing insulin production
for a short period of time (about four to six
hours, as compared to twelve to twenty-four hours
of sulfonylurea drugs.) Therefore these drugs
are used to control the rise of blood glucose
after meals. These drugs are taken at the start
of a meal.
Another class of anti-diabetic
drugs includes Acarbose (Precose) and Miglitol
(Glyset). These drugs act by preventing some glucose
absorption from the intestines. By themselves,
they are weak drugs and need to be combined with
other drugs.Every drug has some potential sideeffects
Sulfonylurea drugs can cause episodes of low blood
sugar, which causes terrifying symptoms such as
shakiness, heart pounding, perspiration and fuzzy
thinking. If you aren’t treated promptly,
you can lapse into a coma. On the other hand,
Pioglitazone (Actos), Rosiglitazone (Avandia)
and Metformin (Glucophage) do not cause low blood
sugar. Sulfonylurea drugs usually cause some weight
gain as well.
A major disadvantage of sulfonylurea drugs is
that they eventually lead to pancreas exhaustion
and then patients have to go on insulin injections.
Repaglinide, nateglinide, acarbose and miglitol
can also cause low blood sugar.
Actos and Avandia can cause weight gain and congestive
heart failure in some patients.
Metformin can cause some
stomach upset as well as diarrhea. Occasionally,
it causes a metallic taste in the mouth and Vitamin
B12 deficiency. Rarely, Metformin can cause a
serious side-effect known as Lactic acidosis,
which can be life-threatening. This rare sideeffect
develops if metformin is used in patients with
kidney failure, liver disease or other serious
diseases such as pneumonia.
Procedures that require contrast agents, such
as CT scans and angiograms, can occasionally induce
kidney failure in diabetic patients. Therefore,
patients should not take Metformin for up to 48
hours after such a procedure. Then a blood test
should be done to check kidney function before
restarting metformin. Diet and exercise are extremely
important Diet is
an extremely important and often misunderstood
part of diabetic treatment. Patients with Type
2 diabetes on oral medications need to eat only
three small meals a day. No snacks. Reduce the
amount of bread, pasta and rice. Avoid cereals,
donuts, muffins, croissants and other bakery products.
Say no to desserts and pizza. Don’t drink
sodas or juices as they are loaded with sugar.
Fruits are good and bad for us. They provide us
with vitamins, but are loaded with natural sugar.
Therefore, eat no more than one
fresh fruit a day. Take a daily multivitamin to
keep your vitamins optimized.
Daily exercise is crucial
to the proper management of diabetes. Aerobic
exercise for about 30 minutes a day reduces insulin
resistance and blood sugar starts decreasing.
Start exercise slowly by walking for about 10
minutes. Gradually increase to brisk walking for
about 30 minutes a day. Before embarking on any
exercise plan, discuss it with your physician.
In summary, every Type 2 diabetic patient, in
addition to diet and exercise, should be on metformin
(Glucophage) and pioglitazone (Actos) or rosiglitazone
(Avandia), provided there are no contra-indications
to the use of these drugs. If diabetes is still
uncontrolled, then another anti-diabetic drug,
such as Prandin, Starlix or glyburide, can be
added. With this new approach, we not only control
blood glucose, but also reduce the devastating
complications of diabetes, especially heart disease