Expansion
Glucagon first, then adrenaline, then cortisol and growth hormone
Expansion
Defences against falling glucose, in order of activation:
- Reduced insulin secretion, at about 4.5 mmol/l
- Glucagon, at about 3.8 mmol/l: stimulates hepatic glycogenolysis and gluconeogenesis. The most important acute defence
- Adrenaline, at about 3.8 mmol/l: glycogenolysis, lipolysis, reduced peripheral uptake, and the autonomic warning symptoms
- Cortisol and growth hormone, over hours: gluconeogenesis and insulin resistance
- Symptoms at about 3.0 mmol/l, cognitive impairment below about 2.8
Two clinically important failures:
- In type 1 diabetes the glucagon response to hypoglycaemia is lost within a few years, leaving adrenaline as the main defence
- Hypoglycaemia unawareness develops after recurrent episodes, because the threshold for adrenaline release falls below the threshold for cognitive impairment. It is partly reversible by scrupulously avoiding hypoglycaemia for several weeks
Beta blockers blunt the adrenergic warning symptoms, leaving sweating, which is cholinergic, as the main remaining clue.