Pathology of diabetes Flashcards
What tissue types have insulin receptors
Skeletal muscle
Adipose
Describe in very simple terms how glucose is metabolised (4)
- Increased blood glucose
- Increased insulin secreted into blood
- Increased glucose uptake by cells by recruiting GLUT 4 transporters to cell membrane of muscle and adipose tissue
- Decreased blood glucose
Polymorphisms of what gene is associated with type 1 diabetes mellitus
Human leukocyte antigen (HLA)
Pathophysiology of type 1 diabetes mellitus
Usually due to autoimmune pancreatic beta-cell destruction (due to lymphocytic infiltration and circulating autoantibodies) in genetically susceptible individuals –> absolute insulin deficiency –> hyperglycaemia
In type 1 diabetes mellitus, beta-cell destruction can proceed sub-clinically for months to years as…
insulitis (inflammation of the beta cell)
- but is rare
Aetiology of type 1 diabetes mellitus (2)
HLA gene polymorphism may increase susceptibility
+
Environmental factors
- viral infections
- altered gut bacteria in infancy
- chemicals
trigger the autoimmune mediated destruction of B cells
What viral infections may trigger the immune-mediated destruction of pancreatic beta cells in type 1 DM
Congenital rubella
Enteroviruses, e.g. coxsackie B
Mumps
Combination of what factors leads to destruction of B cells in type 1 DM
Genes + environment
Aetiology of type 2 DM:
combination of
Insulin resistance (reduced tissue sensitivity to insulin) \+ Relative insulin deficiency (inability to secrete very high levels of insulin)
so failure of B cells to meet increased demand of insulin
Type 2 DM typically seen in those with what characteristics (3)
Overweight/obese
No exercise
Ageing
Pathophysiology of type 2 DM
- process leading up to diabetes (at this stage, individual is not yet diabetic)
- how the above process transitions to type 2 DM
Expanded upper body visceral fat mass –> increased release of free fatty acids in blood –> peripheral insulin resistance –> decreased glucose uptake –> beta cells compensate for this by increasing insulin secretion to get same amount of glucose uptake as usual –> hyper insulinaemia
Eventually, however, the compensatory beta-cell response fails and glucose intolerance develops. Failure of the beta cell to produce sufficient insulin to allow appropriate glucose utilisation at the cellular level is the underlying cause of the transition from insulin resistance to clinical type 2 DM
In type 2 DM, patients often seen with an expanded upper body visceral fat mass (pot belly) which is due to what 2 things
Increased intake of food + lack of exercise
Insulin resistance is associated with obesity in type 2 DM, however what is the important thing to point out about the obesity
Total obesity is not as important as location of adipose tissue that’s causing the insulin resistance
-visceral fat is more metabolically active than subcutaneous fat in producing adipokines that cause insulin resistance
Upper body visceral fat mass (Central adiposity) –> peripheral insulin resistance so need increased insulin secretion to cope with decreased tissue sensitivity to insulin
However diabetes will not occur if…
you can keep increasing insulin secretion substantially
Multiple abnormal genes involved in type 2 DM impair the B cells in what way
Result in inability of B cells to produce large amounts of insulin
Commonest cause of death due to diabetes
MI
Long term complications of DM are due to
poor glycaemic control
Main complication of DM
Vessel disease
- arteries
- arterioles
- capillaries
Macrovascular complication v microvascular complication of DM
Macrovascular
-involves arteries
Microvascular
-involves arterioles or capillaries
DM accelerates what macrovascular disease
Atherosclerosis
How does DM accelerate atherosclerosis - many mechanisms proposed but describe one
Glucose attaches to low density lipoprotein (LDL) which stops LDL from binding to its receptor on liver cells tightly
So LDL can’t be removed from the blood by the liver, therefore stays in blood –> hyperlipidaemia –> atherosclerosis
Arteriole lining consists of several endothelial cells joined together sitting on a layer of basal lamina (basement membrane)
Between these 2 layers is what
A potential space (subendothelial space) which molecules can flux into and out of
A complication of DM is microvascular disease involving arterioles
Arterioles consist of an endothelial lining surrounded by a basal lamina which is further surrounded by smooth muscle
Between the endothelium and basal lamina is a potential space molecules can flux in and out of
In DM, what happens in this potential space
molecules flux into subendothelial space but find it hard to flux back to blood in the lumen –> build up of trapped molecules under the endothelium usually proteins and collagens
Basal lamina also thickens
Arteriolar disease (microvascular complication of DM) is also called
hyaline change
-alteration within cells or in the extracellular space, which gives a homogeneous, glassy, pink appearance in routine histologic sections
Arteriolar complications of DM are most severe where in the body (3)
Kidneys
Peripheral tissues, e.g. foot
-highest risk of morbidity
Eyes
Capillary disease (microvascular complication of DM) involves what change to the capillaries
Increased connective tissue around capillaries
Is genetic predisposition greater in type 1 or type 2 DM
2
