Metformin and epigenetics
Individual approach to the treatment of diabetes mellitus with metformin
To treat not the disease, but the patient – this principle, proclaimed by the famous ancient physician Hippocrates, is becoming increasingly popular in modern "advanced" medicine. So, today Swedish scientists are developing tests, thanks to which it is possible to determine even before the start of treatment of a diabetic patient whether the sugar-lowering drug metformin, widely used in the treatment of type 2 diabetes, especially against the background of overweight, is suitable for him.
Article by García-Calzón et al. Epigenetic markers associated with metformin response and intolerance in drug-naïve patients with type 2 diabetes is published in the journal Science Translational Medicine.
Personalized medicine, which focuses on the individual characteristics of the patient, is increasingly entering our lives. For example, it has already become almost a routine procedure to identify unfavorable genetic variants associated, for example, with a predisposition to cancer, the level of sensitivity to anticancer drugs or anticoagulants that prevent thrombosis.
With type 2 diabetes, the body loses the ability to adequately respond to the hormone insulin, which is produced by the cells of the islets of Langerhans of the pancreas, as a result of which the blood glucose level rises. In the initial stages of the disease, diet and exercise are often enough to normalize the "sugar". But if such measures do not help, then medicinal sugar-reducing agents are prescribed, and metformin, according to international recommendations, is a "first-line" drug.
However, in a considerable (about 20-30%) part of patients, metformin causes side effects, usually in the form of gastrointestinal symptoms: nausea, stomach pain, diarrhea. At the same time, in 5% of patients, these symptoms are so severe that they have to stop taking the medication. By the way, metformin simply does not help almost every third patient with type 2 diabetes, but it does not become obvious immediately, so for some time these people do not actually receive treatment. Therefore, it is so important to identify such patients in advance.
It is known that epigenetic ("supra-genomic") DNA changes, such as methylation (addition of a methyl group -CH3), contribute to the development of type 2 diabetes, which prevents the reading of genetic information. And in the DNA extracted from the patient's blood sample, it is possible to determine molecular markers that will reflect the degree of DNA methylation in insulin-producing cells, i.e. the effectiveness of its secretion.
Scientists from Lund University (Sweden) decided to find out whether there are similar markers for the body's reaction to metformin. To do this, they assessed the degree of DNA methylation in blood samples of 363 people who had been diagnosed with diabetes before starting treatment with metformin. A year later, after analyzing the relationship between the effectiveness of treatment, the presence of side effects and the nature of DNA methylation, they found several such markers.
It turned out that in patients with a higher degree of methylation of DNA marker sites, metformin was on average 2.5 times less effective and 3 times more likely to cause side effects. These sites, by the way, were associated with genes encoding metformin carrier proteins, as well as proteins involved in the regulation of carbohydrate metabolism, which serves as an indirect confirmation of the results obtained.
In the future, clinical trials involving more people are planned to determine the most "successful" molecular markers for use in clinical practice.
As for metformin itself, the scope of its application may be much wider: a few years ago it turned out that this drug is able to inhibit aging and the development of cancer, which has been proven in experiments on laboratory rodents. These results are echoed by statistics: diabetic patients taking metformin have a lower risk of dying from cancer than those taking other antidiabetic drugs.
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