Hypoglycaemia Unawareness

Hypoglycaemia unawareness (impaired awareness of hypoglycaemia) is loss of the autonomic warning symptoms of low glucose, so that neuroglycopenia occurs first, typically at glucose under 3.0 mmol/L. It raises the risk of severe hypoglycaemia several fold.

It affects roughly one in five to one in four adults with type 1 diabetes and a smaller proportion with insulin treated type 2 diabetes. Prevalence rises with duration of diabetes.

Risk factors are recurrent hypoglycaemia, long duration, tight control, previous severe hypoglycaemia, autonomic neuropathy, kidney impairment, alcohol and adrenal insufficiency. Beta blockers mask symptoms.

Pathophysiology.

Recurrent hypoglycaemia lowers the glucose thresholds for adrenaline release, symptoms and cognitive dysfunction. Counter regulation fails (hypoglycaemia associated autonomic failure).

Central adaptation (altered brain glucose handling) plays a part. Strict avoidance of hypoglycaemia for 2 to 3 weeks partly restores awareness.

• No warning symptoms. First signs are confusion, behaviour change, seizure or coma, often noticed by others.
• Nocturnal hypoglycaemia, high rate of severe episodes needing help and fear of hypoglycaemia.
• Severity grading: level 1 glucose under 3.9 mmol/L, level 2 under 3.0 mmol/L, level 3 severe event requiring help.
• Awareness is graded on a single question scale from 1 (always aware) to 7 (never aware); a score of 4 or more indicates impaired awareness.

Red flags.

• Severe hypoglycaemia needing third party help, seizures or loss of consciousness.
• Hypoglycaemia while driving or in hazardous work.
• Recurrent nocturnal events.

• Awareness score (4 or more) and history of severe events over the previous 12 months.
• Continuous glucose data: time under 3.9 mmol/L should be under 4% and time under 3.0 mmol/L under 1%.
• Contributors to exclude: adrenal insufficiency (morning cortisol), coeliac disease (tissue transglutaminase IgA), kidney, liver and thyroid disease, alcohol, drugs (sulphonylureas, beta blockers) and autonomic neuropathy.
• Review insulin doses, injection sites (lipohypertrophy) and meal timing.

• Strict avoidance of hypoglycaemia for 2 to 3 weeks by raising targets (pre-meal 6 to 10 mmol/L) and reducing insulin.
• Continuous glucose monitoring with low and urgent low alerts, ideally with automated insulin delivery or low glucose suspend.
• Structured education for hypoglycaemia awareness. Review diet, exercise and alcohol.
• Basal insulin with a lower nocturnal hypoglycaemia rate (degludec or glargine U300). Stop or reduce sulphonylureas.
• Treat hypoglycaemia: 15 to 20 g oral glucose, repeat at 15 minutes (up to 3 times), then slow release carbohydrate. If unable to take oral intake: glucagon 1 mg intramuscularly or subcutaneously (0.5 mg if under 25 kg) or nasal glucagon 3 mg, or intravenous 10% glucose 150 to 200 mL over 15 minutes (or 20% glucose 75 to 100 mL).
• Advise against driving until awareness returns, and notify the licensing authority as the law requires.
• Islet or pancreas transplantation for persistent severe events despite optimised therapy.

Special groups. Older adults and people with kidney impairment: relax targets (HbA1c 58 to 64 mmol/mol is usual). Pregnancy: hypoglycaemia risk is highest in the first trimester.

Monitoring. Review continuous glucose data and awareness score at every visit and at 3 months after changes.

Referral and escalation. Specialist diabetes team for any severe event or persistent impaired awareness. Transplant assessment for refractory cases.