Diabetic hypoglycaemia

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Consider diabetic hypoglycaemia in a patient with diabetes who has any symptoms or signs of hypoglycaemia, which includes neuroglycopenic and sympathoadrenal signs and symptoms, or if they present following a fall or motor vehicle accident.[1][3] Diabetic hypoglycaemia is confirmed if finger stick measurement of blood glucose is <3.9 mmol/L (<70 mg/dL).[1][3][4]

Severity of diabetic hypoglycaemia is classified as follows:[1][3][4]

Level 3 (severe): no defined blood glucose. A severe event with no defined blood glucose, characterised by altered mental and/or physical status requiring assistance for treatment of hypoglycaemia.[1][3][4][17]
Level 2 (clinically significant; also referred to as clinically important or serious): blood glucose <3.0 mmol/L (<54 mg/dL). This is usually the threshold at which neuroglycopenic symptoms occur, but bear in mind that symptoms of hypoglycaemia usually occur at a higher blood glucose level in children than in adults.[1][3][17] In addition, be aware that a patient with impaired awareness of hypoglycaemia may not present with typical signs and symptoms of hypoglycaemia.[3]
Level 1 (alert value): blood glucose <3.9 mmol/L (<70 mg/dL) and ≥3.0 mmol/L (≥54 mg/dL). Advise the patient that this value should alert them to the possibility of developing level 2 hypoglycaemia and can be used as a threshold to take appropriate actions to prevent this (e.g., carbohydrate ingestion, adjusting medication).[1][5][17]

Clinical presentation

Suspect diabetic hypoglycaemia if a patient with diabetes presents with:

Life-threatening alterations in mental and/or physical functioning.[1][3][4][17] These indicate severe (level 3) hypoglycaemia if they require assistance from another person for recovery, and can include or progress to:[1][3]
- Seizure
- Loss of consciousness
- Coma
- Death
Any typical signs and symptoms of hypoglycaemia, which can be categorised as:
- Neuroglycopenic:
  - Irritability[3]
  - Confusion or problems with short-term memory[1][3]
  - Changes in vision or speech[1][78]
  - Difficulty hearing[1]
  - Lethargy or drowsiness[1][78]
  - Behavioural changes[1]
  - Headache[1]
  - Difficulty concentrating[1]
  - Dizziness[78]
- Sympathoadrenal:
  - Shakiness[1][3][78]
  - Sweating[1][78]
  - Tremor[1][78]
  - Palpitations[1][78]
  - Tachycardia[3]
  - Feeling warm[78]
  - Anxiety[78]
  - Nausea[1]
  - Hunger[1][78]
  - Pallor[1]
A fall or motor vehicle accident.[3]
- These can occur due to reduced consciousness level as a result of hypoglycaemia.[79] In these scenarios, always ascertain the preceding events or precipitants that led to the fall or accident.[79] This is key to identify because hypoglycaemia that causes unconsciousness needs to be addressed to avoid future catastrophes.[79]

Other features include a higher blood glucose than usual when waking up, and bedwetting.

Note that:

Signs and symptoms of hypoglycaemia usually occur at a higher blood glucose level in children than in adults.[1]
- Sympathoadrenal signs and symptoms typically occur before neuroglycopenic symptoms in both children and adults.[1]
- In people without diabetes, sympathoadrenal symptoms may occur from a blood glucose of 3.0 to 3.4 mmol/L (54-61 mg/dL).[80] However, in people with diabetes and chronic recurrent hypoglycaemia, symptoms may occur at a lower blood glucose (and at a higher blood glucose in people with diabetes and chronic hyperglycaemia).[1]
- Neuroglycopenic signs and symptoms typically occur at blood glucose of <3.0 mmol/L (<54 mg/dL).[3] In children (particularly those aged <6 years in practice), these are more common than sympathoadrenal signs and symptoms.[1][81]
Behavioural changes such as irritability, agitation, quietness, and tantrums may be prominent in pre-school children.[1]
In children, always record severe hypoglycaemia that has caused coma or seizure and required parenteral treatment as 'hypoglycaemic coma'.[1] This scenario is a subset of severe hypoglycaemia and should be recorded separately to other forms of severe hypoglycaemia because of the increased risk of repeated severe events.[1]

However, be aware that some patients may not present with typical symptoms of hypoglycaemia, particularly if they have impaired awareness of hypoglycaemia.[1][3] Patients with impaired awareness of hypoglycaemia are at risk of severe (level 3) hypoglycaemia.[4]

Beta-blockers may also reduce symptoms of hypoglycaemia in some patients. The neuroglycopenic response to hypoglycaemia is sympathoadrenal in nature, which can be masked by beta-blockers.[63][82] However, sweating remains unmasked and this may be the only symptom of hypoglycaemia.[48]

History

Take a careful history to identify any risk factors for diabetic hypoglycaemia.

Urgently check if the patient has had previous episodes of level 2 and/or level 3 hypoglycaemia, in order to intervene quickly and prevent further episodes.[3] Patients with previous level 3 hypoglycaemia are at particularly increased risk of further episodes of hypoglycaemia.[4][17] See Diagnostic criteria.

Include in your history any medication the patient is taking that may increase the risk of hypoglycaemia. These include:

Antidiabetic drugs. Certain antidiabetic drugs increase the risk of hypoglycaemia compared with others, including:
- Insulin.[3] Determine the timing of the insulin regimen and peak insulin action in relation to the timing of hypoglycaemia.[1] For instance:[48]
  - Bolus insulin used with meals typically causes postprandial hypoglycaemia
  - Basal insulin typically causes fasting or preprandial hypoglycaemia, but can cause hypoglycaemia at other times (e.g., during increased activity or missed meals)
  - Bolus and basal insulin may cause hypoglycaemia in fasting and fed states, but this is less common.
- Sulfonylureas[17][45]
- Meglitinides[17][46]
Beta-blockers[42]
- These can mask the symptoms and signs of hypoglycaemia, which can predispose patients to severe, life-threatening hypoglycaemia.[63] Non-selective beta-blockers can also impair hepatic and renal release of glucose into the circulation, which can cause hypoglycaemia.[42]

Many other drugs (e.g., certain antibiotics [particularly sulfonamides and fluoroquinolones], quinine, pentamidine, indometacin) have been linked to hypoglycaemia in patients without diabetes, but the evidence is unclear as to whether they cause hypoglycaemia in patients with diabetes.[42] This list of drugs is not exhaustive, and you should consult a drug formulary for more information.

Identify any other risk factors for hypoglycaemia in patients who have diabetes, in order to determine their risk of future episodes, and to minimise the occurrence of these.[3] These include:

Type 1 diabetes[1][2][3]
Extremes of age (adults >60 years and young children)[1][2][3][4]
Poor glycaemic control[49][50]
Intensive glycaemic control efforts (low [<6%] or high [>9%] HbA1c levels)[3][49]
Increased duration of diabetes[2][4][15][17]
Treatment with insulin >5 years[2][4][17]
Impaired cognitive function[3][49][56]
Impaired awareness of hypoglycaemia[1][2][3]
First trimester of pregnancy[2][4][20][21][22][23][24][25][26]
Failure to thrive in children
Poor oral intake (e.g., if there is food insecurity or reduced intake of carbohydrates), weight loss, or malnutrition
Exercise[1][3][4][37]
Renal impairment (e.g., chronic kidney disease, acute kidney injury)[17][64][65]
Liver dysfunction[17][66]
Endocrine disorders (e.g., adrenal insufficiency, hypothyroidism, coeliac disease)[14][67]
Critical illness (e.g., sepsis)[42][83]
Alcohol ingestion.[1][3][4][17][37]

In addition, be aware that patients are at particular risk of severe or asymptomatic hypoglycaemia during sleep (nocturnal hypoglycaemia) because sleep impairs the counter-regulatory hormone response to hypoglycaemia.[1] Suspect nocturnal hypoglycaemia if the patient has any of:[1]

Low pre-breakfast blood glucose
Episodes of confusion, nightmares, or seizures at night
Impaired thinking, altered mood, or headaches when waking up in the morning.

Investigations

Blood glucose

Urgently carry out a blood glucose level for any patient with suspected diabetic hypoglycaemia, which is a finger stick test that is performed at the bedside or in an outpatient setting. In practice, if finger stick testing is not available, start treatment if the patient has typical symptoms and signs of hypoglycaemia.

Confirm diabetic hypoglycaemia if blood glucose is <3.9 mmol/L (<70 mg/dL).[1][3][4]

In clinical practice, this is used as the clinical alert or threshold value that should prompt treatment for hypoglycaemia in diabetes to prevent a further fall in blood glucose.[1][2][3] However, be aware that hypoglycaemia is defined as any fall in blood glucose that exposes a patient to potential harm as there is no single numerical definition of hypoglycaemia for all patients and situations.[1]
Suspect nocturnal hypoglycaemia if the patient's pre-breakfast blood glucose is low.[1]

Take appropriate action according to the severity of the hypoglycaemia.[3][4] Start immediate treatment for any patient with clinically significant (level 2) or severe (level 3) hypoglycaemia.[3] Severity of diabetic hypoglycaemia is classified as follows:[1][3][4]

Level 3 (severe): no defined blood glucose. A severe event characterised by altered mental and/or physical status requiring assistance for treatment of hypoglycaemia.[1][3][4][17]
Level 2 (clinically significant; also referred to as clinically important or serious): blood glucose <3.0 mmol/L (<54 mg/dL). This is usually the threshold at which neuroglycopenic symptoms occur, but bear in mind that symptoms of hypoglycaemia usually occur at a higher blood glucose level in children than in adults.[1][3][17] In addition, be aware that a patient with impaired awareness of hypoglycaemia may not present with typical signs and symptoms of hypoglycaemia.[3]
Level 1 (alert value): blood glucose <3.9 mmol/L (<70 mg/dL) and ≥3.0 mmol/L (≥54 mg/dL). Advise the patient that this value should alert them to the possibility of developing level 2 hypoglycaemia and can be used as a threshold to take appropriate actions to prevent this (e.g., carbohydrate ingestion, adjusting medication).[1][5][17]

Exclusion of other causes

Always consider other, non-diabetic causes of hypoglycaemia. In practice, particularly suspect a non-diabetic cause of hypoglycaemia if the episodes of hypoglycaemia:

Cannot be related to timing of insulin injections, increased activity, or reduced carbohydrate intake
Persist despite changes of insulin doses
Are associated with ketonuria or ketonaemia
Are associated with risk factors for non-diabetic causes of hypoglycaemia.

Other causes of non-diabetic hypoglycaemia include:

Non-diabetic drugs
Liver or renal failure
Sepsis
Adrenal, thyroid, or pituitary dysfunction[17]
Malnutrition.

For more information, see Differentials.