Hypoglycaemia is defined as a blood glucose level below 3.9 mmol/L and is one of the most common acute complications of diabetes treatment. It occurs when blood glucose falls below the level required to meet the body's metabolic demands, usually because of excess insulin or glucose-lowering medication relative to carbohydrate intake or energy expenditure.

Hypoglycaemia is a medical emergency that requires immediate recognition and treatment to prevent neurological injury. If untreated, progressive neuroglycopenia may lead to seizures, coma, permanent brain injury, or death. Recurrent episodes may also result in hypoglycaemia unawareness, in which patients lose the ability to recognize early warning symptoms, increasing the risk of severe hypoglycaemia.

Pathophysiology

Blood glucose is normally maintained through a balance between insulin secretion and counter-regulatory hormones including glucagon, adrenaline, cortisol, and growth hormone. Hypoglycaemia develops when glucose utilization exceeds glucose availability, most commonly because of excessive insulin or insulin secretagogue activity, reduced food intake, increased physical activity, or impaired hepatic glucose production. As plasma glucose falls, autonomic activation produces early adrenergic symptoms such as sweating, tremor, hunger, and palpitations. Further reduction in blood glucose results in inadequate glucose delivery to the brain (neuroglycopenia), causing confusion, behavioural changes, seizures, coma, and potentially irreversible neurological damage. Recurrent hypoglycaemia or long-standing diabetes may impair the normal adrenergic and glucagon responses, leading to hypoglycaemia unawareness and increased risk of severe episodes.

Causes and risk factors

Medication-related factors

• Excess insulin administration

• Sulphonylureas, especially long-acting agents such as glibenclamide

• Delayed or missed meals after taking insulin or oral glucose-lowering medicines

• Drug interactions

• Excessive alcohol consumption

Patient-related factors

• Long duration of diabetes mellitus

• Hypoglycaemia unawareness

• Chronic kidney disease

• Liver disease

• Elderly age

• Malnutrition

• Low body weight

• Pregnancy

Lifestyle-related factors

• Prolonged fasting

• Poor oral intake

• Strenuous or prolonged physical activity

• Vomiting or diarrhoea

• Alcohol intake without food

Medical conditions

• Sepsis

• Adrenal insufficiency

• Pituitary disease

Clinical presentation

Early adrenergic symptoms

• Hunger

• Sweating

• Trembling or shaking

• Anxiety

• Dizziness

• Light-headedness

• Palpitations

• Numbness around the lips and fingers

Neuroglycopenic symptoms

• Headache

• Confusion

• Poor concentration

• Weakness

• Behavioural changes such as irritability, tearfulness, or crying

• Paraesthesia

• Blurred vision

• Drowsiness

Severe hypoglycaemia

• Convulsions

• Seizures

• Loss of consciousness

• Coma

Patients with impaired hypoglycaemia awareness may present directly with severe neurological manifestations without preceding adrenergic warning symptoms.

Diagnosis

Hypoglycaemia is diagnosed by:

• Blood glucose <3.9 mmol/L

• Compatible clinical symptoms

• Resolution of symptoms following correction of blood glucose (Whipple's triad)

Treatment should not be delayed while awaiting laboratory confirmation.

Investigations

Immediate assessment

• Capillary blood glucose

• Vital signs

• Assessment of level of consciousness

Further investigations when indicated

• Renal function tests

• Liver function tests

• Medication review

• Nutritional assessment

• Serum cortisol when adrenal insufficiency is suspected

Management

General principles

• Treat immediately once hypoglycaemia is suspected.

• Confirm blood glucose where possible, but do not delay treatment.

• Identify and correct the underlying cause.

• Monitor closely for recurrent hypoglycaemia.

Non-pharmacological management

Conscious patient

Administer a rapidly absorbed carbohydrate immediately:

• One glass of a sugar-containing drink

OR

• One tablespoon of sugar or honey

Once symptoms improve:

• Give a meal or a long-acting carbohydrate snack such as bread.

If symptoms persist after 5 minutes, repeat the rapid carbohydrate treatment.

Unconscious patient

Maintain airway, breathing, and circulation while initiating emergency treatment.

If intravenous access is unavailable, consider:

• Nasogastric administration of glucose if appropriate

• Rectal glucose where feasible while establishing definitive treatment

Pharmacological management

Severe hypoglycaemia

Administer one of the following immediately:

50% dextrose

• 40–50 mL intravenously

OR

10% dextrose

• 200–300 mL intravenously

If the patient remains unconscious or blood glucose remains below 4 mmol/L after 15 minutes, repeat treatment.

After recovery, continue with:

• 8–10% glucose infusion

If higher concentrations are unavailable, use:

• 5% dextrose infusion

If intravenous access cannot be obtained

Administer:

Glucagon

• 1 mg intramuscularly or subcutaneously as a single dose

Management after recovery

Following recovery:

• Give a long-acting carbohydrate snack such as bread.

• Identify and treat the underlying cause.

• Review insulin or oral glucose-lowering therapy.

• Educate the patient regarding prevention of future episodes.

If hypoglycaemia resulted from:

• Long-acting sulphonylureas

• Long-acting insulin

• Intermediate-acting insulin

• Alcohol

then:

• Monitor blood glucose every 2 hours.

• Continue intravenous 5–10% dextrose infusion for 12–24 hours because recurrent hypoglycaemia is common.

Patients who fail to recover appropriately should be evaluated for alternative causes of impaired consciousness and referred urgently if necessary.

Prevention

Preventive measures include:

• Educating patients to recognize early symptoms of hypoglycaemia.

• Never skipping meals after taking insulin or sulphonylureas.

• Carrying glucose tablets, sugar, or sweets at all times.

• Adjusting insulin or medication doses during illness or changes in activity.

• Eating additional carbohydrates before prolonged exercise.

• Avoiding alcohol on an empty stomach.

• Individualizing glycaemic targets in high-risk patients.

• Reviewing medications regularly, particularly in elderly patients and those with renal impairment.

• Screening patients with recurrent episodes for hypoglycaemia unawareness.

• Encouraging family members and caregivers to recognize and manage severe hypoglycaemia.

Outcome

Most patients recover completely when hypoglycaemia is recognized early and treated promptly. Delayed treatment may result in seizures, coma, permanent neurological injury, or death. Patients with recurrent hypoglycaemia require reassessment of their diabetes management plan to reduce future episodes. Education, regular monitoring, and individualized treatment significantly reduce the risk of recurrent hypoglycaemia and improve long-term safety.