History and exam
Your Organisational Guidance
ebpracticenet urges you to prioritise the following organisational guidance:
Beleid bij acute hypoglykemie met verminderd bewustzijnPublished by: Werkgroep Ontwikkeling Richtlijnen Eerste Lijn (Worel)Last published: 2022La prise en charge de l’hypoglycémie aiguë chez un patient présentant une diminution de la consciencePublished by: Groupe de Travail Développement de recommmandations de première ligneLast published: 2022Key diagnostic factors
common
known diabetes
Suspect diabetic hypoglycaemia if a person with diabetes presents with life-threatening alterations in mental and/or physical functioning, typical neuroglycopenic or sympathoadrenal symptoms of hypoglycaemia, or following a fall or motor accident.[1][3] Hypoglycaemia occurs most commonly in people with type 1 diabetes, but can also occur in people with type 2 diabetes, particularly those treated with insulin or insulin secretagogues (sulfonylureas and meglitinides).[1][2][8][9][17]
presence of risk factors
Identify any risk factors for hypoglycaemia in people who have diabetes, in order to determine their risk of future episodes, and to minimise the occurrence of these.[3] The most strongly associated risk factors include: type 1 diabetes; treatment with insulin, sulfonylureas, or meglitinides; extremes of age (aged <6 years or ≥75 years); sub-optimal glycaemic control (low [<6%] or high [>9%] HbA1c levels) and high glycaemic variability; intensive glycaemic control efforts; previous severe (level 3) or clinically significant (level 2) hypoglycaemia; increased duration of diabetes; treatment with insulin >5 years; impaired cognitive function; impaired awareness of hypoglycaemia; first trimester of pregnancy; failure to thrive in children; poor oral intake (e.g., if there is food insecurity, reduced intake of carbohydrates, or the patient is fasting), weight loss, or malnutrition; end-stage kidney disease; and socio-economic deprivation.[1][2][3][4][17]
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]
Other diagnostic factors
common
irritability
Typical neuroglycopenic symptom of hypoglycaemia.[3] Neuroglycopenic symptoms usually occur at a blood glucose of <3.0 mmol/L (<54 mg/dL) and are more common than sympathoadrenal symptoms in children.[1][3][83] Bear in mind that signs and symptoms of hypoglycaemia usually occur at a higher blood glucose level in children than in adults.[1]
shakiness
Typical sympathoadrenal symptom of hypoglycaemia.[1][3] Sympathoadrenal symptoms usually occur before neuroglycopenic symptoms.[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).[82] 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]
sweating
Typical sympathoadrenal symptom of hypoglycaemia.[1][3] Sympathoadrenal symptoms usually occur before neuroglycopenic signs.[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).[82] 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]
tremor
Typical sympathoadrenal symptom of hypoglycaemia.[1][80] Sympathoadrenal symptoms usually occur before neuroglycopenic symptoms.[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).[82] 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]
palpitations
Typical sympathoadrenal symptom of hypoglycaemia.[1][80] Sympathoadrenal symptoms usually occur before neuroglycopenic symptoms.[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).[82] 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]
tachycardia
Typical sympathoadrenal symptom of hypoglycaemia.[3] Sympathoadrenal symptoms usually occur before neuroglycopenic symptoms.[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).[82] 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]
feeling warm
Typical sympathoadrenal symptom of hypoglycaemia.[80] Sympathoadrenal symptoms usually occur before neuroglycopenic symptoms.[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).[82] 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]
anxiety
Typical sympathoadrenal symptom of hypoglycaemia.[80] Suspect nocturnal hypoglycaemia if the patient experiences altered mood when waking up.[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).[82] 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]
nausea
Typical sympathoadrenal symptom of hypoglycaemia.[1] Sympathoadrenal symptoms usually occur before neuroglycopenic symptoms.[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).[82] 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]
hunger
Typical sympathoadrenal symptom of hypoglycaemia.[1][80] Sympathoadrenal symptoms usually occur before neuroglycopenic symptoms.[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).[82] 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]
pallor
Typical sympathoadrenal symptom of hypoglycaemia.[1] Sympathoadrenal symptoms usually occur before neuroglycopenic symptoms.[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).[82] 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]
higher blood glucose than usual on waking up
Can be a feature of hypoglycaemia.
uncommon
seizure
A sign of severe (level 3) hypoglycaemia (characterised by altered mental and/or physical status requiring the intervention of another person to actively administer carbohydrates or glucagon, or take other corrective actions).[3][4][5][17] In practice, severe hypoglycaemia usually occurs when blood glucose is 1.9 to 2.2 mmol/L (35-40 mg/dL).
Suspect nocturnal hypoglycaemia if the patient experiences seizures at night.[1]
loss of consciousness
A sign of severe (level 3) hypoglycaemia (characterised by altered mental and/or physical status requiring the intervention of another person to actively administer carbohydrates or glucagon, or take other corrective actions).[3][4][5][17] In practice, severe hypoglycaemia usually occurs when blood glucose is 1.9 to 2.2 mmol/L (35-40 mg/dL). The patient may also present with a motor accident or fall due to reduced consciousness level.[3] In these scenarios, always ascertain preceding events or precipitants that led to the fall or accident. This is key to identify because hypoglycaemia that causes unconsciousness needs to be addressed to avoid future catastrophes.
coma
A sign of severe (level 3) hypoglycaemia (characterised by altered mental and/or physical status requiring the intervention of another person to actively administer carbohydrates or glucagon, or take other corrective actions).[3][4][5][17] In practice, severe hypoglycaemia usually occurs when blood glucose is 1.9 to 2.2 mmol/L (35-40 mg/dL).
confusion
Typical neuroglycopenic symptom of hypoglycaemia.[3] Suspect nocturnal hypoglycaemia if the patient experiences confusion during the night, or impaired thinking when waking up.[1] Neuroglycopenic symptoms usually occur at a blood glucose of around <3.0 mmol/L (<54 mg/dL) and are more common in children than sympathoadrenal symptoms.[1][3][83] Bear in mind that signs and symptoms of hypoglycaemia usually occur at a higher blood glucose level in children compared with adults.[1]
problems with short-term memory
Typical neuroglycopenic symptom of hypoglycaemia.[3] Neuroglycopenic symptoms usually occur at a blood glucose of around <3.0 mmol/L (<54 mg/dL) and are more common in children than sympathoadrenal symptoms.[1][3][83] Bear in mind that signs and symptoms of hypoglycaemia usually occur at a higher blood glucose level in children compared with adults.[1]
changes in vision
Typical neuroglycopenic symptom of hypoglycaemia.[1][80] Specifically, blurred or double vision and disturbed colour vision may be present.[1] Neuroglycopenic symptoms usually occur at a blood glucose of around <3.0 mmol/L (<54 mg/dL) and are more common in children than sympathoadrenal symptoms.[1][3][83] Bear in mind that signs and symptoms of hypoglycaemia usually occur at a higher blood glucose level in children compared with adults.[1]
changes in speech
Typical neuroglycopenic symptom of hypoglycaemia.[1] Specifically, slurred speech may be present.[1] Neuroglycopenic symptoms usually occur at a blood glucose of around <3.0 mmol/L (<54 mg/dL) and are more common in children than sympathoadrenal symptoms.[1][3][83] Bear in mind that signs and symptoms of hypoglycaemia usually occur at a higher blood glucose level in children compared with adults.[1]
difficulty hearing
Typical neuroglycopenic symptom of hypoglycaemia.[1] Neuroglycopenic symptoms usually occur at a blood glucose of around <3.0 mmol/L (<54 mg/dL) and are more common in children than sympathoadrenal symptoms.[1][3][83] Bear in mind that signs and symptoms of hypoglycaemia usually occur at a higher blood glucose level in children compared with adults.[1]
lethargy
Typical neuroglycopenic symptom of hypoglycaemia.[1][80] Neuroglycopenic symptoms usually occur at a blood glucose of around <3.0 mmol/L (<54 mg/dL) and are more common in children than sympathoadrenal symptoms.[1][3][83] Bear in mind that signs and symptoms of hypoglycaemia usually occur at a higher blood glucose level in children compared with adults.[1]
Suspect nocturnal hypoglycaemia if the patient experiences lethargy on waking up.[1]
drowsiness
Typical neuroglycopenic symptom of hypoglycaemia.[1] Neuroglycopenic symptoms usually occur at a blood glucose of around <3.0 mmol/L (<54 mg/dL) and are more common in children than sympathoadrenal symptoms.[1][3][83] Bear in mind that signs and symptoms of hypoglycaemia usually occur at a higher blood glucose level in children compared with adults.[1]
quietness
Typical neuroglycopenic symptom of hypoglycaemia.[1] Behavioural changes such as irritability, agitation, quietness, and tantrums may be prominent in young children.[1] Other features may include erratic behaviour.[1] Suspect nocturnal hypoglycaemia if the patient experiences nightmares at night.[1]
Neuroglycopenic symptoms usually occur at a blood glucose of around <3.0 mmol/L (<54 mg/dL) and are more common in children than sympathoadrenal symptoms.[1][3][83] Bear in mind that signs and symptoms of hypoglycaemia usually occur at a higher blood glucose level in children compared with adults.[1]
tantrums
Typical neuroglycopenic symptom of hypoglycaemia.[1] Behavioural changes such as irritability, agitation, quietness, and tantrums may be prominent in young children.[1] Other features may include erratic behaviour.[1] Suspect nocturnal hypoglycaemia if the patient experiences nightmares at night.[1]
Neuroglycopenic symptoms usually occur at a blood glucose of around <3.0 mmol/L (<54 mg/dL) and are more common in children than sympathoadrenal symptoms.[1][3][83] Bear in mind that signs and symptoms of hypoglycaemia usually occur at a higher blood glucose level in children compared with adults.[1]
erratic behaviour
Typical neuroglycopenic symptom of hypoglycaemia.[1] Behavioural changes such as irritability, agitation, quietness, and tantrums may be prominent in young children.[1] Other features may include erratic behaviour.[1] Suspect nocturnal hypoglycaemia if the patient experiences nightmares at night.[1]
Neuroglycopenic symptoms usually occur at a blood glucose of around <3.0 mmol/L (<54 mg/dL) and are more common in children than sympathoadrenal symptoms.[1][3][83] Bear in mind that signs and symptoms of hypoglycaemia usually occur at a higher blood glucose level in children compared with adults.[1]
nightmares
Typical neuroglycopenic symptom of hypoglycaemia.[1] Suspect nocturnal hypoglycaemia if the patient experiences nightmares at night.[1]
Neuroglycopenic symptoms usually occur at a blood glucose of around <3.0 mmol/L (<54 mg/dL) and are more common in children than sympathoadrenal symptoms.[1][3][83] Bear in mind that signs and symptoms of hypoglycaemia usually occur at a higher blood glucose level in children compared with adults.[1]
headache
Typical neuroglycopenic symptom of hypoglycaemia.[1] Suspect nocturnal hypoglycaemia if the patient experiences headache when waking up.[1]
Neuroglycopenic symptoms usually occur at a blood glucose of around <3.0 mmol/L (<54 mg/dL) and are more common in children than sympathoadrenal symptoms.[1][3][83] Bear in mind that signs and symptoms of hypoglycaemia usually occur at a higher blood glucose level in children compared with adults.[1]
difficulty concentrating
Typical neuroglycopenic symptom of hypoglycaemia.[1]
Neuroglycopenic symptoms usually occur at a blood glucose of around <3.0 mmol/L (<54 mg/dL) and are more common in children than sympathoadrenal symptoms.[1][3][83] Bear in mind that signs and symptoms of hypoglycaemia usually occur at a higher blood glucose level in children compared with adults.[1]
dizziness
Typical neuroglycopenic symptom of hypoglycaemia.[80] The patient may have an unsteady gait.[1]
Neuroglycopenic symptoms usually occur at a blood glucose of around <3.0 mmol/L (<54 mg/dL) and are more common in children than sympathoadrenal symptoms.[1][3][83] Bear in mind that signs and symptoms of hypoglycaemia usually occur at a higher blood glucose level in children compared with adults.[1]
fall or motor vehicle accident
Falls and motor vehicle accidents can occur due to reduced consciousness level as a result of hypoglycaemia.[81] Always ascertain the preceding events or precipitants that led to the fall or accident.[81] This is key to identify because hypoglycaemia that causes unconsciousness needs to be addressed to avoid future catastrophes.[81]
bedwetting
Can be a feature of hypoglycaemia.
Risk factors
strong
known diabetes
Hypoglycaemia occurs most commonly in people with type 1 diabetes.[1][2][8][9] However, be aware that hypoglycaemia can occur in people with type 2 diabetes due to treatment with insulin or insulin secretagogues (sulfonylureas and meglitinides).[1][2][8][9][17] The total number of hypoglycaemic events in insulin-treated people with type 2 diabetes may be comparable to, or even exceed, that seen in people with type 1 diabetes, a phenomenon attributed to the higher overall prevalence of type 2 diabetes.[2][10]
use of insulin or sulfonylureas or meglitinides
Treatment with insulin, sulfonylureas, or meglitinides increases the risk of hypoglycaemia compared with other glucose-lowering drugs.[3][4][17][44][45] Rates of hypoglycaemia are highest for individuals treated with intensive insulin therapy (including multiple daily injections of insulin, continuous subcutaneous insulin infusion, or automated insulin delivery systems), followed by basal insulin, followed by sulfonylureas or meglitinides.[3] Combining treatment with insulin and sulfonylureas further increases hypoglycaemia risk.[3]
If the patient is taking insulin, determine the timing of the insulin regimen and peak insulin action with the timing of hypoglycaemia.[1] For instance, bolus insulin used with meals typically causes post-prandial hypoglycaemia. Basal insulin typically causes fasting or pre-prandial 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 uncommon.[46]
In addition, an absolute or relative excess of insulin can lead to hypoglycaemia due to: errors when giving insulin (e.g., too much insulin used for correction of hyperglycemia, or wrong type or dose of insulin given); reduced carbohydrate intake or missed meals; exercise; or concurrent use of alcohol.[1]
age ≥75 years
Older adults, particularly those aged ≥75 years, have higher rates of hypoglycaemia than younger adults.[2][3][17] Older adults may have reduced ability to recognise symptoms of hypoglycaemia and communicate that they need assistance.[1][3] Minor episodes of hypoglycaemia frequently go unrecognised in older adults because they may present with non-specific symptoms such as brief episodes of lightheadedness or vertigo.
In older adults, there is an age-related decline in renal and hepatic function, which can potentiate the effects of glucose-lowering drugs such as sulfonylureas and insulin.[2] There may also be age-related impairment of counter-regulatory hormones such as glucagon and growth hormone.[2] Older patients also have an increase in comorbidities that may contribute to hypoglycaemia.[2]
age <6 years
suboptimal glycaemic control and high glycaemic variability
Suboptimal glycaemic control (both low and high HbA1c levels) and high glycaemic variability are strongly associated with increased risk of severe hypoglycaemia.[3][47] One retrospective study of over 1000 adults with type 2 diabetes looked at self-reported rates of severe hypoglycaemia at different HbA1c levels.[48] The relative risk of severe hypoglycaemia varied across different HbA1c ranges when compared to patients with HbA1c levels of 7% to 7.9%. Specifically, the risk was 1.25 (95% CI 0.99 to 1.57) for those with HbA1c <6%, 1.01 (95% CI 0.87 to 1.18) for HbA1c 6% to 6.9%, 0.99 (95% CI 0.82 to 1.20) for HbA1c 8% to 8.9%, and 1.16 (95% CI 0.97 to 1.38) for HbA1c ≥9%.[48] However, in young people (aged <18 years) with type 1 diabetes, low HbA1c is not a strong risk factor for hypoglycaemia.[1][49][50][51]
People with lower HbA1c levels are also at increased risk of nocturnal hypoglycaemia.[1]
intensive glycaemic control efforts
Adults with intensive glycaemic control (lower HbA1c target; in practice this varies, but is generally <7%) are at increased risk of severe hypoglycaemia versus those with less intensive glycaemic control (higher HbA1c target; generally ≥7% in practice).[3][52] The potential risk of hypoglycaemia often outweighs the benefit of intensive glycaemic control in those with long duration of diabetes, previous episodes of severe hypoglycaemia or hypoglycaemia unawareness, advanced microvascular or macrovascular complications, extensive comorbid conditions, older age, frailty, or limited life expectancy.[3]
previous level 2 or level 3 hypoglycaemia
Urgently identify if the person has had previous episodes of level 2 (clinically significant) or level 3 (severe) hypoglycaemia, in order to intervene quickly and prevent further episodes.[3] Recent episodes (in the preceding 3-6 months) indicate a high risk of future episodes.[3] Level 2 hypoglycaemia is defined by blood glucose <3.0 mmol/L (<54 mg/dL) with or without clinical symptoms.[3][4][5][17] Level 3 hypoglycaemia is characterised by altered mental and/or physical status requiring the intervention of another person to actively administer carbohydrates or glucagon, or take other corrective actions.[3][4][5][17] Repeated episodes of hypoglycaemia can cause impaired awareness of hypoglycaemia, which can in turn increase the risk of hypoglycaemia.[3][17]
increased duration of diabetes
A longer duration of diabetes is associated with an increased risk of hypoglycaemia relative to individuals with shorter disease duration.[2][4][15][17][53] In one study, 18.6% of patients with type 1 diabetes for ≥40 years had experienced an episode of severe hypoglycaemia within the last year.[53]
treatment with insulin >5 years
impaired cognitive function
Cognitive impairment is strongly associated with increased risk of severe hypoglycaemia.[3][47][54] People with cognitive impairment are at risk of hypoglycaemia because of reduced ability to recognise symptoms of hypoglycaemia and communicate that they need assistance.[54] They are also at risk of errors associated with insulin administration, which can lead to hypoglycaemia.
In addition, patients with diabetes who have episodes of hypoglycaemia are at increased risk of developing dementia compared to their counterparts who do not experience hypoglycaemia.[55]
impaired awareness of hypoglycaemia
Occurs when individuals no longer recognise the early signs and symptoms of low blood glucose. This condition often develops over time due to recurrent hypoglycaemia, which blunts the release of counter-regulatory hormones and diminishes the autonomic nervous system response to falling glucose levels.[2][3] As a result, patients may not perceive hypoglycaemia until glucose levels are dangerously low, significantly increasing the risk of severe events.[1][2][56][57]
It is important to determine at what blood glucose level the patient recognises hypoglycaemia, and what symptoms they experience.[1] To reduce this risk, careful insulin dose adjustments, patient education, and use of advanced glucose monitoring technologies such as continuous glucose monitoring (CGM) are essential. CGM can help detect early glucose declines and alert patients before severe hypoglycaemia occurs, even during sleep or when symptoms are absent. In patients with a history of long-term insulin use and recurrent hypoglycaemia, clinicians should reassess insulin regimens, reduce glycaemic targets temporarily, and consider incorporating CGM to improve safety and restore hypoglycaemia awareness.[3]
first trimester of pregnancy
Incidence of diabetic hypoglycaemia increases in early pregnancy, particularly around 10-15 weeks' gestation, in people with both type 1 and type 2 diabetes.[3][20][21][22][23] In pregnant women with pre-existing type 1 diabetes, severe hypoglycaemia occurs around 3 to 5 times more frequently in early pregnancy (but at lower incidence in the third trimester) than in the period before pregnancy.[2][24] Incidence rates of severe hypoglycaemia have been reported as being as high as 19% to 44% in pregnant women who are treated with intensive insulin therapy.[25]
Hypoglycaemia due to gestational diabetes is not covered in this topic.
failure to thrive in children
Decreases glycogen stores, which leads to hypoglycaemia.[58]
poor oral intake
Decreases glycogen stores, which leads to hypoglycaemia.[41][59] If the person is taking insulin, poor oral intake (e.g., if there is food insecurity or reduced intake of carbohydrates) or missed meals may result in a relative insulin excess, which can cause hypoglycaemia.[1] It is important to determine the timing and amount of carbohydrates in any recent food intake, and the peak glucose effect of recent food intake.[1]
weight loss
In insulin-treated patients or those taking insulin secretagogues (e.g., sulfonylureas), significant weight loss can reduce insulin resistance and overall insulin requirements, making previously appropriate doses excessive and increasing the risk of hypoglycaemia. This is especially common in individuals who lose weight rapidly due to dietary changes, bariatric surgery, glucagon-like peptide-1 (GLP-1) receptor agonist use, or illness, without corresponding adjustments in their drug regimen. If drug regimens are not adjusted accordingly, the risk of hypoglycaemia increases, especially when hepatic glycogen stores are depleted, further impairing the body's ability to recover from low glucose levels.[60] It is crucial to closely monitor both glucose levels and body weight, and to reassess insulin or oral hypoglycaemic agent doses during periods of weight change to avoid adverse events and maintain optimal diabetes management.
malnutrition
Malnutrition leads to depletion of glycogen stores, reduced gluconeogenesis, and impaired hormonal counterregulation, all of which compromise the body’s ability to maintain normal glucose levels, especially during fasting or stress.[41][59] In malnourished individuals, even short periods without food can precipitate hypoglycaemia, as the liver lacks the necessary substrates (such as amino acids and lactate) to produce glucose.[41][59] In people with diabetes, malnutrition further heightens hypoglycaemia risk, particularly when glucose-lowering therapies like insulin or sulfonylureas are not adjusted to match reduced caloric intake.
sleep
During sleep, people are at particular risk of severe or asymptomatic hypoglycaemia due to impaired counter-regulatory hormone responses.[1] Sleep blunts the release of hormones such as adrenaline, and reduces the likelihood of awakening in response to adrenergic symptoms like palpitations or sweating. As a result, falling glucose levels may go unnoticed, leading to prolonged hypoglycaemia, which can cause seizures, loss of consciousness, or, in rare cases, sudden death (a phenomenon sometimes referred to as the “dead-in-bed” syndrome in patients with type 1 diabetes). One 2010 study by the Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group reported frequent, prolonged nocturnal hypoglycaemia on 8.5% of nights in both children and adults, but more prolonged episodes in children.[61]
Suspect nocturnal hypoglycaemia if the patient has any of: low pre-breakfast blood glucose; episodes of confusion, nightmares, or seizures at night; or impaired thinking, altered mood, or headaches when waking up in the morning.[1]
Patients with hypoglycaemia unawareness, or a history of severe hypoglycaemia, are at the highest risk for nocturnal episodes. Continuous glucose monitoring (CGM) with low-glucose alerts and alarms is one of the most effective tools to prevent and detect night-time hypoglycaemia. Some CGM systems can even be integrated with insulin pumps to automatically suspend insulin delivery when glucose levels fall or are predicted to fall. Clinicians should evaluate night-time insulin dosing, bedtime snacks, and CGM data trends to reduce risk. Educating patients and carers about the importance of monitoring and recognising night-time hypoglycaemia symptoms (like morning headaches, fatigue, or night sweats) is also crucial for safer diabetes management.
fasting for religious or cultural reasons
Fasting may increase the risk for hypoglycaemia among individuals treated with insulin or insulin secretagogues if not properly planned for.[3]
socio-economic deprivation
Low-income status (includes factors associated with low income, such as living in a socio-economically deprived area), housing insecurity, underinsurance, and food insecurity are strongly associated with increased level 2 or 3 hypoglycaemia risk in patients with diabetes treated with insulin, sulfonylureas, or meglitinides.[3]
end-stage kidney disease
End-stage kidney disease (ESKD) is strongly associated with an increased risk for level 2 or 3 diabetic hypoglycaemia.[3][62] Chronic kidney disease causes loss of renal gluconeogenesis, whereas acute kidney injury can decrease insulin clearance, which in turn leads to hypoglycaemia.[63][64] If individuals with ESKD are treated with insulin and/or sulfonylureas, their treatment needs to be closely monitored and adjusted as estimated glomerular filtration rate declines, and they need to be educated about and closely monitored for hypoglycaemia occurrence.
chronic kidney disease (estimated glomerular filtration rate <60 mL/min/ 1.73 m² or albuminuria)
Chronic kidney disease (CKD) significantly increases the risk of hypoglycaemia in patients with diabetes, especially those treated with insulin or insulin secretagogues.[63][64] As kidney function declines, insulin clearance is reduced, leading to prolonged insulin action; gluconeogenesis is impaired, decreasing the body’s ability to generate glucose during fasting; and renal metabolism of hypoglycaemic agents is altered, increasing drug levels and hypoglycaemic risk. Hypoglycaemia in people with CKD can be prolonged and more severe due to blunted counter-regulatory responses and delayed drug clearance. Regular glucose monitoring, especially with continuous glucose monitoring, can help detect asymptomatic or nocturnal hypoglycaemia in this high-risk group, improving safety and glycaemic control.
weak
female sex
Female sex has been found to be an independent risk factor for hypoglycaemia in multiple studies, although the mechanisms of this relationship are unclear and require further research.[3]
multiple recent episodes of level 1 hypoglycaemia
Associated with increased risk of recurrent episodes.[3] Level 1 hypoglycaemia is defined by blood glucose <3.9 mmol/L (<70 mg/dL) and ≥3.0 mmol/L (≥54 mg/dL) with or without symptoms.
use of hypoglycaemia-causing drugs (non-diabetic)
Non-diabetic drugs can increase the risk of hypoglycaemia in patients with diabetes.[41][65]
In particular, beta-blockers can mask the signs and symptoms of hypoglycaemia, which can predispose to severe, life-threatening hypoglycaemia.[65] Non-selective beta-blockers can also impair hepatic and renal release of glucose into the circulation, which can cause hypoglycaemia.[41]
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.[41] This list of drugs is not exhaustive, and you should consult a drug information source for more information.
Polypharmacy also increases the risk of hypoglycaemia.[3]
exercise
Exercise can increase the risk of hypoglycaemia during, immediately after, or with prolonged delay (up to 24 hours) following the activity.[1][3][4][36][37] This typically occurs in patients with type 1 diabetes treated with insulin. The greater the intensity of exercise and the longer the duration of activity, the greater the risk of hypoglycaemia, with aerobic activities (e.g., walking, jogging, cycling, or swimming) posing more risk than brief anaerobic activities (e.g., sprinting or weightlifting).[36] Exercise induces hypoglycaemia through a variety of mechanisms, which include increased insulin sensitivity and insulin-dependent transport of glucose into the muscles through glucose transporter type 4 (GLUT4) receptors.[36][43] Patients who increase their activity levels over time may experience a reduction in their overall insulin requirements due to the sustained increase in insulin sensitivity.[36]
liver failure
Underlying liver dysfunction leads to loss of hepatic gluconeogenesis.[66]
endocrine disorders
Endocrine disorders such as adrenal insufficiency (including Addison's disease) and hypothyroidism can precipitate hypoglycaemia because they reduce the counter-regulatory response to a drop in blood glucose.[14] Coeliac disease can also increase the risk of hypoglycaemia through malabsorption.[67] It is important to rule out Addison’s disease and coeliac disease in any patient with type 1 diabetes and hypoglycaemia, and particularly in children with frequent, unexplained hypoglycaemia.[1][68][69] The prevalence of these disorders is higher in people with type 1 diabetes than in the general population because these are all autoimmune diseases that share a similar genetic background.[67][70][71]
critical illness
alcohol ingestion
Alcohol ingestion is a common risk factor particularly in adolescents.[1][17] Drinking alcohol can cause hypoglycaemia during and after consumption, particularly if the person has not eaten recently.[3][4][36] In addition, alcohol-related liver disease can lead to hepatic insufficiency, which decreases gluconeogenesis as well as depleting glycogen stores.
severe mental illness
Severe mental illness, including major depressive disorder, is associated with increased hypoglycaemia risk.[3]
presence of cardiovascular disease, neuropathy, or retinopathy
The presence of comorbid cardiovascular disease, neuropathy, or retinopathy has been linked to an increased risk of hypoglycaemia in patients with diabetes.[3]
low health literacy
Low health literacy is a recognised risk factor for hypoglycaemia in people with diabetes.[3] Limited understanding of diabetes management can lead to difficulties interpreting blood glucose readings, adjusting insulin doses, and recognising or treating hypoglycaemic symptoms. This can result in inappropriate drug use, delayed treatment of low blood glucose, and increased risk of severe events.
substance use disorder
Substance use disorder can increase the risk of hypoglycaemia in individuals with diabetes.[3] Alcohol and certain illicit substances may impair gluconeogenesis, alter appetite, or interfere with the recognition of hypoglycaemic symptoms.[72] In addition, cognitive and behavioural effects of substance use can reduce adherence to meal planning, glucose monitoring, and insulin dosing, further increasing risk.[73]
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