Outline the first step in the management of hypoglycaemia patients in the following states: 1. Alert and orientated 2. Drowsy/confused but swallow intact 3. Unconscious or concerned about swallow

1. Alert and orientated Oral sarbohydrates (e.g. juice/sweets or long-acting forms such as a sandwich) 2. Drowsy/confused but swallow intact Buccal glucose (e.g. glucogel) 3. Unconscious or concerned about swallow IV 50 mL 50% glucose NOTE: or 100 mL 20% glucose

ChemPath: Hypoglycaemia Flashcards by Sajed Mangoo

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 sarbohydrates (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

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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

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What is the benefit of giving glucose sublingually?

Bypasses hepatic first-pass metabolism

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

15-20 mins

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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

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What are some possible consequences of extravasation of IV dextrose?

Irritation
Phlebitis

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

Low glucose
Symptoms
Relief of symptoms by administration of glucose

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List some symptoms of hypoglycaemia.

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

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What is a consequence of recurrent episodes of hypoglycaemia?

Hypoglycaemia unawareness (loss of adrenergic symptoms with hypoglycaemia)

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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

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

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

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

Prolonged fast

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What is the gold standard for measuring blood glucose?

Lab glucose

NOTE: this is collected in a grey top container that has fluoride oxalate

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What is the disadvantage of using a blood glucose meter?

Poor prevision at low levels

NOTE: however, it does produce an instant results

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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)

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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

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List some diabetic medications that can causes hypoglycaemia.

Oral hypoglycaemics: sulphonylureas, meglitinides, GLP1 analogues
Insulin

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List some non-diabetic medications that can cause hypoglycaemia.

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

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)

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 normal

List some causes of Hypoinsulinaemic hypoglycaemia.

Fasting/starvation
Strenous exercise
Critical illness
Endocrine deficiencies (adrenal failure, hypopituitarism)
Liver failure
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

List some physiologically explicable causes of neonatal hypoglycaemia.

* Prematurity * IUGR * 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

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 neonates.

* 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)

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

* Insulinoma * Sulphonylurea abuse

What test could help differentiate between these two causes?

Urine or serum sulphonylureas

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

What proportion of insulinomas are malignant?

10%

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 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)

List some genetic causes of hypoglycaemia.

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

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