Diabetes (& endocrine pancreas)

Question 1

What cells make up the Islets of Langerhans and what is their function?

Outline the paracrine feedback system of the islets of Langerhans

Answer 1

• Alpha - glucagon - activates B & D
• Beta - insulin - inhibits A & D
• Delta - somatostatin - inhibits A & B
• PP - polypeptide

Question 2

What are the functions of insulin?

Answer 2

• INsulIN stimulates 2 things to gin IN 2 cells;
  
  • Potassium & glucose

Question 3

Type 1 diabetes

Outline;

• Definition & cause
• Common presentation
  
  • Rare presentation?

Answer 3

Definiton & cause

• Insulin deficiency due to autoimmune islet destruction due to failure in self-tolerance in T cells
  
  • Clonal deletion, T reg & T effector defects
• Genetics
  
  • HLA-DR3/4 (MHC2)
  • CTLA4 & PTPN22 (inhibits T cells)
  • Insulin gene polymorphisms
• Environmental

Common presentation

• Adolescent

Rare presentation

• LADA - latent autoimmune diabetes of adults

Question 4

Type 2 diabetes

Outline

• Definition & cause
• Relationship between obesity, insulin resistance & B cell dysfunction
• Common presentation
  
  • Rare presentation

Answer 4

Definition & cause

• Peripheral resistance to insulin action & inadequate compensatory responce of insulin secretion by B cells
  
  • Environmental factors (obesity,no exercise, calorie/ alcohol excess)
  • Genetic component (not to do with immune tolerance though)
• Resistence predates hyperglycaemia & usually B cell hyperfunction & hyperinsulinaemia ⇒ B cell dysfunction

Obesity, insulin resistence & B cell dysfunction

• 2 metabolic defects caused by Free Fatty Acids (FFAs)!
  
  1. Insulin resistence
     
     • FFA metabolites inhibit insulin signalling (lipotoxic)
     • IL1B ⇒ inhibit insulin signalling
       
       • FFA ⇒ inflammation with Macrophages & B cells ⇒ IL1B
       • FFAs ⇒ adipocytes ⇒ adipocytes ⇒ IL1B
  2. B cell dysfunction
     
     • FFAs ⇒ B cells ⇒ IL1B ⇒ B cell death

Common presentation

• 40 yrs

Rare presentation

• Maturity onset diabetes of young (MODY)
  
  • Autosomal dominant, teenagers get type 2

Question 5

Outline the common presentation of diabetes

Answer 5

• Type 1
  
  • Polydipsia/ uria
  • Weight loss
  • Ketoacidosis
• Type 2
  
  • Asymptomatic
  • Complications eg MI

Question 6

Outline the complications of diabetes

Answer 6

• Vascular disease
  
  • MI, stroke
• Nephropathy
  
  • Microalbminaemia
• Neuropathy & diabetic foot
• Retinopathy
  
  • Background - microaneurysm, haemorrhages, hard exudates (lipid)
  • Pre-proliferative - cotton wool spots, haemorrhages
  • Proliferative - new vessels
  • Maculopathy - microaneurysm ⇒ cap occlusion ⇒ ischaemia ⇒ new vessel formation

Question 7

How do you diagnose diabetes?

Answer 7

• Hyperglycaemia symptoms + 1 raised venous glucose
• 2 raised venous glucose/ OGTT
• HbA1C >=48mmol/L

Raised venous glucose;

• Fasting >=7mmol/L
• Random >=11mmol/L

Oral Glucose Tolerance Test (OGTT);

• 2hr value >=11.1mmol/L

Question 8

How do you treat diabetes type 1 & 2?

Answer 8

Type 1

• Insulin

Type 2

• Metformin
  
  • biguanide
  • Inc insulin sensitivity
• Glitazone
  
  • Inc insulin sensitivity
• Sulfonylurea eg Gliclazide
  
  • Inc insulin secretion
• Insulin