Genes Influence How Strongly Coffee Protects Against Diabetes

Results of various population studies suggest that people who drink lots of coffee have a reduced risk of type 2 diabetes. However, this apparently does not apply to all people in the same way. A European research team has now found evidence that slight differences in a person’s genetic makeup determine whether he or she benefits from drinking coffee or not with regard to diabetes risk. The findings of the DZD research team led by Alexandros Heraclides, Karina Meidtner and Matthias Schulze of the German Institute of Human Nutrition (DIfE) have now been published in the journal "Diabetologia".

In the current study, the researchers analyzed data from 18,638 people, including 8,086 people, who were diagnosed with type 2 diabetes during the course of the study. One goal of the researchers was to investigate the interaction of known diabetes risk gene variants and coffee consumption with regard to type 2 diabetes risk.

“We observed that for several genes associated with diabetes, carriers with genetic risk variants that negatively influence the effect of specific gut hormones benefited more from drinking coffee than non-carriers. People carrying the common gene variant TCF7L2 *, which is associated with elevated diabetes risk, benefited especially,” said Karina Meidtner, who coordinated the study. The gene encodes a protein molecule named transcription factor 7-like 2. Results of other studies indicate that the molecule encoded by the risk gene variant negatively influences the regulation of blood glucose levels by decreasing the effect of the intestinal hormone GLP-1**.

According to the results of the current study, in carriers of the TCF7L2 risk variant, the diabetes risk per daily consumed cup of coffee decreased by up to 7 percent, depending on the total coffee intake per day . By contrast, the coffee consumption of people without the risk variant had neither a positive nor a negative effect on the diabetes risk.

“Our findings point to the metabolic mechanisms which underlie the association we observed between drinking coffee and diabetes risk,” said first author Alexandros Heraclides. “These suggest that coffee stimulates the release of the intestinal hormone GLP-1 and thus compensates for the negative effect of the TCF7L2 risk variant on the effect of the hormone,” the researcher added. Of course, further studies are still needed to substantiate these findings.

“If you tolerate coffee well and enjoy drinking it, you should continue to do so,” said Matthias Schulze, head of the Department of Molecular Epidemiology at DIfE. “The results support the positive health effects that have been observed for the consumption of coffee, in particular for diabetes risk. But on the other hand, you should not feel compelled to start drinking coffee. Your diabetes risk can be considerably influenced by maintaining a healthy weight, not smoking, eating less meat and more whole grain and by exercising regularly,” the nutrition scientist explained. 

Background information
* With the exception of germ cells, each human cell has a double set of chromosomes. This means that most of the genes are usually present twice; this also applies to the TCF7L2 gene investigated in this study.
The genes may be expressed differently and present in different variants, which differ slightly in the base sequence of the genetic material (DNA). The various expression forms of genes are also referred to as alleles. If two different alleles of a gene occur on the two chromosomes on the relevant gene locus, this is called heterozygosity. If two identical alleles occur, this is called homozygosity. The TCF7L2 gene also appears in different variants, some of which are associated with an increased risk of type 2 diabetes. Thus, the investigated TCF7L2 gene variant rs12255372 is present in two forms, the G and the T variant, whereby the latter is associated with an increased type 2 diabetes risk. The “G” stands for the base guanine, which in the T variant is exchanged at a certain position of the DNA chain for the base thymine (T). Due to the double set of chromosomes, people either carry the G variant twice (GG type), the T variant twice (TT type) or they are carriers of both gene variants (GT type). According to the results of the current study, heterozygous carriers (GT type)  had a 40 percent increased risk of developing  diabetes in comparison to homozygous carriers of the G variant (GG type), while homozygous carriers of the risk variant, i.e. of the T variant (TT type), had about a 60 percent increased risk of developing diabetes.

** Glucagon-like peptide-1 (GLP-1): Intestinal L cells secrete GLP-1 after stimulation by carbohydrates, proteins, or fats. The peptide hormone has a half-life of less than two minutes, stimulates insulin secretion while at the same time suppressing the secretion of the insulin antagonist glucagon. Both lead to a lowering of the blood glucose level. Moreover, studies suggest that it restores the insulin sensitivity of the beta cells in pancreas while counteracting beta-cell apoptosis. In addition, GLP-1 inhibits carbohydrate absorption by the intestine and contributes to a satiating effect (Source: Wikipedia).

The InterAct Consortium is a consortium of scientists of the European Prospective Investigation into Cancer and Nutrition (EPIC) study, who initiated the EPIC-InterAct study to investigate the risk factors for type 2 diabetes. More information is available at It is thus part of the EPIC study in which 23 administrative centers in ten European countries are involved with more than 500,000 adult study participants. The population study investigates the relationships between diet, cancer and other chronic diseases such as type 2 diabetes.