Diabetic hypoglycemia

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

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

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

Level 3 (severe): no defined blood glucose. A severe event with no defined blood glucose, characterized by altered mental and/or physical status requiring assistance for treatment of hypoglycemia.[1][3][4][17]
Level 2 (clinically significant; also referred to as clinically important or serious): blood glucose <54 mg/dL (<3.0 mmol/L). This is usually the threshold at which neuroglycopenic symptoms occur, but bear in mind that symptoms of hypoglycemia 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 hypoglycemia may not present with typical signs and symptoms of hypoglycemia.[3]
Level 1 (alert value): blood glucose <70 mg/dL (<3.9 mmol/L) and ≥54 mg/dL (≥3.0 mmol/L). Advise the patient that this value should alert them to the possibility of developing level 2 hypoglycemia 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 hypoglycemia 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) hypoglycemia 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 hypoglycemia, which can be categorized as:
- Neuroglycopenic:
  - Irritability[3]
  - Confusion or problems with short-term memory[1][3]
  - Changes in vision or speech[1][77]
  - Difficulty hearing[1]
  - Lethargy or drowsiness[1][77]
  - Behavioral changes[1]
  - Headache[1]
  - Difficulty concentrating[1]
  - Dizziness[77]
- Sympathoadrenal:
  - Shakiness[1][3][77]
  - Sweating[1][77]
  - Tremor[1][77]
  - Palpitations[1][77]
  - Tachycardia[3]
  - Feeling warm[77]
  - Anxiety[77]
  - Nausea[1]
  - Hunger[1][77]
  - Pallor[1]
A fall or motor vehicle accident.[3]
- These can occur due to reduced consciousness level as a result of hypoglycemia.[78] In these scenarios, always ascertain the preceding events or precipitants that led to the fall or accident.[78] This is key to identify because hypoglycemia that causes unconsciousness needs to be addressed to avoid future catastrophes.[78]

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

Note that:

Signs and symptoms of hypoglycemia 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 54-61 mg/dL (3.0 to 3.4 mmol/L).[79] However, in people with diabetes and chronic recurrent hypoglycemia, symptoms may occur at a lower blood glucose (and at a higher blood glucose in people with diabetes and chronic hyperglycemia).[1]
- Neuroglycopenic signs and symptoms typically occur at blood glucose of <54 mg/dL (<3.0 mmol/L).[3] In children (particularly those ages <6 years in practice), these are more common than sympathoadrenal signs and symptoms.[1][80]
Behavioral changes such as irritability, agitation, quietness, and tantrums may be prominent in pre-school children.[1]
In children, always record severe hypoglycemia that has caused coma or seizure and required parenteral treatment as "hypoglycemic coma."[1] This scenario is a subset of severe hypoglycemia and should be recorded separately to other forms of severe hypoglycemia because of the increased risk of repeated severe events.[1]

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

Beta-blockers may also reduce symptoms of hypoglycemia in some patients. The neuroglycopenic response to hypoglycemia is sympathoadrenal in nature, which can be masked by beta-blockers.[61][81] However, sweating remains unmasked and this may be the only symptom of hypoglycemia.[47]

History

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

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

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

Antidiabetic drugs. Certain antidiabetic drugs increase the risk of hypoglycemia compared with others, including:
- Insulin.[3] Determine the timing of the insulin regimen and peak insulin action in relation to the timing of hypoglycemia.[1] For instance:[47]
  - Bolus insulin used with meals typically causes postprandial hypoglycemia
  - Basal insulin typically causes fasting or preprandial hypoglycemia, but can cause hypoglycemia at other times (e.g., during increased activity or missed meals)
  - Bolus and basal insulin may cause hypoglycemia in fasting and fed states, but this is less common.
- Sulfonylureas[17][44]
- Meglitinides[17][45]
Beta-blockers[41]
- These can mask the symptoms and signs of hypoglycemia, which can predispose patients to severe, life-threatening hypoglycemia.[61] Nonselective beta-blockers can also impair hepatic and renal release of glucose into the circulation, which can cause hypoglycemia.[41]

Many other drugs (e.g., certain antibiotics [particularly sulfonamides and fluoroquinolones], quinine, pentamidine, indomethacin) have been linked to hypoglycemia in patients without diabetes, but the evidence is unclear as to whether they cause hypoglycemia in patients with diabetes.[41] This list of drugs is not exhaustive, and you should consult a drug formulary for more information.

Identify any other risk factors for hypoglycemia in patients who have diabetes, in order to determine their risk of future episodes, and to minimize the occurrence of these. These include:

Type 1 diabetes[1][2][3]
Extremes of age (adults >60 years and young children)[1][2][3][4]
Poor glycemic control[48][49]
Intensive glycemic control efforts (low [<6%] or high [>9%] HbA1c levels)[3][48][49]
Increased duration of diabetes[2][4][15][17]
Treatment with insulin >5 years[2][4][17]
Impaired cognitive function[3][48][55]
Impaired awareness of hypoglycemia[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][62][63]
Liver dysfunction[17][64]
Endocrine disorders (e.g., adrenal insufficiency, hypothyroidism, celiac disease)[14][65]
Critical illness (e.g., sepsis)[41][82]
Alcohol ingestion.[1][3][4][17][37]

In addition, be aware that patients are at particular risk of severe or asymptomatic hypoglycemia during sleep (nocturnal hypoglycemia) because sleep impairs the counterregulatory hormone response to hypoglycemia.[1] Suspect nocturnal hypoglycemia 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 hypoglycemia, 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 hypoglycemia.

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

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

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

Level 3 (severe): no defined blood glucose. A severe event characterized by altered mental and/or physical status requiring assistance for treatment of hypoglycemia.[1][3][4][17]
Level 2 (clinically significant; also referred to as clinically important or serious): blood glucose <54 mg/dL (<3.0 mmol/L). This is usually the threshold at which neuroglycopenic symptoms occur, but bear in mind that symptoms of hypoglycemia 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 hypoglycemia may not present with typical signs and symptoms of hypoglycemia.[3]
Level 1 (alert value): blood glucose <70 mg/dL (<3.9 mmol/L) and ≥54 mg/dL (≥3.0 mmol/L). Advise the patient that this value should alert them to the possibility of developing level 2 hypoglycemia 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, nondiabetic causes of hypoglycemia. In practice, particularly suspect a nondiabetic cause of hypoglycemia if the episodes of hypoglycemia:

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 ketonemia
Are associated with risk factors for nondiabetic causes of hypoglycemia.

Other causes of nondiabetic hypoglycemia include:

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

For more information, see Differentials.