Pathology of Diabetes Mellitus Flashcards
Describe the pancreas
Lobules of glandular tissue surrounded by fat
Describe the normal insulin formation and secretion
- Islet of langerhans = endocrine pancreas
- 2/3 of the Islet cells are B cells
- B cells secrete insulin into the capillaries
What is the effect of the intake of food on insulin?
Food converted to glucose –> stimulates insulin
How is the action of insulin?
Insulin binds its receptor and drives glucose into adipocytes (= fat cells)
- Increase Glc
- Increase insulin
- Increase Glc uptake by cells
- Decrease Glc in serum
What is the aetiology of Type I DM?
• Not entirely known
• Genes found so far:
Molecules that help T cells recognise self from non-self = Human Leukocyte Antigen (HLA) molecules
• Autoimmune attack on islet cells
• Environment: ?chemical, viral infection, bacteria in gut
Why does Human Leukocyte Antigen (HLA) molecules increase risk of Type I DM?
Cannot distinguish own cells from other cells –> autoimmune attack on pancreatic B cells (therefore cannot produce insulin)
Why does autoimmune attack on islet cells increase risk of Type I DM?
Lymphocyte infiltration of islets (insulitis) – destruction of B cells (-> decreased insulin)
What is the effect of destruction of islet?
Decreased insulin
How do genes and environment increase risk of Type I DM?
Destruction of B cells and scarred islet
What is the effect of the destruction of B cells in Type I DM?
Decrease insulin –> increase Glc
What is the aetiology of Type II DM?
Combination of:
• Reduced tissue sensitivity to insulin (insulin resistance)
• Inability to secrete very high levels of insulin
A failure of B cells to meet an increased demand for insulin in the body
• Environment: expanded upper body visceral fat mass (pot belly)
What are the causes of expanded upper body fat?
Increased intake of food + lack of exercise (genes relatively unimportant)
What is the result of expanded upper body visceral fat mass (pot belly)?
Increase free fatty acids in blood, because ‘overweight’ adipocytes are ‘stressed’ and release FA
This causes decreased insulin receptor sensitivity to insulin (peripheral insulin resistance)
But patient is not necessarily diabetic as could be able to produce increased levels of endogenous insulin
Why does increase plasma free FA decrease insulin receptor sensitivity?
Not clear why the FA interfere with the insulin receptor pathway
What is the effect of inefficient insulin receptors?
Some Glc gets into cells but some does not (increase Glc in blood)
In order for Glc to be taken up, more insulin is required to get the same amount of glucose into cells
What is a requirement in a person with central adiposity?
Pancreas needs to secrete more insulin to move glucose into cells
What does central adiposity lead to?
Hyperinsulinaemia
When does diabetes occur in central adiposity?
If the pancreas cannot increase insulin substantially to overcome peripheral insulin resistance
Are there genes which control insulin secretion in the pancreas?
- Many different genes
* Some of these genes control whether you can secrete very large amounts of insulin or not
What type of genes are involved in Type II DM?
Implicated genes are for poor B cell ‘high end’ insulin secretion, not for person increasing their central adiposity
So if you have only a few genes abnormal you will be able to secrete lots of insulin
What occurs in Type II DM?
Insulin secretion does not increase enough to counteract insulin resistance caused by central adiposity
What are the oddities in Type II DM?
Slim person who puts on a small amount of weight may get type II diabetes if they have very high dosage of genes resulting in inability to even modestly raise insulin
Is Type II DM reversible?
Yes, if you slim back down to normal weight
A multiple gene defect of pancreatic B cell insulin production which is unmasked by central adiposity
What is the long-term complications of DM?
- Annual mortality is 5.4% - double the rate of non-diabetics
- Life expectancy is decreased by 5-10 years
- Myocardial infarction is the commonest cause of death
- Result from prolonged poor glycaemic control
