26.5 Path: Diabetes mellitus

Question 1

What are some macrovascular effects due to hyperglycaemia?

Is this the same as in non-diabetic?

Answer 1

Atheroma

Indistinguishable from non-diabetic

Question 2

Why does atheroma in DM occur?

4

Answer 2

1. Increased hepatic production of atherogenic lipoproteins
2. Supression of lipid uptake (peripheral tissues)
3. Abnormal endothelial function (pro-coagulant)
4. Hyperlipidaemia/hypertension

Question 3

What rate does the blood flow change by in a coronary artery atheroma that halves the radius of the vessel?

Answer 3

1/16th the flow

Question 4

What are 4 major clinical problems of microvascular injury in DM?

Answer 4

Diabetic nephropathy
Diabetic retinopathy
Delayed wound healing
Foot ulcers

Question 5

Why do these microvascular complications occur?

Answer 5

Hyperglycaemia effect on cells and ECM

Particularly glycosylation of proteins
initially labile-Schiff bases later stable- AGEs

Question 6

What is often the initial presentation of diabetic nephropathy?

Answer 6

Proteinuria

Question 7

What are 4 significant problems that can cause chronic renal failure? (especially in DM)

Answer 7

Glomerulosclerosis/arteriolosclerosis
Pyelonephritis
Papillary necrosis
Accelerated atherosclerosis in larger arteries

Question 8

What are typical histological signs of diabetic nephropathy?

Answer 8

Spherical nodules (Kimmelstiel-Wilson) arising in mesangium that become collagen

Hyaline arteriolosclerosis (by proteinaceous material)

Question 9

What do we see on EM in diabetic nephropathy?

Answer 9

Glomerular basement membrane thickening

Question 10

What is the most common cause of end stage kidney disease in Australia (and thus dialysis)?

Answer 10

Diabetic nephropathy

Question 11

What proportion of DM patients does diabetic retinopathy affect?

Answer 11

80% after 20 years

Question 12

What is the primary process of diabetic retinopathy?

Answer 12

Ischaemia due to microvascular injury/reduced perfusion

vascular proliferation is a response

Question 13

Why does wound healing struggle to occur in DM?

Answer 13

Impaired perfusion (microvascular injury) mainly, also due to other reasons

Question 14

What are the three metabolic pathways that explain how chronic hyperglycaemia can be damaging to the tissues?

Answer 14

• Advanced glycosylation end products
• Activation of protein kinase C
• Intracellular hyperglycaemia and abnormal Polyol pathways

Question 15

What are AGEs derived from? What do they affect?

Answer 15

Derived from glucose

React with producs from ICM/ECM

They have an effect on endothelial and inflammatory cell function (bind to RAGE)

Question 16

What does Activation of PKC do?

Answer 16

Many changes to capillary bed (e.g. wall thickening, abnormal endothelial function etc.)

Question 17

What does Polyol do?

Answer 17

Alters normal intracellular signalling

Glutathione reduced

Question 18

What can occur in the liver in DM?

Answer 18

Non-alcoholic steatohepatitis/NAFLD (especially in Type 2)