Diabetes - Pathology

Question 1

Outline the potential macrovascular complications of diabetes

Answer 1

Myocardial infarction (2-5 x higher)
Stroke (3 x higher)
Peripheral vascular disease (5 x higher)

Question 2

Describe the retinal changes that might be seen in diabetic eye disease

Answer 2

Retinopathy

• non-proliferative: micro-aneurysms, hard exudates, haemorrhages, cotton wool spots
• proliferative: neo-vascularisation

Maculopathy

• Oedema (focal or diffuse)
• Ischaemia

Question 3

Outline the potential macro-vascular complications of diabetes

Answer 3

Diabetic eye disease
 - Retinopathy
 - Maculopathy
Diabetic neuropathy
 - Peripheral neuropathy (glove-stocking distribution)
 - Mononeuritis
 - Autonomic neuropathy
 - Acute sensory peripheral neuropathy
 - Proximal motor neuropathy
Diabetic nephropathy

Question 4

Describe the progression of diabetic nephropathy

Answer 4

1. elevated GFR
2. microalbuminuria
3. proteinuria
   - causes nephrotic syndrome and loss of function

Question 5

How is diabetic nephropathy managed?

Answer 5

Optimise glycaemic control

Blood pressure control - ACE-inhibitors

Question 6

Describe the signs/symptoms of autonomic neuropathy

Answer 6

Erectile dysfunction
Abnormal ECG rhythm responses
Postural hypotension
Gastric stasis, vomiting, diarrhoea
Abnormal sweating
Urinary retention
Peripheral oedema

Question 7

What is a common sign of proximal motor neuropathy? What is an alternative name for this condition?

Answer 7

Painful wasting of the thigh muscle
(Most commonly seen in elderly men)
A.k.a. diabetic amyotrophy

Question 8

Describe the main risks associated with peripheral neuropathy

Answer 8

Ulcers
May need amputation
Infection
Charcot’s foot

Question 9

Which genes are associated with type 1 diabetes?

Answer 9

Human Leukocyte Antigen (HLA) molecules

- these molecules help the T-cells to distinguish self from non-self

Question 10

What is insulitis?

Answer 10

Lymphocyte infiltration of Islets of Langerhans (initial part of the autoimmune attack). This causes destruction of beta-cells.

Question 11

Why does insulitis impair insulin production?

Answer 11

Islets  of  Langerhans  to  become  filled  with 
fibrous  tissue  (scarring).  This  leads  to 
destruction of the islets and therefore less insulin is produced.

Question 12

Outline the aetiology of type 2 diabetes

Answer 12

Combination of:

• Reduced tissue sensitivity to insulin (peripheral insulin resistance)
• Inability of pancreas to secrete very high levels of insulin: i.e. pancreatic B cells are unable to meet an increased demand for insulin in the body.

Question 13

Which genes are implicated in type 2 diabetes?

Answer 13

Genes associated with poor B cell “high end” insulin secretion`

Question 14

How does central adiposity lead to peripheral insulin resistance?

Answer 14

Central adiposity results in increased free fatty acids in the blood. These free fatty acids make the insulin receptors less sensitive to insulin, so that more insulin in needed in order to get the same amount of glucose into the cell. Therefore, the pancreas needs to secrete more insulin.

Question 15

Why does pancreatic function eventually decrease in type 2 diabetes?

Answer 15

High levels of glucose and free fatty acids in the blood
cause toxicity to β-cells by causing oxidative stress (glucotoxicity and lipotoxicity), so over time the β-cells secrete less insulin. This toxicity also triggers apoptosis of the cells, so that both β-cell function
and mass decrease.