Caffeine Can Decrease Insulin Sensitivity in Humans
- 1Department of Internal Medicine, University Medical Center, Nijmegen, the Netherlands
- 2Department of Pharmacology-Toxicology, University Medical Center, Nijmegen, the Netherlands
OBJECTIVE—Caffeine is a central stimulant that increases the release of catecholamines. As a component of popular beverages, caffeine is widely used around the world. Its pharmacological effects are predominantly due to adenosine receptor antagonism and include release of catecholamines. We hypothesized that caffeine reduces insulin sensitivity, either due to catecholamines and/or as a result of blocking adenosine-mediated stimulation of peripheral glucose uptake.
RESEARCH DESIGN AND METHODS—Hyperinsulinemic-euglycemic glucose clamps were used to assess insulin sensitivity. Caffeine or placebo was administered intravenously to 12 healthy volunteers in a randomized, double-blind, crossover design. Measurements included plasma levels of insulin, catecholamines, free fatty acids (FFAs), and hemodynamic parameters. Insulin sensitivity was calculated as whole-body glucose uptake corrected for the insulin concentration. In a second study, the adenosine reuptake inhibitor dipyridamole was tested using an identical protocol in 10 healthy subjects.
RESULTS—Caffeine decreased insulin sensitivity by 15% (P < 0.05 vs. placebo). After caffeine administration, plasma FFAs increased (P < 0.05) and remained higher than during placebo. Plasma epinephrine increased fivefold (P < 0.0005), and smaller increases were recorded in plasma norepinephrine (P < 0.02) and blood pressure (P < 0.001). Dipyridamole did not alter insulin sensitivity and only increased plasma norepinephrine (P < 0.01).
CONCLUSIONS—Caffeine can decrease insulin sensitivity in healthy humans, possibly as a result of elevated plasma epinephrine levels. Because dipyridamole did not affect glucose uptake, peripheral adenosine receptor antagonism does not appear to contribute to this effect.
- AUCIS, area under the insulin sensitivity curve
- CV, coefficient of variation
- FBF, forearm blood flow
- FFA, free fatty acid
- GIR, glucose infusion rate
- HPLC, high-performance liquid chromatography
Address correspondence and reprint requests to Paul Smits, MD, PhD, Professor of Pharmacology, Department of Pharmacology-Toxicology 233, University Medical Center Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands. E-mail:.
Received for publication 10 April 2001 and accepted in revised form 24 October 2001.
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