Hypoglycaemia

Question 1

Define hypoglycaemia.

Answer 1

Plasma glucose:

<4mmol/L in adults

<3.5mmol/L in diabetics

<2.5mmol/L in paediatrics

Normal range: 4.0-5.4mmol/L fasting, 4.0-7.8mmol/L 2 hour OGTT

Question 2

What are the causes of hypoglycaemia in a non-diabetic patient?

Answer 2

In non-diabetics you must EXPLAIN mechanism:

EXogenous drugs, eg insulin, oral hypoglycaemics? access through diabetic in the family? Body-builders may misuse insulin to help stamina. Also: alcohol, eg a binge with no food; aspirin poisoning; ACE-i; β‎-blockers; pentamidine; quinine sulfate; aminoglutethamide; insulin-like growth factor.

Pituitary insufficiency.

Liver failure, plus some rare inherited enzyme defects.

Addison’s disease.

Islet cell tumours (insulinoma) and immune hypoglycaemia (eg anti-insulin receptor antibodies in Hodgkin’s disease).

Non-pancreatic neoplasms, eg fibrosarcomas and haemangiopericytomas.

From pathology:

• Critically unwell
• Organ failure
• Hyperinsulinism
• Post-gastric bypass
• Drugs
• Extreme weight loss
• Factitious (i.e. an artefact)

Question 3

What are the causes of hyperinsulinaemia?

Answer 3

Causes:

• Drugs (sulphonylureas)
• Islet cell tumours (e.g. insulinoma)
• Islet cell hyperplasia

Question 4

Summarise the causes of hypoglycaemia.

Answer 4

Question 5

What are the causes of hypoglycaemia when insulin is low and ketones are high?

Answer 5

• Alcohol
• Pituitary insufficiency
• Addison’s disease

Question 6

What is the cause of a post-prandial hypoglycaemia?

Answer 6

• Post gastric bypass
• Hereditary fructose intolerance
• Early diabetes
• Insulin-sensitive people post-exercise or post-large meal

Question 7

What is Whipple’s triad of hypoglycaemia?

Answer 7

1. Low glucose
2. Symptoms - adrenergic or neuroglycopaenic
3. Relief of symptoms upon treatment

Definition of hypoglycaemia.

Question 8

What is the pathophysiology of hypoglycaemia?

Answer 8

Order of physiological changes upon hypoglycaemia:

• (1) suppression of insulin
• (2) release of glucagon
• (3) release of adrenaline
• (4) release of cortisol

Counter-regulation of blood glucose (see right):

• These methods increase glucose, and so FFA as well
• FFAs enter beta-oxidation cycle to make ATP
• Excess FFAs can metabolise into ketone bodies

Question 9

What is the gold standard for glucose measurement?

Answer 9

Venous glucose - grey-top (fluoride oxalate) bottle

Other types :

Capillary glucose - POC test

Continuous glucose monitoring - small device, but not accurate below 2.2mmol/L

Question 10

What are the most common causes of hypoglycaemia in diabetics?

Answer 10

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

Other:

• Co-existing renal/liver failure alters drug clearance - reduces the doses needed - e.g. sulfonylureas accumulate
• Concurrent Addison’s - hypoglycaemia (polyglandular autoimmune syndrome)
• Poor awareness of hypos

Question 11

Which diabetic medications cause hypoglycaemia?

Answer 11

• Oral Hypoglycaemics:
  
  • Sulphonylureas
  • Meglitinides
  • GLP-1 agents
• Insulin
  
  • Rapid acting with meals
  • Long acting
• Other drugs
  
  • Beta-blockers
  • Salicylates
  • Alcohol (inhibits lipolysis)

Question 12

What investigations should be done to diagnose the cause of hypoglycaemia?

Answer 12

• Insulin levels (exogenous insulin interferes with assays)
• C-peptide
• Drug screen
• Autoantibodies
• Cortisol/GH
• FFAs/blood ketones
• Lactate
• Other specialist tests (e.g. IGFBP, IGF-2, carnitine)

Question 13

What is the half life of C peptide?

Answer 13

30mins

Question 14

What are the causes of hypoinsulinaemic hypoglycaemia?

Answer 14

• Fasting/starvation
• Strenuous exercise
• Critical illness
• Endocrine deficiencies (i.e. hypopituitarism, adrenal failure)
• Liver failure
• Anorexia nervosa

Hypoinsulinaemic = something other than insulin is causing the hypo

Question 15

Why does IGF-2 release in paraneoplastic syndrome cause hypoglycaemia and low FFA?

Answer 15

Big IGF-2 binds to IGF-1 receptors and insulin receptors

So endogenous insulin production is switched off and FFA production is suppressed

Caused by mesenchymal (mesothelioma/fibroblastoma) or epithelial tumours (carcinoma)

Question 16

In what type of diabetes do these occur?

1. Hypoketotic hyperglycaemia
2. Hyperketotic hyperglycaemia

Answer 16

1. Hypoketotic hyperglycaemia - HHS/HONK (T2DM)
2. Hyperketotic hyperglycaemia - DKA (T1DM)

Question 17

How can autoimmune disorders cause hypoglycaemia?

Answer 17

1. Antibodies against insulin R;
   
   • Usually presents with insulin resistance but may sometimes present with hypoglycaemia
2. Antibodies against insulin (= autoimmune insulin syndrome)
   
   • Sudden dissociation of these Ab from insulin may precipitate hypoglycaemia
   • Can be caused by drugs (hydralazine, procainamide)

Question 18

How can autoimmune disorders cause hypoglycaemia?

Answer 18

1. Antibodies against insulin R;
   
   • Usually presents with insulin resistance but may sometimes present with hypoglycaemia
2. Antibodies against insulin (= autoimmune insulin syndrome)
   
   • Sudden dissociation of these Ab from insulin may precipitate hypoglycaemia
   • Can be caused by drugs (hydralazine, procainamide)

Question 19

How can autoimmune disorders cause hypoglycaemia?

Answer 19

1. Antibodies against insulin R;
   
   • Usually presents with insulin resistance but may sometimes present with hypoglycaemia
2. Antibodies against insulin (= autoimmune insulin syndrome)
   
   • Sudden dissociation of these Ab from insulin may precipitate hypoglycaemia
   • Can be caused by drugs (hydralazine, procainamide)

Question 20

How can autoimmune disorders cause hypoglycaemia?

Answer 20

1. Antibodies against insulin R;
   
   • Usually presents with insulin resistance but may sometimes present with hypoglycaemia
2. Antibodies against insulin (= autoimmune insulin syndrome)
   
   • Sudden dissociation of these Ab from insulin may precipitate hypoglycaemia
   • Can be caused by drugs (hydralazine, procainamide)

Question 21

What is the management of hypoglycaemia?

Answer 21