Caffeine Can Decrease Insulin Sensitivity in Humans
TL;DR: Caffeine can decrease insulin sensitivity in healthy humans, possibly as a result of elevated plasma epinephrine levels, and peripheral adenosine receptor antagonism does not appear to contribute to this effect.
Abstract: OBJECTIVE —Caffeine is a central stimulant that increases the release of catecholamines. As a component of popular beverages, caffeine is widely used around the world. Its pharmacological effects are predominantly due to adenosine receptor antagonism and include release of catecholamines. We hypothesized that caffeine reduces insulin sensitivity, either due to catecholamines and/or as a result of blocking adenosine-mediated stimulation of peripheral glucose uptake. RESEARCH DESIGN AND METHODS —Hyperinsulinemic-euglycemic glucose clamps were used to assess insulin sensitivity. Caffeine or placebo was administered intravenously to 12 healthy volunteers in a randomized, double-blind, crossover design. Measurements included plasma levels of insulin, catecholamines, free fatty acids (FFAs), and hemodynamic parameters. Insulin sensitivity was calculated as whole-body glucose uptake corrected for the insulin concentration. In a second study, the adenosine reuptake inhibitor dipyridamole was tested using an identical protocol in 10 healthy subjects. RESULTS —Caffeine decreased insulin sensitivity by 15% ( P P P P P P CONCLUSIONS —Caffeine can decrease insulin sensitivity in healthy humans, possibly as a result of elevated plasma epinephrine levels. Because dipyridamole did not affect glucose uptake, peripheral adenosine receptor antagonism does not appear to contribute to this effect.
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TL;DR: Current available evidence suggests that it may be prudent for pregnant women to limit coffee consumption to 3 cups/d providing no more than 300 mg/d of caffeine to exclude any increased probability of spontaneous abortion or impaired fetal growth, and there is little evidence that coffee consumption increases the risk of cancer.
Abstract: Coffee is a complex mixture of chemicals that provides significant amounts of chlorogenic acid and caffeine. Unfiltered coffee is a significant source of cafestol and kahweol, which are diterpenes that have been implicated in the cholesterolraising effects of coffee. The results of epidemiological research suggest that coffee consumption may help prevent several chronic diseases, including type 2 diabetes mellitus, Parkinson’s disease and liver disease (cirrhosis and hepatocellular carcinoma). Most prospective cohort studies have not found coffee consumption to be associated with significantly increased cardiovascular disease risk. However, coffee consumption is associated with increases in several cardiovascular disease risk factors, including blood pressure and plasma homocysteine. At present, there is little evidence that coffee consumption increases the risk of cancer. For adults consuming moderate amounts of coffee (3‐4 cups/d providing 300‐400 mg/d of caffeine), there is little evidence of health risks and some evidence of health benefits. However, some groups, including people with hypertension, children, adolescents, and the elderly, may be more vulnerable to the adverse effects of caffeine. In addition, currently available evidence suggests that it may be prudent for pregnant women to limit coffee consumption to 3 cups/d providing no more than 300 mg/d of caffeine to exclude any increased probability of spontaneous abortion or impaired fetal growth.
943 citations
Cites background from "Caffeine Can Decrease Insulin Sensi..."
...42 , 43 , 44 , 45 Several randomized controlled trials have examined the effect of coffee consumption for 2–4 weeks on serum glucose and insulin levels....
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TL;DR: The present review discusses the most relevant methodological considerations and highlights specific recommendations regarding number of subjects, sex, subject status, inclusion and exclusion criteria, pre-test conditions, CHO test dose, blood sampling procedures, sampling times, test randomisation and calculation of glycaemic response area under the curve.
Abstract: The glycaemic index (GI) concept was originally introduced to classify different sources of carbohydrate (CHO)-rich foods, usually having an energy content of > 80 % from CHO, to their effect on post-meal glycaemia. It was assumed to apply to foods that primarily deliver available CHO, causing hyperglycaemia. Low-GI foods were classified as being digested and absorbed slowly and high-GI foods as being rapidly digested and absorbed, resulting in different glycaemic responses. Low-GI foods were found to induce benefits on certain risk factors for CVD and diabetes. Accordingly it has been proposed that GI classification of foods and drinks could be useful to help consumers make 'healthy food choices' within specific food groups. Classification of foods according to their impact on blood glucose responses requires a standardised way of measuring such responses. The present review discusses the most relevant methodological considerations and highlights specific recommendations regarding number of subjects, sex, subject status, inclusion and exclusion criteria, pre-test conditions, CHO test dose, blood sampling procedures, sampling times, test randomisation and calculation of glycaemic response area under the curve. All together, these technical recommendations will help to implement or reinforce measurement of GI in laboratories and help to ensure quality of results. Since there is current international interest in alternative ways of expressing glycaemic responses to foods, some of these methods are discussed.
881 citations
Cites background from "Caffeine Can Decrease Insulin Sensi..."
...Moreover, caffeine is known to acutely decrease insulin sensitivity in human subjects (Graham et al. 2000; Keijzers et al. 2002)....
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TL;DR: In the cross-sectional studies conducted in northern Europe, southern Europe, and Japan, higher coffee consumption was consistently associated with a lower prevalence of newly detected hyperglycemia, particularly postprandial hyperglyCEmia.
Abstract: ContextEmerging epidemiological evidence suggests that higher coffee consumption
may reduce the risk of type 2 diabetes.ObjectiveTo examine the association between habitual coffee consumption and risk
of type 2 diabetes and related outcomes.Data Sources and Study SelectionWe searched MEDLINE through January 2005 and examined the reference
lists of the retrieved articles. Because this review focuses on studies of
habitual coffee consumption and risk of type 2 diabetes, we excluded studies
of type 1 diabetes, animal studies, and studies of short-term exposure to
coffee or caffeine, leaving 15 epidemiological studies (cohort or cross-sectional).Data ExtractionInformation on study design, participant characteristics, measurement
of coffee consumption and outcomes, adjustment for potential confounders,
and estimates of associations was abstracted independently by 2 investigators.Data SynthesisWe identified 9 cohort studies of coffee consumption and risk of type
2 diabetes, including 193 473 participants and 8394 incident cases of
type 2 diabetes, and calculated summary relative risks (RRs) using a random-effects
model. The RR of type 2 diabetes was 0.65 (95% confidence interval [CI], 0.54-0.78)
for the highest (≥6 or ≥7 cups per day) and 0.72 (95% CI, 0.62-0.83)
for the second highest (4-6 cups per day) category of coffee consumption compared
with the lowest consumption category (0 or ≤2 cups per day). These associations
did not differ substantially by sex, obesity, or region (United States and
Europe). In the cross-sectional studies conducted in northern Europe, southern
Europe, and Japan, higher coffee consumption was consistently associated with
a lower prevalence of newly detected hyperglycemia, particularly postprandial
hyperglycemia.ConclusionsThis systematic review supports the hypothesis that habitual coffee
consumption is associated with a substantially lower risk of type 2 diabetes.
Longer-term intervention studies of coffee consumption and glucose metabolism
are warranted to examine the mechanisms underlying the relationship between
coffee consumption and type 2 diabetes.
632 citations
17 Mar 2006
TL;DR: These classroom activities, based on the Australian Guide to Healthy Eating, help explore the outcomes and subject matter in the PDHPE K-6 syllabus.
Abstract: These classroom activities, based on the Australian Guide to Healthy Eating, help explore the outcomes and subject matter in the PDHPE K-6 syllabus. The activities for Early Stage 1 focus on the food groups and encourage children to try new foods. Stage 1 activities focus on selecting a variety of foods from the different food groups for healthy eating. Stage 2 activities focus on the importance of eating fruit and vegetables. In Stage 3 students are required to look at their food habits and what they eat each day.
577 citations
Cites background from "Caffeine Can Decrease Insulin Sensi..."
...It has been reported that insulin resistance is increased in peripheral tissues after exposure to caffeine [484] and conversely, the effect of caffeine on thermoregulation has been suggested as a mechanism by which glucose homeostasis is improved [485]....
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TL;DR: Long-term intake of coffee and other caffeinated beverages and decaffeinated coffee in relation to incidence of type 2 diabetes in 2 large prospective cohorts of men and women was examined and whether the associations were modified by smoking and body mass index was examined.
Abstract: The authors found that higher coffee consumption was associated with a lower incidence of type 2 diabetes mellitus, even after adjustment for age, body mass index, and other risk factors. Caffeine ...
573 citations
Cites background from "Caffeine Can Decrease Insulin Sensi..."
...Coffee consumption may be related to diabetes because short-term metabolic studies have suggested that caffeine adversely affects insulin sensitivity and glucose metabolism (3)....
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References
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TL;DR: Methods for the quantification of beta-cell sensitivity to glucose (hyperglycemic clamp technique) and of tissue sensitivity to insulin (euglycemic insulin clamp technique] are described.
Abstract: Methods for the quantification of beta-cell sensitivity to glucose (hyperglycemic clamp technique) and of tissue sensitivity to insulin (euglycemic insulin clamp technique) are described. Hyperglycemic clamp technique. The plasma glucose concentration is acutely raised to 125 mg/dl above basal levels by a priming infusion of glucose. The desired hyperglycemic plateau is subsequently maintained by adjustment of a variable glucose infusion, based on the negative feedback principle. Because the plasma glucose concentration is held constant, the glucose infusion rate is an index of glucose metabolism. Under these conditions of constant hyperglycemia, the plasma insulin response is biphasic with an early burst of insulin release during the first 6 min followed by a gradually progressive increase in plasma insulin concentration. Euglycemic insulin clamp technique. The plasma insulin concentration is acutely raised and maintained at approximately 100 muU/ml by a prime-continuous infusion of insulin. The plasma glucose concentration is held constant at basal levels by a variable glucose infusion using the negative feedback principle. Under these steady-state conditions of euglycemia, the glucose infusion rate equals glucose uptake by all the tissues in the body and is therefore a measure of tissue sensitivity to exogenous insulin.
7,271 citations
TL;DR: A novel estimate of insulin sensitivity that is simple to calculate and provides a reasonable approximation of whole-body insulin sensitivity from the oral glucose tolerance test (OGTT).
Abstract: OBJECTIVE: Several methods have been proposed to evaluate insulin sensitivity from the data obtained from the oral glucose tolerance test (OGTT). However, the validity of these indices has not been rigorously evaluated by comparing them with the direct measurement of insulin sensitivity obtained with the euglycemic insulin clamp technique. In this study, we compare various insulin sensitivity indices derived from the OGTT with whole-body insulin sensitivity measured by the euglycemic insulin clamp technique. RESEARCH DESIGN AND METHODS: In this study, 153 subjects (66 men and 87 women, aged 18-71 years, BMI 20-65 kg/m2) with varying degrees of glucose tolerance (62 subjects with normal glucose tolerance, 31 subjects with impaired glucose tolerance, and 60 subjects with type 2 diabetes) were studied. After a 10-h overnight fast, all subjects underwent, in random order, a 75-g OGTT and a euglycemic insulin clamp, which was performed with the infusion of [3-3H]glucose. The indices of insulin sensitivity derived from OGTT data and the euglycemic insulin clamp were compared by correlation analysis. RESULTS: The mean plasma glucose concentration divided by the mean plasma insulin concentration during the OGTT displayed no correlation with the rate of whole-body glucose disposal during the euglycemic insulin clamp (r = -0.02, NS). From the OGTT, we developed an index of whole-body insulin sensitivity (10,000/square root of [fasting glucose x fasting insulin] x [mean glucose x mean insulin during OGTT]), which is highly correlated (r = 0.73, P < 0.0001) with the rate of whole-body glucose disposal during the euglycemic insulin clamp. CONCLUSIONS: Previous methods used to derive an index of insulin sensitivity from the OGTT have relied on the ratio of plasma glucose to insulin concentration during the OGTT. Our results demonstrate the limitations of such an approach. We have derived a novel estimate of insulin sensitivity that is simple to calculate and provides a reasonable approximation of whole-body insulin sensitivity from the OGTT.
4,988 citations
"Caffeine Can Decrease Insulin Sensi..." refers methods in this paper
...As a modification of a previously described method (18), whole-body insulin sensitivity was calculated as the GIR divided by the plasma insulin concentration during the final 30 min of the study and expressed in mol kg 1 min 1 per mU/l....
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TL;DR: This study suggests that acute increases in plasma insulin within the physiological range elevate sympathetic neural outflow but produce forearm vasodilation and do not elevate arterial pressure in normal humans.
Abstract: Hyperinsulinemia may contribute to hypertension by increasing sympathetic activity and vascular resistance We sought to determine if insulin increases central sympathetic neural outflow and vascular resistance in humans We recorded muscle sympathetic nerve activity (MSNA; microneurography, peroneal nerve), forearm blood flow (plethysmography), heart rate, and blood pressure in 14 normotensive males during 1-h infusions of low (38 mU/m2/min) and high (76 mU/m2/min) doses of insulin while holding blood glucose constant Plasma insulin rose from 8 +/- 1 microU/ml during control, to 72 +/- 8 and 144 +/- 13 microU/ml during the low and high insulin doses, respectively, and fell to 15 +/- 6 microU/ml 1 h after insulin infusion was stopped MSNA, which averaged 215 +/- 15 bursts/min in control, increased significantly (P less than 0001) during both the low and high doses of insulin (+/- 54 and +/- 93 bursts/min, respectively) and further increased during 1-h recovery (+152 bursts/min) Plasma norepinephrine levels (119 +/- 19 pg/ml during control) rose during both low (258 +/- 25; P less than 002) and high (285 +/- 95; P less than 001) doses of insulin and recovery (316 +/- 23; P less than 001) Plasma epinephrine levels did not change during insulin infusion Despite the increased MSNA and plasma norepinephrine, there were significant (P less than 0001) increases in forearm blood flow and decreases in forearm vascular resistance during both doses of insulin Systolic pressure did not change significantly during infusion of insulin and diastolic pressure fell approximately 4-5 mmHg (P less than 001) This study suggests that acute increases in plasma insulin within the physiological range elevate sympathetic neural outflow but produce forearm vasodilation and do not elevate arterial pressure in normal humans
1,116 citations
"Caffeine Can Decrease Insulin Sensi..." refers background in this paper
...These data reflect systemic vasodilation and sympathetic activation, both of which have been previously described as a consequence of hyperinsulinemia (19)....
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TL;DR: The ability of troglitazone to reduce insulin resistance and improves glucose tolerance in obese subjects with either impaired or normal glucose tolerance could be useful in preventing NIDDM.
Abstract: Background Troglitazone decreases insulin resistance and hyperglycemia in patients with non-insulin-dependent diabetes mellitus (NIDDM), but its effects on subjects without diabetes are not known. Methods We performed oral and intravenous glucose-tolerance tests, studies with the euglycemic-hyperinsulinemic clamp, meal-tolerance tests, and 24-hour blood-pressure measurements at base line and after the administration of troglitazone, 200 mg orally twice daily, or placebo for 12 weeks in 18 nondiabetic obese subjects, 9 of whom had impaired glucose tolerance. Results The mean (±SD) rates of glucose disposal increased from 4.7 ±1.7 to 6.0 ±1.7 mg per kilogram of body weight per minute (P = 0.004) and from 9.0 ±1.8 to 9.9 ±1.3 mg per kilogram per minute (P = 0.02) during insulin infusions of 40 and 300 mU per square meter of body-surface area per minute, respectively, in the troglitazone group. The insulin-sensitivity index, calculated from the results of intravenous glucose-tolerance tests, increased from 0....
954 citations
"Caffeine Can Decrease Insulin Sensi..." refers background in this paper
...The decrease in insulin sensitivity we documented as result of caffeine ingestion is close to the magnitude of the increase in insulin sensitivity that can be achieved with glucose-lowering agents, such as metformin (20) and thiazolidinedione derivatives (21), and is therefore clinically relevant....
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TL;DR: In this article, the effect of epinephrine on tissue sensitivity to insulin, and the relative contributions of peripheral vs. hepatic resistance to impaired insulin action, have not been defined.
Abstract: Endogenous release of epinephrine after stress as well as exogenous epinephrine infusion are known to result in impaired glucose tolerance. Previous studies of man and animals have demonstrated that this effect of epinephrine results from inhibition of insulin secretion and augmentation of hepatic glucose production. However, the effect of epinephrine on tissue sensitivity to insulin, and the relative contributions of peripheral vs. hepatic resistance to impaired insulin action, have not been defined. Nine young normal-weight subjects were studied with the insulin clamp technique. Plasma insulin was raised by approximately 100 muU/ml while plasma glucose concentration was maintained at basal levels by a variable glucose infusion. Under these conditions of euglycemia, the amount of glucose metabolized equals the glucose infusion rate and is a measure of tissue sensitivity to insulin. Subjects received four studies: (a) insulin (42.6 mU/m(2).min), (b) insulin plus epinephrine (0.05 mug/kg.min), (c) insulin plus epinephrine plus propranolol (1.43 mug/kg.min), and (d) insulin plus propranolol. During insulin administration alone, glucose metabolism averaged 5.49+/-0.58 mg/kg.min. When epinephrine was infused with insulin, glucose metabolism fell by 41% to 3.26 mg/kg.min (P 100 muU/ml. When propranolol was administered with epinephrine, total glucose metabolism was restored to control values and hepatic glucose production suppressed normally. Propranolol alone had no effect on insulin-mediated glucose metabolism. These results indicate that epinephrine, acting primarily through a beta-adrenergic receptor, markedly impairs tissue sensitivity to an increase in plasma insulin levels, and that this effect results from both peripheral and hepatic resistance to the action of insulin.
544 citations
"Caffeine Can Decrease Insulin Sensi..." refers methods in this paper
...Using the euglycemic clamp technique, Deibert and DeFronzo (9) showed that epinephrine infusion reduced tissue sensitivity to insulin by 50%....
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...Because the epinephrine level attained in that study was fourfold higher than that in our study, the 15% fall in insulin sensitivity we observed may be comparable with data reported by Deibert and DeFronzo....
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