Effect of Caffeine on the Recognition of and Responses to Hypoglycemia in Humans

15 October 1993 | Volume 119 Issue 8 | Pages 799-804

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: Eight 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.

Author and Article Information

From Yale University School of Medicine, New Haven, Connecticut.
Requests for Reprints: David Kerr, MD, Royal Bournemouth Hospital, Castle Lane East, Bournemouth, Dorset, England BH7 7DW.
Acknowledgments: The authors thank Aida Grossman and Andrea Belous for help with measurements of hormone levels, Val Pascale for his help with randomization and for supplying the drinks, and Dr. Lawrence M. Brass for his comments.
Grant Support: By grants DK 20495, RR 00125, RR 06022, and NS 28227 from the National Institutes of Health and in part by gifts to the Yale Stroke Program.