Complications of Diabetes Mellitus

A Global Perspective

Jahangir Moini, Matthew Adams, Anthony LoGalbo

• Publisher: CRC Press
• Year: 2022
• ISBN:
  9781000554960
• Edition: 1
• Topic: Medizin
• Subtopic: Endokrinologie & Stoffwechsel

Diabetes mellitus is a global epidemic with severe complications that can be of great cost. This book focuses on the complications of hypertension, heart attack or heart failure, stroke, blindness, nephropathy, neuropathy, amputations, and death, along with the prevalence and prevention of disease development. It explains distribution of the disease by age and gender, such as the development of type II diabetes in relation to obesity, which is more prevalent in younger age groups. Global mortality and costs of complications are significant, as the disease affects all ages, races, and ethnicities, making this book an invaluable resource for healthcare professionals and students everywhere.

Key Features

• A useful ready reference for students, physicians, and healthcare professionals detailing the latest diagnostic tests and treatments of diabetes and its complications

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• Explains how heart failure and stroke are deadly complications of diabetes along with kidney failure and life-threatening infections

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• Establishes how cancer is linked to diabetes – a fact many people are not aware of – this book details the six types of cancer that may result from the disease, along with an individualized focus on the different "areas" of issues that occur from diabetes

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• Discusses the effect of diabetes on the minds of patients, in relation to depression, anxiety, panic, PTSD, eating disorders, delirium, and dementia

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Part I Introduction

CHAPTER 1 Pathophysiology of Diabetes

DOI: 10.1201/9781003226727-2

Diabetes mellitus is a disease state that is related to the availability and effectiveness of insulin in the body. Type 1 diabetes involves a total lack of insulin, resulting from autoimmune destruction of pancreatic beta cells. Autoimmune destruction occurs in genetically susceptible people, triggered by environmental factors and progressing over months to years. This eventually results in symptomatic hyperglycemia and the classic signs and symptoms of the disease. Type 2 diabetes is characterized by the body’s peripheral tissues being resistant to the effects of insulin. Both classifications of diabetes lack the signaling effect of insulin, while glucagon and other metabolic signals are of normal or high levels. Diabetes mellitus is due to an imbalance in carbohydrate metabolism and resultant effects upon other metabolic pathways. Insulin resistance causes the body to react, even though it is present at extreme levels. This form differs from type 1 diabetes in that the liver can still manufacture glycogen. Lipolysis is controlled due to the presence of insulin. Plasma lipoproteins are usually elevated, often due to poor nutrition and obesity. Pancreatic failure leads to decreased insulin production and secretion. The brain continually requires glucose in order to function normally. Hypoglycemia is often caused by drugs used to treat diabetes mellitus, which include insulin and the oral antihyperglycemic medications.

The Function of Insulin in Metabolism

Insulin is an anabolic hormone, normally present in individuals that consume healthy diets. It is a signaling factor that stimulates storage of excess nutrients, including glycogen and triglycerides, in the form of adipose fat. Insulin mostly affects the liver, adipose tissue, and striated muscles. Its synthesis and release is stimulated by glucose, but potentiated by amino acids. In the liver, insulin stimulates glycogenesis, fatty acid synthesis, glycolysis, and the pentose phosphate pathway. In adipose tissue, insulin stimulates uptake of glucose and fatty acids, and triglyceride synthesis. This is also known as energy storage. In skeletal muscles, insulin stimulates glucose uptake, glycogenesis, and synthesis of proteins. Insulin does not influence metabolism of glucose in the brain or red blood cells.

The liver can manufacture glucose, but glycogen synthesis is reduced. Without insulin, gluconeogenesis is uncontrolled. Therefore, blood glucose levels increase, and blood glucose remains in the body. The muscle and fat tissues are simultaneously starved for glucose. Glucagon secretion is not linked to blood glucose levels, yet insulin is important in the regulation of glucagon secretion. Gluconeogenesis, glycogenolysis, and lipolysis are processes in the body that become stimulated. Increased lipolysis causes elevation of free fatty acids in the blood. Fatty acid molecules are partly taken up by the liver, and incorporated into lipoproteins. This increases levels of very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL), risk factors for heart disease. Ketone bodies are produced by excessive lipolysis, unable to be inhibited without insulin. Dangerous ketoacidosis can develop if ketone levels are extremely elevated. Administration of insulin is required.

Glucose Metabolism

Glucose is a molecule made up of six carbons. It is a very efficient form of fuel for the body. When metabolized in the presence of oxygen, it is broken down to form carbon dioxide and water. The brain and nervous tissues use glucose as the source of most of their required energy. Other tissues and organ systems use fatty acids and ketones as fuel. The brain is unable to synthesize or store sufficient glucose to last for more than several minutes. A continual glucose supply from the systemic circulation is required for the cerebrum to function normally. Brain death can be due to severe and prolonged hypoglycemia. Significant brain dysfunction occurs because of only moderate hypoglycemia. Glucose is obtained from the circulation by tissues. Hypoglycemia is extremely dangerous in comparison to hyperglycemia. There is rigid control of blood glucose levels while fasting, and they remain between 70 and 99 mg/dL, which is equivalent to between 4.0 and 5.5 mmol/L. After eating, blood glucose levels rise. Insulin is released from the beta cells of the pancreas, allowing glucose to be transported into the body cells. Approximately 66% of the glucose contained in each meal is removed from the blood, and stored in the liver or skeletal muscles as glycogen. When the liver and skeletal muscles become saturated with glycogen, remaining glucose is converted into fatty acids by the liver. These are stored as triglycerides in the adipose tissue’s fat cells.

Blood glucose levels decrease to below normal between meals. The liver then converts the stored glycogen back into glucose via glycogenolysis. The glucose is released as part of a homeostatic mechanism regulating blood glucose within normal ranges. Skeletal muscles contain stored glycogen, but do not contain the enzyme glucose-6-phosphatase. This enzyme allows glucose to be broken down, enabling it to pass through cell membranes and enter the bloodstream. The enzyme only has limited usefulness in muscle cells. The liver synthesizes more glucose from amino acids, glycerol, and lactic acid via gluconeogenesis. Glucose is either directly released into the circulation, or stored as glycogen.

The glycemic index is a value that is assigned to foods, based on the speed in which they cause increases in blood glucose levels. Foods that are low on the glycemic index (GI) scale usually release glucose slowly and steadily, while foods high on the glycemic index release glucose quickly. The lower GI foods aid in weight loss, but those high on the scale aid in energy recovery after exercise, or to prevent hypoglycemia. Therefore, people with diabetes or prediabetes should consume more of the lower GI foods. This is because faster release of glucose from the higher GI foods results in spikes in blood sugar levels. Good glucose control is maintained by the slow and steady release of glucose from the lower GI foods. Table 1.1 summarizes examples of the lower and higher GI foods.

Table 1.1: Lower and Higher Glycemic Index (GI) Foods

Lower GI Foods (20–49)	Higher GI Foods (70–100)
Oat bran	Grits
Apples	Pineapple
Green beans	Soda
Asparagus	Potatoes
Barley	Most breads
Almonds	Rice
Skim milk	Candy
Blueberries	Most Chinese foods
Chickpeas	Sweet tea
Avocado	Pretzels
Peanuts	Most breakfast cereals
Low-fat or Greek yogurt	Pastries

Carbohydrates in food are well known with regard to increasing blood glucose. The total amount of carbohydrates consumed, as well as the actual food choice itself, plays roles in this. For example, one serving of white rice quickly spikes blood glucose – just like eating pure sugar. Therefore, it is very important to choose good sources of carbohydrates in order to prevent diabetes mellitus and many other conditions. Good carbohydrate choices can also reduce risks for heart disease and cancer. The GI rates the effect of each type of food upon blood glucose, compared with the same amount of pure glucose. A food with a GI of 25 boosts the blood glucose only 25% as pure glucose. A food with a GI of 95 or higher has the same effect as pure glucose. To summarize further, low GI foods include most but not all fruits and vegetables, beans, grains that have not been heavily processed, low-dairy foods, and nuts. Moderate GI foods include corn, couscous, and a few of the healthier breakfast cereals that are wheat-based. The high GI foods include white bread, most crackers, bagels, cakes, croissants, doughnuts, and most of the packaged breakfast cereals. Suggestions by dietitians regarding replacing higher GI foods with lower ones include the following:

1. ∎ Instead of a baked potato – Bulgur (which is a cereal made from whole wheat that is partially boiled and then dried)
2. ∎ Instead of white bread – Whole-grain bread
3. ∎ Instead of cornflakes – Bran flakes
4. ∎ Instead of instant oatmeal – Steel-cut oats
5. ∎ Instead of white rice – Brown rice

Foods that contain no carbohydrates and are not assigned a GI include fish, meat, most nuts, poultry, herbs, oils, and spices. The GI is also affected by the ripeness of foods, the type of cooking method, the type of sugar contained, and the amount of processing that has been done before being sold. The GI is not the same as the glycemic load (GL), which is not based on the amount of food eaten, but is based on the number of carbohydrates in the food source, and how these affect blood glucose. Therefore, it is important to consider both the GI and the GL when selecting foods to help support healthy levels of blood glucose.

The benefits of a low glycemic diet include improved blood glucose regulation, increased weight loss, and reduced cholesterol levels. A low GI diet can reduce blood glucose and improve sugar management in individuals with type 2 diabetes. This diet can increase short-term weight loss, but additional study is needed to determine how long-term weight management is affected. The diet can lower total cholesterol and LDL cholesterol. The diet should mostly contain fruits, non-starchy vegetables, whole grains, legumes, meat, seafood, oils, nuts, seeds, herbs, and spices. It should limit breads, rice, cereals, pasta, starchy vegetables, baked foods, snacks, and beverages that have been sweetened with sugar. The lowest GI fruits include apples, strawberries, and dates, while the highest GI fruits include watermelon and pineapple. The lowest GI vegetables include boiled carrots and boiled sweet potatoes, while the highest GI vegetables include boiled potatoes and boiled pumpkin. The lowest GI grains include barley and quinoa, while the highest GI grains include white bread and white rice. Legumes such as soybeans, kidney beans, chickpeas, and lentils are all low GI foods. Lower GI dairy products or dairy alternatives include soymilk, skim milk, and whole milk, while higher choices in this classification include ice cream and rice milk. The highest GI sweetener is pure table sugar, while the lowest is fructose.

Carbohydrate tolerance is a term that refers to the body’s individualized ability to tolerate carbohydrates. Not everyone tolerates them the same, and there are three different subtypes of carbohydrate tolerance: Low, medium, and high. These can be determined via glucose challenge tests or glucose tolerance tests. The dietary requirements for each type of carbohydrate tolerance are listed below:

1. ∎ Low – 25% carbohydrates, 40% fats, 35% proteins
2. ∎ Moderate – 35% carbohydrates, 35% fats, 30% proteins
3. ∎ High – 50% carbohydrates, 30% fats, 20% proteins

Fat Metabolism

The most efficiently utilized form of fuel is fat, providing 9 kcal/g of stored energy. Carbohydrates and proteins each provide 4 kcal/g. About 40% of calories in the average diet of many countries are obtained from fats. This is equivalent to the percentage obtained from carbohydrates. Fats are a primary source of energy during resting or exercise. The use of fats for energy is just as vital as the use of carbohydrates. When carbohydrates and proteins are consumed in excess of what is needed by the body, they are converted into triglycerides, which are stored in adipose tissue. Each triglyceride contains three fatty acids, linked by a molecule of glycerol. Fatty acids are processed to be used as energy sources by lipases. These are enzymes that break triglycerides down into their component molecules.

The glycerol molecule enters the glycolytic pathway. It is used with glucose to produce energy, or to produce more glucose. Fatty acids are moved to tissues, where they are metabolized for energy. Most body cells can use fatty acids interchangeably with glucose for energy. This occurs everywhere except in the brain, nervous tissue, and red blood cells. Many cells utilize fatty acids for fuel, but fatty acids cannot be converted into glucose needed by the brain for energy. Much of the initial breakdown of fatty acids occurs in the liver, mostly when excess fatty acids are being utilized for energy. The liver uses just a small amount of fatty acids for its energy needs. The remainder are converted into ketones, which enter the bloodstream. As fat is broken down, such as when fasting, many ketones are released into the bloodstream. Ketones are organic acids, so the release of excessive ketones, such as in diabetes, can cause ketoacidosis. This is an acute complication of diabetes mellitus.

Protein Metabolism

Proteins are needed in order for body structures to be formed. These structures include genes, enzymes, contractile muscle components, hemoglobin, some hormones, and the bone matrix. Proteins are made from amino acids. Unlike the fatty acids or glucose, the body has a limited ability to store excess amounts of amino acids. Most of the stored amino acids are inside body proteins. Amino acids that are excessive in comparison to what is needed for protein synthesis are converted into fatty acids, glucose, or ketones. Then they are stored, or used as fuel for metabolism. Fatty acids cannot be converted into glucose. Therefore, proteins are broken down, with the amino acids used as a primary substrate for gluconeogenesis. This occurs when metabolic needs exceed food intake.

Hyperglycemia

Hyperglycemia is the primary manifestation of diabetes mellitus. It develops from impaired insulin secretion plus varied amounts of peripheral insulin resistance. Hyper...