AstraZeneca has delivered this text only version of the course to serve those users who have difficulty accessing the interactive version.
You can access it here: Demo Interactive Version
Further information can be found at: "Diabetes" main page
More tutorials at: eCME Homepage
Publication Date: January 2006
Welcome to the "type 2 Diabetes" course.
Before beginning, please take a moment to read the course details.
Course Details
Course Length: Approximately 3 hours. Your time may vary based on modem speed, prerequisite knowledge and other factors.
Date Published: January 2006
Valid Until: January, 2009
The name "diabetes mellitus" comes from the Greek word, diabetes, for "siphon" and mellitus, meaning “honey” which together describe two of the hallmark symptoms of diabetes; the passage of large amounts of urine, and the fact that the urine is “sweet” because blood glucose exceeds normal levels and glucose leaks from the kidney into the urine.
This course provides a medical backgrounder on type 2 diabetes. It is divided into the following sections:
The first section, EPIDEMIOLOGY, lists the risk factors associated with diabetes, and describes the current data for disease prevalence, with a focus on the association of diabetes with cardiovascular disease.
The second section, AETIOLOGY, defines the two types of diabetes, and describes the organs and processes of normal glucose metabolism. It also covers the pathophysiology and progression of diabetes including a description of insulin resistance and the metabolic syndrome.
The third section, DIAGNOSIS, describes the clinical features of diabetes and the common tests and guidelines used to diagnose diabetes and insulin resistance.
The fourth section, PROGNOSIS, describes the complications that occur from long-term diabetes. These include affects on the eyes, kidneys, nervous system and the cardiovascular system, and each is covered in detail.
The fifth section, TREATMENT, covers the non-pharmacological approaches and the agents currently used to treat type 2 diabetes, including insulin treatment.
Back to TopThis section defines the two types of diabetes, and describes the organs and processes of normal glucose metabolism. It also covers the pathophysiology and progression of diabetes including a description of insulin resistance and the metabolic syndrome.
After you finish this section, you should be able to:
These are the objectives for this section. You will be tested on these objectives in the final assessment.
There are two main types of diabetes mellitus, type 1 diabetes and type 2 diabetes. This lesson defines each type, describes their very different aetiology, and lists the diagnostic criteria for diabetes. Other types of diabetes mellitus include gestational diabetes, latent autoimmune diabetes in adults (LADA) and secondary diabetes, i.e. caused by other conditions or pharmacotherapy. Another form of diabetes, diabetes insipidus, is caused by abnormalities in the antidiuretic hormone (vasopressin) and is characterized by heavy and frequent urination but normal blood sugar levels.
These less common forms of diabetes will not be covered in this course. Unless otherwise stated, in this course diabetes refers to type 2 diabetes.
There are two main types of diabetes.
Type 1 diabetes is an autoimmune disease in which self-reactive immune cells mount a response to, and destroy the insulin producing beta cells of the islet of Langerhans in the pancreas. Type 1 diabetes generally strikes early in life and is often referred to as juvenile diabetes. Patients have to be treated with insulin replacement therapy. Hence type 1 diabetes was previously referred to as insulin-dependent diabetes mellitus (IDDM).
This course will primarily explore type 2 diabetes, which represents 90% or more of all diabetes cases. Type 2 diabetes is characterised by disorders of insulin action and insulin secretion, either of which may be the predominant feature. There is a reduced responsiveness of the tissues to the actions of insulin (which is referred to as insulin resistance). To differentiate it from IDDM, type 2 diabetes was previously, and misleadingly, called non-insulin dependent diabetes mellitus (NIDDM). It is also often referred to as “adult onset” diabetes. It is also often referred to as "adult onset" diabetes, although this definition is no longer used as both adults and children can develop type 2 diabetes.
Diabetes mellitus is a syndrome of disturbed carbohydrate, lipid, and protein metabolism. It has however historically been defined on the basis of disturbed carbohydrate metabolism, specifically, increased glucose levels.
The diagnostic criteria, in terms of glucose levels, vary slightly between Europe and the US. The units used to express glucose levels also vary; click on the button shown. Click on Continue when you are ready.
Rollover Button: Units: Europe vs. US
In most European countries glucose concentrations are expressed as mmol/L, while in
the US, they are expressed as mg/dL. You should check which units are used in your
country. We will use the following format for the rest of this course: mmol/L (mg/dL)
Note: 1 mmol/L of glucose = 18 mg/dL.
In Europe, the WHO criteria are used, which are shown in this table. The remaining parts of the table are covered in lesson 15.
In the US, the diagnostic value for fasting plasma glucose was 140 mg/dL (7.8 mmol/L) until 1997, when the American Diabetes Association lowered it to 126 mg/dL (7.0 mmol/L).
The key organs involved in glucose and energy metabolism are the liver, pancreas, adipose tissue, and skeletal muscle. Several hormones, especially insulin and glucagon, tightly coordinate biochemical events in these organs and tissues to ensure glucose levels are maintained within a very narrow range. This tight control of glucose levels is important because the central nervous system requires a continuous supply of glucose in order to meet its energy requirements.
The key organs involved in glucose and energy metabolism are the liver, skeletal muscle, adipose tissue, and pancreas. The liver synthesises glucose via two pathways: glycogenolysis and gluconeogenesis. Glycogenolysis is the breakdown of glycogen to produce glucose. Following glycogen breakdown, glucose leaves the liver through the hepatic veins, and is delivered to the vital organs, such as the brain.
Gluconeogenesis is the synthesis of glucose from other substrates, primarily glycerol, from triglyceride breakdown in adipose tissue, and amino acids, from protein breakdown in the muscle. Adipose tissue stores triglycerides. These can be broken down into free fatty acids and glycerol. The free fatty acids can be used as an energy source, and the glycerol can act as a substrate for gluconeogenesis. The protein in the muscle can be broken down to amino acids, which circulate to the liver, where they can be used as substrate for gluconeogenesis.
Any glucose taken up by the muscle can either be utilised as an energy source or can be converted to lactate, which can circulate to the liver, where it is also a substrate in the gluconeogenesis pathway.
Insulin is secreted by specialised beta cells and glucagon by alpha cells found in the islet of Langerhans in the pancreas.
Insulin’s primary role is to lower glucose levels, and its activity is counter balanced by glucagon. Following a meal, the insulin:glucagon ratio favours insulin, while during fasting periods it favours glucagon.
Roll your cursor over each organ to review the metabolism for that organ.
Lipids are fat-like molecules that include simple lipids, such as cholesterol and free fatty acids, and complex lipids, such as cholesterol esters and triglyceride. Free fatty acids, stored as triglycerides in adipose tissue, are an important source of energy. As lipids are insoluble in water, they are transported in the blood as lipoprotein complexes.
This lesson describes the changes in lipids associated with type 2 diabetes, termed diabetic dyslipidaemia, which can increase the risk of atherosclerosis.
The main lipid abnormalities seen in patients with type 2 diabetes are:
Roll your cursor over each section of the table for more information on each.
Rollover:
Triglycerides are produced by the esterification of glycerol with three fatty acid molecules. They are stored mainly in adipose tissue and provide a source of energy through the release of fatty acids. Plasma triglyceride levels increase in patients with type 2 diabetes, mainly due to the increase in production of the triglyceride-rich very low-density lipoprotein (VLDL) particles by the liver. Overproduction of VLDL is stimulated by the increased availability of free fatty acids caused by over nutrition.
High-density lipoprotein (HDL) takes up excess cholesterol from the tissues and transports it to the liver for breakdown or recycling. High levels of HDL are protective against cardiovascular disease. Insulin-resistance increases the breakdown of HDL, thus lowering plasma HDL levels and reducing their cardioprotective properties.
Low-density lipoprotein (LDL) transports cholesterol via the blood from the liver to the tissues. LDL is the principle lipoprotein implicated in atherosclerosis and high levels are a risk factor for cardiovascular disease. Although overall levels of LDL are normal or only slightly raised in patients with type 2 diabetes, levels of small-dense LDL particles are increased. These small-dense LDL particles are rich in triglyceride and are a particularly atherogenic form of LDL.
In this section we will cover the progression of type 2 diabetes. We will begin with the early defects in insulin secretion and discuss the steps leading to more advanced stages of the disease. Progression through these stages is marked by varying degrees of insulin resistance. In this disease, cells become resistant to the effects of insulin.
The progression from normal glucose regulation to type 2 diabetes is represented in this figure. In the normal metabolic state, insulin keeps the levels of fasting plasma glucose within a normal range. There is normal insulin sensitivity at this point in time.
When a susceptible person consumes large meals continually and does not exercise, this chronic caloric excess results in a series of changes in energy metabolism. Over a period of time, usually several years to decades, insulin resistance develops, i.e. a state where there is an impaired response to normal, and elevated, levels of insulin. Initially, the body compensates for this by producing more insulin (a stage of compensatory hyperinsulinaemia), and although there may be only a minor increase in the levels of fasting glucose, particularly in the early stages, the insulin resistance leads progressively to an ever-worsening state of impaired glucose regulation.
Eventually, the beta cells in the pancreas producing insulin begin to fail, and the compensatory hyperinsulinaemia that has kept fasting glucose levels as near to normal as possible, can no longer be maintained. Fasting glucose levels begin to rise to those at which a diagnosis of type 2 diabetes can be made, and the signs and symptoms, such as increased thirst and frequency of urination, associated with uncontrolled hyperglycaemia become apparent.
Excess caloric intake can eventually lead to insulin resistance, particularly in people with a genetic predisposition to diabetes. Once an individual undergoes chronic over nutrition, liver triglycerides eventually build up to a level that places them at risk for cardiovascular disease. These factors, along with others, are hallmarks of metabolic syndrome, which is discussed in this lesson.
Some people have a genetic predisposition to diabetes, which when combined with other factors, such as over nutrition and lack of exercise, increases the risk of developing the disease. During weight gain, fat cells progressively enlarge, storing increasing amounts of triglyceride. Excess fat intake in combination with increased release of fatty acids from the fat tissues will lead to accumulation of fatty acids in the circulation. These are eventually taken up by the muscle and liver tissue, which leads to insulin resistance in these tissues. The beta cell compensates by secreting more insulin to maintain normal glucose handling.
If chronic over nutrition continues, and liver triglycerides build up, eventually, the capacity of the liver to store triglyceride is exceeded. When this occurs, the liver produces increased levels of triglyceride-rich lipoproteins, mainly very low-density lipoprotein (VLDL) particles. This in turn leads to increased triglyceride and small-dense low-density lipoprotein (LDL) levels and reduced HDL cholesterol levels.
When you are ready, click on Continue.
Many people with impaired glucose regulation or type 2 diabetes also have several other cardiovascular risk factors, which commonly occur together. This disorder is referred to as the ‘metabolic syndrome. Although the pathogenesis of the metabolic syndrome and each of its components is not completely understood, central obesity and insulin resistance are now recognised as important factors.
The hallmark features of the metabolic syndrome include impaired glucose regulation, atherogenic dyslipidaemia, hypertension, and abdominal obesity. Thus, metabolic syndrome is a condition that promotes atherosclerosis and increases the risk of cardiovascular events through the aggregation of different metabolic disorders.
The definitions and diagnostic criteria for metabolic syndrome vary slightly between Europe and the US. Click on the button to view a table that summarizes the WHO, NCEP ATP III, and IDF guidelines.
This "drag and drop" progress check will test your knowledge of the information presented in this section. Because your score will not be recorded, you may take the progress check as many times as you would like.
Please feel free to review the lessons as often as required to successfully complete the progress check.
Match the terms with the appropriate groups. Match the terms with the correct definitions. Not all terms are used.