Download LESSON 3.6 WORKBOOK Obesity and Metabolic diseases:

LESSON 3.6 WORKBOOK
Obesity and Metabolic diseases:
Diabetes and Heart disease
DEFINITIONS OF TERMS
Diabetes mellitus — The
most common form of diabetes.
Caused by a deficiency in the
action of insulin. Results in high
blood glucose concentrations
and urinary glucose excretion.
Throughout Unit 3 we have explored how the
brain regulates eating. We have also seen that
hunger signals may not adapt after weight loss,
perhaps contributing to the weight regain that
often occurs when people have lost weight by
dieting. Here we further explore the consequences of obesity by focusing on diabetes and heart
disease.
For a complete list of defined
terms, see the Glossary.
Wo r k b o o k
Lesson 3.6
Type 2 Diabetes
Figure 1: People with type 1
diabetes inject insulin to replace
what the pancreas fails to make.
You may already know that there are two types of diabetes
mellitus: type 1 and type 2. Type 1 diabetes is believed to
be genetic, is not associated with obesity, and results from
dysfunction of the pancreas, which fails to make insulin.
While the exact cause is unknown, it is thought that the
body’s immune system attacks the pancreas, damaging the
insulin-producing cells. People that are diagnosed with type
1 diabetes must take insulin when they eat food since their
body cannot create its own. Because insulin is a protein,
it must be administered through an injection. Taking the
protein orally would not work because it would simply be
digested in the stomach by peptidases. The onset of type
1 diabetes is normally in children, hence type 1 diabetes is
often called juvenile diabetes.
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141
LESSON READINGS
Type 2 diabetes is different, in that it develops over time and is highly correlated with obesity. With the
current rise in obesity in the United States, the number of people diagnosed with type 2 diabetes has
also grown, and we will focus on its mechanisms and consequences here. The onset of type 2 diabetes
has been historically in people between 30 and 50 years old, so it has been called adult onset diabetes.
However, the increase in childhood obesity in recent years has led to a rise in type 2 diabetes in young
people, so the terms juvenile and adult diabetes are easy to misunderstand.
Insulin'
Insulin'
Receptor'
Figure 2: Insulin binds to
the insulin receptor, leading
to uptake and storage of
blood glucose.
Cause of type 2 diabetes
Type 2 diabetes is highly correlated with obesity, but how obesity
relates to the onset of diabetes is poorly understood. In healthy
individuals, insulin is released from the pancreas and binds to
insulin receptors located on cells in the liver, muscles and other
organs. When insulin binds to insulin receptors, a series of
enzymatic reactions and processes take place, leading to the
downstream actions of insulin, such as bringing glucose into the
muscles or telling the liver to package glucose and fatty acids for
storage.
Initially, an individual with type 2 diabetes will release insulin from
the pancreas in response to high glucose as usual, but the receptors in the liver, muscles and other tissues fail to respond normally.
This results in a high blood glucose concentration, as well as
high blood insulin. Insulin resistance is the term used to describe this lack of normal response to insulin.
The pancreas will then continue to make more and more insulin to overcome the insulin resistance, until it
eventually burns out and insulin production ceases. This is one reason that unmanaged type 2 diabetes
often progresses from insulin resistance to both insulin resistance and poor insulin production, requiring
insulin injections.
Wo r k b o o k
Lesson 3.6
Researchers are still actively
trying to understand how
weight gain connects to insulin
resistance. Although there is
some evidence that inflammation
may damage the insulin
receptors, there is a lot remaining
to be discovered!
Ulcer Figure 3: Years
of high blood
glucose in diabetics can lead to
un-healing ulcers.
If left untreated,
amputation may
be needed.
1. Which of the following would you
NOT expect to occur with insulin
resistance?
aa. Increased blood glucose.
bb. Increased blood insulin.
cc. Poor storage of glucose as
glycogen.
dd. Increased gluconeogenesis.
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142
LESSON READINGS
Long-term consequences of living with diabetes
DEFINITIONS OF TERMS
Diabetes is a major risk factor for heart disease and stroke, and is the leading cause of kidney failure
and blindness in adults. The reason for these impairments varies by tissue, but the common cause is
that extra glucose left in the blood binds to proteins, disrupting their functions. If unregulated, high blood
glucose can lead to malfunctions in wound healing, resulting to ulcers (especially in the foot). If these
ulcers are not cared for properly, amputation may ensue. Because type 2 diabetes is so common now
and can negatively impact the body in many ways, diabetes has become the seventh leading cause of
death in the United States.
Treatment involves lifestyle changes
Atherosclerosis — A disease
of the arteries characterized by
deposits of fat.
Cardiovascular — Describes
something that involves the heart
or the blood vessels (arteries and
veins).
Heart disease — A structural
or functional abnormality of the
heart or blood vessels.
Vascular — Describes something that involves the arteries
and veins.
For a complete list of defined
terms, see the Glossary.
Weight loss is the most effective treatment of type 2 diabetes. In fact if diagnosed early, type 2 diabetes can usually
be completely reversed through weight loss. People living
with type 2 diabetes must also monitor their blood glucose
levels to ensure that they don’t get too high. Although
some medications can increase insulin sensitivity, these
medications alone cannot completely cure type 2 diabetes.
Although type 2 diabetes starts as insulin resistance, if not
managed, it may progress to the point that the pancreas
becomes dysfunctional. In this case, just like people living
with type 1 diabetes, so called 'brittle' type 2 diabetics must
track their blood glucose concentrations and administer
their own insulin.
Figure 4: Using a glucose monitor, diabetics can track their blood
glucose concentrations.
Eating a healthy diet and exercising are the best interventions for someone diagnosed with type 2 diabetes. Remember that exercise acts like insulin, and brings glucose into the muscles cells even when insulin
is not present. Because of this exercise is an effective way to lower blood glucose concentrations even
in individuals with insulin resistance. Eating a diet with a low glycemic index may also help to keep blood
glucose concentrations within the healthy range.
Heart disease and atherosclerosis
Wo r k b o o k
Lesson 3.6
Heart disease, also called cardiovascular disease, is a term that refers to several conditions that affect
the heart and vascular system. We will focus on atherosclerosis because it is the most common type
of heart disease. Other types of heart disease include congestive heart failure and heart attack. Together,
heart disease is the leading cause of death for both men and women in the United States.
2. Which of the following is a
recommended treatment for type 2
diabetes?
aa. Increase carbohydrate
consumption.
bb. Increase physical activity.
cc. Eat foods with a high glycemic
index.
dd. Take cholesterol-lowering drugs.
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143
LESSON READINGS
Development of atherosclerosis
Atherosclerosis is a disease of fatty plaques building up in the vascular system. This is like a clog in a
pipe that prohibits the normal flow of water. These plaques are made up of fat, cholesterol, and immune
cells. While heart disease primarily affects older adults, the formation of atherosclerotic plaques begins in
childhood. An atherosclerotic plaque develops in 4 steps:
1. Fat traveling in the blood within LDL vesicles
become altered by inflammatory proteins,
causing the recruitment of immune cells.
DEFINITIONS OF TERMS
Blood clot — A mass of coagulated blood.
Fatty streak — The first visibly
obvious step in the development
of atherosclerosis. Fatty streaks
are made up of immune cells and
lipoproteins (LDL).
Plaque — A region of fatty
deposit on an artery wall that has
been encapsulated by cells lining
the arteries.
2. The immune cells engulf the LDL, and stick
to the side of an artery. This is called a fatty
streak; nearly everyone has fatty streaks
in their arteries by their twenties! If you are
otherwise healthy, the atherosclerosis will not
progress beyond this stage.
3. If a cap of cells grows around the fatty streak,
it becomes a plaque. Plaques are relatively
stable, but can cause problems because
they reduce blood flow.
Figure 5: The stages in atherosclerosis
development.
4. If a plaque becomes too big, or if the cap of cells is too thin, the plaque can rupture. This causes a
blood clot to form. The clot can stay locally, impeding blood flow, or can dislodge from the artery
wall and block blood flow in another location. If the clot travels to an artery in the heart it can cause
heart failure. If the clot travels to the brain it can cause a stroke.
Like insulin resistance, inflammation plays a pivotal role in
the development of atherosclerosis. If someone has high
LDL cholesterol in their blood as well as an abundance of
inflammatory proteins, the beginning stages of atherosclerosis are likely to occur. This is why people at risk for heart
disease are often recommended to take a low daily dose
of aspirin, which is an anti-inflammatory drug.
For a complete list of defined
terms, see the Glossary.
Wo r k b o o k
Lesson 3.6
Forma4on of Fa#y Plaque Blood Clot Streak
Rupture of Plaque Figure 6: Atherosclerosis can
cause a heart attack if blood flow
is blocked in an artery in the
heart.
Living with heart disease
There is no treatment for heart disease. Instead, a person
with heart disease should adhere to a healthy diet and
exercise regularly in the hope of preventing plaque rupture.
3. Atherosclerosis can result in:
aa. Fatty streaks.
bb. Heart attack.
cc. Stroke.
dd. All of the above.
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144
LESSON READINGS
If the plaque does rupture this may result in a heart attack (also called a myocardial infarction), which can
be lethal. People that are more likely to have heart disease are those that are overweight, smoke, have
high blood pressure or high LDL cholesterol levels, and those under chronic stress. There are some medications available to lower blood pressure and cholesterol levels, which may be able to lower heart attack
risk. Heart disease is sometimes called the “silent killer” because there are often no symptoms associated
with heart disease until a heart attack occurs.
DEFINITIONS OF TERMS
How does obesity contribute to these diseases?
Obesity is a risk factor for several disorders and diseases, including the two we talked about in this lesson.
Others include some types of cancer, sleep apnea, osteoarthritis, infertility and gallstones.
Gallstones — Crystals of bile
acids that form in the gallbladder
that can cause sever pain and
blockage of the bile duct.
Macrophage — A large cell that
is involved in the body’s immune
response.
Osteoarthritis — A loss of
cartilage in the joints that results
in pain and stiffness.
Sleep apnea — A temporary
stopping of breathing that occurs
during sleep.
For a complete list of defined
terms, see the Glossary.
Wo r k b o o k
Lesson 3.6
What is it about obesity that contributes to the malfunction of so many body systems? In recent years,
researchers have discovered one key aspect of obesity is that it seems to cause chronic low-level
inflammation. You’ve probably experienced inflammation as the red color, swelling and heat that occur
around a scrape or cut. Inflammation is also what causes the fever, aches and pains during the flu. On the
molecular level, inflammation is the release of key inflammatory proteins by immune cells. When we get
injured, immune cells will travel to the site of injury and release these proteins, which will expedite the healing process and kill off pathogens. Obesity is associated with chronic low-levels of inflammatory proteins
circulating in the blood, but why are they there and what are they doing?
Does obesity cause inflammation?
Not all adipose tissue is created equal and this
may relate to how adipocytes store fat. For
adipose tissue to accommodate the excess
storage of triglycerides seen in obesity, it can
either make more cells or increase the size
of the existing cells. In the latter scenario, the
cells can actually grow too large and essentially burst, causing immune cells to enter the
adipose tissue and clean up the mess. An
important immune cell that surrounds these
broken adipose cells is the macrophage.
Macrophages are found in the adipose tissue
of both lean and obese individuals, however
the type of macrophage is different. In lean
individuals, the macrophages are generally
Lean-Adipose-
Obese-Adipose-
An#$Inflammatory-MacrophageInflammatory-MacrophageFigure 7: Adipose tissue in lean individuals
generally has anti-inflammatory macrophages,
while obese individuals usually have
inflammatory macrophages.
4. Which of the following is a symptom
of heart disease?
aa. There are no symptoms until
heart attack or stroke.
bb. Headaches.
cc. Excessive thirst.
dd. Fatigue.
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145
LESSON READINGS
anti-inflammatory. During obesity, the type of macrophages tends to be inflammatory, thereby increasing
inflammatory factors that travel thoughout the body. This inflammation may be to blame for destruction of
insulin receptors which causes insulin resistance, and may also be the cause of leptin resistance, which
we discussed in the previous lesson. Chronic low-level inflammation may also be the reason why some
obese people are more likely to develop certain types of cancer, including colorectal cancer and breast
cancer. Stay tuned because future research in this area is promising and may lead to better treatments
and preventative measures for obesity-associated diseases.
Can people who are obese be healthy?
Figure 8: Some obese people
are just as metabolically fit as lean
people, possibly because they do
not develop chronic inflammation.
Wo r k b o o k
Lesson 3.6
Fortunately some obese individuals will never develop
diabetes, heart disease or cancer. The reason for this
may be because these people do not have the typical
low-grade chronic inflammation that other obese individuals exhibit. In fact, chronic low-levels of inflammation are associated with being metabolically unhealthy,
regardless of weight. The reason why some people will
have increased inflammation with weight gain, while
others do not, is currently unknown. Unfortunately
there is no easy test that determines whether an obese
individual is among the few that will not have chronic
inflammation, so the best health measure to take is to
prevent weight gain.
5. Chronic inflammation in obese
individuals may be caused by?
aa. Fever.
bb. Swelling.
cc. Smaller adipose cells.
dd. Macrophages.
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146
STUDENT RESPONSES
Now that you know the mechanisms of type 2 diabetes and atherosclerosis, what types of foods and nutrients would you
recommend to prevent these diseases? Hint: Think about ways to prevent obesity, as well as lower blood LDL.
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Remember to identify your
sources
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Wo r k b o o k
Lesson 3.6
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147
TERMS
TERM
For a complete list of defined
terms, see the Glossary.
Wo r k b o o k
Lesson 3.6
DEFINITION
Atherosclerosis
A disease of the arteries characterized by deposits of fat.
Blot Clot
A mass of coagulated blood.
Cardiovascular
Describes something that involves the heart or the blood vessels (arteries and veins).
Diabetes Mellitus
The most common form of diabetes. Caused by a deficiency in the action of insulin. Results in high blood
glucose concentrations and urinary glucose excretion.
Fatty Streak
The first visibly obvious step in the development of atherosclerosis. Fatty streaks are made up of immune
cells and lipoproteins (LDL).
Gallstones
Crystals of bile acids that form in the gallbladder that can cause sever pain and blockage of the bile duct.
Heart Disease
A structural or functional abnormality of the heart or blood vessels.
Macrophage
A large cell that is involved in the body’s immune response.
Osteoarthritis
A loss of cartilage in the joints that results in pain and stiffness.
Plaque
A region of fatty deposit on an artery wall that has been encapsulated by cells lining the arteries.
Sleep Apnea
A temporary stopping of breathing that occurs during sleep.
Vascular
Describes something that involves the arteries and veins.
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