Hypoglycaemia Flashcards
Define hypoglycaemia.
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
What are the causes of hypoglycaemia in a non-diabetic patient?
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)
What are the causes of hyperinsulinaemia?
Causes:
- Drugs (sulphonylureas)
- Islet cell tumours (e.g. insulinoma)
- Islet cell hyperplasia
Summarise the causes of hypoglycaemia.
What are the causes of hypoglycaemia when insulin is low and ketones are high?
- Alcohol
- Pituitary insufficiency
- Addison’s disease
What is the cause of a post-prandial hypoglycaemia?
- Post gastric bypass
- Hereditary fructose intolerance
- Early diabetes
- Insulin-sensitive people post-exercise or post-large meal
What is Whipple’s triad of hypoglycaemia?
- Low glucose
- Symptoms - adrenergic or neuroglycopaenic
- Relief of symptoms upon treatment
Definition of hypoglycaemia.
What is the pathophysiology of hypoglycaemia?
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
What is the gold standard for glucose measurement?
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
What are the most common causes of hypoglycaemia in diabetics?
- 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
Which diabetic medications cause hypoglycaemia?
- Oral Hypoglycaemics:
- Sulphonylureas
- Meglitinides
- GLP-1 agents
-
Insulin
- Rapid acting with meals
- Long acting
- Other drugs
- Beta-blockers
- Salicylates
- Alcohol (inhibits lipolysis)
What investigations should be done to diagnose the cause of hypoglycaemia?
- 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)
What is the half life of C peptide?
30mins
What are the causes of hypoinsulinaemic hypoglycaemia?
- 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
Why does IGF-2 release in paraneoplastic syndrome cause hypoglycaemia and low FFA?
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)
What is the management of hypoglycaemia?
