The DOI matches its Crossref record; 41 of the 42 references it cites were found in a registry or an index.
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. 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 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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Moreover, caffeine is known to acutely decrease insulin sensitivity in human subjects (Graham et al. 2000;Keijzers et al. 2002).”
From Glycaemic index methodology (2005) · cites this paper as Keijzers et al. 2002
Citations
Cites
Glucose clamp technique: a method for quantifying insulin secretion and resistance.
DeFronzo, R. A., Tobin, J. D., & Andres, R. (1979) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1979.237.3.e214 · Cited by 7,425
Matsuda, M., & DeFronzo, R. A. (1999) · Diabetes Care · doi:10.2337/diacare.22.9.1462 · Cited by 5,621
Hyperinsulinemia produces both sympathetic neural activation and vasodilation in normal humans.
Anderson, E. A., Hoffman, R. P., Balon, T. W., Sinkey, C. A., & Mark, A. L. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115260 · Cited by 1,075
Improvement in Glucose Tolerance and Insulin Resistance in Obese Subjects Treated with Troglitazone
Nolan, J. J., Ludvik, B. H., Beerdsen, P., Joyce, M., & Olefsky, J. M. (1994) · New England Journal of Medicine · doi:10.1056/nejm199411033311803 · Cited by 914
Barone, J. J., & Roberts, H. R. (1996) · Food and Chemical Toxicology · doi:10.1016/0278-6915(95)00093-3 · Cited by 705
Epinephrine-induced insulin resistance in man
Deibert, D. C., & Defronzo, R. A. (1980) · Journal of Clinical Investigation · doi:10.1172/jci109718 · Cited by 557 · cited 2×
“Using the euglycemic clamp technique, Deibert and DeFronzo (9) showed that epinephrine infusion reduced tissue sensitivity to insulin by 50%.”
Tolerance to the humoral and hemodynamic effects of caffeine in man.
Robertson, D., Wade, D., Workman, R., Woosley, R. L., & Oates, J. A. (1981) · Journal of Clinical Investigation · doi:10.1172/jci110124 · Cited by 501 · cited 1×
“Chronic use of caffeine (and related methylxanthine derivatives) is known to result in attenuation of both humoral and pressor effects that are associated with acute ingestion (37), perhaps due to upregulation of adenosine receptors (38).”
On the Mechanism of Action of Theophylline and Caffeine
Fredholm, B. B. (1985) · Acta Medica Scandinavica · doi:10.1111/j.0954-6820.1985.tb01650.x · Cited by 228
Vergauwen, L., Hespel, P., & Richter, E. A. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117104 · Cited by 158
Kuroda, M., Honnor, R. C., Cushman, S. W., Londos, C., & Simpson, I. A. (1987) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)75918-3 · Cited by 155
Vannucci, S. J., Nishimura, H., Satoh, S., Cushman, S. W., Holman, G. D., & Simpson, I. A. (1992) · Biochemical Journal · doi:10.1042/bj2880325 · Cited by 133
Evidence for an Antagonism Between Caffeine and Adenosine in the Human Cardiovascular System
Smits, P., Boekema, P., Abreu, R. D., Thien, T., & vanʼt Laar, A. (1987) · Journal of Cardiovascular Pharmacology · doi:10.1097/00005344-198708000-00002 · Cited by 128
Self-citationCirculatory effects of coffee in relation to the pharmacokinetics of caffeine
Smits, P., Thien, T. A., & Laar, A. V. (1985) · The American Journal of Cardiology · doi:10.1016/0002-9149(85)90412-6 · Cited by 117
Self-citationWidén, E., Eriksson, J. G., & Groop, L. (1992) · Diabetes · doi:10.2337/diab.41.3.354 · Cited by 110
Sollevi, A., Östergren, J., Fagrell, B., & Hjemdahl, P. (1984) · Acta Physiologica Scandinavica · doi:10.1111/j.1748-1716.1984.tb07443.x · Cited by 100
Adenosine stimulates glycolytic flux in isolated perfused rat hearts by A1-adenosine receptors
Wyatt, D. A., Edmunds, M. C., Rubio, R., Berne, R. M., Lasley, R. D., & Mentzer, R. M. (1989) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1989.257.6.h1952 · Cited by 100
Han, D. H., Hansen, P. A., Nolte, L. A., & Holloszy, J. O. (1998) · Diabetes · doi:10.2337/diabetes.47.11.1671 · Cited by 92
Willemsen, J. J., Ross, H. A., Jacobs, M. C., Lenders, J. W. M., Thien, T., Swinkels, L. M. J. W., & Benraad, T. J. (1995) · Clinical Chemistry · doi:10.1093/clinchem/41.10.1455 · Cited by 91
Strain-gauge plethysmography; theoretical and practical notes on a new design.
Brakkee, A. J. M., & Vendrik, A. J. H. (1966) · Journal of Applied Physiology · doi:10.1152/jappl.1966.21.2.701 · Cited by 91
Insulin resistance and vasodilation in essential hypertension. Studies with adenosine.
Natali, A., Bonadonna, R. C., Santoro, D., Galvan, A. Q., Baldi, S., Frascerra, S., Palombo, C., Ghione, S., & Ferrannini, E. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117498 · Cited by 89
Effects of caffeine on glucose tolerance: A placebo-controlled study
PIZZIOL, A., Tikhonoff, V., Paleari, C. D., Russo, E., Mazza, A., Ginocchio, G., Onesto, C., Pavan, L., Casiglia, E., & Pessina, A. (1998) · European Journal of Clinical Nutrition · doi:10.1038/sj.ejcn.1600657 · Cited by 77
Is Coffee Consumption a Contributor to Cardiovascular Disease?
Wilson, P. W. F. (1989) · Archives of Internal Medicine · doi:10.1001/archinte.1989.00390050125025 · Cited by 71
Tissue‐specific effects of in vivo adenosine receptor blockade on glucose uptake in Zucker rats
Crist, G. H., Xu, B., LaNoue, K. F., & Lang, C. H. (1998) · The FASEB Journal · doi:10.1096/fasebj.12.13.1301 · Cited by 70
Fredholm, B. B. (1978) · Acta Physiologica Scandinavica · doi:10.1111/j.1748-1716.1978.tb06062.x · Cited by 67
Acute effects of caffeine ingestion at rest in humans with impaired epinephrine responses
van Soeren, M., Mohr, T. T., Kjær, M., & Graham, T. E. (1996) · Journal of Applied Physiology · doi:10.1152/jappl.1996.80.3.999 · Cited by 64
Budohoski, L., Challis, R. A. J., McManus, B., & Newsholme, E. A. (1984) · FEBS Letters · doi:10.1016/0014-5793(84)80820-0 · Cited by 64
Cardiovascular Effects of Caffeine and Stress in Regular Coffee Drinkers
Lane, J. D., & Williams, R. B. (1987) · Psychophysiology · doi:10.1111/j.1469-8986.1987.tb00271.x · Cited by 63
Hemodynamic and humoral effects of coffee after β1-selective and nonselective β-blockade
Smits, P., Hoffmann, H. J., Thien, T. A., Houben, H. H. M. L., & Laar, A. V. '. (1983) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.1983.145 · Cited by 61
Self-citationThe role of epinephrine in the circulatory effects of coffee
Smits, P., Pieters, G., & Thien, T. (1986) · Clinical Pharmacology and Therapeutics · doi:10.1038/clpt.1986.203 · Cited by 60
Self-citationMostaza, Vega, Snell, & Grundy, S. M. (1998) · Journal of Internal Medicine · doi:10.1046/j.1365-2796.1998.00298.x · Cited by 59
Challis, R. A. J., Budohoski, L., McManus, B., & Newsholme, E. A. (1984) · Biochemical Journal · doi:10.1042/bj2210915 · Cited by 55
Froldi, G., & Belardinelli, L. (1990) · Circulation Research · doi:10.1161/01.res.67.4.960 · Cited by 54
Adenosine potentiates insulin-stimulated myocardial glucose uptake in vivo
Law, W. R., & Raymond, R. M. (1988) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1988.254.5.h970 · Cited by 52
The effects of chronic caffeine administration on peripheral adenosine receptors.
Zhang, Y., & Wells, J. N. (1990) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)12725-0 · Cited by 49
Debrah, K., Haigh, R. A., Sherwin, R., Murphy, J., & Kerr, D. E. (1995) · Clinical Science · doi:10.1042/cs0890475 · Cited by 36
The cardiovascular interaction between caffeine and nicotine in humans
Smits, P., Temme, L., & Thien, T. A. (1993) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.1993.131 · Cited by 30
Self-citationDose-dependent inhibition of the hemodynamic response to dipyridamole by caffeine
Smits, P., Straatman, C., Pijpers, E., & Thien, T. (1991) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.1991.178 · Cited by 30
Self-citationAgata, J., Miyazaki, Y., Takada, M., Murakami, H., Masuda, A., Miura, T., Ura, N., & Shimamoto, K. (1998) · Hypertension Research · doi:10.1291/hypres.21.57 · Cited by 28
Andersson, P.-E., Lind, L., Berne, C., Berglund, L., & Lithell, H. (1999) · Journal of Internal Medicine · doi:10.1046/j.1365-2796.1999.00549.x · Cited by 8
Untersuchungen über die Wirkung von Coffein auf ausgewählte Stoffwechselparameter in vivo
Sachs, M., & Forster, H. (1984) · Zeitschrift für Ernährungswissenschaft · doi:10.1007/bf02021472 · Cited by 7
Insulin-resistant hyperglycemia produced by aminophylline.
Jc, P., Lazarus, N. R., Yamaguchi, N., Gutman, R. A., & Recant, L. (1972) · PubMed · Cited by 1
Flagged first, then by citations
1 of the 42 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Coffee and Health: A Review of Recent Human Research
Higdon, J. V., & Frei, B. (2006) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408390500400009 · Cited by 1,090
Brouns, F., Bjorck, I., Frayn, K. N., Gibbs, A. L., Lang, V., Slama, G., & Wolever, T. M. S. (2005) · Nutrition Research Reviews · doi:10.1079/nrr2005100 · Cited by 1,093
Curriculum, K. (2006) · Cited by 768
Coffee Consumption and Risk of Type 2 Diabetes: A Systematic Review
van Dam, R. M., & Hu, F. B. (2005) · JAMA · doi:10.1001/jama.294.1.97 · Cited by 662
Coffee and its Consumption: Benefits and Risks
Butt, M. S., & Sultan, M. T. (2011) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408390903586412 · Cited by 631
Metadata
- Authors
- Keijzers, G. B., De Galan, B. E., Tack, C. J., & Smits, P.
- Affiliations
- Department of Internal Medicine, University Medical Center, Nijmegen, the Netherlands
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2002-02-01
- Volume
- 25
- Issue
- 2
- Pages
- 364-369
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W2112839007
- Cited by
- 358
- References
- 42
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 9 · 2023: 8 · 2022: 16 · 2021: 13 · 2020: 14 · 2019: 14 · 2018: 11 · 2017: 11 · 2016: 9 · 2015: 17 · 2014: 19 · 2013: 23 · 2012: 20
- FWCI
- 10.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes Care (publishedVersion)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- European Commission
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Coffee research and impacts
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- caffeine, insulin sensitivity, insulin resistance, catecholamines, epinephrine, norepinephrine, adenosine receptor antagonism, dipyridamole, free fatty acids, glucose uptake, hyperinsulinemic-euglycemic clamp, blood pressure
- MeSH terms
- Adult, Central Nervous System Stimulants, Caffeine, Dipyridamole, Double-Blind Method, Epinephrine, Female, Humans, Hyperinsulinism, Insulin, Insulin Resistance, Male, Norepinephrine, Phosphodiesterase Inhibitors, Glucose Clamp Technique
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review