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This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
Key points
- Defined as blood glucose <3.5 mmol/L (some use <4.0 as threshold for treatment in diabetes)
- Most common cause: drug-induced in diabetes (insulin, sulfonylureas). Also: alcohol, liver failure, Addison's, insulinoma
- Whipple's triad: symptoms of hypoglycaemia + documented low glucose + symptom resolution with glucose correction
- Autonomic symptoms: tremor, sweating, palpitations, hunger. Neuroglycopenic: confusion, drowsiness, seizure, coma
- Treatment — conscious: rapid-acting glucose (glucose tabs, Lucozade, juice). Unconscious: IM glucagon 1 mg or IV glucose 10%
- Impaired awareness of hypoglycaemia: loss of autonomic warning symptoms — affects ~25% of long-standing T1DM. Strict hypo avoidance ≥4 weeks can restore awareness
Overview
Hypoglycaemia is defined as a blood glucose level below the normal fasting range, conventionally <3.5 mmol/L. In diabetes management, a threshold of <4.0 mmol/L is used to prompt treatment ("four is the floor"). Symptoms arise from two mechanisms: autonomic (sympathoadrenal) activation and neuroglycopenia (inadequate glucose delivery to the brain). The most common cause by far is drug-induced hypoglycaemia in patients with diabetes treated with insulin or sulfonylureas (gliclazide, glipizide). Non-diabetic hypoglycaemia is uncommon and requires investigation — causes include alcohol excess, liver failure, adrenal insufficiency, insulinoma, non-islet cell tumours (producing IGF-2), and reactive (postprandial) hypoglycaemia.
Epidemiology
Hypoglycaemia is the most common acute complication of insulin therapy. Patients with T1DM experience an average of 2 symptomatic episodes per week, with severe hypoglycaemia (requiring third-party assistance) affecting approximately 30% per year. In T2DM, hypoglycaemia risk is highest with insulin and sulfonylureas — metformin, SGLT2 inhibitors, and DPP-4 inhibitors carry minimal risk. Impaired awareness of hypoglycaemia affects approximately 25% of patients with long-standing T1DM and significantly increases risk of severe episodes. Alcohol is an important cause of hypoglycaemia — particularly in binge drinking (inhibits gluconeogenesis).
Clinical Features
Symptoms
Autonomic (adrenergic/cholinergic): tremor, sweating, palpitations, anxiety, hunger, pallor — occur first
Neuroglycopenic: confusion, difficulty concentrating, slurred speech, visual disturbance
Behavioural change: irritability, aggression (may mimic intoxication)
Drowsiness, reduced consciousness, seizures, coma
Nocturnal hypoglycaemia: night sweats, morning headache, nightmares, confusion on waking
Impaired awareness: neuroglycopenic symptoms WITHOUT preceding autonomic warning
Signs
Tachycardia, sweating, pallor, tremor
Confusion, aggression, abnormal behaviour
Focal neurological deficit (rare — can mimic stroke)
Seizure (generalised tonic-clonic)
Reduced GCS, coma
Investigations
First-line
Capillary blood glucose<3.5 mmol/L confirms hypoglycaemia (in context of symptoms). Treat immediately — do not delay for laboratory confirmation
Second-line
Lab glucoseIf doubt about capillary accuracy or medicolegal significance
Whipple's triad assessmentFor non-diabetic hypoglycaemia: symptoms present, documented low glucose, and resolution with glucose correction
Specialist
Investigations for non-diabetic hypoglycaemia (during episode)Paired glucose + insulin + C-peptide + cortisol + sulfonylurea screen. High insulin + high C-peptide = insulinoma. High insulin + low C-peptide = exogenous insulin. Sulfonylureas raise both
72 h supervised fastGold standard for insulinoma — monitor glucose, insulin, C-peptide, proinsulin during fast until symptomatic or glucose <2.2 mmol/L
CT/MRI pancreasLocalise insulinoma if biochemically confirmed
Short Synacthen testIf adrenal insufficiency suspected as cause
1
Conscious and able to swallow
- 15–20 g fast-acting glucose: glucose tablets (Dextrose), Lucozade, fruit juice, GlucoGel
- Recheck glucose after 10–15 min. Repeat if still <4.0 mmol/L (up to 3 times)
- Once glucose >4.0: follow with long-acting carbohydrate (biscuit, sandwich, next meal)
- If on insulin pump: check pump function, consider temporary basal rate reduction
2
Unconscious or unable to swallow
- IM glucagon 1 mg (pre-filled syringe or nasal formulation): onset 10–15 min
- IV glucose: 100 mL of 10% glucose (or 50 mL of 20% glucose) over 10–15 min via large-bore cannula
- Avoid 50% glucose (hypertonic — causes phlebitis and tissue necrosis if extravasated)
- Glucagon may be less effective in: alcohol-related hypo (depleted glycogen), liver disease, sulfonylurea-induced (may stimulate more insulin)
- Recovery position, protect airway until consciousness regained
3
Sulfonylurea-induced hypoglycaemia
- Prolonged hypoglycaemia risk due to long drug half-life (especially glibenclamide)
- Admission and monitoring for at least 24–48 h
- Consider IV glucose infusion (may need sustained dextrose for 24+ h)
- Discontinue sulfonylurea and review need for alternative agent
4
Prevention and education
- Review insulin/sulfonylurea doses and timing
- Address modifiable factors: missed meals, excess alcohol, exercise without carb adjustment
- Assess for impaired awareness of hypoglycaemia (Gold/Clarke scoring)
- If impaired awareness: strict hypo avoidance for ≥4 weeks (can partially restore awareness)
- Consider CGM/isCGM with alarms for recurrent or severe hypoglycaemia
- DVLA: must notify and meet driving standards. Cannot drive if impaired awareness
Complications
- Seizures: Prolonged neuroglycopenia can cause generalised seizures
- Brain injury: Sustained severe hypoglycaemia can cause permanent neurological damage (particularly hippocampus)
- Cardiac arrhythmias: QT prolongation during hypoglycaemia → arrhythmia risk. "Dead in bed" syndrome in T1DM
- Falls and injuries: Particularly in elderly patients
- Road traffic accidents: Impaired awareness while driving
- Impaired awareness of hypoglycaemia: Progressive loss of autonomic symptoms with recurrent episodes — vicious cycle. Strict avoidance can restore
UKMLA Exam Tips
- 1Hypoglycaemia treatment: glucose if conscious (15–20 g), glucagon IM if unconscious, IV glucose if access available
- 2Sulfonylurea hypo is PROLONGED — may need 24–48 h IV glucose infusion. Admit and monitor
- 3Metformin, SGLT2i, DPP-4i, pioglitazone: very LOW risk of hypoglycaemia. Insulin and SU: HIGH risk
- 4Insulinoma: fasting hypoglycaemia + high insulin + high C-peptide + negative sulfonylurea screen. 72 h fast is diagnostic
- 5Exogenous insulin overdose: high insulin + LOW C-peptide (exogenous insulin suppresses endogenous production)
- 6Alcohol inhibits gluconeogenesis → can cause severe prolonged hypoglycaemia, especially if glycogen-depleted
- 7DVLA: patients with recurrent severe hypo or impaired awareness must stop driving and notify DVLA
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