Chemical Pathology 16 - Hypoglycaemia

Question 1

How should hypoglycaemia be managed if the patient is alert and oriented?

Answer 1

Juice(short acting)and a sandwich (longer acting)
Continuous monitoring and treat cause

Question 2

How should hypoglycaemia be managed if the patient is drowsy, but not unconscious?

Answer 2

Bucchal glucose (this bypasses 1st pass metabolism)
Continuous monitoring and treat cause

eg hypostop/glucogel

**start thinking about IV access incase

Question 3

How should hypoglycaemia be managed if the patient is unconscious or has a reduced swallow reflex?

Answer 3

IV glucose 20%
Continuous monitoring and treat cause

Question 4

If the patient si deteriorating/refractory to oral/IV glucose what can you give?

Answer 4

IM/SC 1mg glucagon

Question 5

What is the definition of hypoglycaemia?

Answer 5

Whipple’s triad

1) Glucose level
- <4mmol/L
- <3.5 in diabetcs

<2.5 in neonates (confirm)

2) symptoms
a) neuroglycopenic
b) adrenergic
c) asymptomatic
3) relief of symptoms with glucose

Question 6

What are the possible symptoms of hypoglycaemia?

Answer 6

Adrenergic symptoms - tremors and sweating
Neuroglycopaenic symptoms - somnolence and confusion
None - in some type 1 diabetic

Question 7

What is the body’s physiological response to hypoglycaemia, and which of these responses if the first?

Answer 7

1st - reduced insulin

2nd: release of glucagon by alpha cells in the pancreas

3rd: hypothalamus detects hypoglycaemia–>release of ACTH and GH from anterior pituitary

i.e. pancreas responds first then the hypothalamus/pituitary axis

Question 8

Recall the effects of glucagon

Answer 8

Directly:
1. Decreases peripheral glucose uptake
2. Increases glycogenolysis
3. Increases gluconeogenesis in the liver and kidneys
4. Increases lipolysis
This then leads to:
1. Increased glucose
2. Inceased free fatty acids
Fatty acids undergo beta oxidation –> ketones

Question 9

What is the best measure of glucose?

Answer 9

Venous glucose (way better than capillary)

**in grey top tube in lab**

Question 10

What is the commonest cause of hypoglycaemia?

Answer 10

Diabetes

Question 11

Recall 5 differentials for the cause of hypoglycaemia in diabetic patients

Answer 11

1. Medications
   e. g. insulin, gliclazide (sulfonylurea), GLP1 analogues such as liraglutide/semaglutide

*also beta blockers - impaired hypoglycaemia awareness

2. Inadequate CHO intake (T1D especially)
3. Impaired awareness (eg EtOH)
4. Exercise
5. Co-existing renal/liver failure, autoimmune conditions like addison’s

Question 12

Recall 6 differentials for the cause of hypoglycaemia in a NON-diabetic patient

Answer 12

1. Critically unwell pt
2. Organ failure
3. Hyperinsulinism
4. Drugs
5. Extreme weight loss
6. Factitious
7. REACTIVE HYPOGLYCAEMIA (post-prandial)- sugar spike and crash - can signifiy early T2DM

Question 13

What class of drug is gliclazide?

Answer 13

Sulphonylurea

Question 14

Which 2 classes of oral diabetic drug are most likely to cause a hypo?

Answer 14

Sulphonylureas (eg gliclazide)
GLP-1 agents

Question 15

Recall 3 non-diabetes drugs that can cause a hypo

Answer 15

Beta blockers (impair adrenergic response so have impaired awareness of symptoms)
Salicylates - impair regulation of glucose
Alcohol

Question 16

In a neonate with hypoglycaemia but no ketones, what is the likely diagnosis?

Answer 16

Inborn error of fatty acid metabolism

hypoketotic hypoglycaemia - e.g. MCAD deficiency

Question 17

Recall 3 possible causes of hyperinsulinaemic hypoglycaemia

Answer 17

high c peptide (endogenous)

1. Insulinoma (islet cel tumour)
2. Drugs- GLP1 and sulfonylurea - these stimulate endogenous insulin production
3. Islet cell hyperplasia

low c-peptide (exogenous)

Basc taking too much insulin

**before you diagnosie an insulinoma, you need to do a SULFONYLUREA drug screen to make sure that they are not abusing sulfonylureas**

Question 18

Recall 3 causes of islet cell hyperplasia in the neonate

Answer 18

1. Infant of a diabetic mother
2. Beckworth Wiedmann syndrome - hypogluycaemia, hyperinsulinism/high insulin (congenital overgrowth syndrome)
3. Nesidioblastosis - hyperplasia of insulin-producing islet B-cells–>overproduction of insulin

Question 19

How can non-islet cell tumours cause hypoglycaemia?

Answer 19

This is a RARE case - most likely to occur in mesothelioma/ carcinoma of the lung
These tumours secrete ‘big IGF-2’ (paraneoplastic syndrome) which binds to both IGF-1 and insulin receptors
In this case, insulin and C peptide will both be low

Question 20

What are the 4 first basic biochemical tests that should be done in hypoglycaemia investigation?

Answer 20

1. Glucose
2. Insulin
3. C peptide
4. Drug screen

Question 21

Recall 5 advanced biochemical tests that can be used in investigating a hypoglycaemia

Answer 21

Ketones and FFAs
IGF studies
Ammonia
Lactate
Inborn error of metabolism screen

Question 22

What is the best measure of inuslin?

Answer 22

C-peptide

*has a longer half life than insulin and also is a better marker of endogenous insulin production*

Question 23

Causes of hypoinsulinaemic hypoglycaemia

Answer 23

+ also non-islet cell tumour (see explanation in diff flashcard)

Question 24

In hypoinsulinaemic hypoglycaemia, if you see LOW KETONES what does that signifyt?

Answer 24

FATTY ACID OXIDATION DEFECT

because usually when you have hypoglycaemia–>low insulin–>increased fatty acid metabolism –> increased FFAs

**esp in neonates**