Pathology of Diabetes Mellitus

Question 1

What is the normal macroscopic structure of the pancreas?

Answer 1

Lobules of glandular tissue surrounded by fat

Question 2

Insulin is secreted by what?

Answer 2

Beta cells (islet of langerhans)

Question 3

Insulin is secreted into what?

Answer 3

Blood via capillaries

Question 4

What is the function of Human Leukocyte Antigen?

Answer 4

Helps T-cells recognise self from non-self

Question 5

What is insulitis?

Answer 5

Lymphocyte infiltration of islets (autoimmune mediated)

Question 6

What is the result of insulitis?

Answer 6

Destruction of B cells

Reduced insulin

Question 7

What is believed to be a cause of T1DM?

Answer 7

Environmental triggers:
- Chemicals
- Gut flora changed in infancy
- Viral infection
GENES

Question 8

How are viruses suspected to cause T1DM?

Answer 8

Molecular mimicry

Question 9

What is the cause of T2DM?

Answer 9

Reduced tissue sensitivity to insulin

Inability to secrete hight levels of insulin

Question 10

What is T2DM?

Answer 10

A failure of the B-cells to meet an increased demand for insulin in the body

Question 11

What is the environmental cause of T2DM?

Answer 11

Upper body fat mass
Increased intake of food
Lack of exercise

Question 12

What is the effect of increased upper body fat mass? Why?

Answer 12

Increased free fatty acids in blood

Overweight adipocytes stressed to release FAs

Question 13

Increased free fatty acids in blood leads to what?

Answer 13

Decreased insulin receptor sensitivity to insulin

Question 14

How is the role of the pancreas changed in a patient with central adiposity?

Answer 14

More insulin is needed to move in the same amount of glucose

Question 15

Decreased insulin receptor sensitivity to insulin causes what?

Answer 15

Decreased removal of glucose from the blood

So MORE insulin is secreted

Question 16

What is peripheral insulin resistance?

Answer 16

Increased insulin needed to cope with decreased tissue sensitivity to insulin

Question 17

No diabetes will occur in peripheral insulin resistance when?

Answer 17

When the individual can substantially increase insulin secretion

Question 18

How is the amount of insulin secreted by the pancreas controlled?

Answer 18

GENES

Cant produce HIGH levels of insulin

Question 19

Which genes are implicated for T2DM?

Answer 19

Genes for Beta cell high end insulin secretion

Question 20

What factors do genes not appear to be for in T2DM?

Answer 20

Peripheral insulin resistance

Increased central adiposity

Question 21

What is the ONLY genetic factor of T2DM?

Answer 21

Whether or not Beta cells can secrete insulin bigly

Question 22

What is the annual mortality of T2DM?

Answer 22

5.4%

Question 23

What is the LE of someone with T2DM?

Answer 23

Reduced by 5-10 years

Question 24

What is the most common CoD in T2DM patients?

Answer 24

MI

Question 25

Long term complications of T2DM are a result of what?

Answer 25

Prolonged poor glycaemic control

Question 26

What is the main complication of T2DM?

Answer 26

Large vessel disease | Small vessel disease

Question 27

What are the macrovascular complications of T2DM?

Answer 27

Acceleration of atherosclerosis

Question 28

What are the increases in risk of CHD, MI and Stroke?

Answer 28

CHD - 2-20x MI - 2-5x Stroke 2-3x

Question 29

What mechanisms are proposed for poor glycaemic control causing accelerated atherosclerosis in large vessels?

Answer 29

Glucose attaches to LDLs, this stops LDLs binding to liver cell receptors LDLs not removed by liver --> Hyperlipidaemia

Question 30

What mechanisms are proposed for poor glycaemic control causing accelerated atherosclerosis in small vessels?

Answer 30

DM causes molecules to flux into subendothelial space but not flux back out Molecules trapped under endothelial cells Thickening of the basal lamina

Question 31

What is hyaline change?

Answer 31

Body-wide arteriolar disease causing ischaemia

Question 32

What are the increased risks of amputation, end stage renal disease and blindness?

Answer 32

Amputation - 40x ESRD - 25x Blindness - 20x

Question 33

What is a Kimmelstiel-Wilson lesion?

Answer 33

Nodule of connective tissue in the glomerulus caused by DM

Question 34

How does glycosylation cause small vessel disease?

Answer 34

Non-enzymatic binding of glucoses to proteins which starts reversible and progresses

Question 35

When does glycosylation cause irreversible damage in DM?

Answer 35

Covalent bonding of glucose to proteins | AGEs (advanced glycosylation end-product) formation

Question 36

How is the activity of glycosylated collagen in arteriole walls changed in DM?

Answer 36

Glycosylated collagen binds to albumin causing albumin to accumulate in the subendothelial space of arterioles

Question 37

Why do arteriolar basal lamina proteins become irremovable in DM?

Answer 37

GLYCOSYLATION proteins cross link to their neighbours

Question 38

What is the net effect of glycosylation of proteins in the basal lamina of arterioles?

Answer 38

Small arteriolar disease Accumulation of trapped plasma proteins Accumulation of cross-linked basal lamina proteins These persist in basal lamina even in normoglycaemia