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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. ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ 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. ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ 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. ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ 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. ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ 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. ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ 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. ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ ________________________________ 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. _____________________________________________________________________________________________________ _____________________________________________________________________________________________________ _____________________________________________________________________________________________________ _____________________________________________________________________________________________________ _____________________________________________________________________________________________________ _____________________________________________________________________________________________________ ____________________________________________________________________________________________________ Remember to identify your sources _____________________________________________________________________________________________________ _____________________________________________________________________________________________________ _____________________________________________________________________________________________________ _____________________________________________________________________________________________________ _____________________________________________________________________________________________________ _____________________________________________________________________________________________________ _____________________________________________________________________________________________________ _____________________________________________________________________________________________________ _____________________________________________________________________________________________________ _____________________________________________________________________________________________________ _____________________________________________________________________________________________________ _____________________________________________________________________________________________________ _____________________________________________________________________________________________________ _____________________________________________________________________________________________________ _____________________________________________________________________________________________________ _____________________________________________________________________________________________________ Wo r k b o o k Lesson 3.6 _____________________________________________________________________________________________________ ___________________________________________________________________________________________ 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. 148