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How Diabetes Works

by Craig C. Freudenrich, Ph.D.

Odds are that you know someone with diabetes mellitus , possibly Diabetes Mellitus
even someone who has to take insulin each day to manage the The name "diabetes
disease. Diabetes is a growing health problem in the United States mellitus" means "sweet
and has risen about six -fold since 1950, now affecting urine." It stems from ancient
approximately 16 million Americans. About one-third of those 16 times, when physicians
would taste a patient's urine
million do not know that they have the disease. Diabetes-related as a part of diagnosis.
health care costs total nearly $100 billion per year and are
increasing. Diabetes contributes to over 200,000 deaths each year.

Photo courtesy Eli Lilly & Company

Insulin is what diabetics lack and need for treatment.

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.

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In this edition of HowStuffWorks, 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.

Insulin, Glucagon and Blood Glucose

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.

A glucose molecule

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.

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The pancreas has many islets that contain insulin -producing

beta cells and glucagon-producing alpha cells.

Insulin is made and secreted by the beta cells of the Pancreas

pancreatic islets, small islands of endocrine cells in the Your pancreas is located on the
pancreas. Insulin is a protein hormone that contains 51 amino left side of your body, in the
acids. Insulin is required by almost all of the body's cells, but its abdomen below your stomach.
major targets are liver cells, fat cells and muscle cells. For these It produces many digestive
enzymes that break down food
cells, insulin does the following: (exocrine function) and
hormones (endocrine function)
? Stimulates liver and muscle cells to store glucose in that regulate blood glucose.
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.

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Insulin and glucagon have opposite effects on liver and other

tissues for controlling blood-glucose levels.

So, what happens when you do not eat? In times of fasting, your Glucagon
pancreas releases glucagon so that your body can produce At very high concentrations,
glucose. Glucagon is another protein hormone that is made and generally above the maximum
secreted by the alpha cells of the pancreatic islets. Glucagon levels found in the body,
acts on the same cells as insulin, but has the opposite effects: glucagon can act on fat cells to
break down fats into fatty acids
and glycerol, releasing the fatty
? Stimulates the liver and muscles to break down stored acids into the bloodstream.
glycogen (glycogenolysis) and release the glucose However, this is a
? Stimulates gluconeogenesis in the liver and kidneys pharmacological effect, not a
physiological one.

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

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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).

Glucose Tolerance Test

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.

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 Animal Models

diabetes) is caused by a lack of insulin. This type is found in five Scientists can study Type 1
percent to 10 percent of diabetics and usually occurs in children diabetes in rats or mice by
or adolescents. Type 1 diabetics have an abnormal glucose- injecting them with an antibiotic
tolerance test and little or no insulin in their blood. In Type 1 called streptozotocin, which
destroys the beta cells to
diabetics, the beta cells of the pancreatic islets are destroyed, produce diabetes. Type 2
possibly by the person's own immune system, genetic or diabetes is mimicked in a
environmental factors. genetically altered strain of
mice that become obese and
diabetic as they age.
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.

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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 (see Understanding Gestational Diabetes to learn more).

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.

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.

The high blood glucose in diabetes produces glucose in the

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urine and frequent urination through effects on the kidneys.

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.
? Your pancreatic alpha cells secrete glucagon, and glucagon levels in your

blood rise.
? Glucagon acts on your liver and muscles to breakdown stored glycogen and

release glucose into the blood.

? Glucagon also act on your liver and kidneys to produce and release glucose

by gluconeogenesis.
? 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 (see How Your Kidneys Work for details on filtration and reabsorption).

? 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.

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The lack of insulin or insulin resistance acts on many organs

to produce a variety of effects.

? 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.

? 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.
? Metabolism of fatty acids leads to the production of acidic ketones in the blood

(ketoacidosis), which can lead to breathing 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.

? Your hands and feet may feel cold because your high blood -glucose levels cause poor

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blood circulation.
1. High blood glucose increases the osmotic pressure of your blood.
2. The increased osmotic pressure draws water from your tissues, causing them to
become dehydrated.
3. The water in your blood gets lost by the kidneys as urine, which decreases your
blood volume.
4. 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.

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.

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.

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A commercial blood-glucose monitor

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 Preventing Diabetes
you to press a button and infuse insulin. If you inject too much Type 2 diabetes can be
insulin, you can drive your blood-glucose level well below normal prevented or reduced by
(hypoglycemia ). This can cause you to feel light-headed and exercising frequently and
shaky because your brain cells are not receiving enough glucose watching your weight,
especially as you get older.
(mild episodes can be relieved by eating a candy bar or drinking Take the Diabetes Risk Test to
juice). If your blood glucose goes really low, you can lapse into a determine your risk for
coma (insulin shock), which can be life -threatening. In addition developing diabetes.
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

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? 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. See
What Are the Specific Drugs Used for Type 2 Diabetes? for details.

There are a number of alternative treatments for diabetes. These Diabetes Research
alternative treatments are not widely accepted, mainly due to Researchers at Duke University
lack of scientific research on their effectiveness or lack of Medical Center announced in
scientific consensus. Such treatments include: June 2001 that "specially
encapsulated insulin-producing
pancreas cells from pigs have
? Acupuncture - This is an Eastern medical treatment kept a diabetic baboon from
whereby needles are inserted at various centers in the needing insulin for more than
body to release natural painkillers, which may help in nine months." Since the
managing painful nerve damage in diabetes. treatment, the baboon's insulin
levels have remained normal
and the animal has not required
? Biofeedback - This psychological technique involves using additional islet -cell therapy.
meditation, relaxation and stress-reduction methods to
manage and relieve pain. According to the head of Duke's
islet-cell transplant program, Dr.
? Chromium - Additional chromium in your diet may help Emmanuel Opara, the hope is
that this finding could end the
your body make a glucose-tolerance factor that helps insulin injections that millions of
improve insulin action. However, the scientific information people take daily for the
on chromium supplementation in diabetes is insufficient, treatment of Type 1 diabetes.
and no consensus exists. The research may also benefit
a small number of Type 2
diabetes patients who require
? Magnesium - Diabetics tend to be deficient in magnesium, daily insulin injections because
which can worsen the complications of diabetes, especially they are unable to process
Type 2. The exact nature of the relationship between insulin properly (versus most
magnesium and diabetes is still under research, and no Type 2 cases, in which the body
does not produce insulin
consensus has been reached. correctly). To read more about
the research that Dr. Opara and
? Vanadium - Vanadium may normalize blood glucose in his team have conducted, click
Type 1 and 2 diabetic animals, but there is not enough here.
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 (for more information, see Pancreatic Islet Transplantation).

To learn more about diabetes, see the links on the next page.

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Lots More Information!

Related HowStuffWorks Articles

? How Your Kidneys Work

? How Food Works
? How Cells Work
? How Fat Cells Work
? How Fats Work
? How Blood Works
? How Muscles Work
? How Your Immune System Works
? How Prenatal Testing Works
? How Human Reproduction Works
? How Exercise Works
? How Calories Work
? How Dieting Works
? How Atoms Work

More Great Links!

General Information

? American Diabetes Association Home Page

? Diabetes Education Network
? What Are Drug Treatments for Type 2 Diabetes?
? The Diabetes Mall
? Joslin Diabetes Center
? Diabetes Mellitus Pathology Tutorial
? Juvenile Diabetes Foundation International
? Duke University Medical Center Press Release: Transplanted Pig Islet Cells Keep
Diabetic Baboon Off Insulin (June 2001)
? National Diabetes Education Initiative
? WebMD/Lycos: Diabetes Mellitus
? LillyDiabetes.com
? The Biology Project: Carbohydrate Metabolism Regulation Problem Set
? Hormones of the Pancreas
? Glucagon.com

U.S. Centers for Disease Control & Prevention (CDC)

? National Diabetes Fact Sheet

? Diabetes: Frequently Asked Questions
? The Prevention and Treatment of Complications of Diabetes Mellitus: A Guide for
Primary Care Practitioners
? Diabetes: A Serious Public Health Problem At-a-Glance 2001

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

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? Do Your Level Best

? Prevent Diabetes Problems Booklets
? Devices for Taking Insulin
? Kidney Diseases of Diabetes
? Foot Care Kit for Diabetes: Help Prevent Amputations
? Pancreatic Islet Transplantation
? Know Your Blood Sugar Numbers (PDF)
? Medicines for People with Diabetes
? The Pima Indians: Pathfinders for Health
? Hypoglycemia
? Are You at Risk for Gestational Diabetes?
? Understanding Gestational Diabetes
? Alternative Therapies for Diabetes
? Diabetes Overview
? Principles for Controlling Your Diabetes for Life

The Merck Manual

? Diabetes Mellitus
? Diabetic Ketoacidosis
? Hypoglycemia
? Nonketotic Hyperglycemic-Hyperosmolar Coma

Discovery Health

? Diabetes Mellitus
? Diabetes Type I
? Diabetes Type II
? Diabetic Nephropathy
? Diabetic Neuropathy
? Diabetic Ketoacidosis
? Diabetes and Exercise
? Diabetes and Feet
? Diabetic Foot Ulcer
? Diabetes and Infections

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http://www.howstuffworks.com/diabetes.htm/printable 5/6/2002