TY - JOUR
T1 - Effect of caffeine on the recognition of and responses to hypoglycemia in humans
AU - Kerr, David
AU - Sherwin, Robert S.
AU - Pavalkis, Frank
AU - Fayad, Pierre B.
AU - Sikorski, Lori
AU - Rife, Frances
AU - Tamborlane, William V.
AU - During, Matthew J.
PY - 1993/10/15
Y1 - 1993/10/15
N2 - 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.
AB - 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.
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U2 - 10.7326/0003-4819-119-8-199310150-00005
DO - 10.7326/0003-4819-119-8-199310150-00005
M3 - Article
C2 - 8379601
AN - SCOPUS:0027763243
SN - 0003-4819
VL - 119
SP - 799
EP - 804
JO - Annals of internal medicine
JF - Annals of internal medicine
IS - 8
ER -