title: Caffeine can decrease insulin sensitivity in humans.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Internal Medicine, University Medical Center Nijmegen, 6500 HB Nijmegen, the Netherlands.
authors.forename: Gerben B
authors.initials: GB
authors.lastname: Keijzers
authors.forename: Bastiaan E
authors.initials: BE
authors.lastname: De Galan
authors.forename: Cees J
authors.initials: CJ
authors.lastname: Tack
authors.forename: Paul
authors.initials: P
authors.lastname: Smits
mesh_terms: D000328:Adult; D002110:Caffeine / Q000009:adverse effects*; D000697:Central Nervous System Stimulants / Q000009:adverse effects*; D004176:Dipyridamole / Q000494:pharmacology; D004311:Double-Blind Method; D004837:Epinephrine / Q000097:blood; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism*; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D008297:Male; D009638:Norepinephrine / Q000097:blood; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology
chemical_list: D000697:Central Nervous System Stimulants; D007328:Insulin; D010726:Phosphodiesterase Inhibitors; D002110:Caffeine; D004176:Dipyridamole; D009638:Norepinephrine; D004837:Epinephrine