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


METHODS
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.


METHODS
Yale Clinical Research Center.


METHODS
Eight healthy, nonobese volunteers (5 men; age range, 20 to 33 years).


METHODS
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 VMCA 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.
Kerr
D
D
Yale University School of Medicine, New Haven, Connecticut.
Sherwin
R S
RS
Pavalkis
F
F
Fayad
P B
PB
Sikorski
L
L
Rife
F
F
Tamborlane
W V
WV
During
M J
MJ
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology*; D002395:Catecholamines / Q000097:blood; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D005947:Glucose / Q000378:metabolism*; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007003:Hypoglycemia / Q000097:blood / Q000503:physiopathology*; D008297:Male
D001786:Blood Glucose; D002395:Catecholamines; D002110:Caffeine; D013006:Growth Hormone; D005947:Glucose; D006854:Hydrocortisone