Association of coffee consumption and CYP1A2 polymorphism with risk of impaired fasting glucose in hypertensive patients


Whether and how coffee use influences glucose metabolism is still a matter for debate. We investigated whether baseline coffee consumption is longitudinally associated with risk of impaired fasting glucose in a cohort of 18-to-45 year old subjects screened for stage 1 hypertension and whether CYP1A2 polymorphism modulates this association. A total of 1,180 nondiabetic patients attending 17 hospital centers were included. Seventy-four percent of our subjects drank coffee. Among the coffee drinkers, 87 % drank 1–3 cups/day (moderate drinkers), and 13 % drank over 3 cups/day (heavy drinkers). Genotyping of CYP1A2 SNP was performed by real time PCR in 639 subjects. At the end of a median follow-up of 6.1 years, impaired fasting glucose was found in 24.0 % of the subjects. In a multivariable Cox regression coffee use was a predictor of impaired fasting glucose at study end, with a hazard ratio (HR) of 1.3 (95 % CI 0.97–1.8) in moderate coffee drinkers and of 2.3 (1.5–3.5) in heavy drinkers compared to abstainers. Among the subjects stratified by CYP1A2 genotype, heavy coffee drinkers carriers of the slow *1F allele (59 %) had a higher adjusted risk of impaired fasting glucose (HR 2.8, 95 % CI 1.3–5.9) compared to abstainers whereas this association was of borderline statistical significance among the homozygous for the A allele (HR 1.7, 95 % CI 0.8–3.8). These data show that coffee consumption increases the risk of impaired fasting glucose in hypertension particularly among carriers of the slow CYP1A2 *1F allele.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2


  1. 1.

    Fox CS, Coady S, Sorlie PD, D’Agostino RB Sr, Pencina MJ, Vasan RS, et al. Increasing cardiovascular disease burden due to diabetes mellitus: the Framingham Heart Study. Circulation. 2007;115:1544–50.

    Article  PubMed  Google Scholar 

  2. 2.

    Tuomilehto J, Eriksson J. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001;344:1343–50.

    Article  CAS  PubMed  Google Scholar 

  3. 3.

    Huxley R, Lee CM, Barzi F, Timmermeister L, Czernichow S, Perkovic V, et al. Coffee, decaffeinated coffee, and tea consumption in relation to incident type 2 diabetes mellitus: a systematic review with meta-analysis. Arch Intern Med. 2009;169:2053–63.

    Article  PubMed  Google Scholar 

  4. 4.

    Jiang X, Zhang D, Jiang W. Coffee and caffeine intake and incidence of type 2 diabetes mellitus: a meta-analysis of prospective studies. Eur J Nutr. 2014;53:25–38.

    Article  CAS  PubMed  Google Scholar 

  5. 5.

    van Dam RM, Dekker JM, Nijpels G, Stehouwer CD, Bouter LM, Heine RJ. Coffee consumption and incidence of impaired fasting glucose, impaired glucose tolerance, and type 2 diabetes: the Hoorn Study. Diabetologia. 2004;47:2152–9.

    Article  CAS  PubMed  Google Scholar 

  6. 6.

    Agardh EE, Carlsson S, Ahlbom A, Efendic S, Grill V, Hammar N, et al. Coffee consumption, type 2 diabetes and impaired glucose tolerance in Swedish men and women. J Intern Med. 2004;255:645–52.

    Article  CAS  PubMed  Google Scholar 

  7. 7.

    Yamaji T, Mizoue T, Tabata S, Ogawa S, Yamaguchi K, Shimizu E, et al. Coffee consumption and glucose tolerance status in middle-aged Japanese men. Diabetologia. 2004;47:2145–51.

    Article  CAS  PubMed  Google Scholar 

  8. 8.

    Rebello SA, Chen CH, Naidoo N, Xu W, Lee J, Chia KS, et al. Coffee and tea consumption in relation to inflammation and basal glucose metabolism in a multi-ethnic Asian population: a cross-sectional study. Nutr J. 2011;10:61–70.

    Article  PubMed Central  PubMed  Google Scholar 

  9. 9.

    Moisey LL, Kacker S, Bickerton AC, Robinson LE, Graham TE. Caffeinated coffee consumption impairs blood glucose homeostasis in response to high and low glycemic index meals in healthy men. Am J Clin Nutr. 2008;87:1254–61.

    CAS  PubMed  Google Scholar 

  10. 10.

    van Dam RM, Pasman WJ, Verhoef P. Effects of coffee consumption on fasting blood glucose and insulin concentrations: randomized controlled trials in healthy volunteers. Diabetes Care. 2004;27:2990–2.

    Article  PubMed  Google Scholar 

  11. 11.

    Gavrieli A, Fragopoulou E, Mantzoros CS, Yannakoulia M. Gender and body mass index modify the effect of increasing amounts of caffeinated coffee on postprandial glucose and insulin concentrations; a randomized, controlled, clinical trial. Metabolism. 2013;62:1099–106.

    Article  CAS  PubMed  Google Scholar 

  12. 12.

    American Diabetes Association. Executive summary: standards of medical care in diabetes—2012. Diabetes Care. 2012;35(Suppl 1):S4–10.

    Google Scholar 

  13. 13.

    Sartori M, Semplicini A, Siffert W, Mormino P, Mazzer A, Pegoraro F, et al. G-protein beta3-subunit gene 825T allele and hypertension: a longitudinal study in young grade I hypertensives. Hypertension. 2003;42:909–14.

    Article  CAS  PubMed  Google Scholar 

  14. 14.

    Palatini P, Dorigatti F, Santonastaso M, Cozzio S, Biasion T, Garavelli G, et al. Association between coffee consumption and risk of hypertension. Ann Med. 2007;39:545–53.

    Article  CAS  PubMed  Google Scholar 

  15. 15.

    Cornelis MC, El-Sohemy A, Kabagambe EK, Campos H. Coffee, CYP1A2 genotype, and risk of myocardial infarction. JAMA. 2006;295:1135–41.

    Article  CAS  PubMed  Google Scholar 

  16. 16.

    Palatini P, Ceolotto G, Ragazzo F, Dorigatti F, Saladini F, Papparella I, et al. CYP1A2 genotype modifies the association between coffee intake and the risk of hypertension. J Hypertens. 2009;27:1594–601.

    Article  CAS  PubMed  Google Scholar 

  17. 17.

    Wang Y, Wang QJ. The prevalence of prehypertension and hypertension among US adults according to the new joint national committee guidelines: new challenges of the old problem. Arch Intern Med. 2004;164:2126–34.

    Article  PubMed  Google Scholar 

  18. 18.

    Casiglia E, Paleari CD, Petucco S, Bongiovì S, Colangeli G, Baccilieri MS, et al. Haemodynamic effects of coffee and purified caffeine in normal volunteers: a placebo-controlled clinical study. J Hum Hypertens. 1992;6:95–9.

    CAS  PubMed  Google Scholar 

  19. 19.

    Palatini P, Canali C, Graniero GR, Rossi GP, De Toni R, Santonastaso M, et al. Relationship of plasma renin activity with caffeine intake and physical training in mild hypertensive men. Eur J Epidemiol. 1996;12:485–91.

    Article  CAS  PubMed  Google Scholar 

  20. 20.

    Winnicki M, Bonso E, Dorigatti F, Longo D, Zaetta V, Mattarei M, et al. Effect of body weight loss on blood pressure after 6 years of follow-up in stage 1 hypertension. Am J Hypertens. 2006;19:1103–9.

    Article  PubMed  Google Scholar 

  21. 21.

    Palatini P, Penzo M, Canali C, Pessina AC. Validation of the A&D TM-2420 model 7 for ambulatory blood pressure monitoring and effect of microphone replacement on its performance. J Ambul Monit. 1991;4:281–8.

    Google Scholar 

  22. 22.

    O’Brien E, Mee F, Atkins N. O’ Malley K. Accuracy of the Spacelabs 90207 determined by the British Hypertension Society protocol. J Hypertens. 1991;9:573–5.

    Article  PubMed  Google Scholar 

  23. 23.

    National Center for Biotechnology Information. dbSNP Home Page. Accessibility verified on Feb 04, 2014.

  24. 24.

    Keijzers GB, De Galan BE, Tack CJ, Smits P. Caffeine can decrease insulin sensitivity in humans. Diabetes Care. 2002;25:364–9.

    Article  CAS  PubMed  Google Scholar 

  25. 25.

    Thong FS, Derave W, Kiens B, Graham TE, Ursø B, Wojtaszewski JF, et al. Caffeine-induced impairment of insulin action but not insulin signaling in human skeletal muscle is reduced by exercise. Diabetes. 2002;51:583–90.

    Article  CAS  PubMed  Google Scholar 

  26. 26.

    Pizziol A, Tikhonoff V, Paleari CD, Russo E, Mazza A, Ginocchio G, et al. Effects of caffeine on glucose tolerance: a placebo controlled study. Eur J Clin Nutr. 1998;52:846–9.

    Article  CAS  PubMed  Google Scholar 

  27. 27.

    Mougios V, Ring S, Petridou A, Nikolaidis MG. Duration of coffee- and exercise-induced changes in the fatty acid profile of human serum. J Appl Physiol. 2003;94:476–84.

    Article  CAS  PubMed  Google Scholar 

  28. 28.

    Lane JD, Barkauskas CE, Surwit RS, Feinglos MN. Caffeine impairs glucose metabolism in type 2 diabetes. Diabetes Care. 2004;27:2047–8.

    Article  CAS  PubMed  Google Scholar 

  29. 29.

    Battram DS, Arthur R, Weekes A, Graham TE. The glucose intolerance induced by caffeinated coffee ingestion is less pronounced than that due to alkaloid caffeine in men. J Nutr. 2006;136:1276–80.

    CAS  PubMed  Google Scholar 

  30. 30.

    Moisey LL, Robinson LE, Graham TE. Consumption of caffeinated coffee and a high carbohydrate meal affectspostprandial metabolism of a subsequent oral glucose tolerance test in young, healthy males. Br J Nutr. 2010;103:833–41.

    Article  CAS  PubMed  Google Scholar 

  31. 31.

    Bonita JS, Mandarano M, Shuta D, Vinson J. Coffee and cardiovascular disease: in vitro, cellular, animal, and human studies. Pharmacol Res. 2007;55:187–98.

    Article  CAS  PubMed  Google Scholar 

  32. 32.

    Johnston KL, Clifford MN, Morgan LM. Coffee acutely modifies gastrointestinal hormone secretion and glucose tolerance in humans: glycemic effects of chlorogenic acid and caffeine. Am J Clin Nutr. 2003;78:728–33.

    CAS  PubMed  Google Scholar 

  33. 33.

    Shearer J, Farah A, de Paulis T, Bracy DP, Pencek RR, Graham TE, et al. Quinides of roasted coffee enhance insulin action in conscious rats. J Nutr. 2003;133:3529–32.

    CAS  PubMed  Google Scholar 

  34. 34.

    Gu L, Gonzalez FJ, Kalow W, Tang BK. Biotransformation of caffeine, paraxanthine, theobromine and theophylline by cDNA-expressed human CYP1A2 and CYP2E1. Pharmacogenetics. 1992;2:73–7.

    Article  CAS  PubMed  Google Scholar 

  35. 35.

    Sachse C, Brockmoller J, Bauer S, Roots I. Functional significance of a C to A polymorphism in intron 1 of the cytochrome P450 1A2 (CYP1A2) gene tested with caffeine. Br J Clin Pharmacol. 1999;47:445–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. 36.

    Han XM, Ou-Yang DS, Lu PX, Jiang CH, Shu Y, Chen XP, et al. Plasma caffeine metabolite ratio (17X/137X) in vivo associated with G-2964A and C734 polymorphisms of human CYP1A2. Pharmacogenetics. 2001;11:429–35.

    Article  CAS  PubMed  Google Scholar 

  37. 37.

    Avogaro A, Toffolo G, Valerio A, Cobelli C. Epinephrine exerts opposite effects on peripheral glucose disposal and glucose-stimulated insulin secretion: a stable label intravenous glucose tolerance test minimal model study. Diabetes. 1996;45:1373–8.

    Article  CAS  PubMed  Google Scholar 

  38. 38.

    Thong FS, Graham TE. Caffeine-induced impairment of glucose tolerance is abolished by beta-adrenergic receptor blockade in humans. J Appl Physiol. 2002;92:2347–52.

    Article  CAS  PubMed  Google Scholar 

  39. 39.

    Fredholm BB. Astra Award Lecture: adenosine, adenosine receptors and the actions of caffeine. Pharmacol Toxicol. 1995;76:93–101.

    Article  CAS  PubMed  Google Scholar 

  40. 40.

    Green MS, Symons MJA. Comparison of the logistic risk function and the proportional hazards model in prospective epidemiologic studies. J Chronic Dis. 1983;36:715–24.

    Article  CAS  PubMed  Google Scholar 

  41. 41.

    Peduzzi P, Holford T, Detre K, Chan YK. Comparison of the logistic and Cox regression models when outcome is determined in all patients after a fixed period of time. J Chronic Dis. 1987;40:761–7.

    Article  CAS  PubMed  Google Scholar 

  42. 42.

    Annesi I, Moreau T, Lellouch J. Efficiency of the logistic regression and Cox proportional hazards models in longitudinal studies. Stat Med. 1989;8:1515–21.

    Article  CAS  PubMed  Google Scholar 

  43. 43.

    van Dam RM, Feskens EJ. Coffee consumption and risk of type 2 diabetes mellitus. Lancet. 2002;9344:1477–8.

    Google Scholar 

  44. 44.

    van Dam RM, Willett WC, Manson JE, Hu FB. Coffee, caffeine, and risk of type 2 diabetes: a prospective cohort study in younger and middle-aged US women. Diabetes Care. 2006;2:398–403.

    Google Scholar 

  45. 45.

    Hjellvik V, Tverdal A, Strom H. Boiled coffee intake and subsequent risk for type 2 diabetes. Epidemiology. 2011;3:418–21.

    Article  Google Scholar 

  46. 46.

    Sartorelli DS, Fagherazzi G, Balkau B, Touillaud MS, Boutron-Ruault MC, de Lauzon-Guillain B, et al. Differential effects of coffee on the risk of type 2 diabetes according to meal consumption in a French cohort of women: the E3N/EPIC cohort study. Am J Clin Nutr. 2010;4:1002–12.

    Article  Google Scholar 

Download references


The study was funded by the University of Padova, Padova, Italy, and by the Associazione “18 Maggio 1370”, San Daniele del Friuli, Italy.

Conflict of interest

The authors have no financial interest in the subject matter or materials discussed in the manuscript.

Author information



Corresponding author

Correspondence to Paolo Palatini.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Palatini, P., Benetti, E., Mos, L. et al. Association of coffee consumption and CYP1A2 polymorphism with risk of impaired fasting glucose in hypertensive patients. Eur J Epidemiol 30, 209–217 (2015).

Download citation


  • Coffee
  • Caffeine
  • Hypertension
  • Prediabetes
  • CYP1A2
  • Genes