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roasted coffee blend positively affects glucose metabolism and insulin resistance in humans
Food Research International 89 (2016) 1023–1028
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Long-term consumption of a green/roasted coffee blend positively affects glucose metabolism and insulin resistance in humans Beatriz Sarriá ⁎, Sara Martínez-López, Raquel Mateos, Laura Bravo-Clemente Department of Metabolism and Nutrition, Institute of Food Science, Technology and Nutrition (ICTAN-CSIC), Spanish National Research Council (CSIC), José Antonio Nováis 10, 28040 Madrid, Spain
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Article history: Received 22 July 2015 Received in revised form 29 December 2015 Accepted 31 December 2015 Available online 4 January 2016 Keywords: Coffee Type 2 diabetes mellitus Glucose Insulin HOMA Glucagon Glucose-dependent insulinotropic polypeptide Glucagon-like peptide-1
a b s t r a c t Protective health effects of coffee could have a widespread impact on public health considering the high intake of this beverage in industrialized countries. However, certain of coffee's health effects are contradictory such as those on type 2 diabetes mellitus (T2DM). Green coffee is richer in antioxidant phenols than roasted coffee, and thus it is likely to be a healthier option. This work evaluated the effects of long-term consumption of green coffee consumption, blended with roasted beans to improve palatability, on different glucose homeostasis markers as T2DM risk factors. A, randomized, controlled, crossover study was performed in 52 healthy men and women who consumed three servings/day of the green/roasted (35:65) coffee blend for 8 weeks during the intervention in comparison with not consuming coffee in the control stage. At the beginning and end of the coffee and control interventions, blood samples were collected, body weight measured, and dietary records and physical activity questionnaires completed. After the coffee intervention, fasting glucose levels and HOMAIR values were significantly lower, whereas QUICKI values were higher showing improved insulin sensitivity. Fasting glucagon levels decreased, which may be associated with the increase in the glucagon-like peptide-1 (GLP-1), whereas C-peptide, glucose-dependent insulinotropic polypeptide (GIP), insulin, and HOMA-β were not affected. In conclusion, regularly consuming the green/roasted coffee blend may be recommended to prevent T2DM and reduce cardiovascular risk. © 2016 Elsevier Ltd. All rights reserved.
1. Introduction The worldwide prevalence of type 2 diabetes mellitus (T2DM) is increasing globally and may reach 366 million people by 2030 (Ding, Bhupathiraju, Chen, van Dam, & Hu, 2014). T2DM is associated with variable degrees of insulin resistance, impaired insulin secretion, moderate to severe beta-cell apoptosis and increased hepatic glucose production. Unlike type 1 diabetes mellitus, the onset of T2DM is slow and the metabolic abnormalities that lead to hyperglycemia are established long before overt diabetes. Hepatic glucose production is the main contributor to fasting plasma glucose concentration and is regulated primarily by plasma insulin and glucagon concentrations (Abdul-Ghani, Williams, DeFronzo, & Stern, 2006). In turn, incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which are secreted in response to food intake, contribute to the regulation of glucagon and glucose-dependent insulin secretion. Both incretins stimulate insulin secretion, although they exert opposing effects on glucagon, since GLP-1 suppresses and GIP enhances glucagon secretion (Yabe et al., 2015). The effects of the incretin hormones are
⁎ Corresponding author at: Institute of Food Science, Technology and Nutrition (ICTANCSIC), José Antonio Novais 10, 28040 Madrid, Spain. E-mail address: [email protected] (B. Sarriá).
http://dx.doi.org/10.1016/j.foodres.2015.12.032 0963-9969/© 2016 Elsevier Ltd. All rights reserved.
very limited during fasting conditions, as circulating concentrations of GLP-1 and GIP are low (Nolan & Færch, 2012). Many studies have shown that dietary components or foods affect postprandial glucose, glucagon, insulin and incretin hormones; however, less have examined the effects of regular consumption of dietary components on the fasting concentrations of the glucose metabolism related biomarkers. Particularly, studies looking into the effects of micronutrients and phytochemicals on glucose metabolism are scarce. Advances in understanding the anti-diabetic actions of dietary flavonoids have been recently reviewed by Babu, Liu, and Gilbert (2013). In a previous revision by van Dam (2006), consumption of coffee, rich in hydroxycinnamic acids and caffeine, was pointed to affect postprandial glucose metabolism rather than fasting glucose levels. Some human trials have shown that glucose tolerance is reduced shortly after ingestion of caffeine or caffeinated coffee, suggesting that short-term coffee consumption could increase the risk of diabetes (Olthof, van Dijk, Deacon, Heine, & van Dam, 2011). However, there is increasing scientific evidence that supports an inverse relationship between coffee consumption and T2DM (Akash, Rehman, & Chen, 2014), being stronger the association with decaffeinated coffee (Pereira, Parker, & Folsom, 2006); therefore, it has been suggested that the positive, T2DM protective effects of coffee are associated with non-caffeine compounds. Coffee contains diterpens (cafestol and kahweol, up to 0.6% of final weight), and micronutrients, among which outstands magnesium
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(Ding et al., 2014), but it is also a rich source of polyphenols (up to 11% of the coffee bean). The main phenolic compounds in green coffee are hydroxycinnamic acids, mostly 3-, 4-, and 5-caffeoylquinic acids (3-, 4- and 5-CQA), 3,4-, 3,5-, and 4,5-dicaffeoylquinic acids (3,4-, 3,5-, and 4,5-DCQA), and 3-, 4-, and 5-feruloylquinic acids (3-, 4-, and 5-FQA), among others (Alonso-Salces, Serra, Reniero, & Héberger, 2009). Roasting drastically degrades and/or transforms green coffee polyphenols (Perrone, Farah, & Donangelo, 2012; Schenker et al., 2002; Somporn, Kamtuo, Theerakulpisut, & Siriamornpun, 2011) inducing the formation of Maillard reaction products and quinides. The intake of green coffee products has increased in recent years as a healthier option than roasted coffee (Kozuma, Tsuchiya, Kohori, Hase, & Tokimitsu, 2005), although its bitter taste limits green coffee acceptance. Bearing this in mind, a blend of green and roasted beans can be an alternative well accepted by coffee consumers with greater health potential than traditional roasted coffee. Considering the high intake of this beverage, particularly in industrialized countries where it is the largest source of dietary antioxidants (Tunnicliffe & Shearer, 2008), the health protective effects of coffee could have a widespread impact on the population health. Moreover, coffee could be recommended to patients at risk of T2DM as a supplementary therapy in preventing the further progression of the disease or to prevent the onset in healthy and at risk adults. Therefore, the aim of this work was to evaluate the effects of long term consumption of a green/roasted (35/65) coffee blend on glucose homeostasis markers, as T2DM risk factors, in healthy adults, attempting to understand the mechanisms involved.
2.3. Dietary control and compliance
2. Experimental methods 2.1. Subjects This study was conducted according to the guidelines laid down in the Declaration of Helsinki and all procedures were approved by the Clinical Research Ethics Committee of Hospital Universitario Puerta de Hierro Majadahonda in Madrid (Spain). Written informed consent was obtained from all subjects. Volunteer recruitment was carried out through placing advertisements in the Universidad Complutense campus as well as through giving short talks between lectures. The inclusion criteria were: being non-diabetic (excluded by the results of a glucose test and health questionnaire), non-vegetarian, non-smoker, nonpregnant women and men, between 18 and 55 y old, not suffering from any other chronic pathology and presenting a body mass index between 20 and 25 kg/m2. None had taken dietary supplements, laxatives, or antibiotics six months before the start of the study. Fifty-three subjects initially accepted to participate in the study, however 52 completed it. Baseline characteristics of the volunteers are shown in Table 1. 2.2. Study design This was a randomized, controlled, crossover study carried out in free-living people. After a 2 week run in stage, subjects were randomly assigned to the coffee or control intervention, lasting 8 weeks each, which were separated by a 2 week washout period. During the coffee intervention, volunteers consumed three times a day the soluble green/ roasted coffee blend, the first at breakfast, the second between breakfast and lunch, and the third between lunch and dinner. In the control Table 1 Baseline characteristics of the participants in the study
Age (years) Body mass index (kg/m2)
intervention, instead of the coffee product, the study participants had water or an isotonic drink, free of sugar, polyphenols and methylxanthines. The soluble green/roasted coffee blend, which was commercialized at the time of the study, was provided by the manufacturing company in unlabelled, individual sachets containing 2 g of coffee (equivalent to two teaspoons, quantity that can reasonably be used to prepare a cup of coffee). The coffee studied contained 85.1 ± 1.6 mg/g (dry matter) of total hydroxycinnamic acids (mainly chlorogenic acid) and 20.0 ± 1.8 mg/g (dry matter) of caffeine. Therefore, volunteers daily consumed 6 g of the coffee blend which provided 510.6 and 120 mg of total hydroxycinnamic acids and caffeine, respectively. The green/roasted coffee blend was particularly interesting to study because on the one hand, it is richer in chlorogenic acid than roasted coffee and thus was expected to be healthier, and on the other hand, the blend keeps the organoleptic properties of roasted coffee (which green coffee lacks) that are much appreciated by coffee drinkers, adding to its acceptability by consumers. From the run-in stage till the end of the study, foods rich in polyphenols and methylxanthines were restricted. Hydroxycinnamic acids are abundant in a variety of fruits and vegetables, such as chard, artichoke, eggplant, broccoli, loquats, tangerines, oranges, apricot, cherries, plums, prunes, grapes, raisins, blueberries and other fruits of the forest. All these foods were constrained, as well as coffee, mate, cocoa, and tea and derived drinks. On the other hand, ferulic acid and its derivatives are the most abundant hydroxycinnamic acids found in cereals, thus whole grain products were also restricted along the study.
Women (n = 32)
Men (n = 20)
29.4 ± 9.5 21.7 ± 2.5
29.8 ± 8.9 24.8 ± 2.7
Data represents mean ± standard deviation of mean.
Subjects were asked to maintain the same dietary habits along the study. Their dietary intake was regularly evaluated to control any possible changes. Volunteers were instructed on how to fill in the dietary records before starting the study. In the run in stage and at the end of the two intervention periods, volunteers were asked to complete a 72-hour detailed food intake report, specifying the ingredients and amounts of food consumed, including serving weights (when possible) or household measurements. Compliance was controlled by counting the number of coffee sachets provided to the volunteers before and after the intervention, as well as by weekly calling the volunteers. In order to assess dietary composition, the program DIAL [Department of Nutrition and Bromathology I. School of Pharmacy. Complutense University of Madrid (UCM), Spain] was used. 2.4. Blood samples Blood samples were drawn after 8–10 h overnight fasting at baseline and at the last day of the control and coffee intervention. Serum (without anticoagulant) and plasma (EDTA-coated tubes) were separated by centrifugation and frozen at −80 °C until analysis. 2.5. Diabetes biomarkers and related indexes Fasting glucose was analyzed using a colorimetric kit (Sprinreact). Fasting insulin, as well as GIP, GLP-1, C-peptide, and glucagon were analyzed using the Bio-Rad Multiplex Diabetes kit on Bio-Plex MAGPIX system. Using fasting glucose and insulin data, Homeostasis Model Assessment indexes were calculated to estimate insulin resistance (HOMA-IR) and beta cell function (HOMA-β) according to the equations by Matthews et al. (1985): HOMA-IR = [Glucose (mg/dL) × Insulin (mU/L)] / 405; HOMA-β = [(Insulin (mU/L) × 360) / (Glucose (mg/dL) − 63)]. Another model to calculate beta- cell function, the insulin/glucose ratio, was also used (Meier et al., 2001). In addition, the Quantitative Insulin Sensitivity Check Index (QUICKI) was calculated according to the formula by Katz et al. (2000): QUICKI = 1 / [log Insulin (mU/L) + log Glucose (mg/dL)].
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2.6. Physical activity and body weight Participants were asked to maintain their usual level of physical activity during the study. Volunteers filled out a questionnaire before starting the study to evaluate their physical activity including that involved in their occupation; afterwards this was calculated using the program ADN [Department of Nutrition and Bromathology I, School of Pharmacy, Complutense University of Madrid (UCM), Spain]. At baseline and the end of each stage of the study, volunteer's body weight was monitored using the weighing system BC-418 MA (Tanita Corporation). 2.7. Statistical analysis Data are presented as means ± standard error of the mean, unless specified otherwise. Prior to statistical analysis, normality of distribution and homogeneity of variance were verified using the Kolmogorov–Smirnov and Levene tests, respectively. The general linear model of the variance for repeated measures was used to assess the effects of consuming coffee, followed by a Bonferroni test to compare the stages in pairs. Statistical significance was set at P b 0.05 and the analysis was undertaken using the SPSS statistical package (version 21.0, SPSS Inc., IBM Company). 3. Results Attending to volunteers' reports and to the number of servings returned after the intervention, dietary compliance was high. The 72hour detailed food intake reports showed that energy, protein, carbohydrate, dietary fiber, lipid and the polyunsaturated/saturated ratio did not show differences along the study. However, the consumption of the coffee blend significantly reduced body weight (Table 2). Baseline fasting glucose concentration values were within the range of normality according to the Spanish Society of Clinical Biochemistry and Molecular Pathology (SEQC) (Table 3), and insulin results were in agreement with previous studies (Lecoultre et al., 2014; Meier et al., 2001). The values of HOMA-IR were similar to those earlier observed in healthy adults (Acosta, Escalona, Maiz, Pollak, & Leighton, 2002; Lichnovská, Gwozdziewiczová, & Hrebícek, 2002). Insulin sensitivity results, estimated through the QUICKI index (Table 3), which keeps a good correlation with HOMA-IR index as both are calculated from the values of fasting glucose and insulin, were similar to those described by Katz et al. (2000) in healthy volunteers. Finally, the values of HOMA-β index observed were analogous to those reported by Meier et al. (2001) in healthy controls. Among all the aforementioned glucose homeostasis biomarkers and related indexes, only glucose and HOMA-IR decreased after the coffee intervention, in contrast to insulin sensitivity which increased, being the values observed after the coffee intervention significantly different to basal and control data.
Table 2 Reported energy, macronutrient and dietary fiber intakes, PUFA/SFA intake ratio and body weight.
Intake per day Energy (Kcal) Protein (g) Carbohydrate (g) Dietary fiber (g) Lipid (g) PUFA/SFA Body weight (kg)
Basal
Control
Coffee
P
1870.12 ± 72.15 83.81 ± 3.31 181.59 ± 8.21 15.23 ± 0.82 77.94 ± 3.16 0.42 ± 0.02 63.01 ± 1.71
1854.83 ± 63.50 77.73 ± 2.93 175.77 ± 6.59 15.99 ± 0.81 74.19 ± 2.46 0.39 ± 0.02 62.85 ± 1.73
1801.46 ± 60.11 76.46 ± 2.84 174.25 ± 7.56 15.47 ± 0.75 72.20 ± 3.46 0.46 ± 0.03 62.31 ± 1.76
N.S. N.S. N.S. N.S. N.S. N.S. 0.024
Data represents mean ± standard error of mean. P values were assessed using the general linear model of variance for repeated measures.
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Table 3 Effects of regularly consuming the green/roasted coffee blend on fasting glucose and insulin levels and indexes of insulin resistance/sensitivity (HOMA-IR/QUICKI) and pancreatic function (HOMA-β, insulin/glucose) in healthy subjects. Basal Glucose (mg/dL) Insulin (mU/L) HOMA-IR HOMA-β (%) Insulin/glucose [(mU/L)/(mg/dL)] QUICKI C-peptide (pg/mL)
Control
Coffee
P
75.47 ± 1.10 a 76.50 ± 1.24 a 72.35 ± 1.1 b 0.007 8.20 ± 0.45 8.42 ± 0.45 7.73 ± 0.44 N.S. 1.67 ± 0.06 a 1.72 ± 0.05 a 1.47 ± 0.05 b 0.001 180.52 ± 18.69 159.63 ± 18.42 179.27 ± 20.71 N.S. 0.07 ± 0.01 0.08 ± 0.01 0.07 ± 0.01 N.S. 0.36 ± 0.00 a 0.35 ± 0.00 a 0.36 ± 0.00 b 0.008 924.74 ± 28.88 923.47 ± 28.52 882.47 ± 30.26 N.S.
Data represents mean ± standard error of mean. HOMA-IR: homeostasis model assessment of insulin resistance; HOMA-β: homeostasis model assessment of beta cell function; QUICKI: quantitative insulin sensitivity check index. P values were assessed using the general linear model of variance for repeated measures. a.b Mean values within a row with unlike letters were significantly different according to the Bonferroni test.
In agreement to insulin results, C-peptide concentrations did not change due to coffee consumption. Contrarily, glucagon concentration significantly changed along the study, showing lower values after the control and coffee intervention than at baseline (Fig. 1A). Glucagon concentrations were similar to those described by Knop et al. (2013) in obese (BMI = 32 ± 1 kg/m2) but otherwise healthy men. The decrease in glucagon concentration may be related with the significant increase in GLP-1 levels after the coffee intervention compared to baseline values (Fig. 1B). Differently, there were not significant changes in GIP levels (Fig. 1C). Insulin, glucagon, C-peptide, GLP-1 and GIP values were within the ranges observed by Wang, Zhou, Yaung, Ma, and Geng (2010).
4. Discussion There are many epidemiological and prospective cohort studies that point to an inverse association between the effects of habitual coffee consumption and the risk of T2DM (revised in van Dam, 2006; Ding et al., 2014). In contrast, long term, randomized, controlled interventions are scarce, although necessary to understand the tolerance to the acute effects of coffee components developed after sustained consumption, to elucidate the underlying mechanisms involved in regular consumption and to establish causality of the effects observed in epidemiological and cohort studies. Caffeine intake has been associated with an acute reduction in insulin sensitivity due to increased epinephrine release, declining this effect after continued intake (van Dam, 2006). When dose-dependency of caffeine metabolism under multiple dosing (4.2 and 12 mg/kg/day of caffeine, divided in 6 doses) was randomly tested in healthy subjects, complete tolerance to the effects of caffeine was developed after 5 days (Denaro, Brown, Jacob, & Benowitz, 1991). Conversely, another study in healthy volunteers described that caffeine tolerance development takes longer, as after consuming 1 L of coffee/day (caffeine intake was not specified) for 2 weeks, fasting glucose concentrations were higher compared to baseline, whereas after 4 weeks not (van Dam, Pasman, & Verhoef, 2004). It is likely that in the present study caffeine tolerance occurred, because the dose of caffeine was relatively low (120 mg/day, i.e. 2.1 and 1.5 mg/kg/day for women and men, respectively) and the coffee intervention was 8 weeks long. Nevertheless, according to observational studies (using caffeinated and decaffeinated coffee) the inverse association between coffee consumption and risk of T2DM should be attributed to coffee's content in chlorogenic acid rather than caffeine (Ding et al., 2014). In agreement, attending to the bioavailability studies in humans carried out in our group using the green/roasted coffee (Martínez-López, Sarriá, Baeza, Mateos, & Bravo-Clemente, 2014; Mateos et al., 2015), methylxanthines in the coffee blend may have contributed to the biological activity of the coffee product observed,
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Fig. 1. Effects of consuming the green/roasted coffee blend on the concentration of A) Glucagon; B) GLP-1: glucagon like peptide-1; and C) GIP: glucose- dependent insulinotrophic peptide. Data represents mean ± standard error of mean. Different letters represent statistically significant differences between the stages of the study (P b 0.05).
although to a lower extent than the phenolic compounds in coffee as the time circulating in plasma of the phenolic metabolites was higher. Phenolic acids in coffee and their degradation products formed during roasting (quinides) may impact glucose absorption in the intestine through the inhibition of glucose-6-phosphate translocase-1, an enzyme known to play a role in intestinal glucose transport, and reducing the sodium gradient driven apical glucose transport (McCarty, 2005). According to in vitro (Arion et al., 1997) and animal studies (Herling et al., 1999), another possible mechanism responsible for the benefits of chlorogenic acid and its derivatives on glucose metabolism is the decrease of hepatic glucose output through inhibition of glucose-6 phosphatase. The third mechanism is supported by a metabolic study in ileostomy patients, suggesting that most of the chlorogenic acid
absorbed in the small intestine is absorbed intact and may be extensively metabolized in the liver (Olthof, Hollman, & Katan, 2001). The aforementioned mechanisms may explain the decrease in fasting glucose levels observed in the present study after regularly consuming coffee. This outcome is in agreement with previous observational studies (Hino et al., 2007; Pham et al., 2014) and a clinical trial (van Dam et al., 2004) but not with other interventions (Kempf et al., 2010; Rebello et al., 2011). It would have been interesting to carry out an oral glucose tolerance test or a meal tolerance test to better understand the underlying physiology beyond the fasting state. According to the literature, glucose increase in the oral glucose tolerance test is lower in habitual coffee drinkers than in non-drinkers (Rustenbeck et al., 2014; van Dam et al., 2004; Yamaji et al., 2004), and there are no changes in fasting or postprandial glucose and insulin (30 min and 2 h after intake) responses between consuming 4 or 8 cups of coffee/day for 4 weeks (Kempf et al., 2010). In contrast to fasting glucose concentrations, fasting insulin levels did not change after the coffee intervention, but interestingly C-peptide levels were reduced 4.7% and thus a positive tendency at insulin production can be inferred, which possibly might have been observed if the study had been longer and/or the intake of coffee higher. The C-peptide outcome is in accordance with a cross-sectional study that described that greater intakes of caffeinated and decaffeinated coffee were associated with lower fasting C-peptide concentrations in healthy women, being stronger the caffeinated coffee and C-peptide relationship in obese and overweight women (27 and 20% reduction, respectively) than in normoweight (11%; Wu, Willet, Hankinson, & Giovannnucci, 2005). Thus, it is possible that in this study, because the participants presented a BMI under 25 kg/m2, the effect of coffee on C-peptide was attenuated. Interestingly, the changes in glucose and insulin observed after the coffee intervention resulted in a decrease in insulin resistance and increase of insulin sensitivity, according to the HOMA-IR (which reflects hepatic more than peripheral insulin resistance, Nolan & Færch, 2012) and QUICKI indexes, respectively. An inverse association between coffee consumption and HOMA-IR has been reported in epidemiological and cross-sectional studies carried out in different ethnic populations although not in a Japanese study (Pham et al., 2014), neither in three randomized, controlled trials (Kempf et al., 2010; Ohnaka et al., 2012; Wedick et al., 2011). However, when the results of the Japanese study (Pham et al., 2014) were stratified by BMI, an inverse association between coffee and HOMA-IR was observed in the overweight/obese subjects but not in the normoweight, which could be related to the stronger inverse association between caffeinated coffee and C-peptide in obese and overweight women than normoweight (Wu et al., 2005). Perhaps the inverse association between coffee consumption and HOMA-IR was attenuated in the present study because subjects' BMI b25 kg/m2, nevertheless the beneficial effect of coffee on HOMA-IR was observed and reached the level of statistical significance. In contrast to HOMA-IR, HOMA-β has been less rigorously evaluated and is a less robust estimate of beta-cell function (Nolan & Færch, 2012). Therefore, the insulin/glucose ratio was also calculated. According to both indexes of beta-cell function, regular consumption of the coffee blend did not produce changes, which is in accordance with epidemiological studies in healthy subjects (Agardh et al., 2004; Rebello et al., 2011). In T2DM, glucagon secretion is enhanced; in fact, hyperglucagonemia contributes importantly to the hyperglycemia observed in T2DM patients. Suppression of glucagon secretion is a possible treatment of the disease (Knop et al., 2013), and drugs that suppress glucagon secretion or antagonize the glucagon receptor have already been developed (Christensen, Bagger, Vilsbøll, & Knop, 2011). Activation of GLP-1 receptors effectively inhibits glucagon secretion in humans, decelerating gastric emptying, inhibiting food intake, and elevating insulin secretion (Christensen et al., 2011). There are incretin-based therapies based on two major classes of drugs: GLP-1 receptor agonists and DPP-4 inhibitors, which increase
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GLP-1 receptor signaling by means of an exogenous GLP-1 analog and enhancement of endogenous GLP-1 levels, respectively. In contrast to the aforementioned pharmacological treatments based on targeting the alpha-cell, the effects of dietary compounds on glucagon secretion and incretin hormones have been less studied. In a recent trial, 30 day resveratrol supplementation suppressed postprandial glucagon response without affecting fasting glucagon levels (Knop et al., 2013). In contrast, in the present work the intake of the green/roasted coffee decreased fasting glucagon levels compared to baseline, which may be related to the increase of GLP-1 concentration after the coffee intervention. Although the mechanism of GLP-1 inhibition on glucagon secretion is not entirely clear, it has been previously described at normal fasting glucose levels (Christensen et al., 2011) in agreement with the present study. In order to control lifestyle confounding factors that may influence the risk of developing T2DM, such as smoking, age and body mass index, these factors were considered when the inclusion criteria was established. The volunteers who carried out this study were nonsmokers and their age and body mass were within a narrow range, thus minimizing their possible influence. Physical activity and dietary intake are other confounding factors that were followed and controlled, as far as possible, through questionnaires. Attending to participants' answers, they were sedentary and maintained their physical activity unaltered along the study (data not shown). Concerning dietary intake, confounding factors known to affect T2DM are energy, polyunsaturated/saturated fat and dietary fiber intake (Zhang, Lee, Cowan, Fabsitz, & Howard, 2011), which showed no changes during the study. Participants were instructed to avoid or use minimum amount of milk with the coffee, and non-caloric sweeteners were recommended instead of sugar. All these factors were controlled so the effects on glucose metabolism observed could be attributed to the consumption of the green/ roasted coffee blend as far as possible. 5. Strengths & limitations One strength of this study was its design (randomized, controlled and crossover) and in addition, each intervention lasted 8 weeks. Confounding factors, which may influence the effects of coffee drinking, such as BMI, physical activity, smoking, and certain other dietary factors were considered at setting the inclusion criteria and monitored through questionnaires. Limitations of the study: fasting glucose was measured at baseline and after the interventions; however, an oral glucose tolerance test was not carried out. We relied the absence of diabetes on a fasting glucose blood test and a self-reported health questionnaire filled out before the start of the study. 6. Conclusions This study supports that regularly consuming the green/roasted coffee blend lowers fasting glucose levels and insulin resistance and increases insulin sensitivity. In addition, fasting glucagon levels decrease, which may be associated with the increase in fasting GLP-1 concentrations. All these effects positively contribute to the prevention of T2DM and lower cardiovascular risk. Therefore, the use of the green/ roasted coffee blend within a balanced diet could be recommended to patients at risk of T2DM as a supplementary therapy or to healthy adults in order to prevent the onset of the disease. Considering the high intake of coffee in industrialized countries, these results are of interest from a public health viewpoint. Acknowledgments This work was funded by the Spanish Ministry of Science and Innovation (projects AGL2010-18269 and Consolider-Ingenio CSD200700063). The authors thank L. T. Cayuelas and M. Jiménez-Romano for analyzing the 72 h food records and Nestlé España, S.A. for providing the coffee and packing it in blind monodosis especially for the study.
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S.M.-L. thanks the Spanish National Research Council for her predoctoral fellowship under the JAE-Pre program funded by the European Social Fund (JAE-Pre 097. BOE 17-12-2008). All authors revised and approved the final version of the manuscript. The authors declare no conflicts of interest. References Abdul-Ghani, M. A., Williams, K., DeFronzo, R., & Stern, M. (2006). Risk of progression to type 2 diabetes based on relationship between postload plasma glucose and fasting plasma glucose. Diabetes Care, 29, 1613–1618. Acosta, A. M., Escalona, M., Maiz, A., Pollak, F., & Leighton, F. (2002). Determinación del índice de resistencia insulínica mediante HOMA en una población de la Región Metropolitana de Chile. Revista Médica de Chile, 130, 1227–1231. Agardh, E. E., Carlsson, S., Ahlbom, A., Efendic, S., Grill, V., Hammar, N., et al. (2004). Coffee consumption, type 2 diabetes and impaired glucose tolerance in Swedish men and women. Journal of Internal Medicine, 255, 645–652. Akash, M. S., Rehman, K., & Chen, S. (2014). Effects of coffee on type 2 diabetes mellitus. Nutrition, 30, 755–763. Alonso-Salces, R. M., Serra, F., Reniero, F., & Héberger, K. (2009). Botanical and geographical characterization of green coffee (Coffea arabica and Coffea canephora): Chemometric evaluation of phenolic and methylxanthine contents. Journal of Agricultural and Food Chemistry, 57, 4224–4235. Arion, W. J., Canfield, W. K., Ramos, F. C., Schindler, P. W., Burger, H. J., Hemmerle, H., et al. (1997). Chlorogenic acid and hydroxynitrobenzaldehyde: New inhibitors of hepatic glucose 6-phosphatase. Archives of Biochemistry and Biophysics, 339, 315–322. Babu, P. V., Liu, D., & Gilbert, E. R. (2013). Recent advances in understanding the anti-diabetic actions of dietary flavonoids. Journal of Nutritional Biochemistry, 24, 1777–1789. Christensen, M., Bagger, J. I., Vilsbøll, T., & Knop, F. K. (2011). The alpha-cell as target for type 2 diabetes therapy. The Review of Diabetic Studies, 8, 369–381. van Dam, R. M. (2006). Coffee and type 2 diabetes: From beans to beta-cells. Nutrition, Metabolism, and Cardiovascular Diseases, 16, 69–77. van Dam, R. M., Pasman, W. J., & Verhoef, P. (2004). Effects of coffee consumption on fasting blood glucose and insulin concentrations: Randomized controlled trials in healthy volunteers. Diabetes Care, 27, 2990–2992. Denaro, C. P., Brown, C. R., Jacob, P. I. I. I., & Benowitz, N. L. (1991). Effects of caffeine with repeated dosing. European Journal of Clinical Pharmacology, 40, 273–278. Ding, M., Bhupathiraju, S. N., Chen, M., van Dam, R. M., & Hu, F. B. (2014). Caffeinated and decaffeinated coffee consumption and risk of type 2 diabetes: A systematic review and a dose–response meta-analysis. Diabetes Care, 37, 569–586. Herling, A. W., Burger, H., Schubert, G., Hemmerle, H., Schaefer, H., & Kramer, W. (1999). Alterations of carbohydrate and lipid intermediary metabolism during inhibition of glucose-6-phosphatase in rats. European Journal of Pharmacology, 386, 75–82. Hino, A., Adachi, H., Enomoto, M., Furuki, K., Shigetoh, Y., Ohtsuka, M., et al. (2007). Habitual coffee but not green tea consumption is inversely associated with metabolic syndrome: An epidemiological study in a general Japanese population. Diabetes Research and Clinical Practice, 76, 383–389. Katz, A., Nambi, S. S., Mather, K., Baron, A. D., Follmann, D. A., Sullivan, G., & Quon, M. J. (2000). Quantitative insulin sensitivity check index: A simple, accurate method for assessing insulin sensitivity in humans. The Journal of Clinical Endocrinology and Metabolism, 85, 2402–2410. Kempf, K., Herder, C., Erlund, I., Kolb, H., Martin, S., Carstensen, et al. (2010). Effects of coffee consumption on subclinical inflammation and other risk factors for type 2 diabetes: A clinical trial. The American Journal of Clinical Nutrition, 91, 950–957. Knop, F. K., Konings, E., Timmers, S., Schrauwen, P., Holst, J. J., & Blaak, E. E. (2013). Thirty days of resveratrol supplementation does not affect postprandial incretin hormone responses, but suppresses postprandial glucagon in obese subjects. Diabetic Medicine, 30, 1214–1218. Kozuma, K., Tsuchiya, S., Kohori, J., Hase, T., & Tokimitsu, I. (2005). Antihypertensive effect of green coffee bean extract on mildly hypertension subjects. Hypertension Research, 28, 711–718. Lecoultre, V., Carrel, G., Egli, L., Binnert, C., Boss, A., MacMillan, E. L., et al. (2014). Coffee consumption attenuates short-term fructose-induced liver insulin resistance in healthy men. The American Journal of Clinical Nutrition, 99, 268–275. Lichnovská, R., Gwozdziewiczová, S., & Hrebícek, J. (2002). Gender differences in factors influencing insulin resistance in elderly hyperlipemic non-diabetic subjects. Cardiovascular Diabetology, 1, 4–13. Martínez-López, S., Sarriá, B., Baeza, G., Mateos, R., & Bravo-Clemente, L. (2014). Pharmacokinetics of caffeine and its metabolites in plasma and urine after consuming a soluble green/roasted coffee blend by healthy subjects. Food Research International, 64, 125–133. Mateos, R., Gómez-Juaristi, M., Martínez-López, S., Baeza, G., Amigo-Benavent, M., Sarriá, B., & Bravo-Clemente, L. (2015). Bioavailability of hydroxycinnamate derivatives after consuming a soluble green/roasted coffee blend by healthy humans. Poster presented in the international. EuroFoodChem XVIII, Madrid: Congress. Matthews, D. R., Hosker, J. P., Rudenski, A. S., Naylor, B. A., Treacher, D. F., & Turner, R. C. (1985). Homeostasis model assessment: Insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia, 28, 412–419. McCarty, M. F. (2005). A chlorogenic acid-induced increase in GLP-1 production may mediate the impact of heavy coffee consumption on diabetes risk. Medical Hypotheses, 64, 48–53. Meier, J. J., Hücking, K., Holst, J. J., Deacon, C. F., Schmiegel, W. H., & Nauck, M. A. (2001). Reduced insulinotropic effect of gastric inhibitory polypeptide in first-degree relatives of patients with type 2 diabetes. Diabetes, 50, 2497–2504.
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B. Sarriá et al. / Food Research International 89 (2016) 1023–1028
Nolan, J. J., & Færch, K. (2012). Estimating insulin sensitivity and beta cell function: Perspectives from the modern pandemics of obesity and type 2 diabetes. Diabetologia, 55, 2863–2867. Ohnaka, K., Ikeda, M., Maki, T., Okada, T., Shimazoe, T., Adachi, M., et al. (2012). Effects of 16-week consumption of caffeinated and decaffeinated instant coffee on glucose metabolism in a randomized controlled trial. Journal of Nutritional Biochemistry, 207426. Olthof, M. R., Hollman, P. C., & Katan, M. B. (2001). Chlorogenic acid and caffeic acid are absorbed in humans. Journal of Nutrition, 131, 66–71. Olthof, M. R., van Dijk, A. E., Deacon, C. F., Heine, R. J., & van Dam, R. M. (2011). Acute effects of decaffeinated coffee and the major coffee components chlorogenic acid and trigonelline on incretin hormones. Nutrition and Metabolism, 8, 10. Pereira, M. A., Parker, E. D., & Folsom, A. R. (2006). Coffee consumption and risk of type 2 diabetes mellitus: An 11-year prospective study of 28,812 postmenopausal women. Archives of Internal Medicine, 166, 1311–1316. Perrone, D., Farah, A., & Donangelo, C. M. (2012). Influence of coffee roasting on the incorporation of phenolic compounds into melanoidins and their relationship with antioxidant activity of the brew. Journal of Agricultural and Food Chemistry, 60, 4265–4275. Pham, N. M., Nanri, A., Kochi, T., Kuwahara, K., Tsuruoka, H., Kurotani, K., et al. (2014). Coffee and green tea consumption is associated with insulin resistance in Japanese adults. Metabolism, 63, 400–408. Rebello, S. A., Chen, C. H., Naidoo, N., Xu, W., Lee, J., Chia, K. S., et al. (2011). Coffee and tea consumption in relation to inflammation and basal glucose metabolism in a multiethnic Asian population: A cross-sectional study. Nutrition Journal, 2 (10:61). Rustenbeck, I., Lier-Glaubit, Z. V., Willenborg, M., Eggert, F., Engelhardt, U., & Jörns, A. (2014). Effect of chronic coffee consumption on weight gain and glycaemia in a mouse model of obesity and type 2 diabetes. Nutrition and Diabetes, 4, e123. Schenker, S., Heinemann, C., Huber, M., Pompizzi, R., Perren, R., & Escher, R. (2002). Impact of roasting conditions on the formation of aroma compounds in coffee beans. Journal of Food Science, 67, 60–66.
Somporn, C., Kamtuo, A., Theerakulpisut, P., & Siriamornpun, S. (2011). Effects of roasting degree on radical scavenging activity, phenolics and volatile compounds of Arabica coffee beans (Coffea Arabica L. cv. Carimor). International Journal of Food Science and Technology, 46, 2287–2296. Tunnicliffe, J. M., & Shearer, J. (2008). Coffee, glucose homeostasis, and insulin resistance: Physiological mechanisms and mediators. Applied Physiology, Nutrition, and Metabolism, 33, 1290–1300. Wang, Q. S., Zhou, H., Yaung, D., Ma, L., & Geng, W. (2010). www.bio-rad.com/webroot/ web/pdf/lsr/literature/Bulletin_5985A.pdf Wedick, N. M., Brennan, A. M., Sun, Q., Hu, F. B., Mantzoros, C. S., & van Dam, R. M. (2011). Effects of caffeinated and decaffeinated coffee on biological risk factors for type 2 diabetes: A randomized controlled trial. Nutrition Journal, 13 (10:93). Wu, T., Willet, W. C., Hankinson, S. E., & Giovannnucci, E. (2005). Caffeinated coffee, decaffeinated coffee, and caffeine in relation to plasma C-peptide levels: A marker of insulin secretion in U.S. women. Diabetes Care, 28, 1390–1396. Yabe, D., Kuroe, A., Watanabe, K., Iwasaki, M., Hamasaki, A., Hamamoto, Y., et al. (2015). Early phase glucagon and insulin secretory abnormalities, but not incretin secretion, are similarly responsible for hyperglycemia after ingestion of nutrients. Journal of Diabetes and its Complications, 29, 413–421. Yamaji, T., Mizoue, T., Tabata, S., Ogawa, S., Yamaguchi, K., Shimizu, E., et al. (2004). Coffee consumption and glucose tolerance status in middle-aged Japanese men. Diabetologia, 47, 2145–2151. Zhang, Y., Lee, E. T., Cowan, L. D., Fabsitz, R. R., & Howard, B. V. (2011). Coffee consumption and the incidence of type 2 diabetes in men and women with normal glucose tolerance: The Strong Heart Study. Nutrition, Metabolism, and Cardiovascular Diseases, 21, 418–423.
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Food Research International journal homepage: www.elsevier.com/locate/foodres
Long-term consumption of a green/roasted coffee blend positively affects glucose metabolism and insulin resistance in humans Beatriz Sarriá ⁎, Sara Martínez-López, Raquel Mateos, Laura Bravo-Clemente Department of Metabolism and Nutrition, Institute of Food Science, Technology and Nutrition (ICTAN-CSIC), Spanish National Research Council (CSIC), José Antonio Nováis 10, 28040 Madrid, Spain
a r t i c l e
i n f o
Article history: Received 22 July 2015 Received in revised form 29 December 2015 Accepted 31 December 2015 Available online 4 January 2016 Keywords: Coffee Type 2 diabetes mellitus Glucose Insulin HOMA Glucagon Glucose-dependent insulinotropic polypeptide Glucagon-like peptide-1
a b s t r a c t Protective health effects of coffee could have a widespread impact on public health considering the high intake of this beverage in industrialized countries. However, certain of coffee's health effects are contradictory such as those on type 2 diabetes mellitus (T2DM). Green coffee is richer in antioxidant phenols than roasted coffee, and thus it is likely to be a healthier option. This work evaluated the effects of long-term consumption of green coffee consumption, blended with roasted beans to improve palatability, on different glucose homeostasis markers as T2DM risk factors. A, randomized, controlled, crossover study was performed in 52 healthy men and women who consumed three servings/day of the green/roasted (35:65) coffee blend for 8 weeks during the intervention in comparison with not consuming coffee in the control stage. At the beginning and end of the coffee and control interventions, blood samples were collected, body weight measured, and dietary records and physical activity questionnaires completed. After the coffee intervention, fasting glucose levels and HOMAIR values were significantly lower, whereas QUICKI values were higher showing improved insulin sensitivity. Fasting glucagon levels decreased, which may be associated with the increase in the glucagon-like peptide-1 (GLP-1), whereas C-peptide, glucose-dependent insulinotropic polypeptide (GIP), insulin, and HOMA-β were not affected. In conclusion, regularly consuming the green/roasted coffee blend may be recommended to prevent T2DM and reduce cardiovascular risk. © 2016 Elsevier Ltd. All rights reserved.
1. Introduction The worldwide prevalence of type 2 diabetes mellitus (T2DM) is increasing globally and may reach 366 million people by 2030 (Ding, Bhupathiraju, Chen, van Dam, & Hu, 2014). T2DM is associated with variable degrees of insulin resistance, impaired insulin secretion, moderate to severe beta-cell apoptosis and increased hepatic glucose production. Unlike type 1 diabetes mellitus, the onset of T2DM is slow and the metabolic abnormalities that lead to hyperglycemia are established long before overt diabetes. Hepatic glucose production is the main contributor to fasting plasma glucose concentration and is regulated primarily by plasma insulin and glucagon concentrations (Abdul-Ghani, Williams, DeFronzo, & Stern, 2006). In turn, incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which are secreted in response to food intake, contribute to the regulation of glucagon and glucose-dependent insulin secretion. Both incretins stimulate insulin secretion, although they exert opposing effects on glucagon, since GLP-1 suppresses and GIP enhances glucagon secretion (Yabe et al., 2015). The effects of the incretin hormones are
⁎ Corresponding author at: Institute of Food Science, Technology and Nutrition (ICTANCSIC), José Antonio Novais 10, 28040 Madrid, Spain. E-mail address: [email protected] (B. Sarriá).
http://dx.doi.org/10.1016/j.foodres.2015.12.032 0963-9969/© 2016 Elsevier Ltd. All rights reserved.
very limited during fasting conditions, as circulating concentrations of GLP-1 and GIP are low (Nolan & Færch, 2012). Many studies have shown that dietary components or foods affect postprandial glucose, glucagon, insulin and incretin hormones; however, less have examined the effects of regular consumption of dietary components on the fasting concentrations of the glucose metabolism related biomarkers. Particularly, studies looking into the effects of micronutrients and phytochemicals on glucose metabolism are scarce. Advances in understanding the anti-diabetic actions of dietary flavonoids have been recently reviewed by Babu, Liu, and Gilbert (2013). In a previous revision by van Dam (2006), consumption of coffee, rich in hydroxycinnamic acids and caffeine, was pointed to affect postprandial glucose metabolism rather than fasting glucose levels. Some human trials have shown that glucose tolerance is reduced shortly after ingestion of caffeine or caffeinated coffee, suggesting that short-term coffee consumption could increase the risk of diabetes (Olthof, van Dijk, Deacon, Heine, & van Dam, 2011). However, there is increasing scientific evidence that supports an inverse relationship between coffee consumption and T2DM (Akash, Rehman, & Chen, 2014), being stronger the association with decaffeinated coffee (Pereira, Parker, & Folsom, 2006); therefore, it has been suggested that the positive, T2DM protective effects of coffee are associated with non-caffeine compounds. Coffee contains diterpens (cafestol and kahweol, up to 0.6% of final weight), and micronutrients, among which outstands magnesium
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(Ding et al., 2014), but it is also a rich source of polyphenols (up to 11% of the coffee bean). The main phenolic compounds in green coffee are hydroxycinnamic acids, mostly 3-, 4-, and 5-caffeoylquinic acids (3-, 4- and 5-CQA), 3,4-, 3,5-, and 4,5-dicaffeoylquinic acids (3,4-, 3,5-, and 4,5-DCQA), and 3-, 4-, and 5-feruloylquinic acids (3-, 4-, and 5-FQA), among others (Alonso-Salces, Serra, Reniero, & Héberger, 2009). Roasting drastically degrades and/or transforms green coffee polyphenols (Perrone, Farah, & Donangelo, 2012; Schenker et al., 2002; Somporn, Kamtuo, Theerakulpisut, & Siriamornpun, 2011) inducing the formation of Maillard reaction products and quinides. The intake of green coffee products has increased in recent years as a healthier option than roasted coffee (Kozuma, Tsuchiya, Kohori, Hase, & Tokimitsu, 2005), although its bitter taste limits green coffee acceptance. Bearing this in mind, a blend of green and roasted beans can be an alternative well accepted by coffee consumers with greater health potential than traditional roasted coffee. Considering the high intake of this beverage, particularly in industrialized countries where it is the largest source of dietary antioxidants (Tunnicliffe & Shearer, 2008), the health protective effects of coffee could have a widespread impact on the population health. Moreover, coffee could be recommended to patients at risk of T2DM as a supplementary therapy in preventing the further progression of the disease or to prevent the onset in healthy and at risk adults. Therefore, the aim of this work was to evaluate the effects of long term consumption of a green/roasted (35/65) coffee blend on glucose homeostasis markers, as T2DM risk factors, in healthy adults, attempting to understand the mechanisms involved.
2.3. Dietary control and compliance
2. Experimental methods 2.1. Subjects This study was conducted according to the guidelines laid down in the Declaration of Helsinki and all procedures were approved by the Clinical Research Ethics Committee of Hospital Universitario Puerta de Hierro Majadahonda in Madrid (Spain). Written informed consent was obtained from all subjects. Volunteer recruitment was carried out through placing advertisements in the Universidad Complutense campus as well as through giving short talks between lectures. The inclusion criteria were: being non-diabetic (excluded by the results of a glucose test and health questionnaire), non-vegetarian, non-smoker, nonpregnant women and men, between 18 and 55 y old, not suffering from any other chronic pathology and presenting a body mass index between 20 and 25 kg/m2. None had taken dietary supplements, laxatives, or antibiotics six months before the start of the study. Fifty-three subjects initially accepted to participate in the study, however 52 completed it. Baseline characteristics of the volunteers are shown in Table 1. 2.2. Study design This was a randomized, controlled, crossover study carried out in free-living people. After a 2 week run in stage, subjects were randomly assigned to the coffee or control intervention, lasting 8 weeks each, which were separated by a 2 week washout period. During the coffee intervention, volunteers consumed three times a day the soluble green/ roasted coffee blend, the first at breakfast, the second between breakfast and lunch, and the third between lunch and dinner. In the control Table 1 Baseline characteristics of the participants in the study
Age (years) Body mass index (kg/m2)
intervention, instead of the coffee product, the study participants had water or an isotonic drink, free of sugar, polyphenols and methylxanthines. The soluble green/roasted coffee blend, which was commercialized at the time of the study, was provided by the manufacturing company in unlabelled, individual sachets containing 2 g of coffee (equivalent to two teaspoons, quantity that can reasonably be used to prepare a cup of coffee). The coffee studied contained 85.1 ± 1.6 mg/g (dry matter) of total hydroxycinnamic acids (mainly chlorogenic acid) and 20.0 ± 1.8 mg/g (dry matter) of caffeine. Therefore, volunteers daily consumed 6 g of the coffee blend which provided 510.6 and 120 mg of total hydroxycinnamic acids and caffeine, respectively. The green/roasted coffee blend was particularly interesting to study because on the one hand, it is richer in chlorogenic acid than roasted coffee and thus was expected to be healthier, and on the other hand, the blend keeps the organoleptic properties of roasted coffee (which green coffee lacks) that are much appreciated by coffee drinkers, adding to its acceptability by consumers. From the run-in stage till the end of the study, foods rich in polyphenols and methylxanthines were restricted. Hydroxycinnamic acids are abundant in a variety of fruits and vegetables, such as chard, artichoke, eggplant, broccoli, loquats, tangerines, oranges, apricot, cherries, plums, prunes, grapes, raisins, blueberries and other fruits of the forest. All these foods were constrained, as well as coffee, mate, cocoa, and tea and derived drinks. On the other hand, ferulic acid and its derivatives are the most abundant hydroxycinnamic acids found in cereals, thus whole grain products were also restricted along the study.
Women (n = 32)
Men (n = 20)
29.4 ± 9.5 21.7 ± 2.5
29.8 ± 8.9 24.8 ± 2.7
Data represents mean ± standard deviation of mean.
Subjects were asked to maintain the same dietary habits along the study. Their dietary intake was regularly evaluated to control any possible changes. Volunteers were instructed on how to fill in the dietary records before starting the study. In the run in stage and at the end of the two intervention periods, volunteers were asked to complete a 72-hour detailed food intake report, specifying the ingredients and amounts of food consumed, including serving weights (when possible) or household measurements. Compliance was controlled by counting the number of coffee sachets provided to the volunteers before and after the intervention, as well as by weekly calling the volunteers. In order to assess dietary composition, the program DIAL [Department of Nutrition and Bromathology I. School of Pharmacy. Complutense University of Madrid (UCM), Spain] was used. 2.4. Blood samples Blood samples were drawn after 8–10 h overnight fasting at baseline and at the last day of the control and coffee intervention. Serum (without anticoagulant) and plasma (EDTA-coated tubes) were separated by centrifugation and frozen at −80 °C until analysis. 2.5. Diabetes biomarkers and related indexes Fasting glucose was analyzed using a colorimetric kit (Sprinreact). Fasting insulin, as well as GIP, GLP-1, C-peptide, and glucagon were analyzed using the Bio-Rad Multiplex Diabetes kit on Bio-Plex MAGPIX system. Using fasting glucose and insulin data, Homeostasis Model Assessment indexes were calculated to estimate insulin resistance (HOMA-IR) and beta cell function (HOMA-β) according to the equations by Matthews et al. (1985): HOMA-IR = [Glucose (mg/dL) × Insulin (mU/L)] / 405; HOMA-β = [(Insulin (mU/L) × 360) / (Glucose (mg/dL) − 63)]. Another model to calculate beta- cell function, the insulin/glucose ratio, was also used (Meier et al., 2001). In addition, the Quantitative Insulin Sensitivity Check Index (QUICKI) was calculated according to the formula by Katz et al. (2000): QUICKI = 1 / [log Insulin (mU/L) + log Glucose (mg/dL)].
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2.6. Physical activity and body weight Participants were asked to maintain their usual level of physical activity during the study. Volunteers filled out a questionnaire before starting the study to evaluate their physical activity including that involved in their occupation; afterwards this was calculated using the program ADN [Department of Nutrition and Bromathology I, School of Pharmacy, Complutense University of Madrid (UCM), Spain]. At baseline and the end of each stage of the study, volunteer's body weight was monitored using the weighing system BC-418 MA (Tanita Corporation). 2.7. Statistical analysis Data are presented as means ± standard error of the mean, unless specified otherwise. Prior to statistical analysis, normality of distribution and homogeneity of variance were verified using the Kolmogorov–Smirnov and Levene tests, respectively. The general linear model of the variance for repeated measures was used to assess the effects of consuming coffee, followed by a Bonferroni test to compare the stages in pairs. Statistical significance was set at P b 0.05 and the analysis was undertaken using the SPSS statistical package (version 21.0, SPSS Inc., IBM Company). 3. Results Attending to volunteers' reports and to the number of servings returned after the intervention, dietary compliance was high. The 72hour detailed food intake reports showed that energy, protein, carbohydrate, dietary fiber, lipid and the polyunsaturated/saturated ratio did not show differences along the study. However, the consumption of the coffee blend significantly reduced body weight (Table 2). Baseline fasting glucose concentration values were within the range of normality according to the Spanish Society of Clinical Biochemistry and Molecular Pathology (SEQC) (Table 3), and insulin results were in agreement with previous studies (Lecoultre et al., 2014; Meier et al., 2001). The values of HOMA-IR were similar to those earlier observed in healthy adults (Acosta, Escalona, Maiz, Pollak, & Leighton, 2002; Lichnovská, Gwozdziewiczová, & Hrebícek, 2002). Insulin sensitivity results, estimated through the QUICKI index (Table 3), which keeps a good correlation with HOMA-IR index as both are calculated from the values of fasting glucose and insulin, were similar to those described by Katz et al. (2000) in healthy volunteers. Finally, the values of HOMA-β index observed were analogous to those reported by Meier et al. (2001) in healthy controls. Among all the aforementioned glucose homeostasis biomarkers and related indexes, only glucose and HOMA-IR decreased after the coffee intervention, in contrast to insulin sensitivity which increased, being the values observed after the coffee intervention significantly different to basal and control data.
Table 2 Reported energy, macronutrient and dietary fiber intakes, PUFA/SFA intake ratio and body weight.
Intake per day Energy (Kcal) Protein (g) Carbohydrate (g) Dietary fiber (g) Lipid (g) PUFA/SFA Body weight (kg)
Basal
Control
Coffee
P
1870.12 ± 72.15 83.81 ± 3.31 181.59 ± 8.21 15.23 ± 0.82 77.94 ± 3.16 0.42 ± 0.02 63.01 ± 1.71
1854.83 ± 63.50 77.73 ± 2.93 175.77 ± 6.59 15.99 ± 0.81 74.19 ± 2.46 0.39 ± 0.02 62.85 ± 1.73
1801.46 ± 60.11 76.46 ± 2.84 174.25 ± 7.56 15.47 ± 0.75 72.20 ± 3.46 0.46 ± 0.03 62.31 ± 1.76
N.S. N.S. N.S. N.S. N.S. N.S. 0.024
Data represents mean ± standard error of mean. P values were assessed using the general linear model of variance for repeated measures.
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Table 3 Effects of regularly consuming the green/roasted coffee blend on fasting glucose and insulin levels and indexes of insulin resistance/sensitivity (HOMA-IR/QUICKI) and pancreatic function (HOMA-β, insulin/glucose) in healthy subjects. Basal Glucose (mg/dL) Insulin (mU/L) HOMA-IR HOMA-β (%) Insulin/glucose [(mU/L)/(mg/dL)] QUICKI C-peptide (pg/mL)
Control
Coffee
P
75.47 ± 1.10 a 76.50 ± 1.24 a 72.35 ± 1.1 b 0.007 8.20 ± 0.45 8.42 ± 0.45 7.73 ± 0.44 N.S. 1.67 ± 0.06 a 1.72 ± 0.05 a 1.47 ± 0.05 b 0.001 180.52 ± 18.69 159.63 ± 18.42 179.27 ± 20.71 N.S. 0.07 ± 0.01 0.08 ± 0.01 0.07 ± 0.01 N.S. 0.36 ± 0.00 a 0.35 ± 0.00 a 0.36 ± 0.00 b 0.008 924.74 ± 28.88 923.47 ± 28.52 882.47 ± 30.26 N.S.
Data represents mean ± standard error of mean. HOMA-IR: homeostasis model assessment of insulin resistance; HOMA-β: homeostasis model assessment of beta cell function; QUICKI: quantitative insulin sensitivity check index. P values were assessed using the general linear model of variance for repeated measures. a.b Mean values within a row with unlike letters were significantly different according to the Bonferroni test.
In agreement to insulin results, C-peptide concentrations did not change due to coffee consumption. Contrarily, glucagon concentration significantly changed along the study, showing lower values after the control and coffee intervention than at baseline (Fig. 1A). Glucagon concentrations were similar to those described by Knop et al. (2013) in obese (BMI = 32 ± 1 kg/m2) but otherwise healthy men. The decrease in glucagon concentration may be related with the significant increase in GLP-1 levels after the coffee intervention compared to baseline values (Fig. 1B). Differently, there were not significant changes in GIP levels (Fig. 1C). Insulin, glucagon, C-peptide, GLP-1 and GIP values were within the ranges observed by Wang, Zhou, Yaung, Ma, and Geng (2010).
4. Discussion There are many epidemiological and prospective cohort studies that point to an inverse association between the effects of habitual coffee consumption and the risk of T2DM (revised in van Dam, 2006; Ding et al., 2014). In contrast, long term, randomized, controlled interventions are scarce, although necessary to understand the tolerance to the acute effects of coffee components developed after sustained consumption, to elucidate the underlying mechanisms involved in regular consumption and to establish causality of the effects observed in epidemiological and cohort studies. Caffeine intake has been associated with an acute reduction in insulin sensitivity due to increased epinephrine release, declining this effect after continued intake (van Dam, 2006). When dose-dependency of caffeine metabolism under multiple dosing (4.2 and 12 mg/kg/day of caffeine, divided in 6 doses) was randomly tested in healthy subjects, complete tolerance to the effects of caffeine was developed after 5 days (Denaro, Brown, Jacob, & Benowitz, 1991). Conversely, another study in healthy volunteers described that caffeine tolerance development takes longer, as after consuming 1 L of coffee/day (caffeine intake was not specified) for 2 weeks, fasting glucose concentrations were higher compared to baseline, whereas after 4 weeks not (van Dam, Pasman, & Verhoef, 2004). It is likely that in the present study caffeine tolerance occurred, because the dose of caffeine was relatively low (120 mg/day, i.e. 2.1 and 1.5 mg/kg/day for women and men, respectively) and the coffee intervention was 8 weeks long. Nevertheless, according to observational studies (using caffeinated and decaffeinated coffee) the inverse association between coffee consumption and risk of T2DM should be attributed to coffee's content in chlorogenic acid rather than caffeine (Ding et al., 2014). In agreement, attending to the bioavailability studies in humans carried out in our group using the green/roasted coffee (Martínez-López, Sarriá, Baeza, Mateos, & Bravo-Clemente, 2014; Mateos et al., 2015), methylxanthines in the coffee blend may have contributed to the biological activity of the coffee product observed,
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Fig. 1. Effects of consuming the green/roasted coffee blend on the concentration of A) Glucagon; B) GLP-1: glucagon like peptide-1; and C) GIP: glucose- dependent insulinotrophic peptide. Data represents mean ± standard error of mean. Different letters represent statistically significant differences between the stages of the study (P b 0.05).
although to a lower extent than the phenolic compounds in coffee as the time circulating in plasma of the phenolic metabolites was higher. Phenolic acids in coffee and their degradation products formed during roasting (quinides) may impact glucose absorption in the intestine through the inhibition of glucose-6-phosphate translocase-1, an enzyme known to play a role in intestinal glucose transport, and reducing the sodium gradient driven apical glucose transport (McCarty, 2005). According to in vitro (Arion et al., 1997) and animal studies (Herling et al., 1999), another possible mechanism responsible for the benefits of chlorogenic acid and its derivatives on glucose metabolism is the decrease of hepatic glucose output through inhibition of glucose-6 phosphatase. The third mechanism is supported by a metabolic study in ileostomy patients, suggesting that most of the chlorogenic acid
absorbed in the small intestine is absorbed intact and may be extensively metabolized in the liver (Olthof, Hollman, & Katan, 2001). The aforementioned mechanisms may explain the decrease in fasting glucose levels observed in the present study after regularly consuming coffee. This outcome is in agreement with previous observational studies (Hino et al., 2007; Pham et al., 2014) and a clinical trial (van Dam et al., 2004) but not with other interventions (Kempf et al., 2010; Rebello et al., 2011). It would have been interesting to carry out an oral glucose tolerance test or a meal tolerance test to better understand the underlying physiology beyond the fasting state. According to the literature, glucose increase in the oral glucose tolerance test is lower in habitual coffee drinkers than in non-drinkers (Rustenbeck et al., 2014; van Dam et al., 2004; Yamaji et al., 2004), and there are no changes in fasting or postprandial glucose and insulin (30 min and 2 h after intake) responses between consuming 4 or 8 cups of coffee/day for 4 weeks (Kempf et al., 2010). In contrast to fasting glucose concentrations, fasting insulin levels did not change after the coffee intervention, but interestingly C-peptide levels were reduced 4.7% and thus a positive tendency at insulin production can be inferred, which possibly might have been observed if the study had been longer and/or the intake of coffee higher. The C-peptide outcome is in accordance with a cross-sectional study that described that greater intakes of caffeinated and decaffeinated coffee were associated with lower fasting C-peptide concentrations in healthy women, being stronger the caffeinated coffee and C-peptide relationship in obese and overweight women (27 and 20% reduction, respectively) than in normoweight (11%; Wu, Willet, Hankinson, & Giovannnucci, 2005). Thus, it is possible that in this study, because the participants presented a BMI under 25 kg/m2, the effect of coffee on C-peptide was attenuated. Interestingly, the changes in glucose and insulin observed after the coffee intervention resulted in a decrease in insulin resistance and increase of insulin sensitivity, according to the HOMA-IR (which reflects hepatic more than peripheral insulin resistance, Nolan & Færch, 2012) and QUICKI indexes, respectively. An inverse association between coffee consumption and HOMA-IR has been reported in epidemiological and cross-sectional studies carried out in different ethnic populations although not in a Japanese study (Pham et al., 2014), neither in three randomized, controlled trials (Kempf et al., 2010; Ohnaka et al., 2012; Wedick et al., 2011). However, when the results of the Japanese study (Pham et al., 2014) were stratified by BMI, an inverse association between coffee and HOMA-IR was observed in the overweight/obese subjects but not in the normoweight, which could be related to the stronger inverse association between caffeinated coffee and C-peptide in obese and overweight women than normoweight (Wu et al., 2005). Perhaps the inverse association between coffee consumption and HOMA-IR was attenuated in the present study because subjects' BMI b25 kg/m2, nevertheless the beneficial effect of coffee on HOMA-IR was observed and reached the level of statistical significance. In contrast to HOMA-IR, HOMA-β has been less rigorously evaluated and is a less robust estimate of beta-cell function (Nolan & Færch, 2012). Therefore, the insulin/glucose ratio was also calculated. According to both indexes of beta-cell function, regular consumption of the coffee blend did not produce changes, which is in accordance with epidemiological studies in healthy subjects (Agardh et al., 2004; Rebello et al., 2011). In T2DM, glucagon secretion is enhanced; in fact, hyperglucagonemia contributes importantly to the hyperglycemia observed in T2DM patients. Suppression of glucagon secretion is a possible treatment of the disease (Knop et al., 2013), and drugs that suppress glucagon secretion or antagonize the glucagon receptor have already been developed (Christensen, Bagger, Vilsbøll, & Knop, 2011). Activation of GLP-1 receptors effectively inhibits glucagon secretion in humans, decelerating gastric emptying, inhibiting food intake, and elevating insulin secretion (Christensen et al., 2011). There are incretin-based therapies based on two major classes of drugs: GLP-1 receptor agonists and DPP-4 inhibitors, which increase
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GLP-1 receptor signaling by means of an exogenous GLP-1 analog and enhancement of endogenous GLP-1 levels, respectively. In contrast to the aforementioned pharmacological treatments based on targeting the alpha-cell, the effects of dietary compounds on glucagon secretion and incretin hormones have been less studied. In a recent trial, 30 day resveratrol supplementation suppressed postprandial glucagon response without affecting fasting glucagon levels (Knop et al., 2013). In contrast, in the present work the intake of the green/roasted coffee decreased fasting glucagon levels compared to baseline, which may be related to the increase of GLP-1 concentration after the coffee intervention. Although the mechanism of GLP-1 inhibition on glucagon secretion is not entirely clear, it has been previously described at normal fasting glucose levels (Christensen et al., 2011) in agreement with the present study. In order to control lifestyle confounding factors that may influence the risk of developing T2DM, such as smoking, age and body mass index, these factors were considered when the inclusion criteria was established. The volunteers who carried out this study were nonsmokers and their age and body mass were within a narrow range, thus minimizing their possible influence. Physical activity and dietary intake are other confounding factors that were followed and controlled, as far as possible, through questionnaires. Attending to participants' answers, they were sedentary and maintained their physical activity unaltered along the study (data not shown). Concerning dietary intake, confounding factors known to affect T2DM are energy, polyunsaturated/saturated fat and dietary fiber intake (Zhang, Lee, Cowan, Fabsitz, & Howard, 2011), which showed no changes during the study. Participants were instructed to avoid or use minimum amount of milk with the coffee, and non-caloric sweeteners were recommended instead of sugar. All these factors were controlled so the effects on glucose metabolism observed could be attributed to the consumption of the green/ roasted coffee blend as far as possible. 5. Strengths & limitations One strength of this study was its design (randomized, controlled and crossover) and in addition, each intervention lasted 8 weeks. Confounding factors, which may influence the effects of coffee drinking, such as BMI, physical activity, smoking, and certain other dietary factors were considered at setting the inclusion criteria and monitored through questionnaires. Limitations of the study: fasting glucose was measured at baseline and after the interventions; however, an oral glucose tolerance test was not carried out. We relied the absence of diabetes on a fasting glucose blood test and a self-reported health questionnaire filled out before the start of the study. 6. Conclusions This study supports that regularly consuming the green/roasted coffee blend lowers fasting glucose levels and insulin resistance and increases insulin sensitivity. In addition, fasting glucagon levels decrease, which may be associated with the increase in fasting GLP-1 concentrations. All these effects positively contribute to the prevention of T2DM and lower cardiovascular risk. Therefore, the use of the green/ roasted coffee blend within a balanced diet could be recommended to patients at risk of T2DM as a supplementary therapy or to healthy adults in order to prevent the onset of the disease. Considering the high intake of coffee in industrialized countries, these results are of interest from a public health viewpoint. Acknowledgments This work was funded by the Spanish Ministry of Science and Innovation (projects AGL2010-18269 and Consolider-Ingenio CSD200700063). The authors thank L. T. Cayuelas and M. Jiménez-Romano for analyzing the 72 h food records and Nestlé España, S.A. for providing the coffee and packing it in blind monodosis especially for the study.
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S.M.-L. thanks the Spanish National Research Council for her predoctoral fellowship under the JAE-Pre program funded by the European Social Fund (JAE-Pre 097. BOE 17-12-2008). All authors revised and approved the final version of the manuscript. The authors declare no conflicts of interest. References Abdul-Ghani, M. A., Williams, K., DeFronzo, R., & Stern, M. (2006). Risk of progression to type 2 diabetes based on relationship between postload plasma glucose and fasting plasma glucose. Diabetes Care, 29, 1613–1618. Acosta, A. M., Escalona, M., Maiz, A., Pollak, F., & Leighton, F. (2002). Determinación del índice de resistencia insulínica mediante HOMA en una población de la Región Metropolitana de Chile. Revista Médica de Chile, 130, 1227–1231. Agardh, E. E., Carlsson, S., Ahlbom, A., Efendic, S., Grill, V., Hammar, N., et al. (2004). Coffee consumption, type 2 diabetes and impaired glucose tolerance in Swedish men and women. Journal of Internal Medicine, 255, 645–652. Akash, M. S., Rehman, K., & Chen, S. (2014). Effects of coffee on type 2 diabetes mellitus. Nutrition, 30, 755–763. Alonso-Salces, R. M., Serra, F., Reniero, F., & Héberger, K. (2009). Botanical and geographical characterization of green coffee (Coffea arabica and Coffea canephora): Chemometric evaluation of phenolic and methylxanthine contents. Journal of Agricultural and Food Chemistry, 57, 4224–4235. Arion, W. J., Canfield, W. K., Ramos, F. C., Schindler, P. W., Burger, H. J., Hemmerle, H., et al. (1997). Chlorogenic acid and hydroxynitrobenzaldehyde: New inhibitors of hepatic glucose 6-phosphatase. Archives of Biochemistry and Biophysics, 339, 315–322. Babu, P. V., Liu, D., & Gilbert, E. R. (2013). Recent advances in understanding the anti-diabetic actions of dietary flavonoids. Journal of Nutritional Biochemistry, 24, 1777–1789. Christensen, M., Bagger, J. I., Vilsbøll, T., & Knop, F. K. (2011). The alpha-cell as target for type 2 diabetes therapy. The Review of Diabetic Studies, 8, 369–381. van Dam, R. M. (2006). Coffee and type 2 diabetes: From beans to beta-cells. Nutrition, Metabolism, and Cardiovascular Diseases, 16, 69–77. van Dam, R. M., Pasman, W. J., & Verhoef, P. (2004). Effects of coffee consumption on fasting blood glucose and insulin concentrations: Randomized controlled trials in healthy volunteers. Diabetes Care, 27, 2990–2992. Denaro, C. P., Brown, C. R., Jacob, P. I. I. I., & Benowitz, N. L. (1991). Effects of caffeine with repeated dosing. European Journal of Clinical Pharmacology, 40, 273–278. Ding, M., Bhupathiraju, S. N., Chen, M., van Dam, R. M., & Hu, F. B. (2014). Caffeinated and decaffeinated coffee consumption and risk of type 2 diabetes: A systematic review and a dose–response meta-analysis. Diabetes Care, 37, 569–586. Herling, A. W., Burger, H., Schubert, G., Hemmerle, H., Schaefer, H., & Kramer, W. (1999). Alterations of carbohydrate and lipid intermediary metabolism during inhibition of glucose-6-phosphatase in rats. European Journal of Pharmacology, 386, 75–82. Hino, A., Adachi, H., Enomoto, M., Furuki, K., Shigetoh, Y., Ohtsuka, M., et al. (2007). Habitual coffee but not green tea consumption is inversely associated with metabolic syndrome: An epidemiological study in a general Japanese population. Diabetes Research and Clinical Practice, 76, 383–389. Katz, A., Nambi, S. S., Mather, K., Baron, A. D., Follmann, D. A., Sullivan, G., & Quon, M. J. (2000). Quantitative insulin sensitivity check index: A simple, accurate method for assessing insulin sensitivity in humans. The Journal of Clinical Endocrinology and Metabolism, 85, 2402–2410. Kempf, K., Herder, C., Erlund, I., Kolb, H., Martin, S., Carstensen, et al. (2010). Effects of coffee consumption on subclinical inflammation and other risk factors for type 2 diabetes: A clinical trial. The American Journal of Clinical Nutrition, 91, 950–957. Knop, F. K., Konings, E., Timmers, S., Schrauwen, P., Holst, J. J., & Blaak, E. E. (2013). Thirty days of resveratrol supplementation does not affect postprandial incretin hormone responses, but suppresses postprandial glucagon in obese subjects. Diabetic Medicine, 30, 1214–1218. Kozuma, K., Tsuchiya, S., Kohori, J., Hase, T., & Tokimitsu, I. (2005). Antihypertensive effect of green coffee bean extract on mildly hypertension subjects. Hypertension Research, 28, 711–718. Lecoultre, V., Carrel, G., Egli, L., Binnert, C., Boss, A., MacMillan, E. L., et al. (2014). Coffee consumption attenuates short-term fructose-induced liver insulin resistance in healthy men. The American Journal of Clinical Nutrition, 99, 268–275. Lichnovská, R., Gwozdziewiczová, S., & Hrebícek, J. (2002). Gender differences in factors influencing insulin resistance in elderly hyperlipemic non-diabetic subjects. Cardiovascular Diabetology, 1, 4–13. Martínez-López, S., Sarriá, B., Baeza, G., Mateos, R., & Bravo-Clemente, L. (2014). Pharmacokinetics of caffeine and its metabolites in plasma and urine after consuming a soluble green/roasted coffee blend by healthy subjects. Food Research International, 64, 125–133. Mateos, R., Gómez-Juaristi, M., Martínez-López, S., Baeza, G., Amigo-Benavent, M., Sarriá, B., & Bravo-Clemente, L. (2015). Bioavailability of hydroxycinnamate derivatives after consuming a soluble green/roasted coffee blend by healthy humans. Poster presented in the international. EuroFoodChem XVIII, Madrid: Congress. Matthews, D. R., Hosker, J. P., Rudenski, A. S., Naylor, B. A., Treacher, D. F., & Turner, R. C. (1985). Homeostasis model assessment: Insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia, 28, 412–419. McCarty, M. F. (2005). A chlorogenic acid-induced increase in GLP-1 production may mediate the impact of heavy coffee consumption on diabetes risk. Medical Hypotheses, 64, 48–53. Meier, J. J., Hücking, K., Holst, J. J., Deacon, C. F., Schmiegel, W. H., & Nauck, M. A. (2001). Reduced insulinotropic effect of gastric inhibitory polypeptide in first-degree relatives of patients with type 2 diabetes. Diabetes, 50, 2497–2504.
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B. Sarriá et al. / Food Research International 89 (2016) 1023–1028
Nolan, J. J., & Færch, K. (2012). Estimating insulin sensitivity and beta cell function: Perspectives from the modern pandemics of obesity and type 2 diabetes. Diabetologia, 55, 2863–2867. Ohnaka, K., Ikeda, M., Maki, T., Okada, T., Shimazoe, T., Adachi, M., et al. (2012). Effects of 16-week consumption of caffeinated and decaffeinated instant coffee on glucose metabolism in a randomized controlled trial. Journal of Nutritional Biochemistry, 207426. Olthof, M. R., Hollman, P. C., & Katan, M. B. (2001). Chlorogenic acid and caffeic acid are absorbed in humans. Journal of Nutrition, 131, 66–71. Olthof, M. R., van Dijk, A. E., Deacon, C. F., Heine, R. J., & van Dam, R. M. (2011). Acute effects of decaffeinated coffee and the major coffee components chlorogenic acid and trigonelline on incretin hormones. Nutrition and Metabolism, 8, 10. Pereira, M. A., Parker, E. D., & Folsom, A. R. (2006). Coffee consumption and risk of type 2 diabetes mellitus: An 11-year prospective study of 28,812 postmenopausal women. Archives of Internal Medicine, 166, 1311–1316. Perrone, D., Farah, A., & Donangelo, C. M. (2012). Influence of coffee roasting on the incorporation of phenolic compounds into melanoidins and their relationship with antioxidant activity of the brew. Journal of Agricultural and Food Chemistry, 60, 4265–4275. Pham, N. M., Nanri, A., Kochi, T., Kuwahara, K., Tsuruoka, H., Kurotani, K., et al. (2014). Coffee and green tea consumption is associated with insulin resistance in Japanese adults. Metabolism, 63, 400–408. Rebello, S. A., Chen, C. H., Naidoo, N., Xu, W., Lee, J., Chia, K. S., et al. (2011). Coffee and tea consumption in relation to inflammation and basal glucose metabolism in a multiethnic Asian population: A cross-sectional study. Nutrition Journal, 2 (10:61). Rustenbeck, I., Lier-Glaubit, Z. V., Willenborg, M., Eggert, F., Engelhardt, U., & Jörns, A. (2014). Effect of chronic coffee consumption on weight gain and glycaemia in a mouse model of obesity and type 2 diabetes. Nutrition and Diabetes, 4, e123. Schenker, S., Heinemann, C., Huber, M., Pompizzi, R., Perren, R., & Escher, R. (2002). Impact of roasting conditions on the formation of aroma compounds in coffee beans. Journal of Food Science, 67, 60–66.
Somporn, C., Kamtuo, A., Theerakulpisut, P., & Siriamornpun, S. (2011). Effects of roasting degree on radical scavenging activity, phenolics and volatile compounds of Arabica coffee beans (Coffea Arabica L. cv. Carimor). International Journal of Food Science and Technology, 46, 2287–2296. Tunnicliffe, J. M., & Shearer, J. (2008). Coffee, glucose homeostasis, and insulin resistance: Physiological mechanisms and mediators. Applied Physiology, Nutrition, and Metabolism, 33, 1290–1300. Wang, Q. S., Zhou, H., Yaung, D., Ma, L., & Geng, W. (2010). www.bio-rad.com/webroot/ web/pdf/lsr/literature/Bulletin_5985A.pdf Wedick, N. M., Brennan, A. M., Sun, Q., Hu, F. B., Mantzoros, C. S., & van Dam, R. M. (2011). Effects of caffeinated and decaffeinated coffee on biological risk factors for type 2 diabetes: A randomized controlled trial. Nutrition Journal, 13 (10:93). Wu, T., Willet, W. C., Hankinson, S. E., & Giovannnucci, E. (2005). Caffeinated coffee, decaffeinated coffee, and caffeine in relation to plasma C-peptide levels: A marker of insulin secretion in U.S. women. Diabetes Care, 28, 1390–1396. Yabe, D., Kuroe, A., Watanabe, K., Iwasaki, M., Hamasaki, A., Hamamoto, Y., et al. (2015). Early phase glucagon and insulin secretory abnormalities, but not incretin secretion, are similarly responsible for hyperglycemia after ingestion of nutrients. Journal of Diabetes and its Complications, 29, 413–421. Yamaji, T., Mizoue, T., Tabata, S., Ogawa, S., Yamaguchi, K., Shimizu, E., et al. (2004). Coffee consumption and glucose tolerance status in middle-aged Japanese men. Diabetologia, 47, 2145–2151. Zhang, Y., Lee, E. T., Cowan, L. D., Fabsitz, R. R., & Howard, B. V. (2011). Coffee consumption and the incidence of type 2 diabetes in men and women with normal glucose tolerance: The Strong Heart Study. Nutrition, Metabolism, and Cardiovascular Diseases, 21, 418–423.