EFFECT OF CAFFEINE ON RECOGNITION OF AND PHYSIOLOGICAL-RESPONSES TO HYPOGLYCEMIA IN INSULIN-DEPENDENT DIABETES

Background For the patient with diabetes, hypoglycaemia unawareness-ie , the warning signs of falling blood glucose are missing-is potentiall y dangerous. One study has suggested that, in healthy volunteers, caff eine might be a helpful treatment. Our study looked at two effects of caffeine ingestion (250 mg) on the brain-namely, a decrease in cerebra l blood flow and an increase in brain glucose use-to see if the recogn ition of and physiological responses to hypoglycaemia were altered in patients with insulin-dependent diabetes mellitus (IDDM). Methods 12 p atients 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 a t 5 mmol/L, patients consumed, in a double-blind, crossover design, 25 0 mg caffeine or matched placebo. We recorded middle cerebral artery v elocity (V-MCA), counterregulatory hormone levels, and cognitive funct ion, and patients recorded hypoglycaemia symptoms on a visual analogue scale. Results Caffeine caused an immediate and sustained fall in V-M CA of 10 cm/s, from 60 to 50 cm/s (95% Cl -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 w ith: greater awareness of hypoglycaemia in 9 patients, significantly m ore intense autonomic and neuroglycopenic symptoms, and higher levels of adrenaline, cortisol, and growth hormone. Cognitive function (laten cy of P-300 evoked potentials) deteriorated to the same extent in both studies at this glucose level. Interpretation The sustained fall in V -MCA and augmented sympathoadrenal and symptomatic responses during mo derate hypoglycaemia suggest caffeine as a potentially useful treatmen t for diabetic patients who have difficulty recognising the onset of h ypoglycaemia.