Potential mechanisms

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Researchers have yet to discover a plausible mechanism to explain the associations between consumption of regular coffee or decaffeinated coffee and a lower risk of developing type 2 diabetes.

A role for caffeine?

Since coffee and tea are the main sources of caffeine in the diet in most countries, it is difficult to directly separate an effect of caffeine from coffee. However, since decaffeinated coffee is reported to have a similar size association as regular coffee, it is unlikely that caffeine plays a key role in the inverse association for development of type 2 diabetes.

Paradoxically, acute caffeine intake leads to glucose intolerance and insulin insensitivity, while chronic caffeine has only a small effect on glucose metabolism28,29. An acute study further tested for the effects of caffeine in women with or without gestational diabetes. Caffeine did not affect glucose and insulin levels in the group without gestational diabetes. However caffeine impaired insulin sensitivity in women with gestational diabetes30.

Other constituents

Other coffee constituents, in particular antioxidants like chlorogenic acid and trigonelline, reduce early glucose and insulin levels at 15 minutes in oral glucose tolerance tests (OGTT) whereas decaffeinated soluble coffee showed no effect in this test31. These observations are in good accordance with the data of a French study reporting the strongest association for coffee consumed at lunchtime5. A 2017 literature review postulated that chlorogenic acid (CGA) may have a significant impact on glucose metabolism regulation and, therefore, on related disorders including diabetes32. Some researchers have suggested that CGA may be involved in lipid and glucose metabolism regulation and may be associated with a lower risk of hepatic steatosis, cardiovascular disease, and diabetes. It may also have hepato-protective effects by protecting from chemical or lipopolysaccharide induced injuries33.  

Coffee may contribute to the total antioxidant load of the diet, and in turn may help to limit oxidative stress. This may help to limit the development of type 2 diabetes34,35. This potential role for coffee in reducing oxidative stress is interesting, although this hypothesis has not yet been verified.

An analytical study of key biomarkers for diabetes suggested that coffee polyphenols may have anti-diabetic effects but further replications with large samples of both genders were recommended36. Some preliminary clinical trials have suggested that individual polyphenols in coffee may have specific effects, including improvement of glycemic control in subjects with insulin resistance, reduction of blood glucose and HbA1c levels and the improvement of insulin secretion and resistance. However, further work in this area is required to clarify any effects of compounds in coffee37.

Coffee could also partly inhibit postprandial hyperglycemia and hence prevent the occurrence of type 2 diabetes38. According to a cross-sectional multi-ethnic study on 954 non-diabetic adults, the effect of caffeinated coffee is positively related to insulin sensitivity while decaffeinated coffee improves pancreatic beta-cells function39.

Effect on subclinical inflammation

A Finnish study tested the effects of progressively increasing coffee consumption in obese volunteers in a medium term intervention trial (in the first month, participants abstained from coffee, for the second month 4 cups of coffee were consumed per day and in the third month, participants had 8 cups per day). No effects in the OGTT were seen. Coffee consumption appeared to have beneficial effects on some markers of subclinical inflammation, considered to be risk factors for type 2 diabetes40.

A Greek study, which controlled for oxidative stress and inflammatory biomarkers, suggested that the inverse association between habitual coffee drinking and diabetes was found to be mediated by serum amyloid A levels (serum amyloid A is a lipoprotein that may be associated with chronic inflammation in the body)14.

Associations with liver function

Some researchers have expressed an interest in exploring associations between coffee consumption, type 2 diabetes, liver function and metabolic syndrome. Aspects of interest include the effect of senescence, or ageing, of the liver, and the concurrent occurrence of fatty liver disease, which may be more prevalent in those with metabolic syndrome: a combination of diabetes, high blood pressure, and obesity.

In 2011, researchers at Harvard conducted a randomised controlled trial looking at the effects of caffeinated and decaffeinated coffee on biological risk factors for type 2 diabetes. They compared participants who consumed either 5 cups per day of soluble caffeinated coffee, decaffeinated coffee, or no coffee for 8 weeks. Compared with consuming no coffee, consumption of caffeinated coffee increased adiponectin and interleukin-6 concentrations, possibly reflecting anti-inflammatory and insulin sensitizing effects, whilst consumption of decaffeinated coffee decreased fetuin-A concentrations, a biomarker for inflammation and liver function. No significant differences were found between treatment groups for measures of glucose tolerance, insulin sensitivity and insulin secretion. The authors concluded that improvements in adipocyte and liver function, as indicated by changes in adiponectin and feutin-A concentrations, may contribute to beneficial metabolic effects of long-term coffee consumption41.

Other potential mechanisms

Among the other mechanisms studied, a Dutch study did not find that either magnesium, potassium, caffeine or blood pressure were involved in coffee or tea’s association with type 2 diabetes4.

One Japanese study investigated a possible association between psychological factors and diabetes, reporting that the risk of diabetes increased with an increasing stress level, especially among men; and among women who showed an increasing level of type A behaviour (i.e. behaviour patterns linked to competitive drive, speed and impatience, aggressiveness and irritability)42. This study also observed an inverse association between coffee consumption and incidence of diabetes. Interestingly, further research has suggested that coffee consumption was inversely associated with depressive symptoms amongst a group of patients with type 2 diabetes. The authors suggested this might be due to biologically active compounds in coffee in addition to caffeine43.

A US case-control study on postmenopausal women examined whether plasma levels of sex hormones and sex hormone-binding globulin (SHBG) could account for the inverse association between coffee consumption and type 2 diabetes risk, building on data that implicated the important roles of sex hormones in the development of type 2 diabetes. SHBG may directly mediate intracellular signaling of sex hormones. The study found a correlation between coffee consumption and plasma levels of SHBG. This association was not found for decaffeinated coffee and tea. The authors note that these findings suggest SHBG may account for the inverse association between caffeinated coffee and type 2 diabetes risk44.

Coffee consumption has been related to a decreased risk of type 2 diabetes mellitus among those with high levels of serum γ-glutamyltransferase. A 2012 study in a Japanese population examined the association between coffee and glucose tolerance and the effect modification of serum γ-glutamyltransferase on this association. These authors found coffee drinking to be protective against glucose intolerance. Furthermore, they suggested that the observed possible effect modification of serum γ-glutamyltransferase on the protective association between coffee and type 2 diabetes warrants further research45.

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