Synopsis: Altha Roberts Edgren Ken R. Wells Jacqueline L. Longe
Source Citation: "Diabetes mellitus."
Altha Roberts Edgren. and Ken R. Wells. The Gale Encyclopedia of
Medicine. Ed. Jacqueline L. Longe. 3rd ed. Detroit: Gale, Online
update, 2007. 5 vols.
Definition: Diabetes mellitus
is a condition in which the pancreas no longer produces enough insulin
or cells stop responding to the insulin that is produced, so that
glucose in the blood cannot be absorbed into the cells of the body.
Symptoms include frequent urination, lethargy, weight loss, excessive
thirst, and hunger. The treatment includes changes in diet, oral
medications, and in some cases, daily injections of insulin or Byetta
(exenatide), the first in a class of injectible medicines called
incretin mimetics to improve blood sugar levels in type 2 diabetes.
Description: Diabetes mellitus
is a chronic disease that causes serious health complications including
renal (kidney) failure, heart disease, stroke, limb amputation, and
blindness. Approximately 20 million Americans have diabetes, according
to the American Diabetes Association. Unfortunately, as many as
one-half are unaware they have it. The World Health Organization (WHO)
estimates that as of 2007, 200 million people worldwide have diabetes,
including 50 million in China, 32 million in India, 8.4 million in
Indonesia, 33 million in Europe, 7 million in Africa, and 2 million in
Mexico.
Background : Every cell in the human body needs energy
in order to function. The body's primary energy source is glucose, a
simple sugar resulting from the digestion of foods containing
carbohydrates (sugars and starches). Glucose from the digested food
circulates in the blood as a ready energy source for any cells that
need it. Insulin is a hormone or chemical produced by cells in the
pancreas, an organ located behind the stomach. Insulin bonds to a
receptor site on the outside of cell and acts like a key to open a
doorway into the cell through which glucose can enter. Some of the
glucose can be converted to concentrated energy sources like glycogen
or fatty acids and saved for later use. When there is not enough
insulin produced or when the doorway no longer recognizes the insulin
key, glucose stays in the blood rather entering the cells. The
body will attempt to dilute the high level of glucose in the blood, a
condition called hyperglycemia, by drawing water out of the cells and
into the bloodstream in an effort to dilute the sugar and excrete it in
the urine. It is not unusual for people with undiagnosed diabetes to be
constantly thirsty, drink large quantities of water, and urinate
frequently as their bodies try to get rid of the extra glucose. This
creates high levels of glucose in the urine. At the same time
that the body is trying to get rid of glucose from the blood, the cells
are starving for glucose and sending signals to the body to eat more
food, thus making patients extremely hungry. To provide energy for the
starving cells, the body also tries to convert fats and proteins to
glucose. The breakdown of fats and proteins for energy causes acid
compounds called ketones to form in the blood. Ketones also will be
excreted in the urine. As ketones build up in the blood, a condition
called ketoacidosis can occur. This condition can be life threatening
if left untreated, leading to coma and death.
Types of diabetes mellitus Type
I diabetes, sometimes called juvenile diabetes, begins most commonly in
childhood or adolescence. In this form of diabetes, the body produces
little or no insulin. It is characterized by a sudden onset and occurs
more frequently in populations descended from Northern European
countries (Finland, Scotland, Scandinavia) than in those from Southern
European countries, the Middle East, or Asia. In the United States,
approximately three people in 1,000 develop Type I diabetes. This form
also is called insulin-dependent diabetes because people who develop
this type need to have daily injections of insulin. Brittle
diabetics are a subgroup of Type I where patients have frequent and
rapid swings of blood sugar levels between hyperglycemia (a condition
where there is too much glucose or sugar in the blood) and hypoglycemia
(a condition where there are abnormally low levels of glucose or sugar
in the blood). These patients require several injections of different
types of insulin during the day to keep the blood sugar level within a
fairly normal range. The more common form of diabetes, Type II,
occurs in approximately 3-5% of Americans under 50 years of age, and
increases to 10-15% in those over 50. More than 90% of the diabetics in
the United States are Type II diabetics. Sometimes called age-onset or
adult-onset diabetes, this form of diabetes occurs most often in people
who are overweight and who do not exercise. It is also more common in
people of Native American, Hispanic, and African-American descent.
People who have migrated to Western cultures from East India, Japan,
and Australian Aboriginal cultures also are more likely to develop Type
II diabetes than those who remain in their original countries. Type
II is considered a milder form of diabetes because of its slow onset
(sometimes developing over the course of several years) and because it
frequently can be controlled with diet and oral medication. The
consequences of uncontrolled and untreated Type II diabetes, however,
are the just as serious as those for Type I. This form is also called
noninsulin-dependent diabetes, a term that is somewhat misleading. Many
people with Type II diabetes can control the condition with diet and
oral medications, however, insulin injections are sometimes necessary
if treatment with diet and oral medication is not working. Another
form of diabetes called gestational diabetes can develop during
pregnancy and generally resolves after the baby is delivered. This
diabetic condition develops during the second or third trimester of
pregnancy in about 2% of pregnancies. In 2004, the incidence of
gestational diabetes were reported to have increased 35% in 10 years.
Children of women with gestational diabetes are more likely to be born
prematurely, have hypoglycemia, have an excess of body fat, or have
severe jaundice at birth. The condition usually is treated by diet,
however, insulin injections may be required. These women who have
diabetes during pregnancy are at higher risk for developing Type II
diabetes within 5-10 years. Diabetes also can develop as a
result of pancreatic disease, alcoholism, malnutrition, or other severe
illnesses that stress the body.
Causes and symptoms: Causes The causes of diabetes mellitus
are unclear, however, there seem to be both hereditary (genetic factors
passed on in families) and environmental factors involved. Research has
shown that some people who develop diabetes have common genetic
markers. In Type I diabetes, the immune system, the body's defense
system against infection, is believed to be triggered by a virus or
another microorganism that destroys cells in the pancreas that produce
insulin. In Type II diabetes, age, obesity, and family history of
diabetes play a role. In Type II diabetes, the pancreas may
produce enough insulin, however, cells have become resistant to the
insulin produced and it may not work as effectively. Symptoms of Type
II diabetes can begin so gradually that a person may not know that he
or she has it. Early signs are lethargy, extreme thirst, and frequent
urination. Other symptoms may include sudden weight loss, slow wound
healing, urinary tract infections, gum disease, or blurred vision. It
is not unusual for Type II diabetes to be detected while a patient is
seeing a doctor about another health concern that is actually being
caused by the yet undiagnosed diabetes. Individuals who are at high risk of developing Type II diabetes mellitus include people who:
Are obese (more than 20% above their ideal body weight)
have a relative with diabetes mellitus
belong to a high-risk ethnic population (African-American, Native American, Hispanic, or Native Hawaiian)
have been diagnosed with gestational diabetes or have delivered a baby weighing more than 9 lbs (4 kg)
have high blood pressure (140/90 mmHg or above)
have a high density lipoprotein cholesterol level less than or equal to
35 mg/dL and/or a triglyceride level greater than or equal to 250 mg/dL
have had impaired glucose tolerance or impaired fasting glucose on previous testing
Several common medications can impair the body's use of insulin,
causing a condition known as secondary diabetes. These medications
include treatments for high blood pressure (furosemide, clonidine, and
thiazide diuretics), drugs with hormonal activity (oral contraceptives,
thyroid hormone, progestins, and glucocorticorids), and the
anti-inflammation drug indomethacin. Several drugs that are used to
treat mood disorders (such as anxiety and depression) also can impair
glucose absorption. These drugs include haloperidol, lithium carbonate,
Zyprexa (olanzapine), Seroquel (quetiapine), phenothiazines, tricyclic
antidepressants, and adrenergic agonists. Other medications that can
cause diabetes symptoms include isoniazid, nicotinic acid, cimetidine,
protease inhibitors used to treat HIV, and heparin. A 2004 study found
that low levels of the essential mineral chromium in the body may be
linked to increased risk for diseases associated with insulin
resistance.
Symptoms: Symptoms of diabetes can develop suddenly
(over days or weeks) in previously healthy children or adolescents, or
can develop gradually (over several years) in overweight adults over
the age of 40. The classic symptoms include feeling tired and sick,
frequent urination, excessive thirst, excessive hunger, and weight loss. Ketoacidosis,
a condition due to starvation or uncontrolled diabetes, is common in
Type I diabetes. Ketones are acid compounds that form in the blood when
the body breaks down fats and proteins. Symptoms include abdominal
pain, vomiting, rapid breathing, weight loss, extreme lethargy, and
drowsiness. Patients with ketoacidosis will also have a sweet breath
odor. Left untreated, this condition can lead to coma and death. With
Type II diabetes, the condition may not become evident until the
patient presents for medical treatment for some other condition. A
patient may have heart disease, chronic infections of the gums and
urinary tract, blurred vision, numbness in the feet and legs, or
slow-healing wounds. Women may experience genital itching.
Diagnosis: Diabetes is suspected based on symptoms. Urine
tests and blood tests can confirm a diagnosis of diabetes based on the
amount of glucose found. Urine can also detect ketones and protein in
the urine that may help diagnose diabetes and assess how well the
kidneys are functioning. These tests also can be used to monitor the
disease once the patient is on a standardized diet, oral medications,
or insulin.
Urine tests: Clinistix and Diastix are paper strips or
dipsticks that change color when dipped in urine. The test strip is
compared to a chart that shows the amount of glucose in the urine based
on the change in color. The level of glucose in the urine lags behind
the level of glucose in the blood. Testing the urine with a test stick,
paper strip, or tablet that changes color when sugar is present is not
as accurate as blood testing, however it can give a fast and simple
reading. It is no longer considered appropriate for use by diabetics as
a means to assess glucose control. Ketones in the urine can be
detected using similar types of dipstick tests (Acetest or Ketostix).
Ketoacidosis can be a life-threatening situation in Type I diabetics,
so having a quick and simple test to detect ketones can assist in
establishing a diagnosis sooner. Another dipstick test can
determine the presence of protein or albumin in the urine. Protein in
the urine can indicate problems with kidney function and can be used to
track the development of renal failure. A more sensitive test for urine
protein uses radioactively tagged chemicals to detect microalbuminuria,
small amounts of protein in the urine, that may not show up on dipstick
tests.
Blood tests Fasting glucose test Blood is
drawn from a vein in the patient's arm after a period at least eight
hours when the patient has not eaten, usually in the morning before
breakfast. The red blood cells are separated from the sample and the
amount of glucose is measured in the remaining plasma. A plasma level
of 7 mmol/L (126) mg/L) or greater can indicate diabetes. The fasting
glucose test is usually repeated on another day to confirm the results. Diabetes mellitus Wrinkled, dehydrated skin of a person in a diabetic coma. Untreated diabetes mellitus results in elevated blood glucose levels, causing a variety of symptoms that can culminate in a diabetic coma. (Photo Researchers, Inc. Reproduced by permission.)
Postprandial glucose test Blood is taken right after the patient has eaten a meal. Oral glucose tolerance test Blood
samples are taken from a vein before and after a patient drinks a
thick, sweet syrup of glucose. In a non-diabetic, the level of glucose
in the blood goes up immediately after the drink and then decreases
gradually as insulin is used by the body to metabolize, or absorb, the
sugar. In a diabetic, the glucose in the blood goes up and stays high
after drinking the sweetened liquid. A plasma glucose level of 11.1
mmol/L (200 mg/dL) or higher at two hours after drinking the syrup
confirms the diagnosis of diabetes. A diagnosis of diabetes is
confirmed if there are symptoms of diabetes and a plasma glucose level
of at least 11.1 mmol/L, a fasting plasma glucose level of at least 7
mmol/L; or a two-hour plasma glucose level of at least 11.1 mmol/L
during an oral glucose tolerance test. Home blood glucose
monitoring kits are available so patients with diabetes can monitor
their own levels. A small needle or lancet is used to prick the finger
and a drop of blood is collected and analyzed by a monitoring device.
Some patients may test their blood glucose levels several times during
a day and use this information to adjust their doses of insulin.
Treatment: There is currently no cure for diabetes. The
condition, however, can be managed so that patients can live a
relatively normal life. Treatment of diabetes focuses on two goals:
keeping blood glucose within normal range and preventing the
development of long-term complications. Careful monitoring of diet,
exercise, and blood glucose levels are as important as the use of
insulin or oral medications in preventing complications of diabetes. In
2003, the American Diabetes Association updated its Standards of Care
for the management of diabetes. These standards help manage health care
providers in the most recent recommendations for diagnosis and
treatment of the disease.
Dietary changes: Diet and moderate exercise are the
first treatments implemented in diabetes. For many Type II diabetics,
weight loss may be an important goal in helping them to control their
diabetes. A well-balanced, nutritious diet provides approximately
50-60% of calories from carbohydrates, approximately 10-20% of calories
from protein, and less than 30% of calories from fat. The number of
calories required by an individual depends on age, weight, and activity
level. The calorie intake also needs to be distributed over the course
of the entire day so surges of glucose entering the blood system are
kept to a minimum. Keeping track of the number of calories
provided by different foods can become complicated, so patients usually
are advised to consult a nutritionist or dietitian. An individualized,
easy to manage diet plan can be set up for each patient. Both the
American Diabetes Association and the American Dietetic Association
recommend diets based on the use of food exchange lists. Each food
exchange contains a known amount of calories in the form of protein,
fat, or carbohydrate. A patient's diet plan will consist of a certain
number of exchanges from each food category (meat or protein, fruits,
breads and starches, vegetables, and fats) to be eaten at meal times
and as snacks. Patients have flexibility in choosing which foods they
eat as long as they stick with the number of exchanges prescribed. For
many Type II diabetics, weight loss is an important factor in
controlling their condition. The food exchange system, along with a
plan of moderate exercise, can help them lose excess weight and improve
their overall health.
Oral medications: Oral medications are available to
lower blood glucose in Type II diabetics. In 1990, 23.4 million
outpatient prescriptions for oral antidiabetic agents were dispensed.
By 2001, the number had increased to 91.8 million prescriptions. Oral
antidiabetic agents accounted for more than [dollar]6 billion dollars
in worldwide retail sales per year in the early twenty-first century
and were the fastest-growing segment of diabetes drugs. there are five
distinct classes of hypoglycemic agents available, each class
displaying unique pharmacologic properties. These classes are the
sulfonylureas, meglitinides, biguanides, thiazolidinediones and
alpha-glucosidase inhibitors. In patients for whom diet and exercise do
not provide adequate glucose control, therapy with a single oral agent
can be tried. The drugs first prescribed for Type II diabetes are in a
class of compounds called sulfonylureas and include tolbutamide,
tolazamide, acetohexamide, and chlorpropamide. Newer drugs in the same
class are now available and include glyburide, glimeperide, and
glipizide. How these drugs work is not well understood, however, they
seem to stimulate cells of the pancreas to produce more insulin. New
medications that are available to treat diabetes include Glucophage
(metformin), Precose (acarbose), Glycet (miglitol), Actos
(pioglitazone), and Avandia (rosiglitazone). The choice of medication
depends in part on the individual patient profile. All drugs have side
effects that may make them inappropriate for particular patients. Some
for example, may stimulate weight gain or cause stomach irritation, so
they may not be the best treatment for someone who is already
overweight or who has stomach ulcers. Others, like metformin, have been
shown to have positive effects such as reduced cardiovascular
mortality. While these medications are an important aspect of treatment
for Type II diabetes, they are not a substitute for a well planned diet
and moderate exercise. Oral medications have not been shown effective
for Type I diabetes, in which the patient produces little or no insulin. Constant
advances are being made in development of new oral medications for
persons with diabetes. In 2003, a drug called Metaglip combining
glipizide and metformin was approved in a single tablet. Along with
diet and exercise, the drug was used as initial therapy for Type 2
diabetes. Another drug approved by the U.S. Food and Drug
Administration (FDA) combines metformin and rosiglitazone (Avandia), a
medication that increases muscle cells' sensitivity to insulin. It is
marketed under the name Avandamet. As of 2007, there were a number of
combination drugs available and more were under development. So many
new drugs are under development that it is best to stay in touch with a
physician for the latest information; physicians can find the best
drug, diet and exercise program to fit an individual patient's need. In
2007, a study in the New England Journal of Medicine suggested the use
of Avandia (rosiglitazone) increased the risk of a heart attack by 43%
and dying from heart disease by 64%. Other studies regarding Avandia
and its effect on heart health were underway as of mid-2007. In July
2007, an FDA advisory panel recommended that Avandia and Actos
(pioglitazone) carry stronger warnings on their labels.
Insulin: Patients with Type I diabetes need daily
injections of insulin to help their bodies use glucose. The amount and
type of insulin required depends on the height, weight, age, food
intake, and activity level of the individual diabetic patient. Some
patients with Type II diabetes may need to use insulin injections if
their diabetes cannot be controlled with diet, exercise, and oral
medication. Injections are given subcutaneously, that is, just under
the skin, using a small needle and syringe, using an injection pen, or
an insulin pump. Injection sites can be anywhere on the body where
there is looser skin, including the upper arm, abdomen, or upper thigh. Purified
human insulin is most commonly used. Insulin from animal sources is no
longer used. Insulin may be given as an injection of a single dose of
one type of insulin once a day. Different types of insulin can be mixed
and given in one dose or split into two or more doses during a day.
Patients who require multiple injections over the course of a day may
be able to use an insulin pump that administers small doses of insulin
on demand. The small battery-operated pump is worn outside the body and
is connected to a needle that is inserted into the abdomen. Pumps can
be programmed to inject small doses of insulin at various times during
the day, or the patient may be able to adjust the insulin doses to
coincide with meals and exercise. Regular insulin is fast-acting
and starts to work within 15-30 minutes, with its peak glucose-lowering
effect about two hours after it is injected. Its effects last for about
four to six hours. NPH (neutral protamine Hagedorn) and Lente insulin
are intermediate-acting, starting to work within one to three hours and
lasting up to 18-26 hours. Ultra-lente is a long-acting form of insulin
that starts to work within four to eight hours and lasts up to 24 hours. Hypoglycemia,
or low blood sugar, can be caused by too much insulin, too little food
(or eating too late to coincide with the action of the insulin),
alcohol consumption, or increased exercise. A patient with symptoms of
hypoglycemia may be hungry, cranky, confused, and tired. The patient
may become sweaty and shaky. Left untreated, the patient can lose
consciousness or have a seizure. This condition is sometimes called an
insulin reaction and should be treated by giving the patient something
sweet to eat or drink like a candy, sugar cubes, fruit juice, or
another high sugar snack.
Surgery:
Transplantation of a healthy pancreas into a
diabetic patient is a successful treatment, however, this transplant is
usually done only if a kidney transplant is performed at the same time.
Although a pancreas transplant is possible, it is not clear if the
potential benefits outweigh the risks of the surgery and drug therapy
needed.
Alternative treatment: Since diabetes can be
life-threatening if not properly managed, patients should not attempt
to treat this condition without medical supervision. A variety of
alternative therapies can be helpful in managing the symptoms of
diabetes and supporting patients with the disease. Acupuncture can help
relieve the pain associated with diabetic neuropathy by stimulation of
certain points. A qualified practitioner should be consulted. Herbal
remedies also may be helpful in managing diabetes. Although there is no
herbal substitute for insulin, some herbs may help adjust blood sugar
levels or manage other diabetic symptoms. Some options include:
fenugreek (Trigonella foenum-graecum ) has been shown in some studies to reduce blood insulin and glucose levels while also lowering cholesterol
bilberry (Vaccinium myrtillus ) may lower blood glucose levels, as well as helping to maintain healthy blood vessels
garlic (Allium sativum ) may lower blood sugar and cholesterol levels
onions (Allium cepa ) may help lower blood glucose levels by freeing insulin to metabolize them
cayenne pepper (Capsicum frutescens ) can help relieve pain in the peripheral nerves (a type of diabetic neuropathy)
gingko (Gingko biloba ) may maintain blood flow to the retina, helping to prevent diabetic retinopathy
Other alternative medicine therapies for controlling blood sugar
include chromium picolinate, alpha lipoic acid, cinnamon, evening
primrose oil, and pygenol (pine bark extract). Any therapy that lowers
stress levels also can be useful in treating diabetes by helping to
reduce insulin requirements. Among the alternative treatments that aim
to lower stress are hypnotherapy, biofeedback, and meditation.
Prognosis: Uncontrolled diabetes is a leading cause of
blindness, end-stage renal disease, and limb amputations. It also
doubles the risks of heart disease and increases the risk of stroke.
Eye problems including cataracts, glaucoma, and diabetic retinopathy
also are more common in diabetics. Diabetic peripheral
neuropathy is a condition where nerve endings, particularly in the legs
and feet, become less sensitive. Diabetic foot ulcers are a particular
problem since the patient does not feel the pain of a blister, callous,
or other minor injury. Poor blood circulation in the legs and feet
contribute to delayed wound healing. The inability to sense pain along
with the complications of delayed wound healing can result in minor
injuries, blisters, or calluses becoming infected and difficult to
treat. In cases of severe infection, the infected tissue begins to
break down and rot away. The most serious consequence of this condition
is the need for amputation of toes, feet, or legs due to severe
infection.
Heart disease and kidney disease are common complications of
diabetes. Long-term complications may include the need for kidney
dialysis or a kidney transplant due to kidney failure. Babies born to diabetic mothers have an increased risk of birth defects and distress at birth.
