History and exam

Your Organizational Guidance

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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: 2022

Key diagnostic factors

common

known diabetes

Suspect diabetic hypoglycemia if a person with diabetes presents with life-threatening alterations in mental and/or physical functioning, typical neuroglycopenic or sympathoadrenal symptoms of hypoglycemia (see entries below), or following a fall or motor accident.​[1][3]​​ Hypoglycemia 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 secretagogs (sulfonylureas and meglitinides).[1][2][8]​​[9][17]

presence of risk factors

Identify any risk factors for hypoglycemia in people who have diabetes, in order to determine their risk of future episodes, and to minimize the occurrence of these.[3] The most common risk factors include:

  • Type 1 diabetes​[1][2][3]

  • Antidiabetic drugs[3][4][44][45]​​

  • Extremes of age​[1][2][3][4]

  • Poor glycemic control[48][49]​​

  • Intensive glycemic control efforts (low [<6%] or high [>9%] HbA1c levels)[3][48][49]

  • Previous severe (level 3) or clinically significant (level 2) hypoglycemia[3]

  • 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.

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] 

For more information see Risk factors, below.

Other diagnostic factors

common

irritability

Typical neuroglycopenic symptom of hypoglycemia.[3] Neuroglycopenic symptoms usually occur at a blood glucose of <54 mg/dL (<3.0 mmol/L) and are more common than sympathoadrenal symptoms in children.​[1][3][80]​​ Bear in mind that signs and symptoms of hypoglycemia usually occur at a higher blood glucose level in children than in adults.[1]

shakiness

Typical sympathoadrenal symptom of hypoglycemia.​[1][3] Sympathoadrenal symptoms usually occur before neuroglycopenic symptoms.[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]

sweating

Typical sympathoadrenal symptom of hypoglycemia.​[1][3]​ Sympathoadrenal symptoms usually occur before neuroglycopenic signs.[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]

tremor

Typical sympathoadrenal symptom of hypoglycemia.[1][77]​​ Sympathoadrenal symptoms usually occur before neuroglycopenic symptoms.[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]

palpitations

Typical sympathoadrenal symptom of hypoglycemia.[1][77]​ Sympathoadrenal symptoms usually occur before neuroglycopenic symptoms.[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]

tachycardia

Typical sympathoadrenal symptom of hypoglycemia.[3] Sympathoadrenal symptoms usually occur before neuroglycopenic symptoms.[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]

feeling warm

Typical sympathoadrenal symptom of hypoglycemia.[77] Sympathoadrenal symptoms usually occur before neuroglycopenic symptoms.[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]

anxiety

Typical sympathoadrenal symptom of hypoglycemia.[77] Suspect nocturnal hypoglycemia if the patient experiences altered mood when waking up.[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]

nausea

Typical sympathoadrenal symptom of hypoglycemia.[1] Sympathoadrenal symptoms usually occur before neuroglycopenic symptoms.[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]

hunger

Typical sympathoadrenal symptom of hypoglycemia.[1][77]​ Sympathoadrenal symptoms usually occur before neuroglycopenic symptoms.[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]

pallor

Typical sympathoadrenal symptom of hypoglycemia.[1] Sympathoadrenal symptoms usually occur before neuroglycopenic symptoms.[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]

higher blood glucose than usual on waking up

Can be a feature of hypoglycemia.

uncommon

seizure

A sign of severe (level 3) hypoglycemia (characterized 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 hypoglycemia usually occurs when blood glucose is 35-40 mg/dL (1.9 to 2.2 mmol/L).

Suspect nocturnal hypoglycemia if the patient experiences seizures at night.[1]

loss of consciousness

A sign of severe (level 3) hypoglycemia (characterized 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 hypoglycemia usually occurs when blood glucose is 35-40 mg/dL (1.9 to 2.2 mmol/L). 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 hypoglycemia that causes unconsciousness needs to be addressed to avoid future catastrophes. 

coma

A sign of severe (level 3) hypoglycemia (characterized 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 hypoglycemia usually occurs when blood glucose is 35-40 mg/dL (1.9 to 2.2 mmol/L).

confusion

Typical neuroglycopenic symptom of hypoglycemia.[3] Suspect nocturnal hypoglycemia 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 <54 mg/dL (<3.0 mmol/L) and are more common in children than sympathoadrenal symptoms.​[1][3][80]​​ Bear in mind that signs and symptoms of hypoglycemia usually occur at a higher blood glucose level in children compared with adults.[1]

problems with short-term memory

Typical neuroglycopenic symptom of hypoglycemia.[3] Neuroglycopenic symptoms usually occur at a blood glucose of around <54 mg/dL (<3.0 mmol/L) and are more common in children than sympathoadrenal symptoms.​[1][3][80]​​ Bear in mind that signs and symptoms of hypoglycemia usually occur at a higher blood glucose level in children compared with adults.[1]

changes in vision

Typical neuroglycopenic symptom of hypoglycemia.[1][77]​​ Specifically, blurred or double vision and disturbed color vision may be present.[1] Neuroglycopenic symptoms usually occur at a blood glucose of around <54 mg/dL (<3.0 mmol/L) and are more common in children than sympathoadrenal symptoms.​[1][3][80]​​ Bear in mind that signs and symptoms of hypoglycemia usually occur at a higher blood glucose level in children compared with adults.[1]

changes in speech

Typical neuroglycopenic symptom of hypoglycemia.[1]​ Specifically, slurred speech may be present.[1] Neuroglycopenic symptoms usually occur at a blood glucose of around <54 mg/dL (<3.0 mmol/L) and are more common in children than sympathoadrenal symptoms.​[1][3][80]​​ Bear in mind that signs and symptoms of hypoglycemia usually occur at a higher blood glucose level in children compared with adults.[1]

difficulty hearing

Typical neuroglycopenic symptom of hypoglycemia.[1]​ Neuroglycopenic symptoms usually occur at a blood glucose of around <54 mg/dL (<3.0 mmol/L) and are more common in children than sympathoadrenal symptoms.​[1][3][80]​​ Bear in mind that signs and symptoms of hypoglycemia usually occur at a higher blood glucose level in children compared with adults.[1]

lethargy

Typical neuroglycopenic symptom of hypoglycemia.[1][77]​​​ Neuroglycopenic symptoms usually occur at a blood glucose of around <54 mg/dL (<3.0 mmol/L) and are more common in children than sympathoadrenal symptoms.​[1][3][80]​​ Bear in mind that signs and symptoms of hypoglycemia usually occur at a higher blood glucose level in children compared with adults.[1]

Suspect nocturnal hypoglycemia if the patient experiences lethargy on waking up.[1]

drowsiness

Typical neuroglycopenic symptom of hypoglycemia.[1]​ Neuroglycopenic symptoms usually occur at a blood glucose of around <54 mg/dL (<3.0 mmol/L) and are more common in children than sympathoadrenal symptoms.​[1][3][80]​​ Bear in mind that signs and symptoms of hypoglycemia usually occur at a higher blood glucose level in children compared with adults.[1]

quietness

Typical neuroglycopenic symptom of hypoglycemia.[1]​ Behavioral changes such as irritability, agitation, quietness, and tantrums may be prominent in young children.[1] Other features may include erratic behavior.[1] Suspect nocturnal hypoglycemia if the patient experiences nightmares at night.[1]

Neuroglycopenic symptoms usually occur at a blood glucose of around <54 mg/dL (<3.0 mmol/L) and are more common in children than sympathoadrenal symptoms.​[1][3][80]​​ Bear in mind that signs and symptoms of hypoglycemia usually occur at a higher blood glucose level in children compared with adults.[1]

tantrums

Typical neuroglycopenic symptom of hypoglycemia.[1]​ Behavioral changes such as irritability, agitation, quietness, and tantrums may be prominent in young children.[1] Other features may include erratic behavior.[1] Suspect nocturnal hypoglycemia if the patient experiences nightmares at night.[1]

Neuroglycopenic symptoms usually occur at a blood glucose of around <54 mg/dL (<3.0 mmol/L) and are more common in children than sympathoadrenal symptoms.​[1][3][80]​​ Bear in mind that signs and symptoms of hypoglycemia usually occur at a higher blood glucose level in children compared with adults.[1]

erratic behavior

Typical neuroglycopenic symptom of hypoglycemia.[1]​ Behavioral changes such as irritability, agitation, quietness, and tantrums may be prominent in young children.[1] Other features may include erratic behavior.[1] Suspect nocturnal hypoglycemia if the patient experiences nightmares at night.[1]

Neuroglycopenic symptoms usually occur at a blood glucose of around <54 mg/dL (<3.0 mmol/L) and are more common in children than sympathoadrenal symptoms.​[1][3][80]​​ Bear in mind that signs and symptoms of hypoglycemia usually occur at a higher blood glucose level in children compared with adults.[1]

nightmares

Typical neuroglycopenic symptom of hypoglycemia.[1] Suspect nocturnal hypoglycemia if the patient experiences nightmares at night.[1]

Neuroglycopenic symptoms usually occur at a blood glucose of around <54 mg/dL (<3.0 mmol/L) and are more common in children than sympathoadrenal symptoms.​[1][3][80]​​ Bear in mind that signs and symptoms of hypoglycemia usually occur at a higher blood glucose level in children compared with adults.[1]

headache

Typical neuroglycopenic symptom of hypoglycemia.[1] Suspect nocturnal hypoglycemia if the patient experiences headache when waking up.[1]

Neuroglycopenic symptoms usually occur at a blood glucose of around <54 mg/dL (<3.0 mmol/L) and are more common in children than sympathoadrenal symptoms.​[1][3][80]​​ Bear in mind that signs and symptoms of hypoglycemia usually occur at a higher blood glucose level in children compared with adults.[1]

difficulty concentrating

Typical neuroglycopenic symptom of hypoglycemia.[1] 

Neuroglycopenic symptoms usually occur at a blood glucose of around <54 mg/dL (<3.0 mmol/L) and are more common in children than sympathoadrenal symptoms.​[1][3][80]​​ Bear in mind that signs and symptoms of hypoglycemia usually occur at a higher blood glucose level in children compared with adults.[1]

dizziness

Typical neuroglycopenic symptom of hypoglycemia.[77]​ The patient may have an unsteady gait.[1]

Neuroglycopenic symptoms usually occur at a blood glucose of around <54 mg/dL (<3.0 mmol/L) and are more common in children than sympathoadrenal symptoms.​[1][3][80]​​ Bear in mind that signs and symptoms of hypoglycemia 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 hypoglycemia.[78]​ 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]

bedwetting

Can be a feature of hypoglycemia.

Risk factors

strong

type 1 diabetes

Hypoglycemia occurs most commonly in people with type 1 diabetes.​[1][2][8][9]​​​​​ However, be aware that hypoglycemia can occur in people with type 2 diabetes due to treatment with insulin or insulin secretagogs (sulfonylureas and meglitinides).​[1][2][8][9][17]​​​ The total number of hypoglycemic events in people with type 2 diabetes who are treated with insulin may be as high as, or higher than, in people with type 1 diabetes, due to the higher overall prevalence of type 2 diabetes.[2][10]​​​

antidiabetic drugs

Treatment with insulin, sulfonylureas, or meglitinides increases the risk of hypoglycemia compared with other antidiabetic drugs.[3][4]​​​​​[17][44][45][46]​​​​​

If the patient is taking insulin, 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 uncommon.

In addition, an absolute or relative excess of insulin can lead to hypoglycemia due to:[1]

  • 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

  • Concurrent use of alcohol.

age >60 years

Older adults, particularly those ages >60 years, have higher rates of hypoglycemia than younger adults.[1][2][3][17] Older adults may have reduced ability to recognize symptoms of hypoglycemia and communicate that they need assistance.​[1][3] Minor episodes of hypoglycemia frequently go unrecognized in older adults because they may present with nonspecific symptoms such as brief episodes of lightheadedness or vertigo.

In older adults, there is age-related decline in renal and hepatic function, which can potentiate the effects of antidiabetic drugs such as sulfonylureas and insulin.[2] There may also be age-related impairment of counterregulatory hormones in older adults such as glucagon and growth hormone.[2] Older patients also have an increase in comorbidities that may contribute to hypoglycemia.[2]

age <6 years

Young children have higher rates of hypoglycemia than young adults.​[1][2][3] Young children may have reduced ability to recognize symptoms of hypoglycemia and communicate that they need assistance.​[1][3]

Young children are also at increased risk of nocturnal hypoglycemia.[1]

poor glycemic control

Poor glycemic control (both low and high HbA1c levels) is strongly associated with increased risk of severe hypoglycemia.[48]​ One retrospective study of over 1000 adults with type 2 diabetes looked at self-reported rates of severe hypoglycemia at different HbA1c levels.[49]​ Compared with patients with HbA1c levels of 7% to 7.9%, the relative risk of severe hypoglycemia was 1.25 (95% CI 0.99 to 1.57), 1.01 (95% CI 0.87 to 1.18), 0.99 (95% CI 0.82 to 1.20), and 1.16 (95% CI 0.97 to 1.38) among those with HbA1c levels of <6%, 6% to 6.9%, 8% to 8.9%, and ≥9%, respectively.[49] However, in young people (those ages <18 years in practice) with type 1 diabetes, low HbA1c is no longer a strong risk factor for hypoglycemia.[1][50][51][52]​​​​​​

People with lower HbA1c levels are also at increased risk of nocturnal hypoglycemia.[1]

intensive glycemic control efforts

Adults with intensive glycemic control (lower HbA1c target; in practice this varies but is generally <7%) are at increased risk of severe hypoglycemia compared to those with less intensive glycemic control (higher HbA1c target; generally ≥7% in practice).[3][53]​​ The potential risk of hypoglycemia outweighs the benefit of intensive glycemic control in those with long duration of diabetes, previous episodes of hypoglycemia, significant atherosclerosis, older age (particularly those >50 years), or frailty.[3]

previous severe (level 3) hypoglycemia

Urgently identify if the person has had previous episodes of level 3 hypoglycemia, in order to intervene quickly and prevent further episodes.[3] Level 3 hypoglycemia is characterized 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 particular, repeated episodes of hypoglycemia can cause impaired awareness of hypoglycemia, which can increase the risk of hypoglycemia.[3][17]

previous clinically significant (level 2) hypoglycemia

Urgently identify if the person has had previous episodes of level 2 hypoglycemia, in order to intervene quickly and prevent further episodes.[3] Level 2 hypoglycemia is defined by blood glucose <54 mg/dL (<3.0 mmol/L) with or without clinical symptoms.[3][4]​​[5][17] In particular, repeated episodes of hypoglycemia can cause impaired awareness of hypoglycemia, which can increase the risk of hypoglycemia.[3][4][17]

increased duration of diabetes

People with longer duration of diabetes are at increased risk of hypoglycemia compared to those with shorter duration.[2][4]​​[15][17][54]​​​​ In one study, 18.6% of patients with diabetes for ≥40 years had experienced an episode of severe hypoglycemia within the last year.[54]

treatment with insulin >5 years

Patients who have been treated with insulin for >5 years are at increased risk of hypoglycemia.[2][4][17]

impaired cognitive function

Cognitive impairment is strongly associated with increased risk of severe hypoglycemia.[3][48][55]​​ People with cognitive impairment are at risk of hypoglycemia because of reduced ability to recognize symptoms of hypoglycemia and communicate that they need assistance.[55] They are also at risk of errors associated with insulin administration, which can lead to hypoglycemia.

Conversely, patients with diabetes who have episodes of hypoglycemia are also at increased risk of dementia compared to those who do not have episodes of hypoglycemia.[56]

impaired awareness of hypoglycemia

Can be caused by recurrent episodes of hypoglycemia, which leads to deficient release of counterregulatory hormones and reduced autonomic response when the patient's blood glucose falls.​[2][3]​​ This means that a person will not experience typical signs and symptoms of hypoglycemia in response to a progressively lower blood glucose, which puts them at increased risk of severe hypoglycemia.​[1][2][57]​​​

Determine at what blood glucose the patient recognizes hypoglycemia, and what symptoms they experience.[1]

first trimester of pregnancy

Incidence of diabetic hypoglycemia increases in early pregnancy, particularly around 10-15 weeks' gestation, in people with type 1 or type 2 diabetes.​[20][21][22][23][24]​​​ In pregnant women with preexisting type 1 diabetes, severe hypoglycemia 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][25]​​ Incidence rates of severe hypoglycemia have been reported as high as 19% to 44% in pregnant women who are treated with intensive insulin therapy.[26]

Hypoglycemia due to gestational diabetes is not covered in this topic.

failure to thrive in children

Decreases glycogen stores, which leads to hypoglycemia.[58]

poor oral intake

Decreases glycogen stores, which leads to hypoglycemia.[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 hypoglycemia.[1] Determine the timing and amount of carbohydrates in any recent food intake, and the peak glucose effect of recent food intake.[1]

weight loss

Accompanied by decreased glycogen stores, which leads to hypoglycemia.[60]

malnutrition

Decreases glycogen stores, which leads to hypoglycemia.[41][59]

sleep

During sleep, people are at particular risk of severe or asymptomatic hypoglycemia because sleep impairs the counterregulatory hormone response to hypoglycemia.[1] Frequent, prolonged nocturnal hypoglycemia may occur on 8.5% of nights in adults and children.[1] However, in children and adolescents with type 1 diabetes, prolonged nocturnal hypoglycemia has been reported to occur on 15% to 25% of nights.[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.

weak

hypoglycemia-causing drugs (nondiabetic)

Nondiabetic drugs can increase the risk of hypoglycemia in patients with diabetes.[41][61]​​

In particular, beta-blockers can mask the signs and symptoms of hypoglycemia, which can predispose 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 fluoroquinolone], 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.

Polypharmacy with many hypoglycemia-causing drugs also increases the risk of hypoglycemia in people with type 2 diabetes.[3]

exercise

Determine the timing, duration, and intensity of exercise or recent activity.[1] Exercise can increase the risk of hypoglycemia during, immediately after, or with prolonged delay (up to 24 hours) following the activity.​[1][3][4][37]​​​ Post-exercise hypoglycemia is caused by increased glucose uptake by exercising muscles. 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 hypoglycemia, with aerobic posing more risk than anaerobic activity.[37]​ Exercise induces hypoglycemia 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.[37][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.[37]

renal failure

Both acute kidney injury and chronic kidney disease can increase the risk of hypoglycemia.[62][63]​​ Chronic kidney disease causes loss of renal gluconeogenesis, whereas acute kidney injury can decrease insulin clearance, which in turn leads to hypoglycemia.[62][63]

liver failure

Underlying liver dysfunction leads to loss of hepatic gluconeogenesis.[64]

endocrine disorders

Endocrine disorders such as adrenal insufficiency (including Addison disease) and hypothyroidism can precipitate hypoglycemia because they reduce the counterregulatory response to a drop in blood glucose.[14]​​​ Celiac disease can also increase the risk of hypoglycemia through malabsorption.[65]​ Rule out Addison and celiac disease in any patient with type 1 diabetes and hypoglycemia, and particularly in children with frequent, unexplained hypoglycemia.[1][66][67]​​​​ The prevalence of these disorders is higher in people with type 1 diabetes than the general population because these are all autoimmune diseases that share a similar genetic background.[65][68][69]​​​​

critical illness

Critical illness (e.g., sepsis) increases metabolic demands and subsequent utilization of glucose, which can cause hypoglycemia.[41] In particular, hypoglycemia due to sepsis is common and thought to be initiated by activation of proinflammatory mediators and counterregulatory hormones.[41]

alcohol ingestion

A common risk factor particularly in adolescents.[1][17]​ Drinking alcohol can cause hypoglycemia during and after consumption, particularly if the person has not eaten recently.[3][4][37] In addition, alcohol-related liver disease can lead to hepatic insufficiency, which decreases gluconeogenesis as well as depleting glycogen stores. 

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