Pathology of diabetes

Question 1

What tissue types have insulin receptors

Answer 1

Skeletal muscle

Adipose

Question 2

Describe in very simple terms how glucose is metabolised (4)

Answer 2

1. Increased blood glucose
2. Increased insulin secreted into blood
3. Increased glucose uptake by cells by recruiting GLUT 4 transporters to cell membrane of muscle and adipose tissue
4. Decreased blood glucose

Question 3

Polymorphisms of what gene is associated with type 1 diabetes mellitus

Answer 3

Human leukocyte antigen (HLA)

Question 4

Pathophysiology of type 1 diabetes mellitus

Answer 4

Usually due to autoimmune pancreatic beta-cell destruction (due to lymphocytic infiltration and circulating autoantibodies) in genetically susceptible individuals –> absolute insulin deficiency –> hyperglycaemia

Question 5

In type 1 diabetes mellitus, beta-cell destruction can proceed sub-clinically for months to years as…

Answer 5

insulitis (inflammation of the beta cell)

- but is rare

Question 6

Aetiology of type 1 diabetes mellitus (2)

Answer 6

HLA gene polymorphism may increase susceptibility

+

Environmental factors

• viral infections
• altered gut bacteria in infancy
• chemicals

trigger the autoimmune mediated destruction of B cells

Question 7

What viral infections may trigger the immune-mediated destruction of pancreatic beta cells in type 1 DM

Answer 7

Congenital rubella
Enteroviruses, e.g. coxsackie B
Mumps

Question 8

Combination of what factors leads to destruction of B cells in type 1 DM

Answer 8

Genes + environment

Question 9

Aetiology of type 2 DM:

combination of

Answer 9

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

Question 10

Type 2 DM typically seen in those with what characteristics (3)

Answer 10

Overweight/obese
No exercise
Ageing

Question 11

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

Answer 11

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

Question 12

In type 2 DM, patients often seen with an expanded upper body visceral fat mass (pot belly) which is due to what 2 things

Answer 12

Increased intake of food + lack of exercise

Question 13

Insulin resistance is associated with obesity in type 2 DM, however what is the important thing to point out about the obesity

Answer 13

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

Question 14

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…

Answer 14

you can keep increasing insulin secretion substantially

Question 15

Multiple abnormal genes involved in type 2 DM impair the B cells in what way

Answer 15

Result in inability of B cells to produce large amounts of insulin

Question 16

Commonest cause of death due to diabetes

Answer 16

MI

Question 17

Long term complications of DM are due to

Answer 17

poor glycaemic control

Question 18

Main complication of DM

Answer 18

Vessel disease

• arteries
• arterioles
• capillaries

Question 19

Macrovascular complication v microvascular complication of DM

Answer 19

Macrovascular
-involves arteries

Microvascular
-involves arterioles or capillaries

Question 20

DM accelerates what macrovascular disease

Answer 20

Atherosclerosis

Question 21

How does DM accelerate atherosclerosis - many mechanisms proposed but describe one

Answer 21

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

Question 22

Arteriole lining consists of several endothelial cells joined together sitting on a layer of basal lamina (basement membrane)

Between these 2 layers is what

Answer 22

A potential space (subendothelial space) which molecules can flux into and out of

Question 23

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

Answer 23

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

Question 24

Arteriolar disease (microvascular complication of DM) is also called

Answer 24

hyaline change
-alteration within cells or in the extracellular space, which gives a homogeneous, glassy, pink appearance in routine histologic sections

Question 25

Arteriolar complications of DM are most severe where in the body (3)

Answer 25

Kidneys
Peripheral tissues, e.g. foot
-highest risk of morbidity
Eyes

Question 26

Capillary disease (microvascular complication of DM) involves what change to the capillaries

Answer 26

Increased connective tissue around capillaries

Question 27

Is genetic predisposition greater in type 1 or type 2 DM

Answer 27

2