Diabetologia (2015) 58:199–200 DOI 10.1007/s00125-014-3425-3
LETTER
Coffee consumption and risk of type 2 diabetes Paolo Palatini
Received: 17 September 2014 / Accepted: 3 October 2014 / Published online: 26 October 2014 # Springer-Verlag Berlin Heidelberg 2014
Keywords Caffeine . Coffee . CYP1A2 . Genetics . Type 2 diabetes
To the Editor: Controversy still exists over the relationship between coffee consumption and risk of type 2 diabetes mellitus. A number of prospective studies have reported a negative association between increased coffee consumption and risk of type 2 diabetes [1]. According to a recent metaanalysis, the incidence of type 2 diabetes decreased by 12% for every two cups per day increase in caffeinated coffee intake, and by 11% for every two cups per day increase in decaffeinated coffee intake [1]. Paradoxically, short-term metabolic studies have shown that caffeinated coffee impairs postprandial glycaemic control [2], an effect not seen with decaffeinated coffee [2], thus casting doubts on the beneficial effects of caffeinated coffee on glucose metabolism. In a recent report published in Diabetologia, Bhupathiraju et al, using data from three large prospective studies, reported that participants who increased their intake of caffeinated coffee by more than one cup per day over a 4 year period had an 11% (95% CI 3%, 18%) lower risk of type 2 diabetes in the subsequent 4 years compared with those who made no changes in their coffee consumption [3]. Conversely, participants who decreased their caffeinated coffee consumption by more than one cup per day had a 17% (95% CI 8%, 26%) higher risk of type 2 diabetes. However, Bhupathiraju et al emphasised only caffeine when discussing the relationship between coffee intake and risk of type 2 diabetes [3] and did not consider the potential beneficial effects of coffee components other than caffeine on glucose metabolism. P. Palatini (*) Department of Medicine, University of Padova, Via Giustiniani, 2, 35128 Padova, Italy e-mail: [email protected]
Coffee is a ‘blend’ of a large number of bioactive chemicals that may have different effects on glycaemic control. Among these, the polyphenols dihydrocaffeic acid and chlorogenic acid seem to act as protective antioxidants and to have beneficial actions on glucose homeostasis [4]. In a previous analysis of the Health Professionals Follow-Up Study, the same group of investigators found that consumption of caffeinated coffee was associated with a 4% lower risk of type 2 diabetes (RR 0.96; 95% CI 0.93, 0.98), and that decaffeinated coffee was associated with a 7% lower risk of type 2 diabetes (RR 0.93; 95% CI 0.89, 0.97) [5]. These findings suggest that coffee components other than caffeine may exert a beneficial effect on glucose metabolism. This concept is supported by the results of experimental studies in rats on diet-induced whole-body insulin resistance, which showed that decaffeinated coffee improved insulinstimulated whole-body glucose disposal during a hyperinsulinaemic–euglycaemic clamp, an effect that was abolished in the rats that received decaffeinated coffee with added caffeine [6]. Thus, it is possible that coffee components other than caffeine may reduce or antagonise the adverse effects of caffeine on glucose metabolism that have been found in intervention studies. It should be pointed out that 95% of caffeine is detoxified through an initial N3-demethylation catalysed by CYP1A2, and that caffeine is an inducer of the enzyme [7]. This enzyme has wide interindividual variability in activity, which is regulated by a genetic polymorphism. Individuals homozygous for the CYP1A2 *1A/*1A genotype are fast caffeine metabolisers, whereas carriers of the *1F allele are slow metabolisers and are therefore more exposed to the effects of caffeine [7]. In a recent study, we investigated whether baseline coffee consumption was longitudinally associated with the risk of impaired glucose tolerance [8]. The analysis was conducted in a cohort of 1,180 non-diabetic young to middle-aged participants screened for stage 1 hypertension who were recruited
200
from 17 hospital centres in north-east Italy. We found that coffee use was a predictor of impaired glucose tolerance after a median follow-up of 6 years. However, the risk of having impaired fasting glucose largely differed according to the participants’ CYP1A2 genotype. Heavy coffee drinkers (≥ four cups of espresso coffee per day) who were carriers of the slow *1F allele (59% of the sample) had a higher adjusted risk of impaired fasting glucose (HR 2.8; 95% CI 1.3, 5.9; p=0.008) compared with abstainers, whereas those participants homozygous for the *1A allele did not show a significant increase in risk irrespective of whether they were heavy (HR 1.71; 95% CI 0.76, 3.84; p=0.20) or moderate (1–3 cups per day) coffee drinkers (HR 1.33; 95% CI 0.67, 2.67; p=0.42). These data suggest that, in participants with the fast CYP1A2 *1A/*1A genotype, the harmful effects of caffeine on glucose metabolism are less marked and are outweighed by the favourable action of polyphenols or other bioactive agents [7, 9, 10]. In contrast, in carriers of CYP1A2*1F allele, who are slow caffeine metabolisers, the adverse effects of caffeine seem to prevail [7, 9, 10]. Similar diverging effects of coffee have been found in other clinical settings. In patients with myocardial infarction, Cornelis et al found that carriers of *1F allele had an increased risk of myocardial infarction with increasing coffee consumption, whereas those homozygous for the *1A allele showed a decrease in risk [9]. In 553 participants from the HARVEST study, we showed that an increased risk of hypertension was present only among carriers of the slow *1F allele, whereas among individuals with *1A/*1A genotype, there was a reduction in risk [10]. These data stress the importance of studying the risk related to coffee drinking in a population by taking individual genetic backgrounds into account to avoid drawing wrong inferences. The distribution of CYP1A2 genotypes may vary in different populations [9, 10], and a study’s overall results will largely depend on the frequency of carriers of the *1F allele in that population. This variability may explain the different results related to the relationship between coffee use and glucose metabolism that have been found in previous studies. The potential for residual confounding due to a failure to control for the effect of unmeasured factors may also explain previous
Diabetologia (2015) 58:199–200
conflicting findings. Interventional studies in participants stratified by CYP1A2 genotype are needed before guidelines regarding coffee consumption for patients at risk of diabetes can be implemented. Funding This letter received no specific funding. Duality of interest The author declares that there is no duality of interest associated with this manuscript. Contribution statement The author was the sole contributor to this paper.
References 1. Jiang X, Zhang D, Jiang W (2014) Coffee and caffeine intake and incidence of type 2 diabetes mellitus: a meta-analysis of prospective studies. Eur J Nutr 53:25–38 2. Moisey LL, Kacker S, Bickerton AC, Robinson LE, Graham TE (2008) Caffeinated coffee consumption impairs blood glucose homeostasis in response to high and low glycemic index meals in healthy men. Am J Clin Nutr 87:1254–1261 3. Bhupathiraju SN, Pan A, Manson JE, Willett WC, van Dam RM, Hu FB (2014) Changes in coffee intake and subsequent risk of type 2 diabetes: three large cohorts of US men and women. Diabetologia 57:1346–1354 4. Johnston KL, Clifford MN, Morgan LM (2003) Coffee acutely modifies gastrointestinal hormone secretion and glucose tolerance in humans: glycemic effects of chlorogenic acid and caffeine. Am J Clin Nutr 78:728–733 5. Bhupathiraju SN, Pan A, Malik VS et al (2013) Caffeinated and caffeine-free beverages and risk of type 2 diabetes. Am J Clin Nutr 97:155–166 6. Shearer J, Farah A, de Paulis T et al (2003) Quinides of roasted coffee enhance insulin action in conscious rats. J Nutr 133:3529–3532 7. Han XM, Ou-Yang DS, Lu PX et al (2001) Plasma caffeine metabolite ratio (17X/137X) in vivo associated with G-2964A and C734 polymorphisms of human CYP1A2. Pharmacogenetics 11:429–435 8. Mos L, Benetti E, Garavelli G et al (2014) Coffee consumption and risk of prediabetes in hypertension: results of the HARVEST study. Eur Heart J 35(Suppl 1):S1018 9. Cornelis MC, El-Sohemy A, Kabagambe EK, Campos H (2006) Coffee, CYP1A2 genotype, and risk of myocardial infarction. JAMA 295:1135–1141 10. Palatini P, Ceolotto G, Ragazzo F et al (2009) CYP1A2 genotype modifies the association between coffee intake and the risk of hypertension. J Hypertens 27:1594–1601
LETTER
Coffee consumption and risk of type 2 diabetes Paolo Palatini
Received: 17 September 2014 / Accepted: 3 October 2014 / Published online: 26 October 2014 # Springer-Verlag Berlin Heidelberg 2014
Keywords Caffeine . Coffee . CYP1A2 . Genetics . Type 2 diabetes
To the Editor: Controversy still exists over the relationship between coffee consumption and risk of type 2 diabetes mellitus. A number of prospective studies have reported a negative association between increased coffee consumption and risk of type 2 diabetes [1]. According to a recent metaanalysis, the incidence of type 2 diabetes decreased by 12% for every two cups per day increase in caffeinated coffee intake, and by 11% for every two cups per day increase in decaffeinated coffee intake [1]. Paradoxically, short-term metabolic studies have shown that caffeinated coffee impairs postprandial glycaemic control [2], an effect not seen with decaffeinated coffee [2], thus casting doubts on the beneficial effects of caffeinated coffee on glucose metabolism. In a recent report published in Diabetologia, Bhupathiraju et al, using data from three large prospective studies, reported that participants who increased their intake of caffeinated coffee by more than one cup per day over a 4 year period had an 11% (95% CI 3%, 18%) lower risk of type 2 diabetes in the subsequent 4 years compared with those who made no changes in their coffee consumption [3]. Conversely, participants who decreased their caffeinated coffee consumption by more than one cup per day had a 17% (95% CI 8%, 26%) higher risk of type 2 diabetes. However, Bhupathiraju et al emphasised only caffeine when discussing the relationship between coffee intake and risk of type 2 diabetes [3] and did not consider the potential beneficial effects of coffee components other than caffeine on glucose metabolism. P. Palatini (*) Department of Medicine, University of Padova, Via Giustiniani, 2, 35128 Padova, Italy e-mail: [email protected]
Coffee is a ‘blend’ of a large number of bioactive chemicals that may have different effects on glycaemic control. Among these, the polyphenols dihydrocaffeic acid and chlorogenic acid seem to act as protective antioxidants and to have beneficial actions on glucose homeostasis [4]. In a previous analysis of the Health Professionals Follow-Up Study, the same group of investigators found that consumption of caffeinated coffee was associated with a 4% lower risk of type 2 diabetes (RR 0.96; 95% CI 0.93, 0.98), and that decaffeinated coffee was associated with a 7% lower risk of type 2 diabetes (RR 0.93; 95% CI 0.89, 0.97) [5]. These findings suggest that coffee components other than caffeine may exert a beneficial effect on glucose metabolism. This concept is supported by the results of experimental studies in rats on diet-induced whole-body insulin resistance, which showed that decaffeinated coffee improved insulinstimulated whole-body glucose disposal during a hyperinsulinaemic–euglycaemic clamp, an effect that was abolished in the rats that received decaffeinated coffee with added caffeine [6]. Thus, it is possible that coffee components other than caffeine may reduce or antagonise the adverse effects of caffeine on glucose metabolism that have been found in intervention studies. It should be pointed out that 95% of caffeine is detoxified through an initial N3-demethylation catalysed by CYP1A2, and that caffeine is an inducer of the enzyme [7]. This enzyme has wide interindividual variability in activity, which is regulated by a genetic polymorphism. Individuals homozygous for the CYP1A2 *1A/*1A genotype are fast caffeine metabolisers, whereas carriers of the *1F allele are slow metabolisers and are therefore more exposed to the effects of caffeine [7]. In a recent study, we investigated whether baseline coffee consumption was longitudinally associated with the risk of impaired glucose tolerance [8]. The analysis was conducted in a cohort of 1,180 non-diabetic young to middle-aged participants screened for stage 1 hypertension who were recruited
200
from 17 hospital centres in north-east Italy. We found that coffee use was a predictor of impaired glucose tolerance after a median follow-up of 6 years. However, the risk of having impaired fasting glucose largely differed according to the participants’ CYP1A2 genotype. Heavy coffee drinkers (≥ four cups of espresso coffee per day) who were carriers of the slow *1F allele (59% of the sample) had a higher adjusted risk of impaired fasting glucose (HR 2.8; 95% CI 1.3, 5.9; p=0.008) compared with abstainers, whereas those participants homozygous for the *1A allele did not show a significant increase in risk irrespective of whether they were heavy (HR 1.71; 95% CI 0.76, 3.84; p=0.20) or moderate (1–3 cups per day) coffee drinkers (HR 1.33; 95% CI 0.67, 2.67; p=0.42). These data suggest that, in participants with the fast CYP1A2 *1A/*1A genotype, the harmful effects of caffeine on glucose metabolism are less marked and are outweighed by the favourable action of polyphenols or other bioactive agents [7, 9, 10]. In contrast, in carriers of CYP1A2*1F allele, who are slow caffeine metabolisers, the adverse effects of caffeine seem to prevail [7, 9, 10]. Similar diverging effects of coffee have been found in other clinical settings. In patients with myocardial infarction, Cornelis et al found that carriers of *1F allele had an increased risk of myocardial infarction with increasing coffee consumption, whereas those homozygous for the *1A allele showed a decrease in risk [9]. In 553 participants from the HARVEST study, we showed that an increased risk of hypertension was present only among carriers of the slow *1F allele, whereas among individuals with *1A/*1A genotype, there was a reduction in risk [10]. These data stress the importance of studying the risk related to coffee drinking in a population by taking individual genetic backgrounds into account to avoid drawing wrong inferences. The distribution of CYP1A2 genotypes may vary in different populations [9, 10], and a study’s overall results will largely depend on the frequency of carriers of the *1F allele in that population. This variability may explain the different results related to the relationship between coffee use and glucose metabolism that have been found in previous studies. The potential for residual confounding due to a failure to control for the effect of unmeasured factors may also explain previous
Diabetologia (2015) 58:199–200
conflicting findings. Interventional studies in participants stratified by CYP1A2 genotype are needed before guidelines regarding coffee consumption for patients at risk of diabetes can be implemented. Funding This letter received no specific funding. Duality of interest The author declares that there is no duality of interest associated with this manuscript. Contribution statement The author was the sole contributor to this paper.
References 1. Jiang X, Zhang D, Jiang W (2014) Coffee and caffeine intake and incidence of type 2 diabetes mellitus: a meta-analysis of prospective studies. Eur J Nutr 53:25–38 2. Moisey LL, Kacker S, Bickerton AC, Robinson LE, Graham TE (2008) Caffeinated coffee consumption impairs blood glucose homeostasis in response to high and low glycemic index meals in healthy men. Am J Clin Nutr 87:1254–1261 3. Bhupathiraju SN, Pan A, Manson JE, Willett WC, van Dam RM, Hu FB (2014) Changes in coffee intake and subsequent risk of type 2 diabetes: three large cohorts of US men and women. Diabetologia 57:1346–1354 4. Johnston KL, Clifford MN, Morgan LM (2003) Coffee acutely modifies gastrointestinal hormone secretion and glucose tolerance in humans: glycemic effects of chlorogenic acid and caffeine. Am J Clin Nutr 78:728–733 5. Bhupathiraju SN, Pan A, Malik VS et al (2013) Caffeinated and caffeine-free beverages and risk of type 2 diabetes. Am J Clin Nutr 97:155–166 6. Shearer J, Farah A, de Paulis T et al (2003) Quinides of roasted coffee enhance insulin action in conscious rats. J Nutr 133:3529–3532 7. Han XM, Ou-Yang DS, Lu PX et al (2001) Plasma caffeine metabolite ratio (17X/137X) in vivo associated with G-2964A and C734 polymorphisms of human CYP1A2. Pharmacogenetics 11:429–435 8. Mos L, Benetti E, Garavelli G et al (2014) Coffee consumption and risk of prediabetes in hypertension: results of the HARVEST study. Eur Heart J 35(Suppl 1):S1018 9. Cornelis MC, El-Sohemy A, Kabagambe EK, Campos H (2006) Coffee, CYP1A2 genotype, and risk of myocardial infarction. JAMA 295:1135–1141 10. Palatini P, Ceolotto G, Ragazzo F et al (2009) CYP1A2 genotype modifies the association between coffee intake and the risk of hypertension. J Hypertens 27:1594–1601
