ChemPath: Hypoglycaemia Flashcards
Outline the first step in the management of hypoglycaemia patients in the following states:
- Alert and orientated
- Drowsy/confused but swallow intact
- Unconscious or concerned about swallow
- Alert and orientated
- Oral carbohydrates (e.g. juice/sweets or long-acting forms such as a sandwich)
- Drowsy/confused but swallow intact
- Buccal glucose (e.g. glucogel)
- Unconscious or concerned about swallow
- IV 50 mL 50% glucose
- NOTE: or 100 mL 20% glucose
What should be considered if a hypoglycaemic patient is deteriorating or does not appear to be responding to the first step in their management?
IM/SC 1 mg glucagon
What is the benefit of giving buccal glucose?
Bypasses hepatic first-pass metabolism
How long is it likely to take for IM glucagon to cause an increase in blood glucose?
15-20 mins
Which group of patients may not respond to IM glucagon?
- Starving
- Anorexic
- Hepatic failure
- These patients will have poor liver glycogen stores that can be accessed by glucagon
What are some possible consequences of extravasation of IV dextrose?
- Irritation
- Phlebitis
Describe the triad of features that is used to define hypoglycaemia.
- Low glucose
- Symptoms
- Relief of symptoms by administration of glucose
List some symptoms of hypoglycaemia.
- Adrenergic: tremors, palpitations, sweating
- Neuroglycopaenic: confusion, coma
What is a consequence of recurrent episodes of hypoglycaemia?
Hypoglycaemia unawareness (loss of adrenergic symptoms with hypoglycaemia)
what blood glucose is hypoglycaemic
<4mmol
Describe the order in which physiological compensatory changes in response to hypoglycaemia take place.
- Suppression of insulin
- Release of glucagon
- Release of adrenaline
- Release of cortisol
What effect does response to hypoglycaemia have on blood glucose and FFA production?
- Increases blood glucose
- Increases FFAs (from lipolysis)
- FFAs –> beta oxidation –> generate ATP - side product is ketone bodies
What investigation may need to be performed to demonstrate hypoglycaemia in an otherwise healthy person?
Prolonged fast
What is the gold standard for measuring blood glucose?
Lab (venous) glucose
NOTE: this is collected in a grey top container that has fluoride oxalate
What is the disadvantage of using a blood glucose meter?
Measures capillary blood glucose - Poor precision at low levels
NOTE: however, it does produce an instant results
List some causes of hypoglycaemia in people without diabetes.
- Fasting
- Paediatric
- Critically unwell
- Organ failure
- Hyperinsulinism
- Post-gastric bypass
- Drugs
- Extreme weight loss
- Factitious (artefact)
List some causes of hypoglycaemia in diabetics.
- Medications (inappropriate insulin)
- Inadequate carbohydrate intake (missed meal)
- Impaired awareness
- Excessive alcohol
- Strenous exercise
- Co-existing autoimmune conditions
List some diabetic medications that can causes hypoglycaemia.
- Oral hypoglycaemics: sulphonylureas, meglitinides, GLP1 analogues
- Insulin
List some non-diabetic medications that can cause hypoglycaemia.
- Beta-blockers - will prevent adrenergic symptoms of hypos, so people don’t know if they having a hypo
- Salicylates
- Alcohol
How could co-morbidities in a diabetic patient lead to increased risk of hypoglycaemia?
- Renal/liver failure could lead to impaired drug clearance - so needs reduction in dose
- Concurrent Addison’s disease could result in hypoglycaemia (polyglandular autoimmune syndrome) - rare
What is continous glucose monitoring?
The device is applied to the abdominal wall with a small cannula that sits in the interstitial space in the subcutaneous fat
What is the main issue with continoues glucose monitoring?
The sensor does not accurately read blood glucose when < 2.2. mmol/L
List some biochemical tests that may help differentiate between causes of hypoglycaemia.
- 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
NOTE: it is important to perform these tests at the time of the hypo (but try not to delay treatment)
why do we measure C-peptide
cleavage product of pro-insulin
What would you expect the insulin and C-peptide levels to be in a hypoglycaemic patient who has anorexia nervosa but not diabetes?
- 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 low and no glycogenolysis can occur
List some causes of Hypoinsulinaemic hypoglycaemia.
- Fasting/starvation
- Strenous exercise
- Critical illness
- Endocrine deficiencies (adrenal failure, hypopituitarism)
- Liver failure - can’t store glycogen
- Anorexia nervosa
NOTE: this is a normal response to hypoglycaemia
What does hypoglycaemia with a high insulin and low C-peptide suggest?
Exogenous insulin is responsible for the hypoglycaemia
Name 3 ketone bodies.
- 3-hydroxybutyrate
- Acetone
- Acetoacetate
What does hypoglycaemia with high FFAs and low ketones suggest?
Fatty acid oxidation defect
Lipolysis occurs when low insulin
List some physiologically explicable causes of neonatal hypoglycaemia.
- Prematurity
- IUGR
- Small for gestational age
- Inadequate glycogen/fat stores
NOTE: this should improve with feeding
What is a pathological cause of neonatal hypoglycaemia?
Inborn errors of metabolism
List some tests that may be useful in the investigation of neonatal hypoglycaemia.
- Insulin/C-peptide
- FFA
- Ketone bodies
- Lactate
- Hepatomegaly
List some causes of neonatal hypoglycaemia with high FFAs and low ketones.
- Fatty acid oxidation defects
- MCAD deficiency
- Carnitine disorders
- HMG-CoA lyase deficiency
- GSD type 1 (gluconeogentic disorder)
List some causes of neonatal hypoglycaemia with low FFAs and low ketones.
- Hyperinsulinism
- Hypopituitarism
List some causes of neonatal hypoglycaemia with high FFAs and high ketones.
- Galactosaemia
- Glycogen storage disease
- Neonatal haemochromatosis
- GH deficiency
- Glucocorticoid deficiency
- Septicaemia
List some causes of inappropriately high insulin levels in hypoglycaemia.
- Islet cell tumours (eg. 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)
glucose is low but insulin is high
State two causes of Hyperinsulinaemic hypoglycaemia with a high C-peptide.
- Insulinoma
- Sulphonylurea abuse
What test could help differentiate between causes of hyperinsulinaemic hypoglycaemia with a high c petide?
Urine or serum sulphonylureas
need to have a -ve sulphonlyurea screen to have insulinoma
what is diagnostic investigation for insulilnoma
72-hour fast
They release insulin periodically –> not having hypos all the time
Describe the mechanism by which beta cells release insulin in response to blood glucose.
- 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
Describe the mechanism of action of sulphonylureas.
They bind to the ATP-sensitive K+ channel making it close independently of ATP
(happens even when there is low glucose)
Leads to insulin exocytosis + release
What proportion of insulinomas are malignant?
10%
what genetic disease is assciated with insulinoma
MEN1
State two causes of Hyperinsulinaemic hypoglycaemia with a low C-peptide.
- Factitious result
- Oral hypoglycaemic usage (not sulphonylureas)
What can cause the following: low glucose, low insulin, low C-peptide, low FFAs and low ketones?
- This suggests that something is pretending to be insulin
- This is non-islet cell tumour 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)
Describe two autoimmune causes of hypoglycaemia.
- 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) - seen in Japan
What is reactive hypoglycaemia?
- Hypoglycaemia following food intake (post-prandial)
- Can occur after gastric bypass
- May be suggestive of early diabetes
- May occur in insulin-sensitive individuals after exercise or large meals
- May be due to hereditary fructose intolerance
