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 Ͻ 0.05 vs. placebo). After caffeine administration, plasma FFAs increased (P Ͻ 0.05) and remained higher than during placebo. Plasma epinephrine increased fivefold (P Ͻ 0.0005), and smaller increases were recorded in plasma norepinephrine (P Ͻ 0.02) and blood pressure (P Ͻ 0.001). Dipyridamole did not alter insulin sensitivity and only increased plasma norepinephrine (P Ͻ 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.
Diabetes Care 25:364 -369, 2002C affeine is one of the most widely consumed "drugs" in the world. The average daily intake per capita in the western world is ϳ300 mg (1), and most of it comes from dietary sources such as coffee, tea, cola drinks, and chocolate. Caffeine is a methylxanthine derivative and a potent adenosine receptor antagonist that exerts its effects both centrally and peripherally because it crosses the blood-brain barrier. Systemic effects of caffeine include an increase in blood pressure and stimulation of the release of catecholamines, particularly epinephrine (2). Local effects of caffeine stem from interaction with interstitial adenosine (3).Data from animal studies have indicated that methylxanthines are involved in insulin-mediated glucose handling and insulin responsiveness in adipose and muscular tissue. In obese Zucker rats, the caffeine-related adenosine receptor antagonist 1,3 dipropyl-8-(acrylic) phenylxanthine was found to inhibit glucose uptake in adipose tissue, whereas the reverse was observed in skeletal muscle (4).Both effects were attributed to adenosine receptor antagonism at the tissue site because the compound does not cross the blood-brain barrier. Studies showing that adenosine or adenosine agonists increase insulin sensitivity in adipos...