Week 9 - Diabetes

Question 1

What types of cells are there in the pancreas and what is their function?

Answer 1

Beta cells = produce insulin and amylin

Alpha cells = release glucagon

Delta cells = produce somatostatin

PP cells = contain pancreatic polypeptide

Question 2

What blood glucose defines hypoglycaemia?

What causes hypoglycaemia int ype 1 and type 2 diabetes?

Answer 2

< 4 mmol/L

Type 1 = excessive exercise, insulin overdose, inadequate carb intake

Type 2 = sulphonylureas, hepatic or renal disease, some drugs

Question 3

What are the 2 causes of the symptoms associated with hypos?

Answer 3

Counter-regulatory activity of SNS = palpitations, anxiety, tremors

Glucose deficiency in brain = hunger, headahce, tingly lips

Question 4

How do you treat ketoacidosis?

Answer 4

• i.v. insulin infusion
• Replacement of fluids and electrolytes
• Treat underlying cause
• Suppress ketogenesis
• Reduce blood glucose
• Correct electrolyte balance

Question 5

What are the acute and chronic complications associated with diabetes?

Answer 5

Acute:

• Hypoglycaemia
• Diabetic ketoacidosis
• Hyperosmolar hyperglycaemic state

Chronic:

• Long-term / secondarycomplications

Question 6

What are 4 microvascular long-term complications of diabetes?

Answer 6

• Retinopathy
  
  • Cause of blindness
  • 4 types = background, pre-proliferative, proliferative, maculopathy
• Nephropathy
  
  • Angio[athy pf capillaries of glomeruli
  • Glomerulosclerosis
• Neuropathy
  
  • Feet, loss of sensation
• Damage of small vessels
  
  • Cause by glycation of proteins and hyperglycaemia

Question 7

What are the 3 macrovascular long-term complications of diabetes?

Answer 7

• CVD
  
  • Premature development, MI, vigorous risk factor management
• Cerebral vascular disease
• Peripheral vascular disease
  
  • Intermittent claudation and ulceration
  • Foot ulcers –> poor blood –> neuropathy –> susceptibility to infection

Question 8

What are 4 secondary causes of diabetes?

Answer 8

• Endocrine
  
  • Cushing’s, acromegaly, phaeochromocytoma
• Pancreatic disease
  
  • Chronic pancreatitis, surgery, CF, tumour
• Genetic disorders
  
  • Down’s syndrome, Prada-Willi
• Drug-induced
  
  • Steroids, beta-blockers, diuretics

Question 9

What is ketogenesis?

Answer 9

Synthesis of ketone bodies by liver from fatty acid breakdown products

Question 10

How do you treat type 1 diabetes?

Answer 10

• Insulin
  
  • Short-acting = soluble analogues
  • Intermediate-acting = isophane
  • Long-acting = insulin zinc suspension analogues
  • Pre-mixed
• • exercise and healthy eating
• Cell replacement therapy
  
  • Islet transplantation

Question 11

How do you treat type 2 diabetes?

How do each of the drugs work?

Answer 11

• Metformin
  
  • • gluconeogenesis, + utilisation
• Sulphonylureas
  
  • • insulin secretion
• Pioglitazone
  
  • Insulin sensitisers
• GLP-1 mimetics or incretin mimetics
  
  • Insulin release
• DDP-4 inhibitors
  
  • Insulin release, no degredation of incretins
• SGLT-2 inhibitors
  
  • Inhibit renal glucose reabsorption

Question 12

What is the blood supply to the pancreas?

Answer 12

Splenic artery

Superior + inferior pancreaticoduodenal arteries

Splenic and superior mesenteric portal vein tributaries

Question 13

What is the sympathetic and parasympathetic innervation of the pancreas?

Answer 13

Abdominopelvic splanchnic nerve

Vagal nerve

Question 14

What are the steps of insulin biosynthesis?

Answer 14

• Preproinsulin synthesis
• Proinsulin transfer
• Proinsulin –> insulin
  
  • C-peptide cleavage
• Insulin stored in secretory granules
• Exocytosis, involving calcium and ATP

Question 15

Which enzymes are involved in proinsulin to insulin synthesis?

Answer 15

• PC2
  
  • cleaves at 65,66
• PC1
  
  • cleaves at 32,33
• Carboxypeptidase H
  
  • Removes 31,32 and 64,65

Question 16

What 3 things are involved in insulin secretion?

What happens with each to release insulin?

Answer 16

• Nutrient stimulus
  
  • ATP:ADP ratio increase
  • Membrane depolarisation
  • Opening of calcium channels
• Protentiators / incretins
  
  • Gut hormones bind with entero-snsular axis
  • Somatostatin inhibits glucagon
• Neural control
  
  • Sympathetic = B adrenoceptor = + insulin release vice versa for alpha
  • Parasympathetic = muscarinic = + insulin release

Question 17

What are the roles of insulin?

Answer 17

• Promote growth and development
• Promote cellular K+ uptake
• Prmote uptake and utilisation of glucose in skeletal muscle and adipose tissue
• Promote fuel storage
• Reduces blood glucose

Question 18

What is glucagon?

When is it released?

Answer 18

Hormone synthesised in islet alpha cells

Stimulated when < 3.5 mmol/L

Inhibited by + blood glucose, insulin, and somatostatin

Question 19

What is somatostatin?

What is its role in relation to insulin?

Answer 19

Peptide hormone synthesised in islet delta cells

Inhibits glucagon and insulin secretion via paracrine mechanism

Question 20

What are the roles of adrenaline, cortisol, and growth hormone in regards to blood glucose?

Answer 20

Adrenaline:

• Energy provision for emergencies and exercise
• Severe hypoglycaemia

Cortisol:

• Mobilisation of fuels during stress
• Prolonged hypoglycaemia

Growth hormone:

• Promotion of growth in prolonged hypoglycaemia

Question 21

What is MODY?

Answer 21

Maturity-onset diabetes of the young

• Non-insulin dependent
• Autosomal dominant inheritance
• Caused by single gene defect altering beta cell function