Diabetes Mellitus

Question 1

What is the overall problem in diabetes mellitus?

Answer 1

Glucose canot be moved from the blood into cells. This leads to high levels of glucose in the blood and not enough in the cells. Cells are starved of glucose and thus energy.

Question 2

How does the body control blood glucose?

Answer 2

The release of insulin and glucagon.

Insulin stimulates uptake of glucose

Glucagon stimulates release of glucose by breakdown of glycogen.

Question 3

Where is insulin and glucagon produced?

Answer 3

Islets of Langerhans

Insulin is produced by beta cells

Glucagon is produced by alpha cells

Question 4

How does insulin decrease the blood glucose?

Answer 4

1. Bind to insulin receptors on muscles and adipose tissue
2. Activation causes vesicles containing glucose transporters inside the cell to fuse with the cell membrane
3. Glucose can now enter through channels into the cell

Question 5

How does glucagon increase blood glucose?

Answer 5

1. Stimulates gluconeogenesis in the liver
2. Stimulates glycogenolysis in the liver

Question 6

What percentage of the population does diabetes mellitus affect?

Answer 6

10%

Question 7

What is the spread of type 1 and type 2 diabetes?

Answer 7

10% Type 1

90% Type 2

Question 8

What happens in diabetes mellitus type 1?

Answer 8

The body does not make enough insulin as beta cells are damage/ destroyed

• Type IV hypersensitivity
  
  • cell-mediated immune response
  • own T cells attack beta cells because of a genetic abnormality causing a loss of self tolerence.
• Less insulin = more in the blood

Question 9

What is the genetic abnormality in type 1 diabetes?

Answer 9

• Mutation in the human leukocyte antigen system
  
  • chromosome 6
  • encodes for the MHC which is important for recognising foreign molecules and for self tolerence.
• HLA-DR3 and HLA-DR4 are common genes associated with type 1
  
  • not all people with these genes will go on the develop diabetes

Question 10

What is the onset of type 1 diabetes?

Answer 10

• Early
• 90% of beta cells are destroyed ebfore symtpoms crop up

Question 11

What are the symtpoms of type 1 diabetes?

Answer 11

• Polyphagia - feeling of hunger
  
  • cells are not getting enough energy
• Glycosuria - glucose in the urine
  
  • too much glucose in the blood cannot be filtered out by kidneys
• Polyuria - increase in urination
  
  • glucose is osmotically active so water follows it
• Polydipsia - dehydration/ thirst
  
  • more glucose = more peeing = less water retention = dehydration

Question 12

What is the treatment of type 1 diabetes mellitus?

Answer 12

Lifelong insulin therapy

• muscle and adipose tissue still have receptors to respond to insulin
• enables cells to uptake glucose

Question 13

What is a serious complication with type 1 diabetes mellitus?

Answer 13

Diabetic ketoacidosis (DKA)

• Lipolysis occurs to generate energy
  
  • fats are broken down into free fatty acids
• liver turns the fatty acids in ketone bodies
  
  • acetoacetic acid and beta-hydroxybutyric acid
• Cells can use fatty acids for energy but the acidity of the blood increases

Question 14

What are the effects of diabetic ketoacidosis on the body?

Answer 14

• Kussmaul respiration
  
  • deep, laboured breathing to reduce CO₂ in the blood = reduced acidity
• Hyperkalaemia
  
  • more protons from acidity enter cells through a H⁺/K⁺ co transporter
  • insulin also normally stimulates the sodium-potassium pump to uptake K⁺
  • overall potassium stores run low
• High anion gap
  
  • large difference in unmeasured ions from ketoacid build up

Question 15

What are the symptoms of diabetic ketoacidosis?

Answer 15

• Fruity breath
• nausea
• vomiting
• mental status changes
• cerebral oedema

Question 16

When can dibabetic ketoacidosis occur?

Answer 16

Occurs even when pt is on insulin therapy

• Stress (infection)
  
  • release adrenaline which stimulates glucagon release
  • increase in blood glucose

Question 17

What is the treatment of a DKA episode?

Answer 17

Reversal of acidosis:

• Fluids
  
  • for dehydration
• Insulin
  
  • lowers blood glucose levels
• Electrolytes

Question 18

What is the mechanism of type 2 diabetes?

Answer 18

The body makes insulin but cells do not respond to it.

• not fully understood by vesicles containing glucose transporters do not move to the cell membrane
• cells display insulin resistance

Question 19

What are the risk factors for type 2 diabetes?

Answer 19

• Obesity
  
  • excess of fat = release of FFA and adipokines (singalling molecules)
  • both cause inflammation which is linked to insulin resistance
• Lack of exercise
• Hypertension
• Genetics
  
  • having a twin with T2DM increases the chance of diabetes regardless of other factors.

Question 20

How do beta cells try to overcome insulin resistance?

Answer 20

Hyperplasia (increased numbers) and hypertrophy (growth in size) of beta cells to release more insulin.

• Increase insulin levels works for the body initally
  
  • insulin levels higher than normal keeps normoglycaemia.
• HOWEVER: beta cells also produce islet amyloid polypeptide (amylin).
  
  • hyperplasia and hypertrophy of beta cells = more amylin
  • leads to amyloid aggregates in the islets over time

The increased work load for beta cells eventually leads to hypotrophy and hypoplasia

Question 21

When does hyperglycaemia arise in type 2 diabetes?

Answer 21

After beta cells have undergone hypoplasia and hypotrophy, insulin levels reduce leading to hyperglycaemia. Sypmtoms of diabetes arise at this point.

Question 22

What are the symptoms of type 2 diabetes?

Answer 22

• Polyuria
• Polydipsia
• Polyphagia
• Glycosuria

Still remains some circulating insulin (unlike type 1) so DKA does not develop.

• Hyperosmolar hyperglycaemia state (HHS)

Question 23

What is HHS?