Effect of caffeine on recognition of and physiological responses to hypoglycaemia in insulin-dependent diabetes

Lancet. 1996 Jan 6;347(8993):19-24. doi: 10.1016/s0140-6736(96)91557-3.


Background: For the patient with diabetes, hypoglycaemia unawareness--ie, the warning signs of falling blood glucose are missing--is potentially dangerous. One study has suggested that, in healthy volunteers, caffeine might be a helpful treatment. Our study looked at two effects of caffeine ingestion (250 mg) on the brain--namely, a decrease in cerebral blood flow and an increase in brain glucose use--to see if the recognition of and physiological responses to hypoglycaemia were altered in patients with insulin-dependent diabetes mellitus (IDDM).

Methods: 12 patients were studied twice. A hyperinsulinaemic glucose clamp was used to maintain plasma glucose at 5 mmol/L for 90 min, followed by 60 min at 3.8 mmol/L, and then 2.8 mmol/L for a further hour. After 30 min at 5 mmol/L, patients consumed, in a double-blind, crossover design, 250 mg caffeine or matched placebo. We recorded middle cerebral artery velocity (VMCA), counterregulatory hormone levels, and cognitive function, and patients recorded hypoglycaemia symptoms on a visual analogue scale.

Results: Caffeine caused an immediate and sustained fall in VMCA of 10 cm/s, from 60 to 50 cm/s (95% CI -5 to -15 cm/s; p < 0.001). At a blood glucose of 3.8 mmol/L, plasma adrenaline levels were twice as high after caffeine than after placebo (difference 524 pmol/L). When glucose was lowered to 2.8 mmol/L, caffeine ingestion was associated with: greater awareness of hypoglycaemia in 9 patients, significantly more intense autonomic and neuroglycopenic symptoms, and higher levels of adrenaline, cortisol, and growth hormone. Cognitive function (latency of P300 evoked potentials) deteriorated to the same extent in both studies at this glucose level.

Interpretation: The sustained fall in VMCA and augmented sympathoadrenal and symptomatic responses during moderate hypoglycaemia suggest caffeine as a potentially useful treatment for diabetic patients who have difficulty recognising the onset of hypoglycaemia.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Blood Glucose / metabolism*
  • Brain / drug effects*
  • Brain / metabolism
  • Caffeine / pharmacology*
  • Cerebral Arteries / drug effects
  • Cerebrovascular Circulation / drug effects
  • Cerebrovascular Circulation / physiology
  • Cognition / drug effects
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / physiopathology
  • Epinephrine / blood
  • Female
  • Glucose / metabolism
  • Growth Hormone / blood
  • Hemodynamics / drug effects
  • Humans
  • Hydrocortisone / blood
  • Hypoglycemia / physiopathology*
  • Insulin / blood
  • Male
  • Middle Aged
  • Perception


  • Blood Glucose
  • Insulin
  • Caffeine
  • Growth Hormone
  • Glucose
  • Hydrocortisone
  • Epinephrine