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How Diabetes Works
BY CRAIG FREUDENRICH, PH.D.
Odds
are that you know someone with diabetes
mellitus, possibly even someone who has to take insulin each day to
manage the disease.
Diabetes
is a growing health problem in the United States and has risen about six-fold
since 1950, now affecting approximately 20.8 million Americans.
About
one-third of those 20.8 million do not know that they have the disease.
Diabetes-related
health care costs total nearly $100 billion per year and are increasing.
Diabetes
contributes to over 200,000 deaths each year.
To
understand diabetes, you first need to know about how your body uses a hormone
called insulin to handle
glucose, a simple sugar that is its main source of energy.
In
diabetes, something goes wrong in your body so that you do not produce insulin
or are not sensitive to it.
Therefore,
your body produces high levels of blood glucose, which act on many organs to
produce the symptoms of the disease.
In
this article, we will examine this serious disease. We will look at how your
body handles glucose.
We'll
find out what insulin is and what it does, how the lack of insulin or
insulin-insensitivity affects your body functions to produce the symptoms of
diabetes, how the disease is currently treated and what future treatments are
in store for diabetics.
Blood Glucose and Insulin
Since
diabetes is a disease that affects your body's ability to use glucose, let's
start by looking at what glucose is and how your body controls it.
Glucose is a simple sugar that provides energy to all of
the cells in your body.
The
cells take in glucose from the blood and break it down for energy (some cells,
like brain cells and red blood cells, rely solely on glucose for fuel).
The
glucose in the blood comes from the food that you eat.
When
you eat food, glucose gets absorbed from your intestines and distributed by the
bloodstream to all of the cells in your body.
Your
body tries to keep a constant supply of glucose for your cells by maintaining a
constant glucose concentration in your blood -- otherwise, your cells would
have more than enough glucose right after a meal and starve in between meals
and overnight.
So,
when you have an oversupply of glucose, your body stores the excess in the
liver and muscles by making glycogen,
long chains of glucose.
When
glucose is in short supply, your body mobilizes glucose from stored glycogen
and/or stimulates you to eat food. The key is to maintain a constant
blood-glucose level.
To
maintain a constant blood-glucose level, your body relies on two hormones
produced in the pancreas that
have opposite actions: insulin and glucagon.
Insulin is made and
secreted by the beta cells of the pancreatic islets, small islands of
endocrine cells in the pancreas.
Insulin
is a protein hormone that contains 51 mino acids.
Insulin
is required by almost all of the body's cells, but its major targets are liver
cells, fat cells and muscle cells.
For
these cells, insulin does the following:
· Stimulates liver and muscle cells to store
glucose in glycogen
· Stimulates fat cells to form fats from
fatty acids and glycerol
· Stimulates liver and muscle cells to make
proteins from amino acids
· Inhibits the liver and kidney cells from
making glucose from intermediate compounds of metabolic pathways (gluconeogenesis)
As such, insulin
stores nutrients right after a meal by reducing the concentrations of glucose,
fatty acids and amino acids in the bloodstream.
Glucagon and Blood Sugar Levels
So, what happens when you do not eat?
In
times of fasting, your pancreas releases glucagon so that your body can produce
glucose.
Glucagon is another
protein hormone that is made and secreted by the alpha
cells of the pancreatic islets.
Glucagon
acts on the same cells as insulin, but has the opposite effects:
· Stimulates the liver and muscles to break down
stored glycogen (glycogenolysis) and
release the glucose
· Stimulates gluconeogenesis in the liver and
kidneys
In contrast to
insulin, glucagon mobilizes glucose from stores inside your body and increases
the concentrations of glucose in the bloodstream -- otherwise, your blood
glucose would fall to dangerously low levels.
So how does your
body know when to secrete glucagon or insulin? Normally, the levels of insulin
and glucagon are counter-balanced in the bloodstream.
For
example, just after you eat a meal, your body is ready to receive the glucose,
fatty acids and amino acids absorbed from the food.
The
presence of these substances in the intestine stimulates the pancreatic beta
cells to release insulin into the blood and inhibit the pancreatic alpha cells
from secreting glucagon.
The
levels of insulin in the blood begin to rise and act on cells (particularly
liver, fat and muscle) to absorb the incoming molecules of glucose, fatty acids
and amino acids.
This
action of insulin prevents the blood-glucose concentration (as well as the
concentrations of fatty acids and amino acids) from substantially increasing in
the bloodstream.
In
this way, your body maintains a steady blood-glucose concentration in
particular.
In contrast, when
you are between meals or sleeping, your body is essentially starving. Your
cells need supplies of glucose from the blood in order to keep going.
During
these times, slight drops in blood-sugar levels stimulate glucagon secretion
from the pancreatic alpha cells and inhibit insulin secretion from the beta
cells. Blood-glucagon levels rise.
Glucagon
acts on liver, muscle and kidney tissue to mobilize glucose from glycogen or to
make glucose that gets released into the blood. This action prevents the
blood-glucose concentration from falling drastically.
As you can see, the
interplay between insulin and glucagon secretions throughout the day help to
keep your blood-glucose concentration constant, staying at about 90 mg per 100
ml of blood (5 millimolar).
GLUCAGON
At
very high concentrations, generally above the maximum levels found in the body,
glucagon can act on fat cells to break down fats into fatty acids and
glycerol, releasing the fatty acids into the bloodstream. However, this is a
pharmacological effect, not a physiological one.
Diabetes
Now that you know how your body handles glucose with
insulin and glucagon, you are ready to understand diabetes.
Diabetes
is classified into three types: Type 1, Type 2 and gestational diabetes.
Type 1 (also
called juvenile diabetes or insulin-dependent diabetes) is caused by a
lack of insulin. This type is found in five percent to 10 percent of diabetics
and usually occurs in children or adolescents. Type 1 diabetics have an
abnormal glucose-tolerance test and little or no insulin in their blood. In
Type 1 diabetics, the beta cells of the pancreatic islets are destroyed,
possibly by the person's own immune system, genetic or environmental factors.
Type 2 (also
called adult-onset diabetes or non-insulin-dependent diabetes) occurs when
the body does not respond or can't use its own insulin (insulin
resistance). Type 2 occurs in 90 percent to 95 percent of diabetics and
usually occurs in adults over the age of 40, most often between the ages of 50
and 60. Type 2 diabetics have an abnormal glucose-tolerance test and higher
than normal levels of insulin in their blood. In Type 2 diabetics, the insulin
resistance is linked to obesity, but we do not know exactly how this occurs.
Some studies suggest that the number of insulin receptors on liver, fat and
muscle cells is reduced, while others suggest that the intracellular pathways
activated by insulin in these cells are altered.
Gestational diabetes can occur in some pregnant women and is similar to
Type 2 diabetes. Gestational diabetics have an abnormal glucose-tolerance test
and slightly higher levels of insulin. During pregnancy, several hormones
partially block the actions of insulin, thereby making the woman less sensitive
to her own insulin. She develops a diabetes that can be managed by special
diets and/or supplemental injections of insulin. It usually goes away after the
baby is delivered.
Regardless of the type of diabetes, diabetics exhibit
several (but not necessarily all) of the following symptoms:
· Excessive
thirst (polydipsia)
· Frequent
urination (polyuria)
· Extreme
hunger or constant eating (polyphagia)
· Unexplained
weight loss
· Presence
of glucose in the urine (glycosuria)
· Tiredness
or fatigue
· Changes
in vision
· Numbness
or tingling in the extremities (hands, feet)
· Slow-healing
wounds or sores
· Abnormally
high frequency of infection
These symptoms can be understood when we see how
insulin deficiency or insulin resistance affects the body's physiology.
DIABETES MELLITUS AND GLUCOSE TOLERANCE
TESET
The name "diabetes
mellitus" means "sweet urine."
It stems from ancient times, when physicians would taste a patient's urine as a
part of diagnosis.
A Glucose Tolerance Test is a diagnostic test for
diabetes. After fasting overnight, you are given a concentrated sugar solution
(50 to 100 grams of glucose) to drink, and your blood is sampled periodically
over the next several hours to test its glucose levels.
Normally,
blood glucose does not rise very much and returns to normal within two to three
hours. In a diabetic, the blood glucose is usually higher after fasting, rises
more after the glucose solution and takes from four to six hours to come down.
Insulin Ineffectiveness
Now that you know the symptoms of diabetes -- high
blood glucose, excessive hunger and thirst, frequent urination -- let's look at
what happens to your body during diabetes.
For
the purposes of this discussion, let's suppose that you have undiagnosed, and
therefore unmanaged, diabetes.
Now,
let's see how the lack of insulin or insulin-resistance affects your body to
produce the clinical symptoms and signs of diabetes:
Your
lack of insulin or insulin resistance directly causes high
blood-glucose levels during fasting and after a meal (reduced glucose
tolerance).
1. Because
your body either does not produce or does not respond to insulin, your cells do
not absorb glucose from your bloodstream, which causes you to have high
blood-glucose levels.
2. Because
your cells have no glucose coming into them from your blood, your body
"thinks" that it is starving.
3. Your
pancreatic alpha cells secrete glucagon, and glucagon levels in your blood rise.
4. Glucagon
acts on your liver and muscles to breakdown stored glycogen and
release glucose into the blood.
5. Glucagon
also act on your liver and kidneys to produce and release glucose by
gluconeogenesis.
6. Both
of these actions of glucagon further raise your blood-glucose levels.
High
blood glucose causes glucose to appear
in your urine.
1. High
blood-glucose levels increase the amount of glucose filtered by your kidneys.
2. The
amount of glucose filtered exceeds the amount that your kidneys can reabsorb.
3. The
excess glucose gets lost into the urine and can be detected by glucose test
strips.
High
blood glucose causes you to urinate
frequently.
1. High
blood glucose increases the amount of glucose filtered by your kidneys.
2. Because
the filtered load of glucose in your kidneys exceeds the amount that they can
reabsorb, glucose remains inside the tubule lumen.
3. The
glucose in the tubule retains water, which increases urine flow through the
tubule.
4. The
increased urine flow causes you to urinate frequently.
The
high blood glucose and increased urine flow make you constantly
thirsty.
1. High
blood-glucose levels increase the osmotic pressure of your blood and directly
stimulate the thirst receptors in your brain.
2. Your
increased urine flow causes you to lose body sodium, which also stimulates your
thirst receptors.
You
are constantly hungry. It's not
clear exactly what stimulates your brain's hunger centers, possibly the lack of
insulin or high glucagon levels.
1. You lose weight despite the fact that you are eating
more frequently. The lack of insulin or insulin-resistance directly
stimulates the breakdown of fats in fat cells and proteins in muscle,
leading to weight loss.
2. Metabolism
of fatty acids leads to the production of acidic ketones in the blood (ketoacidosis), which can lead to brething
problems, the smell of acetone on your breath, irregularities in your heart and
central-nervous-system depression, which leads to coma.
You
feel tired because your cells
cannot absorb glucose, leaving them with nothing to burn for energy.
1. Your hands and feet may feel cold because
your high blood-glucose levels cause poor blood circulation.
2. High
blood glucose increases the osmotic pressure of your blood.
3. The
increased osmotic pressure draws water from your tissues, causing them to
become dehydrated.
4. The
water in your blood gets lost by the kidneys as urine, which decreases your
blood volume.
5. The
decreased blood volume makes your blood thicker (higher concentration of red
blood cells), with a consistency like molasses, and more resistant to flow
(poor circulation).
Your
poor blood circulation causes numbness
in your hands and feet, changes in vision, slow-healing wounds and frequent
infections.
High
blood glucose or lack of insulin may also depress the immune system.
Ultimately, these can lead to gangrene in the limbs and blindness.
Fortunately,
these consequences can be managed by correcting your high blood glucose through
diet, exercise and medications, as we'll discuss next.
BLOOD GLUCOSE MONITORS
To monitor blood glucose, there
are a number of commercial blood-glucose monitors.
Each
one involves reacting a test strip with a drop of blood (finger prick). The
glucose in the blood reacts chemically with an enzyme on the test strip
called glucose oxidase.
The
product of the reaction, gluconate,
combines with another chemical to make the strip turn blue. The device measures
the degree of color change to determine and display the concentration of
glucose in the blood sample.
Treatments
As of now, there is no cure for diabetes; however, the
disease can be treated and managed successfully.
The
key to treating diabetes is to closely monitor and manage your blood-glucose
levels through exercise, diet and medications. The exact treatment regime
depends on the type of diabetes.
If
you have Type 1 diabetes, you lack insulin and must administer it several times
each day. Insulin injections are usually timed around meals to cope with the
glucose load from digestion.
You
must monitor your blood-glucose levels several times a day and adjust the
amounts of insulin that you inject accordingly. This keeps your blood-glucose
concentration from fluctuating wildly.
There
are some implantable insulin infusion pumps that allow you to press a button
and infuse insulin. If you inject too much insulin, you can drive your
blood-glucose level well below normal (hypoglycemia).
This
can cause you to feel light-headed and shaky because your brain cells are not
receiving enough glucose (mild episodes can be relieved by eating a candy bar
or drinking juice).
If
your blood glucose goes really low, you can lapse into a coma (insulin shock), which can be
life-threatening.
In
addition to insulin injections, you have to watch your diet to keep track of
the carbohydrate and fat contents, and you must exercise frequently. This
treatment continues for the rest of your life.
If
you have Type 2 diabetes, you can usually manage it by reducing your body
weight through dieting and exercise.
You
may have to monitor your blood glucose either daily or just when you visit your
doctor. Depending on the severity of your diabetes, you may have to take
medication to aid in controlling your blood glucose.
Most
of the medicines for Type 2 diabetes are oral medications, and their actions
fall into the following categories:
· Stimulating
the pancreas to release more insulin to help reduce blood glucose
· Interfering
with the absorption of glucose by the intestine, thereby preventing glucose
from entering the bloodstream
· Improving
insulin sensitivity
· Reducing
glucose production by the liver
· Helping
to breakdown or metabolize glucose
· Supplementing
insulin directly in the bloodstream through injections
Like
a Type 1 diabetic, a Type 2 diabetic is on this treatment for the rest of his
or her life.
There
are a number of alternative treatments for diabetes. These alternative
treatments are not widely accepted, mainly due to lack of scientific research
on their effectiveness or lack of scientific consensus. Such treatments
include:
· Acupuncture -
This is an Eastern medical treatment whereby needles are inserted at various
centers in the body to release natural painkillers, which may help in managing
painful nerve damage in diabetes.
· Biofeedback -
This psychological technique involves using meditation, relaxation and
stress-reduction methods to manage and relieve pain.
· Chromium -
Additional chromium in your diet may help your body make a glucose-tolerance
factor that helps improve insulin action. However, the scientific information
on chromium supplementation in diabetes is insufficient, and no consensus
exists.
· Magnesium -
Diabetics tend to be deficient in magnesium, which can worsen the complications
of diabetes, especially Type 2. The exact nature of the relationship between
magnesium and diabetes is still under research, and no consensus has been
reached.
· Vanadium -
Vanadium may normalize blood glucose in Type 1 and 2 diabetic animals, but
there is not enough information available for humans. This area is currently
under research.
As
with any medical treatment, you should discuss treatment options with your
physician. For more information on alternative treatments, see the NIDDK
bulletin Alternative Therapies for Diabetes.
One
of the most promising developments for future, perhaps permanent, treatments for
Type 1 diabetes is pancreatic islet
transplantation. In this technique, islets are removed from the pancreas of
a deceased donor and injected through a thin tube (catheter) into the liver of
a diabetic patient. After some time, the islet cells attach to new blood
vessels and begin releasing insulin. Although early studies have shown some
success, rejection of the donor's tissue is a major problem. Research continues
in this field because of its great potential to treat diabetes.
PREVENTING DIABETES
Type 2 diabetes can be prevented
or reduced by exercising frequently and watching your weight, especially as you
get older. Take the Diabetes Risk Test to determine your risk for developing
diabetes.
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