Caffeine is one of the most commonly consumed, biologically active dietary ingredients throughout the world. It is a stimulant found naturally in coffee, tea, chocolate, some soft drinks, energy drinks and certain medicines, and is estimated as being present in the diets of more than 85% of British and North American adults (Henderson et al., 2002; Frary et al., 2005). Under experimental conditions, moderate intakes of caffeine have been shown to disrupt glycaemic control in healthy individuals, therefore supporting the hypothesis that caffeine impairs glucose metabolism in patients with existing diabetes. The aim of this review was to systematically evaluate the evidence for the effects of caffeine ingestion on glycaemic outcome and/or insulin sensitivity in adults with type I, type II and GDM.
Glycaemic impact of caffeine
Consistently elevated post-prandial blood glucose concentrations after the acute ingestion of moderate to high doses of a single daily caffeine supplement (Lane et al., 2004, 2007, 2008; Robinson et al., 2004; Lee et al., 2005) and caffeinated coffee (Jankelson et al., 1967) were observed in type II diabetes and with caffeine supplementation in the single study in GDM (Robinson et al., 2009), indicating a similar impaired glucose response to caffeine and caffeinated drinks that has been reported in healthy nondiabetic controls. Repeated exaggerations of post-prandial glucose, resulting from a single daily dose of caffeine, showed higher mean glucose concentrations (Lane et al., 2008), with the potential to increase HbA1c and, ultimately, the risk of diabetes-related complications.
The effects of caffeine remained present for up to 3 h after caffeine consumption and following a glucose load (Robinson et al., 2004), with regular aerobic exercise failing to alleviate the negative effects (Lee et al., 2005). Caffeine itself had no impact on blood glucose concentrations independently before the administration of a glucose load, further supporting the evidence that caffeine consumption alongside a glucose/carbohydrate load promotes heightened and prolonged hyperglycaemia, independent of factors such as exercise, which might be expected to alleviate the effect.
Although this systematic review clearly demonstrates an enhanced glycaemic effect of caffeine in type II diabetes under experimental short-term conditions, it is important to note that, in daily living, caffeine is ingested not as alkaloid caffeine capsules but predominantly as coffee in adults and as carbonated drinks in children and adolescents (Frary et al., 2005). With the exception of Jankelson et al. (1967), who administered caffeine as a coffee beverage, alkaloid caffeine capsules were used as the supplement of choice and generally in a high single dose. In four out of six studies in type II diabetes, caffeine doses of >350 mg were administered and, for the two studies in type I diabetes, the dose was >400 mg (Table 1), corresponding to the maximum advised daily dose (Health Canada, 2010). Battram et al. (2006) have shown that, in healthy individuals, caffeine exerts a glycaemic effect of up to 40% compared to the same dose of caffeine naturally present within a coffee beverage, suggesting that, in its more common dietary presentation, caffeine induces a more subdued effect. Interestingly, Jankelson et al. (1967) were not only the only study to use coffee as the means of caffeine supplementation, but also showed an enhanced post-prandial glucose effect similar in magnitude to studies using alkaloid caffeine, suggesting that a similar effect can be replicated with moderate doses of coffee consumption.
The dichotomy between the results of these experimental studies and the consistent findings of epidemiological studies showing an inverse relationship between heavy coffee consumption and risk of type II diabetes in healthy nondiabetic adults (Huxley et al., 2009) is conflicting. A number of explanations have been proposed. Coffee has been shown to be a poor marker of caffeine intake, resulting in misclassification (Brown et al., 2001), contains other compounds such as chlorogenic acid, trigonelline and antioxidants, which may counteract the glycaemic effect of caffeine, through their favourable impact on oxidative stress, gluconeogenesis, gut hormones or intestinal microflora (Tunnicliffe & Shearer, 2008), and more recent evidence suggests a potentially beneficial metabolic impact of coffee on adipocytes and liver function (Wedick et al., 2011). Despite various theories, the association between high coffee consumption and lower diabetes risk remains purely correlational. High coffee consumption may simply be a marker for other risk factors (Malik et al., 2010) or, for a variety of reasons, certain sectors of the population may be more prone to the effect of caffeine/caffeinated beverages.
Habitual coffee consumption has been proposed as inducing tolerance to caffeine (Robertson et al., 1981; Denaro et al., 1991) and the disappearance of acute daily side effects. In three studies (Lane et al., 2004, 2007, 2008), the estimated mean habitual coffee consumption ranged from 486 to 526 mg caffeine daily (Table 1), which is in excess of current daily recommendations of no more than 400 mg (Health Canada, 2010). Despite this high intake in older individuals aged 54–63 years, the ingestion of caffeine increased both the glucose response and insulin resistance in response to a carbohydrate challenge. Although estimates of habitual intake applied only to the immediate prestudy periods and cannot be relied on as an estimate of their long-term coffee consumption, it introduces the possibility that habitual coffee drinkers might be predisposed towards the more detrimental effects of caffeine over time.
This review highlights two specific groups who could be considered to be more prone to the negative effects of caffeine on blood glucose. First, Lane et al. (2007) demonstrated that the magnitude of the caffeine effect was correlated with the number of years since the diagnosis of diabetes. Although this trial requires replication to establish and quantify the effect, it suggests that those with type II diabetes may require greater dietary scrutiny of caffeine intake over time. Second, in women with GDM, it was shown that, even with lower ingested intakes of caffeine of approximately 200 mg, which corresponds to the safe recommended dose in pregnant women (FSA, 2011), an increased post-prandial glucose effect after caffeine ingestion and a carbohydrate challenge was apparent (Robinson et al., 2009). The direct correlation between glycaemic control and adverse foetal effects shown in gestational diabetes (Metzger et al., 2008) signifies a group in whom the preliminary results from this relatively high quality, yet small sample sized trial warrant further investigation.
Overall, the evidence for caffeine-induced impairment in the management of type II diabetes could warrant consideration of a change in current dietary practice for caffeine ingestion in this population group. Such guidelines may encourage those with poorly controlled type II diabetes to reduce their daily consumption of caffeine by choosing noncaffeinated beverages as their drink of choice. It can be postulated that, if habitual caffeinated coffee drinkers who have type II diabetes abstain from caffeinated beverages (i.e. lower their overall caffeine intake), then clinically beneficial reductions in post-prandial and overall blood glucose concentrations may be possible. Recently, a single-arm, pre–post design pilot study was conducted to test the effects of caffeine abstinence on blood glucose control over 3 months in participants with type II diabetes who drank caffeinated coffee daily (Lane et al., 2012). The primary outcome of this small trial (n = 7) was a reduction in HbA1c by 0.56% (P = 0.04), with the suggestion that habitual caffeine consumption increases chronic glucose concentrations, and caffeine abstinence may lead to beneficial improvements in chronic glycaemic control.
The significantly elevated post-prandial insulin concentrations following caffeine supplementation, compared to placebo, was observed in three studies in type II diabetes (Lane et al., 2004, 2007; Robinson et al., 2004) and in the single study in women with GDM (Robinson et al., 2009). Hyperglycaemia in conjunction with hyperinsulinaemia indicates a caffeine induced impairment in insulin sensitivity, which has previously been shown in healthy controls following both caffeine ingestion (Greer et al., 2001; Keijzers et al., 2002) and the consumption of caffeinated coffee (Moisey et al., 2008). This would support reduced insulin sensitivity as a mechanism of action for the negative impact of caffeine on glycaemic control.
Further research, in the form of randomised controlled trials, is warranted in individuals with type II diabetes to determine whether reducing or abstaining from caffeine altogether improves long-term glycaemic control (i.e. HbA1c) and, ultimately, the risk of diabetes-related complications. This is also true of GDM where the preservation of both foetal and maternal health is paramount. Determination of a safe ‘upper limit’ for caffeine ingestion is warranted (i.e. a specified amount of caffeine that, when ingested with or after a glucose/carbohydrate load, does not effect blood glucose concentrations). Current research suggests that this amount would be less than 200 mg (equivalent to one to two cups of instant coffee), with the potential to be reduced further for women with GDM where existing daily recommendations are already 200 mg (FSA, 2011) and 300 mg (Health Canada, 2010) for pregnant women. Replication of this study with trials of larger sample size is now required to determine the clinical implications of a regular intake or abstinence of caffeine during pregnancy on long-term glycaemic control and foetal outcomes.
In type I diabetes, there is early evidence of the potentially beneficial uses of caffeine in relation to both increased awareness, and the decreased duration of hypoglycaemic episodes indicating that HbA1c values remain unaffected by caffeine supplementation at 3 months. Patients with type I diabetes face an exacting task when trying to achieve normoglycaemia without inducing recurrent hypoglycaemic episodes that may impact on psychological health and cognitive function, with recurrent severe hypoglycaemia further being associated with depressed mood and poor quality of life (Frier, 2004). Debrah et al. (1996) were the first to indicate that caffeine might have a role in recognising the onset of hypoglycaemia in type I diabetes patients through augmentation of symptomatic and hormonal responses to a modest reduction in blood glucose. The highly significant increase in hypoglycaemic episodes with more intense warning symptoms indicates that caffeine may have the potential to have a beneficial impact.
Nocturnal hypoglycaemia accounts for approximately half of all severe episodes, and is particularly dangerous because the warning symptoms are blunted or absent during sleep (DCCT, 1991). It is of note that caffeine was observed to reduce overall daily hypoglycaemic episodes and also the duration of moderate overnight hypoglycaemic episodes (Richardson et al., 2005) through a validated measure of continuous blood glucose monitoring that can precisely quantify the duration and magnitude of hypoglycaemia. Further trials are now needed to confirm and quantify these results over prolonged time periods using caffeine supplementation and also to determine whether these can be replicated using dietary sources such as coffee or other caffeinated drinks.
The limited research within this area restricts any argument for change in current practice, policy or guidance for caffeine intake. Healthcare professionals should, however, be aware of the current research findings, and should await confirmation regarding the clinical implications of caffeine intake from future research trials. The long-term effects of caffeine intake on glycaemic control in type I diabetes are relatively unknown; however, published trials have shown that caffeine has the potential to play a beneficial role, especially if individuals with the disease either struggle to recognise episodes of hypoglycaemia or if nocturnal hypoglycaemia is problematic.
Further trials are warranted in this population with a greater emphasis on the effects of caffeine on blood glucose concentrations and/or insulin sensitivity. The mechanisms and physiology behind type I and type II diabetes vary greatly, and it is currently unknown whether caffeine exhibits the same effect in both diseases.