Insulin Resistance
Definition
Insulin resistance is not a disease as such but rather a state or condition
in which a person's body tissues have a lowered level of response to insulin, a
hormone secreted by the pancreas that helps to regulate the level of glucose
(sugar) in the body.
As a result, the person's body produces
larger quantities of insulin to maintain normal levels of glucose in the blood.
There is considerable individual
variation in sensitivity to insulin within the general population, with the
most insulin-sensitive persons being as much as six times as sensitive to the hormone as those
identified as most resistant.
Some doctors use an arbitrary number,
defining insulin resistance as a need for 200 or more units of insulin per day to control
blood sugar levels.
Various researchers have estimated that
3-16 percent of the general population in the United States and Canada is
insulin-resistant; another figure that is sometimes given is 70-80 million
Americans.
Insulin resistance can
be thought of as a set of metabolic dysfunctions associated with or
contributing to a range of serious health problems.
These disorders include
1. type 2 diabetes (formerly called adult-onset or non-insulin-dependent
diabetes),
2. the metabolic syndrome (formerly known
as syndrome X),
Some doctors prefer the term
"insulin resistance syndrome" to "metabolic syndrome."
Description
To understand insulin resistance, it may
be helpful for the reader to have a brief account of the way insulin works in
the body.
1] After a person eats a meal, digestive
juices in the small intestine break down starch or complex sugars in the food
into glucose, a simple sugar.
2] The glucose then passes into the
bloodstream.
3] When the concentration of glucose in the
blood reaches a certain point, the pancreas is stimulated to release insulin
into the blood.
4] As the insulin reaches cells in muscle and
fatty (adipose) tissues, it attaches itself to molecules called insulin
receptors on the surface of the cells.
5] The activation of the insulin receptors
sets in motion a series of complex biochemical signals within the cells that
allow the cells to take in the glucose and convert it to energy.
6] If the pancreas fails to produce enough
insulin or the insulin receptors do not function properly, the cells cannot
take in the glucose and the level of glucose in the blood remains high.
The insulin may fail to bind to the insulin receptors for
any of several reasons.
1] Some
persons inherit a gene mutation that leads to the production of a defective
form of insulin that cannot bind normally to the insulin receptor.
2] Others
may have one of two types of abnormalities in the insulin receptors themselves.
3] In type
A, the insulin receptor is missing from the cell surface or does not function
properly.
4] In type
B, the person's immune system produces auto-antibodies
to the insulin receptor.
In the early stages of insulin resistance,
1] The
pancreas steps up its production of insulin in order to control the increased
levels of glucose in the blood.
2] As a
result, it is not unusual for patients to have high blood sugar levels and high
blood insulin levels (a condition known as hyperinsulinemia) at the same time.
3] If
insulin resistance is not detected and treated, however, the islets of Langerhans
(the insulin-secreting groups of cells) in the pancreas may eventually shut
down and decrease in number.
Causes
& symptoms
Causes
The
reasons for the development of insulin resistance are
not completely understood as of the early 2000s, but several factors
that contribute to it have been identified:
·Genetic factors.
Insulin resistance is known to run in families. Genetic mutations may affect
the insulin receptor, the signaling proteins within cells, or the mechanisms of
glucose transport.
·Obesity.
Being overweight keeps the muscles from using insulin properly, as it decreases
the number of insulin receptors on cell surfaces.
·Low level of physical activity. Because muscle tissue takes up 95 percent of the glucose
that insulin helps the body utilize (brain cells and blood cells do not depend
on insulin to help them use glucose), inactivity further reduces the muscles
ability to use insulin effectively.
·Other diseases and disorders. Some disorders—most notably Cushing syndrome and
cirrhosis—and such stresses on the body as trauma,
surgery, malnutrition, or severe infections speed up the breakdown of insulin or
interfere with its effects.
·Certain medications.
Some drugs, including cyclosporine, niacin, and the protease inhibitors used to treat HIV infection, may contribute to insulin resistance.
Symptoms
1] The symptoms of insulin resistance vary considerably from person
to person.
2] Some people may have no noticeable symptoms until they develop
signs of heart disease or are diagnosed with high blood pressure during a
routine checkup.
3] Other patients may come to the doctor with extremely high levels
of blood sugar (hyperglycemia) and such classical symptoms of diabetes as
thirst, frequent urination, and weight loss.
4] A small percentage of patients—most commonly women with
polycystic ovary syndrome—develop a velvet-textured blackish or dark brown
discoloration of the skin known as acanthosis nigricans.
5] This symptom, which is most commonly found on the neck, groin, elbows,
knees, knuckles, or armpits, is thought to appear when high levels of insulin
in the blood spill over into the skin.
6] This spillover activates insulin receptors in the skin and causes
it to develop an abnormal texture and color.
Acanthosis
nigricans occurs more frequently in Hispanic and African American patients than
in Caucasians.
Disorders associated with insulin
resistance
Insulin resistance became an important
field of research in the late 1980s, when doctors first began to understand it
as a precondition of several common but serious threats to health.
As of the early 2000s, insulin
resistance is associated with the following disorders:
·Obesity.
Obesity is not only the most common cause of insulin resistance but is a
growing health concern in its own right. According to the National Institutes
of Health (NIH), the percentage of American adults who meet the criteria for
obesity rose from 25 percent to 33 percent between 1990 and 2000—an increase of
a third within the space of a decade. Obesity is a risk factor for the
development of type 2 diabetes, high blood pressure, and coronary artery
disease.
·Pre-diabetes and type 2 diabetes. The NIH estimates that about 6.3 percent of the American
population has diabetes. Of these 18.3 million people, 5.2 million are
undiagnosed. Type 2 diabetes is much more common than type 1, accounting for
90-95 percent of patients with diabetes. Diabetes increases a person's risk of
blindness, kidney disease,
heart disease and stroke,
disorders of the nervous system, complications during pregnancy, and
dental problems; it also worsens the prognosis for such infectious diseases as influenza or pneumonia.
According to the NIH, a majority of pre-diabetic people will develop type 2
diabetes within 10 years unless they lose between 5 and 7 percent of their body
weight.
·Heart disease.
Insulin resistance has been linked to a group of risk factors for heart disease
and stroke known as the metabolic syndrome (formerly called syndrome X). The
metabolic syndrome, like obesity, has become increasingly prevalent in the
United States since the 1990s; as of the early 2000s, about a quarter of the
general adult population is thought to have it, with the rate rising to 40
percent for adults over the age of 60.
To be diagnosed with the metabolic
syndrome, a person must have three or more of the following risk factors:
a waist circumference greater than 40
in (102 cm) in men or 35 in (88 cm) in women;
a level of blood triglycerides of 150
milligrams per deciliter (mg/dL) or higher; blood pressure of 130/85 Hg or
higher;
fasting blood sugar level of 110 mg/dL
or higher; and a blood level of high-density
lipoprotein (HDL) cholesterol (the so-called "good" cholesterol)
lower than 50 mg/dL for men or 40 mg/dL for women.
·Polycystic ovary syndrome (PCOS). PCOS is an endocrine disorder that develops in 3-10
percent of premenopausal women as a result of the formation of cysts (small
fluid-filled sacs) in the ovaries.
Women with PCOS do not have normal
menstrual periods;
they are often infertile and may
develop hirsutism
(excess body hair) or other indications of high levels of androgens (male sex
hormones) in the blood.
This condition is called hyper-androgenism,
and has been linked to insulin resistance in women with PCOS.
Weight loss in these patients usually
corrects hyperandrogenism and often restores normal ovulation patterns and
fertility.
Diagnosis
Patient history and physical
examination
Because
insulin resistance is a silent condition in many people, the National Institute
of Diabetes and Digestive and Kidney Diseases (NIDDK) recommends that all
adults over the age of 45 be tested for type 2 diabetes. People younger than 45
who are overweight and have one or more of the following risk factors should
also visit their doctor to be tested:
·One or more family members with
diabetes.
·High levels of triglycerides and low
levels of HDL cholesterol as defined by the criteria for metabolic syndrome.
·Hypertension (high blood pressure).
·Giving birth to a baby weighing more
than 9 pounds. In addition to increasing the mother's risk of developing type 2
diabetes, children who are large for their gestational age (LGA) at birth have
an increased risk of developing insulin resistance and metabolic syndrome in
later life.
·Having African American, Hispanic,
Native American, or Asian American/Pacific Islander heritage.
Some signs and symptoms associated with insulin resistance
can be detected by a primary care physician during a routine office visit.
Blood pressure, weight, body shape, and the condition of the
skin can be checked, as well as determining whether the patient meets the
criteria for obesity or is less severely over-weight.
Obesity is determined by the patient's body mass index, or
BMI. The BMI, which is an indirect measurement of the amount of body fat, is
calculated in English units by multiplying a person's weight in pounds by
703.1, and dividing that number by the person's height in inches squared.
1.
A
BMI between 19 and 24 is considered normal;
2.
25-29
is overweight;
3.
30-34
is moderately obese;
4.
35-39
is severely obese; and
5.
40
or higher is defined as morbidly obese.
The doctor may also evaluate the patient for obesity in the
office by measuring the thickness of the skinfold at the back of the upper arm.
The distribution of the patient's weight
is also significant, as insulin resistance is associated with a so-called
"apple-shaped" figure, in which much of the excess weight is carried
around the abdomen.
People whose excess weight is carried on
the hips (the "pearshaped" figure) or distributed more evenly on the
body are less likely to develop insulin resistance.
One way of measuring weight distribution
is the patient's waist-to-hip ratio;
a ratio greater than 1.0 in men or 0.8
in women is strongly correlated with insulin resistance.
Laboratory tests
There is no single laboratory test that
can be used to diagnose insulin resistance by itself as of 2005.
Doctors usually evaluate individual
patients on the basis of specific symptoms or risk factors. The tests most
commonly used include the following:
·Blood glucose tests.
A high level of blood glucose may indicate either that the body is not
producing enough insulin or is not using it effectively.
Two common tests used to screen for
insulin resistance are the fasting glucose test and the glucose tolerance test.
In the fasting glucose test, the
person takes no food after midnight and has their blood glucose level measured
early in the morning.
Normal blood glucose levels after
several hours without food should be below 100 milligrams per deciliter
(mg/dL).
If the level is between 100 and 125
mg/dL, the person has impaired fasting glucose (IFG) or pre-diabetes.
If the level is over 126 and is
confirmed by a second test, the person has diabetes.
In the glucose tolerance test, the
person is given a sugar solution to drink and their blood glucose level is
measured 2 hours later.
A normal level is 140 mg/dL; 140-199
mg/dL indicates impaired glucose tolerance (IGT) or pre-diabetes, while a level
of 200 mg/dL or higher indicates diabetes.
·Tests of blood insulin levels. These help to determine whether high blood glucose
levels are the result of insufficient production of insulin or inefficient use
of insulin.
·Lipid profile test.
This test measures the amount of total cholesterol,
high-density lipoprotein (HDL)
cholesterol,
low-density lipoprotein (LDL)
cholesterol, and triglycerides.
Patients with insulin resistance will
have high levels of LDL
cholesterol and triglycerides with low levels of HDL cholesterol.
·Measurement of blood electrolytes and uric acid. Many patients with the metabolic
syndrome have high blood levels of uric acid.
A highly accurate technique for measuring insulin resistance
is called the euglycemic clamp technique.
The patient's blood insulin level is kept
("clamped") at a high but steady level by continual insulin infusion
while the blood glucose level is monitored at frequent intervals.
Glucose concentrations in the blood are maintained at a
normal level by an adjustable-rate glucose drip.
The amount of glucose needed to maintain a normal blood
glucose level over a given unit of time indicates the degree of insulin
resistance.
This test, however, requires complex equipment and careful
monitoring; it is considered too cumbersome to use in routine screening and is
used mostly by researchers.
Treatment
Lifestyle modifications
Lifestyle
modifications are the first line of treatment in dealing with insulin resistance:
·Weight reduction.
Losing weight increases the body's sensitivity to
insulin.
It is not necessary, however, for
patients to reduce their weight to the ideal levels listed on life insurance
charts.
In recent years, researchers have
found that even a modest weight loss—usually defined as 10 percent of the
patient's pretreatment weight—is enough to control or at least improve insulin
resistance and other health complications of obesity.
Weight reduction is usually
accomplished by a combination of reduced calorie intake and increased physical
activity.
Insulin sensitivity is reported to
improve within a few days of lowered calorie intake, even before the patient
loses a measurable amount of weight.
·Exercise. Regular
exercise improves the body's sensitivity to insulin by increasing the muscles'
uptake of glucose from the bloodstream, by increasing the efficiency of the
circulatory system and glucose transport, and by reducing the amount of fat
around the patient's abdomen.
The American Academy of Family
Practice (AAFP) recommends 30 minutes of moderately intense physical activity
on most or all days of the week for people diagnosed with insulin resistance.
Walking is a very good form of
exercise because it does not require any special equipment other than
comfortable walking shoes, can be combined with doing errands, and can be done
either alone or with a group of friends.
Riding a bicycle is another form of
exercise recommended for weight control.
·Adding foods high in fiber to the diet. A diet high in natural fiber, found
in whole grains and vegetables, lowers the levels of blood insulin as well as lowering
the patient's risk of developing high blood pressure.
·Quitting smoking.
Giving up smoking lowers the risk of heart disease, stroke, or lung cancer as well
as increasing the body's sensitivity to insulin.
·Limiting alcohol consumption. Alcohol is a source of "empty" calories with
little nutritional value of its own.
Key
terms
Acanthosis nigricans
— A dark brownish or blackish discoloration of the skin related to overweight
and high levels of insulin in the blood. Acanthosis nigricans is most likely to
develop in the groin or armpits, or around the back of the neck.
Bariatrics
— The branch of medicine that deals with the prevention and treatment of
obesity and related disorders.
Body mass index (BMI)
— A measurement that has replaced weight as the preferred determinant of
obesity. The BMI can be calculated (in English units) as 703.1 times a person's
weight in pounds divided by the square of the person's height in inches.
Glucose — A
simple sugar produced when carbohydrates are broken down in the small
intestine. It is the primary source of energy for the body. Various tests that
measure blood glucose levels are used in diagnosing insulin resistance.
Hyperandrogenism
— Excessive secretion of androgens (male sex hormones).
Hyperinsulinemia
— The medical term for high levels of insulin in the blood.
Insulin — A
protein hormone secreted by the islets of Langerhans in the pancreas in
response to eating. Insulin carries glucose and amino acids to muscle and adipose
cells and promotes their efficient use and storage.
Islets of Langerhans
— Special structures in the pancreas responsible for insulin secretion among
other functions. They are named for Paul Langerhans, the German researcher who
first identified them in 1869.
Lipids — A
group of fats and fat-like substances that are not soluble in water, are stored
in the body, and serve as a source of fuel for the body.
Metabolic syndrome
— A group of risk factors for heart disease, diabetes, and stroke. It includes
abdominal obesity, high blood pressure, high blood glucose levels, and low
levels of high-density lipoprotein (HDL) cholesterol. The metabolic syndrome is
sometimes called the insulin resistance syndrome.
Metabolism
— The sum of an organism's physical and chemical processes that produce and
maintain living tissue, and make energy available to the organism. Insulin
resistance is a disorder of metabolism.
Obesity —
Excessive weight gain due to accumulation of fat in the body, sometimes defined
as a BMI of 30 or higher, or body weight greater than 30 percent above one s
desirable weight on standard height-weight tables.
Pancreas —
A large gland located behind the stomach near the spleen that secretes
digestive enzymes into the small intestine and insulin into the bloodstream.
Syndrome —
In general, a set of symptoms that occur together as signs of a disease or
disorder.
Syndrome X
— A term that was sometimes used for metabolic syndrome when the syndrome was
first identified in the 1960s.
Triglycerides
— Fatty compounds synthesized from carbohydrates during the process of
digestion and stored in the body's adipose (fat) tissues. High levels of
triglycerides in the blood are associated with insulin resistance.
Type 2 diabetes mellitus
— One of the two major types of diabetes mellitus, characterized by late age of
onset (30 years or older), insulin resistance, high levels of blood sugar, and
little or no need for supple-mental insulin. It was formerly known as
adult-onset or non-insulin-dependent diabetes.
With regard to lifestyle factors, the
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
reported the findings of a study of the effects of lifestyle changes or Metformin
on the incidence of diabetes in a group of over 3200 overweight people with
impaired glucose tolerance, which is a risk factor for developing type 2
diabetes.
The researchers found that the subjects
in the lifestyle modification group, who lowered their food intake and took
30-minute walks five days a week, had a 58-percent lower incidence of diabetes.
The subjects who received Metformin had
a 31-percent lower incidence of diabetes.
Lifestyle changes were most effective in
volunteers over the age of 60, while metformin was most effective in younger
subjects.
In short, the 2002 study confirmed the
beneficial effects of lowered food intake and increased activity as preventive
measures against type 2 diabetes.
Another important part of preventing
insulin resistance is patient education.
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