Hypoglycaemia

Question 1

1. Outline the first step in the management of hypoglycaemic patients in the following states:
   a. Alert and orientated
   b. Drowsy/confused but swallow intact
   c. Unconscious or concerned about swallow

Answer 1

a. Alert and orientated
Oral carbohydrates (e.g. juice/sweets or long-acting forms such as a sandwich)
b. Drowsy/confused but swallow intact
Buccal glucose (e.g. glucogel)
c. Unconscious or concerned about swallow
IV 50 mL 50% glucose
NOTE: or 100 mL 20% glucose

Question 2

2. What should be considered if a hypoglycaemic patient is deteriorating or does not appear to be responding to the first step in their management?

Answer 2

IM/SC 1 mg glucagon

Question 3

3. What is the benefit of giving glucose sublingually?

Answer 3

Bypasses hepatic first-pass metabolism

Question 4

4. How long is it likely to take for IM glucagon to cause an increase in blood glucose?

Answer 4

15-20 mins

Question 5

5. Which group of patients may not respond to IM glucagon?

Answer 5

Starving
Anorexic
Hepatic failure
These patients will have poor liver glycogen stores that can be accessed by glucagon

Question 6

7. Describe the triad of features that is used to define hypoglycaemia.

Answer 6

Low glucose
Symptoms
Relief of symptoms by administration of glucose

Question 7

8. List some symptoms of hypoglycaemia.

Answer 7

Adrenergic: tremors, palpitations, sweating
Neuroglycopaenic: confusion, coma

Question 8

9. What is a consequence of recurrent episodes of hypoglycaemia?

Answer 8

Hypoglycaemia awareness (loss of adrenergic symptoms with hypoglycaemia)

Question 9

10. Describe the order in which physiological compensatory changes in response to hypoglycaemia take place.

Answer 9

Suppression of insulin
Release of glucagon
Release of adrenaline
Release of cortisol

Question 10

11. What effect do these measures have on blood glucose and FFA production?

Answer 10

Increases blood glucose
Increases FFAs
Not all FFAs can be used to generate ATP by beta-oxidation so some of them will become ketone bodies

Question 11

12. What investigation may need to be performed to demonstrate hypoglycaemia in an otherwise healthy person?

Answer 11

Prolonged fast

Question 12

15. List some causes of hypoglycaemia in people without diabetes.

Answer 12

Fasting 
Paediatric
Critically unwell
Organ failure 
Hyperinsulinism
Post-gastric bypass 
Drugs 
Extreme weight loss 
Factitious (artefact)

Question 13

16. List some causes of hypoglycaemia in diabetics.

Answer 13

Medications (inappropriate insulin)
Inadequate carbohydrate intake (missed meal)
Impaired awareness
Excessive alcohol 
Strenuous exercise 
Co-existing autoimmune conditions

Question 14

17. List some diabetic medications that can cause hypoglycaemia.

Answer 14

Oral hypoglycaemics: sulphonylureas, meglitinides, GLP1 analogues
Insulin

Question 15

18. List some non-diabetic medications that can cause hypoglycaemia.

Answer 15

Beta-blockers
Salicylates
Alcohol

Question 16

19. How could co-morbidities in a diabetic patient lead to increased risk of hypoglycaemia?

Answer 16

Renal/liver failure could lead to impaired drug clearance

Concurrent Addison’s disease could result in hypoglycaemia (polyglandular autoimmune syndrome)

Question 17

20. What is continuous glucose monitoring?

Answer 17

The device is applied to the abdominal wall with a small cannula that sits in the interstitial space in the subcutaneous fat

The sensor does not accurately read blood glucose when < 2.2 mmol/L

Question 18

22. List some biochemical tests that may help differentiate between causes of hypoglycaemia.

Answer 18

Insulin levels (NOTE: exogenous insulin can interfere with assays)
C-peptide (marker of endogenous insulin production)
Drug screen
Autoantibodies
Cortisol/GH
Free fatty acids/ketone bodies
Lactate

Question 19

23. What would you expect the insulin and C-peptide levels to be in a hypoglycaemic patient who has anorexia nervosa but not diabetes?

Answer 19

Low insulin and low C-peptide
The patient is hypoglycaemic because of poor liver glycogen stores (not an issue with insulin) so their insulin response will be normal

Question 20

24. List some causes of Hypoinsulinaemic hypoglycaemia.

Answer 20

Fasting/starvation
Strenuous exercise
Critical illness
Endocrine deficiencies (adrenal failure, hypopituitarism)
Liver failure
Anorexia nervosa
NOTE: this is a normal response to hypoglycaemia

Question 21

26. Name 3 ketone bodies.

Answer 21

3-hydroxybutyrate
Acetone
Acetoacetate

Question 22

27. What does hypoglycaemia with high FFAs and low ketones suggest?

Answer 22

Fatty acid oxidation defect

Question 23

28. List some physiologically explicable causes of neonatal hypoglycaemia.

Answer 23

Prematurity
IUGR
Inadequate glycogen/fat stores
NOTE: this should improve with feeding

Question 24

30. List some tests that may be useful in the investigation of neonatal hypoglycaemia.

Answer 24

Insulin/C-peptide
FFA 
Ketone bodies 
Lactate 
Hepatomegaly

Question 25

31. List some causes of neonatal hypoglycaemia with high FFAs and low ketones.

Answer 25

``` Fatty acid oxidation defects MCAD deficiency Carnitine disorders HMG-CoA lyase deficiency GSD type 1 ```

Question 26

32. List some causes of neonatal hypoglycaemia with low FFAs and low ketones.

Answer 26

Hyperinsulinism | Hypopituitarism

Question 27

33. List some causes of neonatal hypoglycaemia with high FFAs and high ketones.

Answer 27

``` Galactosaemia Glycogen storage disease Neonatal haemochromatosis GH deficiency Glucocorticoid deficiency Septicaemia ```

Question 28

34. List some causes of inappropriately high insulin levels in neonates.

Answer 28

Islet cell tumours (e.g. insulinoma) Drugs (e.g. insulin, sulphonylureas) Islet cell hyperplasia • Infant with diabetic mother • Beckwith-Wiedemann syndrome (overgrowth disorder) • Nesidioblastosis (excessive function of beta cells with abnormal microscopic appearance)

Question 29

35. State two causes of Hyperinsulinaemic hypoglycaemia with a high C-peptide.

Answer 29

Insulinoma Sulphonylurea abuse DOURINE OR SERUM SULPHONYLUREAS

Question 30

37. Describe the mechanism by which beta cells release insulin in response to blood glucose.

Answer 30

Glucose crosses the membrane of beta cells and enters glycolysis via glucokinase Glycolysis produces ATP The rise in ATP leads to the closure of ATP-sensitive K+ channels This leads to membrane depolarisation, calcium influx and insulin exocytosis

Question 31

38. Describe the mechanism of action of sulphonylureas.

Answer 31

They bind to the ATP-sensitive K+ channel making it close independently of ATP

Question 32

41. What can cause the following: low glucose, low insulin, low C-peptide, low FFAs and low ketones?

Answer 32

This suggests that something is pretending to be insulin This is non-islet cell hypoglycaemia caused by secretion of big IGF-2 Big IGF-2 binds to IGF-1 receptors and insulin receptors It behaves like insulin, so it causes hypoglycaemia and suppresses insulin and FFA/ketone production It is a paraneoplastic syndrome usually caused by mesenchymal tumours (e.g. mesothelioma, fibroblastoma) and epithelial tumours (carcinoma)

Question 33

42. Describe two autoimmune causes of hypoglycaemia.

Answer 33

Autoimmune conditions – antibodies against insulin receptors can cause insulin resistance and hypoglycaemia (rarely) Autoimmune insulin syndrome – antibodies are directed towards insulin so sudden dissociation of the antibodies can precipitate hypoglycaemia (could be caused by drugs e.g. hydralazine, procainamide)

Question 34

43. List some genetic causes of hypoglycaemia.

Answer 34

``` Glucokinase activating mutation Congenital hyperinsulinism (GLUD-1, HNF4A, HADH, KNJJ11) ```