Diabetes

Question 1

What are the 5 actions of insulin?

Answer 1

Glucose:
1. Dec HGO
2. Inc muscle uptake

Protein:
3. Dec preoteolysis

Fat:
4. Dec lipolysis
5. Dec ketogenesis

Question 2

What are GLUT-4 proteins?

Answer 2

Glucose transporter protein
- high in myocytes and adipocytes
- highly insulin-responsive —> GLUT-4 vesicles fuse
with plasma membrane
- inc glucose intake x7

Question 3

How does insulin act on myocytes? (4)

Answer 3

1. Inc glucose uptake

Dec gluconeogenesis:
2. Dec amino acid production (protein breakdown)
3. Dec uptake of oxygen
4. Inc protein synthesis (dec amino acids)

Question 4

Which hormones act on myocytes during hypoglycaemia? (2)

Answer 4

1. Glucagon —> dec glucose uptake
2. GH —> dec glucose uptake
   —> inc protein breakdown to amino acids
3. IGF-1 —> inc protein breakdown to amino acids
   - inc gluconeogenesis

Question 5

How does insulin act on hepatocytes? (4)

Answer 5

Dec HPO:
1. Dec gluconeogenesis
2. Inc protein synthesis (dec amino acids)
3. Dec ketogenesis
4. Inc glycogenesis

Question 6

Which hormones act on hepatocytes during hypoglycaemia? (2)

Answer 6

1. Glucagon —> inc gluconeogenesis
   —> inc protein breakdown to amino acids
   —> inc ketogenesis
   —> inc glycogenolysis
2. Cortisol —> inc gluconeogenesis
   - inc HPO

Question 7

How does insulin act on adipocytes? (4)

Answer 7

Inc lipid stores:
1. Inc LPL (lipoprotein lipase) —> more triglyceride
breakdown in capillaries —> inc lipid intake
2. Inc triglyceride formation in cells
3. Inc glucose uptake
4. Dec triglyceride breakdown in cells —> dec lipid exit

Question 8

Which hormones act on adipocytes during hypoglycaemia? (2)

Answer 8

1. GH —> inc triglyceride breakdown in cells
2. Cortisol —> inc triglyceride breakdown
   - inc glycerol and NEFA out for gluconeogenesis +
   ketogenesis

Question 9

Where is insulin secreted to and why?

Answer 9

Hepatic portal system
- act on liver very quickly

Question 10

Where is insulin injected in diabetics and why?

Answer 10

Adipose tissue —> slow absorption —> gradual rise in blood glucose

Question 11

Which organ is glucose essential for and why?

Answer 11

Brain
- main energy source (+ partially ketone bodies)
- fatty acids can’t cross blood brain barrier

Question 12

How does diabetes affect ketone body production?

Answer 12

Dec insulin response —> dec glucose uptake —> inc ketone body production for brain
- see high sugar + high ketones in blood (unusual)

Question 13

What are the main differences between the fasted vs fed state?

Answer 13

Fasted:
- blood —> low insulin : glucagon
—> [glucose] 3.0-5.5 mmol/L
—> [NEFA] inc
—> [amino acid] inc (prolongued fasting)
- myocytes —> inc proteinolysis
—> uses lipids (β-ox)
- hepatocytes - inc HPO
—> inc gluconeogenesis
—> inc glycogenolysis
—> inc ketogenesis
- adipocytes —> inc lipolysis

Fed:
- blood —> high insulin : glucagon
- 1st and 2nd phase insulin release
- myocytes —> dec proteinolysis
—> inc protein synthesis
- hepatocytes - dec HPO
—> dec gluconeogenesis
—> inc glycogenesis
- adipocytes —> inc lipogenesis

Question 14

How is diabetes diagnosed? (7)

Answer 14

2 positive tests/ 1 positive tests + symptoms

1. Fasting glucose >6.9 mmol/L
2. Random glucose >11.1 mmol/L
3. Oral glucose tolerance test
   
   • take fasting glucose
   • give 75g glucose load
   • take blood glucose after 2 hours
4. HbA1c >48 mmol/mol

T1DM:
5. Antibodies —> GAD
—> IA2
6. C-peptide
7. Blood ketones

Question 15

What is T1DM?

Answer 15

Autoimmune condition —> insulin deficiency

Question 16

What is diabetic ketoacidosis?

Question 17

What are the 4 symptoms of T1DM?

Answer 17

1. Weight loss
2. Hyperglycaemia
3. Glycosuria —> polyuria
   —> nocturia
   —> polydipsia
   —> polydipsia
4. Ketones in blood and urine —> diabetic
   ketoacidosis

Question 18

How is T1DM treated and what is the main associated complication?

Answer 18

Exogenous insulin (basal-bolus regime)
+ self-monitoring of glucose levels, diet
- too much insulin —> hypoglycaemia
- too little insulin —> hyperglycaemia

Question 19

How does the body prevent hypoglycaemia?

Answer 19

Counterregulatory response:
- inc glucagon, cortisol, GH, catecholamines
- recurrent hypoglycaemia —> lose counterregulatory
response —> impaired awareness of hypoglycaemia

Question 20

What are the symptoms of hypoglycaemia?

Answer 20

Autonomic:
1. Sweating
2. Pallor —> pale
3. Palpitations
4. Shaking

Neuroglycopenic:
5. Slurred speech
6. Poor vision
7. Confusion
8. Seizures
9. Loss of consciousness

Severe hypoglycaemia = need 3rd party assistance
- 1mg glucagon 1M injection

Question 21

What is T2DM?

Answer 21

Prolongued hyperglycaemia —> insulin resistance
- still enough for ketogenesis and proteolysis

Question 22

What are the symptoms of T2DM?

Answer 22

1. Hyperglycaemia
2. Overweight —> inc waist circumference
3. Dyslipidaemia (high cholesterol)
4. Complications —> eyes (leading cause of blindness)
   —> renal
   —> foot
   —> brain (stroke)
   —> heart + vessels
   —> nerves
5. May develop insulin deficiency

Question 23

Which pathways are affected by insulin resistance?

Answer 23

Inc insulin secretion (try to counteract resistance)
1. MAPK —> inc growth and proliferation
- when in blood vessels —> hypertension
2. PI3K-Akt —> inc metabolic actions

Question 24

What are the 6 risk factors of T2DM?

Answer 24

1. Age
2. High BMI
3. Ethnicity
4. PCOS
5. Family history
6. Inactivity

Question 25

How is T2DM managed?

Answer 25

Diet —> dec calories
—> dec fat
—> dec refined carbs
—> inc complex carbs
—> dec Na
—> inc fibre
Meds

Question 26

Which 4 complications must be monitored for in diabetes?

Answer 26

1. Retinopathy
2. Neuropathy
3. Nephropathy
4. Cardiovascular