AJCN EB Program 2010 Early Registration
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Moisey, L. L
Right arrow Articles by Graham, T. E
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Moisey, L. L
Right arrow Articles by Graham, T. E
Agricola
Right arrow Articles by Moisey, L. L
Right arrow Articles by Graham, T. E
American Journal of Clinical Nutrition, Vol. 87, No. 5, 1254-1261, May 2008
© 2008 American Society for Nutrition

ORIGINAL RESEARCH COMMUNICATION

Caffeinated coffee consumption impairs blood glucose homeostasis in response to high and low glycemic index meals in healthy men 1,2,3

Lesley L Moisey, Sita Kacker, Andrea C Bickerton, Lindsay E Robinson and Terry E Graham

1 From the Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada

2 Supported by a grant from the Natural Sciences and Engineering Research Council (NSERC) of Canada Collaborative Health Research Grant (TEG). LER was supported by an NSERC postdoctoral fellowship.

3 Reprints not available. Address correspondence to TE Graham, Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada N1G 2W1. E-mail: terrygra{at}uoguelph.ca.


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: The ingestion of caffeine (5 mg/kg body weight) and a 75-g oral glucose load has been shown to elicit an acute insulin–insensitive environment in healthy and obese individuals and in those with type 2 diabetes.

Objective: In this study we investigated whether a similar impairment in blood glucose management exists when coffee and foods typical of a Western diet were used in a similar protocol.

Design: Ten healthy men underwent 4 trials in a randomized order. They ingested caffeinated (5 mg/kg) coffee (CC) or the same volume of decaffeinated coffee (DC) followed 1 h later by either a high or low glycemic index (GI) cereal (providing 75 g of carbohydrate) mixed meal tolerance test.

Results: CC with the high GI meal resulted in 147%, 29%, and 40% greater areas under the curve for glucose (P < 0.001), insulin (NS), and C-peptide (P < 0.001), respectively, compared with the values for DC. Similarly, with the low GI treatment, CC elicited 216%, 44%, and 36% greater areas under the curve for glucose (P < 0.001), insulin (P < 0.01), and C-peptide (P < 0.01), respectively. Insulin sensitivity was significantly reduced (40%) with the high GI treatment after CC was ingested compared with DC; with the low GI treatment, CC ingestion resulted in a 29% decrease in insulin sensitivity, although this difference was not significant.

Conclusion: The ingestion of CC with either a high or low GI meal significantly impairs acute blood glucose management and insulin sensitivity compared with ingestion of DC. Future investigations are warranted to determine whether CC is a risk factor for insulin resistance.


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Caffeine (1,3,7-trimethylxanthine) is the world's most frequently consumed drug. It is estimated that 80% of Americans consume caffeine-containing products every day (1) and in North American adults, 60–75% of total caffeine intake comes from coffee (2). The ingestion of alkaloid caffeine before an oral glucose tolerance test has been shown to result in an acute insulin–insensitive environment in both healthy (3, 4) and obese (5) men and in those with type 2 diabetes (T2DM) (6, 7). Similarly, when caffeine is given during a hyperinsulinemic-euglycemic clamp, whole-body glucose disposal is decreased by 15–30% compared with placebo (8-10). In contrast to these short-term randomized controlled trials, epidemiologic studies have consistently reported a negative association between increased coffee consumption (>3–4 cups/d) and a lowered risk of development of T2DM (11-19). The precise components of coffee precipitating this effect are unknown, but this paradox raises the question as to whether the effects of caffeine are different from those of CC.

The acute effects of coffee on insulin sensitivity have not been widely investigated. Battram et al (20) compared the effects of alkaloid caffeine, CC, and DC when given before an oral glucose tolerance test and found that caffeine elicited a 50% greater glucose area under the curve (AUC) than placebo, whereas glucose AUC between the CC and placebo treatments did not differ. However, insulin responses in both the caffeine and CC treatments were significantly elevated than those with placebo. More recently, Lane et al (21) reported that ingestion of caffeine (administered in DC) together with an oral nutritional supplement increased postprandial glucose and insulin responses by 28% and 19%, respectively, in middle aged adults with T2DM (21). To our knowledge, in all of the studies either pure glucose was infused or a high glycemic index (GI) liquid drink was used as the carbohydrate challenge. There have been no investigations examining the effects of CC and/or DC on acute insulin sensitivity or blood glucose management when ingested with foods that are typically consumed in the Western diet.

The purpose of this study was to investigate the effect of CC on glucose tolerance and insulin sensitivity after ingestion of high and low GI cereal meals in healthy men. We hypothesized that CC ingestion with either a high or low GI meal would negatively affect acute insulin sensitivity in healthy men.


   SUBJECTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Subjects
Men between 18 and 50 y of age were candidates for the study, and participants were excluded if any of the following criteria were present: 1) a known diagnosis of diabetes or impaired glucose tolerance, 2) a fasting blood glucose concentration >6.0 mmol/L, 3) the use of any medications known to alter glucose metabolism, or 4) a body mass index ≤18.5 or >30 kg/m2. Participants wore light clothing and removed their shoes to allow weight (in kg) and height (in cm) to be measured. All 10 subjects were nonsmokers and were judged to be healthy based on completion of a health screening questionnaire. This study was approved by the University of Guelph Human Ethics Committee. All subjects were fully informed of the purposes of the study, and written informed consent was obtained before their participation. On completion of the study, the subjects were compensated financially.

Experimental design
Before our investigation, we determined that a sample size of 8 subjects would provide 90% power in detecting differences in glucose concentrations with a probability of 0.05. The study followed a randomized crossover design with each subject receiving 4 different study treatments on separate days. Subjects were required to ingest CC or DC 1 hour before ingesting a high or low GI meal. Subjects received either a volume of CC (Maxwell House Original Roast) that was calculated to provide 5 mg caffeine/kg body weight (5 mg/kg) or an equivalent volume of DC of the same brand. Previously, our laboratory established a method of preparing drip-filtered coffee with a known caffeine concentration (22). Preparation of coffee with this method yields 62.1 mg caffeine/100 mL of brewed coffee. Before our experimental trials, we determined the exact volume of CC and DC for each subject. The meals consisted of either high GI (Kellogg's Crispex, London, ON, Canada) or low GI (Kellogg's All Bran, London, ON, Canada) cereal with nonfat milk. Both provided the same volume of milk and an amount of cereal calculated to provide a total meal carbohydrate content of 75 g. The GIs of the mixed meals were 81 and 41, respectively and were calculated with use of a method described elsewhere (23).

The principle researchers were blinded to all of the experimental treatments, but the subjects were not blinded to the cereal treatment. Each trial was separated by 1–2 wk and for a given subject, each trial was conducted at the same time of the day. Treatment allocation was determined before the start of the investigation by using a computer-generated randomization protocol. Two days (48 h) before each trial, subjects were required to abstain from all caffeine- and alcohol-containing products and from strenuous exercise to avoid depletion of muscle glycogen stores.

Experimental protocol
A medically trained technician inserted a Teflon catheter into an antecubital vein and kept it patent with a normal saline infusion. A venous blood sample was taken at time –60 min followed by ingestion of the coffee beverage. One hour after the coffee consumption (t = 0 min), a venous blood sample was taken and the 120-min mixed meal tolerance test (MMTT) was initiated by ingestion of the cereal meal. At each trial, the meal was consumed within 10 min; subsequent resting blood samples were taken at 15, 30, 45, 60, 90, and 120 min after consumption of the meal.

Laboratory analysis
At each time point, a total of {approx}8 mL of blood was withdrawn and partitioned for analysis of the following parameters: whole-blood glucose, serum insulin, serum C-peptide, serum free fatty acids (FFAs), and whole-blood glycerol. At each blood sampling, {approx}2 mL of blood was drawn into a sodium heparinized tube and immediately analyzed for blood glucose with use of a glucose oxidase method (2300 Stat Plus Glucose Analyzer; YSI Life Sciences, Yellow Springs, OH). Three milliliters of blood was drawn into a nonheparinzed tube and allowed to clot at room temperature. Samples were then centrifuged at room temperature for 10 min at 1200 x g, and serum was stored at –20 °C until analyzed for insulin (Coat-A-Count RIA insulin kit; Intermedico Diagnostic Products, Los Angeles, CA), FFAs (NEFA kit; Wako Bioproducts, Richmond, VA), and glycerol (24). Three milliliters of blood was drawn into a nonheparinized tube containing 80 µL of aprotinin (a trypsinogen inhibitor). This tube was also kept at room temperature to allow blood to clot, after which it was centrifuged at room temperature for 10 min at 1200 x g. The serum obtained from this sample was stored at –20 °C for subsequent C-peptide analysis (Human C-peptide RIA kit; Linco Research, St. Charles, MO). All blood metabolites were determined as the mean of duplicate determinations. To minimize the effects of assay variability, samples from each subject were analyzed in the same assay.

Statistical analysis
AUCs for glucose, insulin, and C-peptide were calculated for each of the trials during the 120-min MMTT (t = 0-120 min) with use of the trapezoid method (25). Whole-body insulin sensitivity during the MMTT was estimated for comparison purposes with the equation described by Matsuda and DeFronzo (26). This equation gives an insulin sensitivity index that is significantly correlated (r = 0.73, P < 0.0001) with the rate of whole-body glucose disposal during a hyperinsulinemic-euglycemic clamp (26). Data within each meal treatment were analyzed independently such that the effects of the beverage (CC or DC) taken with the high GI meal were analyzed separately from data within the low GI treatments. Whole-blood glucose, serum insulin, and serum C-peptide AUC data were analyzed for treatment effects by using a one-way analysis of variance (ANOVA) for repeated measures. Differences between treatments at each time point for all parameters measured were also analyzed by using one-way ANOVA for repeated measures. All statistical analyses were performed with the use of the Statistical Analysis System version 8.2 (SAS Institute Inc, Cary, NC) with differences accepted as significant if P < 0.05. All results are presented as means ± SEM.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Subject characteristics
Baseline subject characteristics are summarized in Table 1Go. All subjects met the fasting blood glucose requirement of <6.0 mmol/L. Two of the 10 subjects did not normally consume coffee, and the others were light to moderate consumers of caffeine (1–4 cups of coffee or 1–5 caffeine-containing soft drinks). The volume of coffee ingested by each subject during the trials ranged from 500 to 799 mL (mean: 633 mL).


View this table:
[in this window]
[in a new window]

  		TABLE 1. Baseline subject characteristics1

 
Study baseline
At study baseline (t = –60 min), there were no significant differences in circulating insulin, C-peptide, glucose, FFAs, and glycerol with the high GI (P = 0.60, 0.07, 0.15, 0.38, and 0.64, respectively) or low GI (P = 0.81, 0.58, 0.84, 0.06, and 0.18, respectively) treatments.

Insulin
As expected, serum insulin concentrations rose after ingestion of the high and low GI meals (Figure 1Go). Overall, the 29% increase in insulin AUC with CC was not significant (P = 0.16) in the high GI treatment, but with the low GI treatments, the AUC for insulin after ingestion of CC was significantly greater (44%) than that after DC (Table 2Go). Throughout the MMTT, insulin concentrations with the high GI treatments were only significantly different at t = 120 min (P < 0.05) (Figure 1Go). However, with the low GI treatments, serum insulin was significantly greater at t = 60, 90, and 120 min (P < 0.05) when CC was ingested.


Figure 1
View larger version (9K):
[in this window]
[in a new window]

  		FIGURE 1.. Serum insulin before and during a mixed meal tolerance test for caffeinated coffee (CC) with a high glycemic index (GI) meal (•), decaffeinated coffee (DC) with a high GI meal ({odot}), CC with a low GI meal ({blacktriangledown}), and DC with a low GI meal (Figure 1). CC (5 mg caffeine/kg body weight) or the equivalent volume of DC was ingested at t = –60 min followed by ingestion of a high GI or low GI meal providing 75 g carbohydrate. Data are presented as means (n = 10) with SEM represented by vertical bars. All data were analyzed by using a one-way ANOVA for repeated measures. Data within each meal treatment were analyzed independently such that the effects of the beverage (CC or DC) taken with the high GI meal were analyzed separately from data with the low GI treatments. *Significant difference (P < 0.05) between CC and DC within the high GI treatment at that time. #Significant difference (P < 0.05) between CC and DC within the low GI treatment at that time.

 

View this table:
[in this window]
[in a new window]

  		TABLE 2. Calculated areas under the curve for glucose, insulin, and C-peptide concentrations and calculated insulin sensitivity index (ISI) during the 120-min mixed meal tolerance test (MMTT) in healthy males1

 
C-peptide
Similar to insulin, C-peptide concentrations rose after ingestion of high and low GI meals (Figure 2Go). In both the high and low GI treatments, C-peptide AUC was significantly greater after ingestion of CC (Table 2Go). The serum C-peptide concentration was significantly greater after ingestion of CC at t = 60, 90, and 120 min with the high GI treatment (P < 0.05) and at t = 45, 60, 90 and 120 min with the low GI treatment (P < 0.01) (Figure 2Go).


Figure 2
View larger version (10K):
[in this window]
[in a new window]

  		FIGURE 2.. Serum C-peptide before and during a mixed meal tolerance test for caffeinated coffee (CC) with a high glycemic index (GI) meal (•), decaffeinated coffee (DC) with a high GI meal ({odot}), CC with a low GI meal ({blacktriangledown}), and DC with a low GI meal (Figure 2). CC (5 mg caffeine/kg body weight) or the equivalent volume of DC was ingested at t = –60 min followed by ingestion of a high GI or low GI meal providing 75 g of carbohydrate. Data are presented as means (n = 10) with SEM represented by vertical bars. All data were analyzed by using a one-way ANOVA for repeated measures. Data within each meal treatment were analyzed independently such that the effects of the beverage (CC or DC) taken with the high GI meal were analyzed separately from data with the low GI treatments. *Significant difference (P < 0.05) between CC and DC within the high GI treatment at that time. #Significant difference (P < 0.05) between CC and DC within the low GI treatment at that time.

 
Glucose
Blood glucose rose immediately in all groups after ingestion of the meal (Figure 3Go). Despite the high insulin concentrations associated with CC, in both the high and low GI treatments AUC after ingestion of CC was significantly greater than that after DC (Table 2Go). After ingestion of the high GI meal, the blood glucose concentration was significantly greater at all time points except t = 15 min after ingestion of CC (P < 0.05) (Figure 3Go). Similarly, after ingestion of CC and the low GI meal, the blood glucose concentration was significantly greater than after ingestion of DC at t = 15, 45, 60, 90, and 120 min (P < 0.05).


Figure 3
View larger version (9K):
[in this window]
[in a new window]

  		FIGURE 3.. Blood glucose before and during a mixed meal tolerance test for caffeinated coffee (CC) with a high glycemic index (GI) meal (•), decaffeinated coffee (DC) with a high GI meal ({odot}), CC with a low GI meal ({blacktriangledown}), and DC with a low GI meal (Figure 3). CC (5 mg caffeine/kg body weight) or the equivalent volume of DC was ingested at t = –60 min followed by ingestion of a high GI or low GI meal providing 75 g of carbohydrate. Data are presented as means (n = 10) with SEM represented by vertical bars. All data were analyzed by using a one-way ANOVA for repeated measures. Data within each meal treatment were analyzed independently such that the effects of the beverage (CC or DC) taken with the high GI meal were analyzed separately from data with the low GI treatments. *Significant difference (P < 0.05) between CC and DC with the high GI treatment at that time. #Significant difference (P < 0.05) between CC and DC within the low GI treatment at that time.

 
FFAs
Serum FFA concentrations decreased during the MMTT after ingestion of the meal. After ingestion of CC with the high GI meal, FFA concentrations were significantly higher from t = 0 to 60 min (P < 0.05) compared with those for the DC treatment (Figure 4Go). Similarly, ingestion of CC with the low GI meal resulted in significantly elevated FFA concentrations from t = 0 to 90 min (P < 0.05). With both the high and low GI treatments, FFA concentrations in the CC and DC groups were not significantly different at t = 120 min.


Figure 4
View larger version (9K):
[in this window]
[in a new window]

  		FIGURE 4.. Serum FFAs before and during a mixed meal tolerance test for caffeinated coffee (CC) with a high glycemic index (GI) meal (•), decaffeinated coffee (DC) with a high GI meal ({odot}), CC with a low GI meal ({blacktriangledown}), and DC with a low GI meal (Figure 4). CC (5 mg caffeine/kg body weight) or the equivalent volume of DC was ingested at t = –60 min followed by ingestion of a high GI or low GI meal providing 75 g of carbohydrate. Data are presented as means (n = 10) with SEM represented by vertical bars. All data were analyzed by using a one-way ANOVA for repeated measures. Data within each meal treatment were analyzed independently such that the effects of the beverage (CC or DC) taken with the high GI meal were analyzed separately from data with the low GI treatments. *Significant difference (P < 0.05) between CC and DC with the high GI treatment at that time. #Significant difference (P < 0.05) between CC and DC with the low GI treatment at that time.

 
Glycerol
Glycerol concentrations decreased in a pattern similar to that for FFA (Figure 5Go). In both the high and low GI treatments, the glycerol concentration was significantly greater after ingestion of CC at t = 0 and 60 min (P < 0.05).


Figure 5
View larger version (8K):
[in this window]
[in a new window]

  		FIGURE 5.. Glycerol before and during a MMTT for CC with a high GI meal (•), DC with a high GI meal ({odot}), CC with a low GI meal ({blacktriangledown}), and DC with a low GI meal (Figure 5). CC (5 mg caffeine/kg body weight) or the equivalent volume of DC was ingested at t = –60 min followed by ingestion of a high GI or low GI meal providing 75 g of carbohydrate. Data are presented as means (n = 10) with SEM represented by vertical bars. All data were analyzed by using a one-way ANOVA for repeated measures. Data within each meal treatment were analyzed independently such that the effects of the beverage (CC or DC) taken with the high GI meal were analyzed separately from data with the low GI treatments. *Significant difference (P < 0.05) between CC and DC within the high GI treatment at that time. #Significant difference (P < 0.05) between CC and DC within the low GI treatment at that time.

 
Insulin sensitivity
After ingestion of the high GI meal, whole-body insulin sensitivity decreased significantly (40%) when CC was ingested (Table 2Go). In contrast, despite a 29% reduction in insulin sensitivity index when CC was ingested, insulin sensitivity was not significantly different between the interventions when the low GI meal was ingested (P = 0.065).


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
The acute effect of caffeine on insulin sensitivity has been documented in healthy individuals (3, 4) and in those with T2DM (6, 7). In contrast, there have only been 2 studies examining the acute effects of CC on insulin sensitivity (20, 21) and in both of these studies, subjects were provided with a high GI test beverage providing 75 g of carbohydrate before the coffee administration. The goal of the current study was to examine the effects of CC and DC on glucose and insulin responses when given before both high and low GI cereal meals that are more representative of the Western diet.

Our first hypothesis was confirmed as individuals who consumed CC with a high GI meal experienced a 147% greater glucose AUC, a 29% greater insulin AUC, and a 40% reduction in whole-body insulin sensitivity index. Our second hypothesis was also confirmed as individuals who consumed the low GI cereal also experienced acutely impaired blood glucose management such that after CC ingestion, glucose, insulin, and C-peptide AUCs were 216%, 44%, and 36%, respectively, greater than those with the DC treatment. In addition, there was a strong trend toward reduced (29%) insulin sensitivity when CC was consumed. When these results were compared with those for the high GI treatments, it appears that consumption of CC before a low GI meal results in greater absolute increases in glucose and insulin. The consumption of low GI foods has been shown to have a beneficial effect on glycemic control (27) and is recommended by some national diabetes associations including the Canadian Diabetes Association (28). Our findings are relevant as they demonstrate that the ingestion of CC, a commonly consumed beverage, with a low GI cereal was associated with a pronounced disruption in blood glucose homeostasis. In the low GI trial, the glucose AUC increased from 41 (DC) to 131 (CC) mmol·2 h/L, a level that exceeded the 103 mmol·2 h/L for the high GI cereal when consumed with DC. In other words, although the actual GI for the low GI cereal was 50% of that of the high GI cereal, the apparent GI for the low GI cereal actually exceeded that of the high GI cereal, when the former was associated with CC consumption.

We also observed a reduction in acute insulin sensitivity after ingestion of CC with high and low GI meals. The primary physiologic effect of caffeine when ingested at a dose similar to that provided in our study is adenosine receptor antagonism (29). Thong et al (30) characterized A1 adenosine receptors on the plasma membrane of rodent skeletal muscle. They also showed that activation of these receptors with N6-cyclopentylxanthine (an adenosine receptor agonist) contributed {approx}50% to submaximal insulin-stimulated glucose uptake, and removal of adenosine (via adenosine deaminase) had the opposite effect. In humans, the administration of caffeine during a hyperinsulinemic-euglycemic clamp results in a 50% decrease in insulin-stimulated glucose uptake in the skeletal muscle (10), which translates into a 23–30% reduction in whole-body glucose disposal (8, 10). Although these data support the hypothesis that caffeine mediates its negative effects on glucose tolerance via adenosine receptor antagonism, it has also been proposed that insulin-mediated glucose uptake is impaired via caffeine-stimulated epinephrine release (31). Caffeine stimulates the release of epinephrine, which exerts actions opposite to that of insulin via β-adrenergic stimulation (32). When caffeine is given in the presence of a β-adrenergic receptor antagonist, the insulin antagonistic effects are abolished, suggesting that the negative effects of caffeine on insulin sensitivity are mediated via epinephrine secretion (31). However, the ingestion of caffeine plus the infusion of epinephrine resulted in a significant reduction in whole-body glucose disposal that was not additive of the individual effects of caffeine and epinephrine (33), suggesting that epinephrine is not solely responsible for the negative effects on glucose disposal. It is likely that the primary mechanisms contributing to the negative effects of caffeine on whole-body glucose management involve both β-adrenergic stimulation and adenosine receptor antagonism.

The negative effects of caffeine on acute insulin sensitivity are contradictory to the findings suggesting a reduced incidence of diabetes with habitual coffee consumption (34). Although we have demonstrated that a negative effect on acute blood glucose management occurs with the ingestion of CC, it is important to consider that caffeine makes up only 1.1–2.2% (by weight) (35) of roasted coffee. More than 600 volatile components have been identified in roasted coffee (36), some of which have been extensively studied and are known to possess biologic activity, whereas others remain largely undescribed. It is hypothesized that although caffeine may cause undesirable effects on blood glucose management, there may be other components in coffee that elicit opposite or positive effects. Examples of such compounds, which are not entirely removed during the decaffeination process (37), include chlorogenic acids (CAs) and CA-derived quinides. Shearer et al (38) reported that chronic administration of quinides to conscious Sprague-Dawley rats increased whole-body glucose disposal during a hyperinsulinemic-euglycemic clamp. In a separate study, Johnston et al (39) found that both CC and DC, prepared to provide a standard CA concentration of 2.50 mmol/L, attenuated postprandial glucose-dependent insulinotropic polypeptide secretion. They speculated that CAs may have an antagonistic effect on glucose transport in the intestine; reduced absorption of glucose from the intestine could potentially reduce plasma glucose concentrations after a meal, thus eliciting a positive effect on glucose homeostasis. More recently, Shearer et al (40) found in Sprague-Dawley rats with diet-induced whole-body insulin resistance that 4 wk of instant DC consumption improved insulin-stimulated whole-body glucose disposal during a hyperinsulinemic-euglycemic clamp compared with that in rats who were fed a placebo diet. Furthermore, this positive effect was completely negated in the animals that received instant DC with caffeine, and in fact, glucose disposal was decreased compared with that for the placebo treatment. These findings demonstrate that caffeine, CC, and DC elicit different metabolic effects and also strongly suggests that the effects of DC should be examined extensively.

The findings of this study demonstrate that the ingestion of either a high or low GI meal with CC significantly impairs acute insulin sensitivity compared with the effect of DC. Limitations of the current work include a small number of study participants limited to healthy men and lack of a noncoffee (ie, water) control. Our results have led us to pose several questions that warrant future investigation including the examination of 1) this effect in individuals with abnormal glucose control or with T2DM by using foods typical of the Western diet and 2) the prolonged effects of coffee consumption over a second meal period. Although the clinical relevance of the effects we have documented have yet to be established, this study adds more evidence to the current literature that caffeine and/or CC impairs short-term glycemic control. Given the growing body of evidence, both caffeine and CC should be considered a dietary risk factor for poor glycemic control, and our findings suggest that a simple dietary substitution to DC with a low GI meal may result in improved short-term glycemic control. If a high GI meal is to be consumed, then ingesting CC could be beneficial.


   ACKNOWLEDGMENTS
 
We gratefully acknowledge the subjects for their participation and cooperation, the dedicated technical assistance of Premila Sathasivam and Toni Lucca, and Alison Duncan for leading the statistical analysis.

The authors' responsibilities were as follows—LLM, SK, ACB, and LER: participated in study design; LLM, SK, and ACB: recruited participants; LLM, SK, and ACB: performed data collection and analysis; LLM: writing of manuscript; LER: interpreted data; and TEG: led study design and aided in manuscript preparation. None of the authors had a personal or financial conflict of interest.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Harland BF. Caffeine and nutrition. Nutrition 2000;16:522–6.[Medline]
  2. Nawrot P, Jordan S, Eastwood J, Rotstein J, Hugenholtz A, Feeley M. Effects of caffeine on human health. Food Addit Contam 2003;20:1–30.[Medline]
  3. Pizziol A, Tikhonoff V, Paleari CD, et al. Effects of caffeine on glucose tolerance: a placebo-controlled study. Eur J Clin Nutr 1998;52:846–9.[Medline]
  4. Graham TE, Sathasivam P, Rowland M, Marko N, Greer F, Battram D. Caffeine ingestion elevates plasma insulin response in humans during an oral glucose tolerance test. Can J Physiol Pharmacol 2001;79:559–65.[Medline]
  5. Petrie HJ, Chown SE, Belfie LM, et al. Caffeine ingestion increases the insulin response to an oral-glucose-tolerance test in obese men before and after weight loss. Am J Clin Nutr 2004;80:22–8.[Abstract/Free Full Text]
  6. Robinson LE, Savani S, Battram DS, McLaren DH, Sathasivam P, Graham TE. Caffeine ingestion before an oral glucose tolerance test impairs blood glucose management in men with type 2 diabetes. J Nutr 2004;134:2528–33.[Abstract/Free Full Text]
  7. Lane JD, Barkauskas CE, Surwit RS, Feinglos MN. Caffeine impairs glucose metabolism in type 2 diabetes. Diabetes Care 2004;27:2047–8.[Free Full Text]
  8. Greer F, Hudson R, Ross R, Graham T. Caffeine ingestion decreases glucose disposal during a hyperinsulinemic-euglycemic clamp in sedentary humans. Diabetes 2001;50:2349–54.[Abstract/Free Full Text]
  9. Keijzers GB, de Galan BE, Tack CJ, Smits P. Caffeine can decrease insulin sensitivity in humans. Diabetes Care 2002;25:364–9.[Abstract/Free Full Text]
  10. Thong FS, Derave W, Kiens B, et al. Caffeine-induced impairment of insulin action but not insulin signaling in human skeletal muscle is reduced by exercise. Diabetes 2002;51:583–90.[Abstract/Free Full Text]
  11. van Dam RM, Feskens EJ. Coffee consumption and risk of type 2 diabetes mellitus. Lancet 2002;360:1477–8.[Medline]
  12. Salazar-Martinez E, Willett WC, Ascherio A, et al. Coffee consumption and risk for type 2 diabetes mellitus. Ann Intern Med 2004;140:1–8.[Abstract/Free Full Text]
  13. Rosengren A, Dotevall A, Wilhelmsen L, Thelle D, Johansson S. Coffee and incidence of diabetes in Swedish women: a prospective 18-year follow-up study. J Intern Med 2004;255:89–95.[Medline]
  14. Tuomilehto J, Hu G, Bidel S, Lindstrom J, Jousilahti P. Coffee consumption and risk of type 2 diabetes mellitus among middle-aged Finnish men and women. JAMA 2004;291:1213–9.[Abstract/Free Full Text]
  15. Carlsson S, Hammar N, Grill V, Kaprio J. Coffee consumption and risk of type 2 diabetes in Finnish twins. Int J Epidemiol 2004;33:616–7.[Free Full Text]
  16. Agardh EE, Carlsson S, Ahlbom A, et al. Coffee consumption, type 2 diabetes and impaired glucose tolerance in Swedish men and women. J Intern Med 2004;255:645–52.[Medline]
  17. Yamaji T, Mizoue T, Tabata S, et al. Coffee consumption and glucose tolerance status in middle-aged Japanese men. Diabetologia 2004;47:2145–51.[Medline]
  18. van Dam RM, Willett WC, Manson JE, Hu FB. Coffee, caffeine, and risk of type 2 diabetes: a prospective cohort study in younger and middle-aged U.S. women. Diabetes Care 2006;29:398–403.[Abstract/Free Full Text]
  19. Pereira MA, Parker ED, Folsom AR. Coffee consumption and risk of type 2 diabetes mellitus: an 11-year prospective study of 28 812 postmenopausal women. Arch Intern Med 2006;166:1311–6.[Abstract/Free Full Text]
  20. Battram DS, Arthur R, Weekes A, Graham TE. The glucose intolerance induced by caffeinated coffee ingestion is less pronounced than that due to alkaloid caffeine in men. J Nutr 2006;136:1276–80.[Abstract/Free Full Text]
  21. Lane JD, Hwang AL, Feinglos MN, Surwit RS. Exaggeration of postprandial hyperglycemia in patients with type 2 diabetes by administration of caffeine in coffee. Endocr Pract 2007;13:239–43.[Medline]
  22. Graham TE, Hibbert E, Sathasivam P. Metabolic and exercise endurance effects of coffee and caffeine ingestion. J Appl Physiol 1998;85:883–9.[Abstract/Free Full Text]
  23. Wolever TM, Jenkins DJ, Jenkins AL, Josse RG. The glycemic index: methodology and clinical implications. Am J Clin Nutr 1991;54:846–54.[Abstract/Free Full Text]
  24. Lowry OH, Passonneau JV. Enzymatic analysis: a practical guide. Towowa, NJ: Humana Press, 1993.
  25. Allison DB, Paultre F, Maggio C, Mezzitis N, Pi-Sunyer FX. The use of areas under curves in diabetes research. Diabetes Care 1995;18:245–50.[Abstract]
  26. Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 1999;22:1462–70.[Abstract/Free Full Text]
  27. Brand-Miller J, Hayne S, Petocz P, Colagiuri S. Low-glycemic index diets in the management of diabetes: a meta-analysis of randomized controlled trials. Diabetes Care 2003;26:2261–7.[Abstract/Free Full Text]
  28. Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Canadian Diabetes Association 2003 clinical practice guidelines for the prevention and management of diabetes in Canada. Can J Diabetes 2003;27(suppl 2):S1–S152.
  29. Fredholm BB. Astra Award Lecture: Adenosine, adenosine receptors and the actions of caffeine. Pharmacol Toxicol 1995;76:93–101.[Medline]
  30. Thong FS, Lally JS, Dyck DJ, Greer F, Bonen A, Graham TE. Activation of the A1 adenosine receptor increases insulin-stimulated glucose transport in isolated rat soleus muscle. Appl Physiol Nutr Metab 2007;32:701–10.[Medline]
  31. Thong FS, Graham TE. Caffeine-induced impairment of glucose tolerance is abolished by beta-adrenergic receptor blockade in humans. J Appl Physiol 2002;92:2347–52.[Abstract/Free Full Text]
  32. Avogaro A, Toffolo G, Valerio A, Cobelli C. Epinephrine exerts opposite effects on peripheral glucose disposal and glucose-stimulated insulin secretion: a stable label intravenous glucose tolerance test minimal model study. Diabetes 1996;45:1373–8.[Abstract]
  33. Battram DS, Graham TE, Dela F. Caffeine's impairment of insulin-mediated glucose disposal cannot be solely attributed to adrenaline. J Physiol 200;583:1069-1077.
  34. van Dam RM, Hu FB. Coffee consumption and risk of type 2 diabetes: a systematic review. JAMA 2005;294:97–104.[Abstract/Free Full Text]
  35. Spiller MA. The chemical components of coffee. In: Spiller GA, ed. The methylxanthine beverages and foods: chemistry, consumption, and health effects. New York, NY: Alan R. Liss, 1984;91–147.
  36. Gilbert RM. Caffeine consumption. In:Spiller GA, ed. The methylxanthine beverages and foods: chemistry, consumption, and health effects. New York, NY: Alan R. Liss, 1984;185–213.
  37. Farah A, de Paulis T, Moreira DP, Trugo LC, Martin PR. Chlorogenic acids and lactones in regular and water-decaffeinated arabica coffees. J Agric Food Chem 2006;54:374–81.[Medline]
  38. Shearer J, Farah A, de Paulis T, et al. Quinides of roasted coffee enhance insulin action in conscious rats. J Nutr 2003;133:3529–32.[Abstract/Free Full Text]
  39. Johnston KL, Clifford MN, Morgan LM. Coffee acutely modifies gastrointestinal hormone secretion and glucose tolerance in humans: glycemic effects of chlorogenic acid and caffeine. Am J Clin Nutr 2003;78:728–33.[Abstract/Free Full Text]
  40. Shearer J, Sellars E, Farah A, Graham TE, Wasserman DH. Effects of chronic coffee consumption on glucose kinetics in the conscious rat. Can J Physiol Pharmacol 2007;85:823–30.[Medline]
Received for publication August 28, 2007. Accepted for publication December 12, 2007.





This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Moisey, L. L
Right arrow Articles by Graham, T. E
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Moisey, L. L
Right arrow Articles by Graham, T. E
Agricola
Right arrow Articles by Moisey, L. L
Right arrow Articles by Graham, T. E

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS