Effect of caffeine on the recognition of and responses to hypoglycemia in humans

David Kerr, Robert S. Sherwin, Frank Pavalkis, Pierre B. Fayad, Lori Sikorski, Frances Rife, William V. Tamborlane, Matthew J. During

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61 Scopus citations


Objective: To determine whether two effects of acute caffeine ingestion- decrease in cerebral blood flow and increase in brain glucose use-alter the recognition of and physiologic responses to hypoglycemia. Design: On two occasions, a hyperinsulinemic glucose clamp technique (2 mU/kg body weight per minute) was used to maintain plasma glucose at 5 mmol/L for 90 minutes, followed by 60 minutes at 3.8 mmol/L, and then 2.8 mmol/L. After 30 minutes at 5 mmol/L, participants consumed, using a randomized, double-blind design, caffeine-free cola with or without caffeine (400 mg) added. Setting: Yale Clinical Research Center. Participants: Eighty healthy, nonobese volunteers (5 men; age range, 20 to 33 years). Measurements: Middle cerebral artery velocity (V(MCA)), counter-regulatory hormone levels, hypoglycemic symptoms, and cognitive function (P300 evoked potentials). Results: Caffeine caused an immediate and sustained 23% decrease in V(MCA) from 64 to 49 cm/s (point estimate of difference, +15 cm/s [95% CI, 10 to 21 cm/s], P < 0.001). At a glucose level of 3.8 mmol/L, only the participants given caffeine had warning symptoms and 'felt hypoglycemic.' Moreover, the level of epinephrine was 118% ([CI of point difference, 76% to 158%] [CI, P < 0.001]) higher after caffeine consumption compared with placebo. Similarly, levels of norepinephrine (41% [CI, 26% to 60%], P < 0.002), cortisol (65% [CI, 26% to 78%], P < 0.008), and growth hormone (60% [CI, 16% to 143%], P < 0.05) were higher after caffeine consumption compared with placebo. At 2.8 mmol/L, epinephrine (40% [point estimate of the percentage difference], P < 0.05), norepinephrine (27%, P < 0.05), and cortisol (24%, P < 0.05) levels were higher, participants were more aware (P < 0.02) of hypoglycemia, and P300 latency was prolonged in the group that consumed caffeine (7.2%, P < 0.05). Conclusions: Acute ingestion of caffeine is associated with sympathoadrenal activation and awareness of hypoglycemia at a glucose level not usually considered hypoglycemic. Our data suggest that individuals who ingest moderate amounts of caffeine may develop hypoglycemic symptoms if plasma glucose levels fall into the 'low-normal' range, as might occur in the late postprandial period after ingestion of a large carbohydrate load.

Original languageEnglish (US)
Pages (from-to)799-804
Number of pages6
JournalAnnals of internal medicine
Issue number8
StatePublished - Oct 15 1993
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine

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