A chlorogenic acid-induced increase in GLP-1 production may mediate the impact of heavy coffee consumption on diabetes risk

doi:10.1016/j.mehy.2004.03.037

Medical Hypotheses

Volume 64, Issue 4, 2005, Pages 848-853

https://doi.org/10.1016/j.mehy.2004.03.037 Get rights and content

Abstract

Recent prospective epidemiology links heavy coffee consumption to a substantial reduction in risk for type 2 diabetes. Yet there is no evidence that coffee improves insulin sensitivity and, at least in acute studies, caffeine has a negative impact in this regard. Thus, it is reasonable to suspect that coffee influences the risk for beta cell “failure” that precipitates diabetes in subjects who are already insulin resistant. Indeed, there is recent evidence that coffee increases production of the incretin hormone glucagon-like peptide-1 (GLP-1), possibly owing to an inhibitory effect of chlorogenic acid (CGA – the chief polyphenol in coffee) on glucose absorption. GLP-1 acts on beta cells, via cAMP-dependent mechanisms, to promote the synthesis and activity of the transcription factor IDX-1, crucial for maintaining the responsiveness of beta cells to an increase in plasma glucose. Conversely, the “glucolipotoxicity” thought to initiate and sustain beta cell dysfunction in diabetics can suppress expression of this transcription factor. The increased production of GLP-1 associated with frequent coffee consumption could thus be expected to counteract the adverse impact of chronic free fatty acid overexposure on beta cell function in overweight insulin resistant subjects. CGA's putative impact on glucose absorption may reflect the ability of this compound to inhibit glucose-6-phosphate translocase 1, now known to play a role in intestinal glucose transport. Delayed glucose absorption may itself protect beta cells by limiting postprandial hyperglycemia – though, owing to countervailing effects of caffeine on plasma glucose, and a paucity of relevant research studies, it is still unclear whether coffee ingestion blunts the postprandial rise in plasma glucose. More generally, diets high in “lente carbohydrate”, or administration of nutraceuticals/pharmaceuticals which slow the absorption of dietary carbohydrate, should help preserve efficient beta cell function by boosting GLP-1 production, as well as by blunting the glucotoxic impact of postprandial hyperglycemia on beta cell function.

Section snippets

Why does coffee reduce diabetes risk?

Four recent prospective studies have linked heavy regular use of coffee to decreased risk for type 2 diabetes, including a Harvard analysis that follows up over 120,000 men and women for over a decade [1], [2], [3], [4]. The effect is robust and dose-dependent – in the Harvard study, for those consuming an average of 6 or more cups daily, as opposed to abstainers, relative risk of developing diabetes was found to be 0.46 and 0.71 in men and women, respectively [4]. A trend toward reduced risk

Chlorogenic acid modulates incretin production

How might CGA influence beta cell function? There is recent evidence that CGA can influence incretin production [9]. When subjects ingested sweetened coffee – either caffeinated or decaffeinated – or a comparable intake of sugar in water, the subsequent rise in serum levels of glucose-dependent insulinotrophic peptide (GIP) was suppressed, but the rise in glucagon-like peptide-1 (GLP-1) was enhanced. The same effect is seen following acarbose administration, and likely reflects a retardation of

How CGA slows glucose absorption

Furthermore, there are now theoretical grounds for predicting that CGA can slow glucose absorption. The classical model of intestinal glucose absorption holds that glucose is actively transported through the apical membrane of enterocytes by a sodium gradient-driven glucose transporter, and then exits passively to the interstitial space via GLUT2 transporters in the basolateral membrane. However, intestinal glucose absorption has recently been found to be virtually normal in mice and humans

Chlorogenic acid – another strategy for achieving “Lente Carbohydrate?”

A corollary of this hypothesis is that administration of supplemental CGA with meals (without caffeine) should lower the glycemic index of meals while promoting GLP-1 production and reducing risk for diabetes. The impact of CGA on glycemic index and GLP-1 would of course be readily testable in short-term studies. An extract of green coffee beans rich in CGA (55%) is now commercially available in the US, and would lend itself to such studies.

If such studies demonstrate that CGA can indeed retard

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A chlorogenic acid-induced increase in GLP-1 production may mediate the impact of heavy coffee consumption on diabetes risk

Abstract

Section snippets

Why does coffee reduce diabetes risk?

Chlorogenic acid modulates incretin production

How CGA slows glucose absorption

Chlorogenic acid – another strategy for achieving “Lente Carbohydrate?”

Lancet

Lancet

J. Nutr.

Am. J. Clin. Nutr.

Biomed. Pharmacother.

J. Nutr.

Biochem. Biophys. Res. Commun.

J. Biol. Chem.

J. Biol. Chem.

Lancet

J. Nutr.

J. Nutr.

Gastroenterology

Lancet

Metabolism

Metabolism

Endocrinol. Metab. Clin. North Am.

Am. J. Clin. Nutr.

Ann. Oncol.

Ann. Oncol.

Ann. Oncol.

Coffee and incidence of diabetes in Swedish women: a prospective 18-year follow-up study

J. Intern. Med.

Coffee consumption and risk for type 2 diabetes mellitus

Ann. Intern. Med.

Caffeine can decrease insulin sensitivity in humans

Diabetes Care

Caffeine-induced impairment of insulin action but not insulin signaling in human skeletal muscle is reduced by exercise

Diabetes

Caffeine-induced impairment of glucose tolerance is abolished by beta-adrenergic receptor blockade in humans

J. Appl. Physiol.

Light-to-moderate alcohol intake is associated with enhanced insulin sensitivity

Diabetes Care

Alcohol and insulin sensitivity

Neth. J. Med.

Effects of moderate alcohol intake on fasting insulin and glucose concentrations and insulin sensitivity in postmenopausal women: a randomized controlled trial

JAMA

Effect of moderate alcohol consumption on adiponectin, tumor necrosis factor-alpha, and insulin sensitivity

Diabetes Care

Does coffee drinking increase the risk of coronary heart disease? Results from a meta-analysis

Br. Heart J.

Intestinal effects of alpha-glucosidase inhibitors: absorption of nutrients and enterohormonal changes

Eur. J. Clin. Invest.

Delayed gastric emptying occurs following acarbose administration and is a further mechanism for its anti-hyperglycaemic effect

Diabet. Med.

Prolonged and enhanced secretion of glucagon-like peptide 1 (7–36 amide) after oral sucrose due to alpha-glucosidase inhibition (acarbose) in type 2 diabetic patients

Diabet. Med.

Inhibition of gastric emptying by acarbose is correlated with GLP-1 response and accompanied by CCK release

Am. J. Physiol. Gastrointest. Liver Physiol.

Glucagon-like peptide-I and the control of insulin secretion in the normal state and in NIDDM

Diabetes

The multiple actions of GLP-1 on the process of glucose-stimulated insulin secretion

Diabetes

Enhancing incretin action for the treatment of type 2 diabetes

Diabetes Care