Type one diabetes (R1): theory, clinical features, investigations

Question 1

Physiology
- Name 1 hypoglycaemic hormone
- Name 5 hyperglycaemic hormones

Answer 1

Question 2

Physiology
- Describe how insulin is initially synthesised, and how it’s modified

Answer 2

Question 3

Physiology
- Describe the molecular basis of insulin secretion

Answer 3

Question 4

Physiology
- Describe how insulin binds to its receptor and enables glucose uptake into the cell
- Describe the effects of insulin on skeletal muscle, adipose tissue, and liver

Answer 4

Insulin binding to receptor –> signal cascade –> vesicle of GLUT4 receptors embedded onto cell surface

Question 5

Aetiology
- What genes are implicated?

Answer 5

HLA-DQ/R genes

Question 6

Aetiology
- What environmental factors are imlicated?

Answer 6

Geographical variation in the disease: more common in Europeans
Vitamin D supplementation may be protective
Human enterovirus infection is associated with developing 1D

Question 7

Pathophysiology
- Describe how beta cells are destroyed
- Do autoantibodies form?
- Can it take years before symptoms show?

Answer 7

Type IV hypersensitivity reaction: T cell mediated destruction
Yes
Yes - symptoms show when beta cell mass is sufficiently depleted.

Question 8

Pathophysiology

Answer 8

Question 9

Complications
- Short term complications?
- Long term complications?

Answer 9

Short term: DKA
Long term
- Macrovascular: CVD, stroke, PVD
- Microvascular: retinopathy, neuropathy, nephropathy
- Increased risk of other autoimmune diseases

Question 10

Complications
- Retinopathy: fundoscopy findings?
- Neuropathy: 3 manifestations?

Answer 10

Fundoscopy: cotton wool spots, flare haemorrhages, microaneurysms, neovascularisation
Neuropathy
- Stocking glove distrubtion of sensation loss
- Autonomic nephropathy: gastroparesis, orthostatis hypotension
- Diabetic food disease: ulcers, Charcot’s arthropathy

Question 11

Complications: diabetic ketoacidosis
- What is the biochemical triad?

Answer 11

Hyperglycaemia
Ketonaemia
Metabolic acidosis

Question 12

Complications: DKA
- What are the two most common causes of DKA?

Answer 12

• Discontinued/inadequate insulin
• Infection

Question 13

Complications: DKA
- What are other causes of DKA?

Answer 13

Question 14

Complications: DKA
- How are ketones produced?

Answer 14

Inadequate glucose –> body uses fats for energy
In adipose tissue, lipolysis occurs (fat –> FFA’s + glycerol)
Liver converts FFA’s into ketone bodies
3 beta hydroxybutyrate has dissociated from H+ –> acidaemia

Question 15

Complications: DKA
- Why does hyperkalemia occur?
- Is there hyperkalemia yet low total body potassium? Why?

Answer 15

Yes - as it’s shifted into plasma, which is diuresed.

Question 16

Complications: DKA
- What is the respiratory compensation, and what sign does this give?
- What happens to the anion gap?
- What additional symptoms occur with DKA?

Answer 16

Kussmaul respiration: deep/laboured breathing to blow off CO2
High - due to buildup of ketoacids
Abdominal pain + N&V; when severe, mental state changes (cerebral oedema due to osmosis).

Question 17

Risk factors

Answer 17

• Age (bimodal: 4-6 and 10-14)
• Family history of type 1 diabetes

Question 18

History
- Cardinal symptoms + DKA symptoms?

Answer 18

Question 19

Exam
- General inspection?
- Vital signs?
- Face & neck?
- Abdominal pain?

Answer 19

Question 20

Investigations: diagnosing diabetes with
- Fasting glucose
- Random/non fasting glucose
- Oral glucose tolerance
- Hb1Ac

Answer 20

Question 21

Investigations
- Diagnosing diabetes + DKA (not causes and complications?)
- Bedside, labs, special tests

Answer 21

Question 21

Investigations
- Causes/complications of diabetes + DKA?

Answer 21

Question 22

Patient explanation
- Symptoms?

Answer 22

Question 22

Patient explanation
- Normal physiology?
- Type 1 diabetes?
- What causes T1DM?

Answer 22