Pathology of Diabetes Mellitus Flashcards
What is the pancreas composed of?
Lobules of glandular tissue surrounded by fat
What part of the pancreas is the endocrine pancreas?
Islets of Langerhans
How many of the Islet of Langerhan cells are B cells?
2/3
What does insulin do?
Acts on many tissues, such as fat, where is binds to its receptor and drives glucose into the cell
Explain the pathway of increases glucose uptake from plasma leading to glucose decreasing?
What genetic relationship to the aetiology of type 1 diabetes has been found?
Molecules that help T cells recognise self from non-self (human leukocyte antigen (HLA) molecules)
So, in type 1 diabetes cannot distinguish own cells from other cells so autoimmune attack on B cells
What does the autoimmune attack on B cells in type 1 diabetes cause?
Lymphocyte infiltration of islet (insulitis) leading to destruction of B cells causing decreases insulin production
What environmental triggers are possible linked to type 1 diabetes?
? Chemicals
? Bacteria in gut altered in infancy
? Viral infection (molecules on viral surface mimic molecules on outside of B cells)
What is the aetiology of type 2 diabetes?
Combination of:
- reduced tissue sensitivity to insulin (insulin resistance) and
- inability to secrete very high levels of insulin
What is a major risk factor for type 2 diabetes?
Explanded upper body visceral fat (pot belly)
also called central adiposity, which is how men and woman after menopause put on weight
What does central adiposity occur due to?
Increased intake of food and lack of exercise (genes relatively unimportant)
How does pot belly lead to type 2 diabetes?
Causes increased free fatty acids in blood (patients not yet diabetic) which causes decreases insulin receptor sensitivity
So more insulin is needed to get same amount of glucose into cells
Pancreas reaches point where cannot secrete enough insulin
What does central adiposity lead to?
Hyperinsulinaemia
What are the genetic risks to get type 2 diabetes?
Multiple genes involved in causing inadequate “high level” insulin secretion by B cells
Not HLA genes
Not adiposity genes
What is the link between a gene variant of B cells and type 2 diabetes?
If gene is a variant may promote insulin production at low levels but not high levels, which is needed when there is a decreases receptor sensitivity to insulin
So genes involved in type 2 diabetes are ones for poor B cell ‘high end’ insulin secretion
(if have few abnormal genes can still produce lots of insulin, if may genes are abnormal cannot)
In type 1 and type 2 diabetes is anything wrong with insulin receptors?
Type 1 - nothing wrong with receptors, problem is destruction of B cells and decreased insulin production
Type 2 - problem with receptors, decreased insulin sensitivity (occurs because central adiposity causes receptor complex to not work so insulin cannot bind tightly)
What is the annual mortality of people with diabetes?
5.4%, double what people with no diabetes is
How does life expectancy change due to diabetes?
Decreased by 5-10 years
However, this is not accurate as there are two groups - well managed whos life expectancy barely changes and not well managed whos life expectancy massively drops
What is the commonest cause of death for people with diabetes?
Myocardial infarction
What do long term complications in diabetes occur due to?
Prolonged poor glycaemic control
What is the main complication in diabetes?
Damage to vessels:
- macrovascular complications
- microvascular complications
What is a macrovascular complication of diabetes?
Accelerates atherosclerosis (does not cause it but accelerates it)
What mechanism explains diabetes accelerating atherosclerosis?
Lots of glucose attaches to LDL (low density lipoprotein) due to more than normal levels
Stopping it binding to its receptor on liver cells tightly
So LDL is not removed and stays in blood, causing hyperlipidaemia then atherosclerosis
What is a microvascular complication of diabetes in arterioles?
Molecules flux into subendothelial space but find it hard to flux back to blood
Causing build up of trapped molecules under endothelial cells, basal lamina becomes thickened
Where do microvascular complications due to diabetes (in arterioles) often occur?
Kidneys, peripheral tissues (foot), eyes and arterioles supplying nerves
What are microvascular complications of diabetes in capillaries?
Collagen glycosylation
Cross linked proteins
What is the mechanism of collagen glycosylation?
Glucose added to proteins (which is non-enzymatic reversible at first, but irreversible if covalent bonds form - advanded glycosylation end products (AGEs)
Collagen is glycosylated, collagen is in normal basal lamina and albumin can sometimes get into subendothelial space, albumin does not normally combine with collagen and fluxes out of space with no accumulation
But glycosylated collagen does bind to albumin causing accumulation
What is teh mechanism of cross linked proteins?
Many normal basal lamina proteins do not cross link and can be removed easily
But glycosylated proteins bind their neighbouring proteins
Rigid, crosslinked proteins cannot easily be removed, causing persistence of protein in arteriole wall
What is arteriolar disease also called?
Hyaline change
What does hyaline change cause?
Narrows arteriole causing poor blood flow and then ischaemia
Is microvascular and macrovascular damage reversible?
Is typically irreversible ones it is established, but can stop the decline if achieve good glycaemic control
