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ChemPath: Hypoglycaemia Flashcards

1
Q

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
A
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2
Q

What should be considered if a hypoglycaemic patient is deteriorating or does not appear to be responding to the first step in their management?

A

IM/SC 1 mg glucagon

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3
Q

What is the benefit of giving glucose sublingually?

A

Bypasses hepatic first-pass metabolism

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4
Q

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

A

15-20 mins

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5
Q

Which group of patients may not respond to IM glucagon?

A

Patients with poor liver glycogen stores
* Starving
* Anorexic
* Hepatic failure

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6
Q

What are some possible consequences of extravasation of IV dextrose?

A
  • Irritation
  • Phlebitis
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7
Q

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

A
  • Low glucose
  • Symptoms
  • Relief of symptoms by administration of glucose
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8
Q

List some symptoms of hypoglycaemia.

A

Adrenergic:
* Tremors
* Palpitations
* Sweating
* Hunger

Neuroglycopaenic:
* Confusion
* Drowsiness
* Loss of coordination
* Coma
* Seizures

(Sometimes patients may be asymptomatic)

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9
Q

What is a consequence of recurrent episodes of hypoglycaemia?

A

Hypoglycaemia unawareness (loss of adrenergic symptoms with hypoglycaemia)

Typically affects people on insulin - recurrent hypos

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10
Q

Describe the order in which hormonal compensatory changes in response to hypoglycaemia take place.

A
  • Suppression of insulin
  • Release of glucagon
  • Release of catecholamines
  • Release of cortisol
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11
Q

What are the effects of decreased insulin and increased glucagon?

A
  1. Reduce peripheral uptake of glucose
  2. increase gluconeogenesis
  3. increase glycogenolysis
  4. increase lipolysis - FFA and ketone generation
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12
Q

What is the most common cause of hypoglycaemia?

A

Insulin-induced in diabetics

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13
Q

List some causes of hypoglycaemia in people without diabetes.

A
  • Fasting
  • Paediatric
  • Critically unwell
  • Organ failure
    • Gluconeogenesis occurs in the kidneys
    • Liver stores glycogen
  • Hyperinsulinism
  • Post-gastric bypass
  • Drugs
  • Extreme weight loss
  • Factitious (artefact)
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14
Q

List some causes of hypoglycaemia in diabetics.

A
  • Medications (inappropriate insulin)
  • Inadequate carbohydrate intake (missed meal)
  • Impaired awareness - alcohol
  • Illness and infection
  • Strenous exercise
  • Co-existing autoimmune conditions
    • eg. Addisons
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15
Q

List some diabetic medications that can causes hypoglycaemia.

A
  • Insulin
  • Oral hypoglycaemics: sulphonylureas, meglinitides, GLP-1 analogues
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16
Q

List some non-diabetic medications that can cause hypoglycaemia.

A
  • Beta-blockers
  • Salicylates
  • Alcohol (inhibits lipolysis)
17
Q

How could co-morbidities in a diabetic patient lead to increased risk of hypoglycaemia?

A
  • Renal/liver failure could lead to impaired drug clearance
  • Concurrent Addison’s disease could result in hypoglycaemia (polyglandular autoimmune syndrome)
18
Q

What is continous glucose monitoring?

A

The device is applied to the abdominal wall with a small cannula that sits in the interstitial space in the subcutaneous fat

19
Q

Why might continuous blood glucose monitoring be useful?

A

Can identify patients who suffer from recurrent hypoglycaemia or nocturnal hypoglycaemia

20
Q

What is the main issue with continoues glucose monitoring?

A

The sensor does not accurately read blood glucose when < 2.2. mmol/L

21
Q

What is C-peptide?

A

Cleavage product of proinsulin - proinsulin is cleaved to form active insulin and C-peptide

22
Q

List some biochemical tests that may help differentiate between causes of hypoglycaemia.

A
  • 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)
Thorough history and examination just as important

23
Q

Which two biochemical tests are used to classify hypoglycaemia? What are these 3 types of hypoglycaemia?

A

Blood insulin and C-peptide levels

  1. hypoinsulinaemic hypoglycaemia
  2. hyperinsulinaemic hypoglycaemia
  3. exogenous hypoglycaemia
24
Q

Describe insulin and C-peptide levels in:
1. hypoinsulinaemic hypoglycaemia
2. hyperinsulinaemic hypoglycaemia
3. exogenous hypoglycaemia

A
  1. low insulin, low C-peptide
  2. high insulin, high C-peptide
  3. high insulin, low C-peptide
25
Q

What would you expect the insulin and C-peptide levels to be in a hypoglycaemic patient who has anorexia nervosa but not diabetes?

A
  • Low insulin and low C-peptide - normal response to hypoglycaemia
  • The patient is hypoglycaemic because of poor liver glycogen stores (not an issue with insulin) so their insulin response will be normal
26
Q

List some causes of Hypoinsulinaemic hypoglycaemia.

A
  • Fasting/starvation
  • Strenous exercise
  • Critical illness
  • Endocrine deficiencies (adrenal failure, hypopituitarism)
  • Liver and kidney failure
  • Psychiatric (anorexia nervosa)

NOTE: this is a normal response to hypoglycaemia

27
Q

Name 3 ketone bodies.

A
  • 3-hydroxybutyrate
  • Acetone
  • Acetoacetate
28
Q

List some causes of neonatal hypoglycaemia.

A
  • Prematurity
  • IUGR
  • Maternal gestational diabetes
  • Inadequate glycogen/fat stores

NOTE: this should improve with feeding

29
Q

What would neonatal hypoglcaemia with raised FFA and low ketones suggest?

A

Inborn errors of metabolism
* Medium-chain acyl-CoA dehydrogenase deficiency
* Carnitine disorders

30
Q

List some tests that may be useful in the investigation of neonatal hypoglycaemia.

A
  • Insulin/C-peptide
  • FFA
  • Ketones
  • Lactate
  • LFTs (deranged in MCAD and carnitine disorders)
31
Q

List some causes of neonatal hypoglycaemia with low FFAs and low ketones.

A
  • Hyperinsulinism
  • Hypopituitarism
32
Q

List some causes of neonatal hypoglycaemia with high FFAs and high ketones.

A
  • Galactosaemia
  • Glycogen storage disease
  • Neonatal haemochromatosis
  • GH deficiency
  • Glucocorticoid deficiency
  • Septicaemia
33
Q

List some causes of hyperinsulinaemic hypoglycaemia

A
  • Islet cell tumours (eg. insulinoma)
  • Sulphonylurea overdose
  • Islet cell hyperplasia
    • Infant with diabetic mother
    • Beckwith-Wiedemann syndrome (overgrowth disorder)
    • Nesidioblastosis (excessive function of beta cells with abnormal microscopic appearance)
  • Rare genetic and autoimmune causes
34
Q

State two causes of hyperinsulinaemic hypoglycaemia with a high C-peptide and how would you differentiate between the two?

A
  • Insulinoma
  • Sulphonylurea abuse

Differentiate with urine/serum sulphonylurea screen (required for insulinoma diagnosis)

35
Q

Describe the mechanism by which beta cells release insulin in response to blood glucose.

A
  • 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
36
Q

Describe the mechanism of action of sulphonylureas.

A

They bind to the ATP-sensitive K+ channel making it close independently of ATP

37
Q

What are insulinomas and how are they diagnosed and treated?

A
  • Small solitary adenomas (10% malignant, 8% associated with MEN1)
  • Diagnosis based on biochemistry and imaging
  • Treated vis surgical resection
38
Q

What can cause the following: low glucose, low insulin, low C-peptide, low FFAs and low ketones?

A
  • 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)
39
Q

What is reactive hypoglycaemia and what are some causes?

A

Hypoglycaemia following food intake (post-prandial). Causes include:
* Gastric bypass surgery
* Early diabetes
* Insulin-sensitive individuals after exercise or large meals
* Hereditary fructose intolerance

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