With or Without Diabetes: AGEs Are Risk Factors for Vascular Stiffness
Stiffened and narrowed arteries increase the risk of cardiovascular disease – the most common cause of death in Germany. A new epidemiological study by the German Center for Diabetes Research (DZD) and the German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE) now shows that reduced vascular elasticity is associated with an increased concentration of glycated reaction products, so-called advanced glycation end-products (AGEs) in the skin, both in people with diabetes and in people without this glucose metabolism disorder.
"The correlation between elevated AGE levels and vascular stiffening has only been documented in high-risk patients with chronic diseases, such as diabetes or hypertension," said Dr. Anna Birukov, first author of the study, which has now been published in the journal Cardiovascular Diabetology.
"We wanted to know if this correlation also exists in people with prediabetes and in people with normal metabolism and no cardiometabolic risk." For this purpose, the team from the DZD and DIfE studied 3535 men and women between 64 and 73 years of age from the EPIC-DZD study*.
The focus of the study was on AGEs. They are considered risk molecules for the cell ageing process. AGEs are formed when simple sugars, such as fructose, galactose or glucose, react uncontrollably with the body's own proteins or lipids without enzymes being involved. The end products of this irreversible reaction are glycated proteins or lipids that no longer fulfill their original function, but neither can be utilized by the body. In the course of life, the AGE concentration in the cells therefore increases. AGEs can restrict vascular elasticity by being deposited in the blood vessels, where they are involved in the formation of atherosclerotic plaques. They also contribute to systemic inflammation, endothelial damage and oxidative stress, which are also considered risk factors for vascular stiffening, cardiovascular disease and type 2 diabetes.
Skin autofluorescence as indicator
With the aid of a special measuring device, the AGE reader, the concentration of AGEs in the skin can be measured quickly and non-invasively: An ultraviolet light beam directed at the skin produces a fluorescent glow in some AGE molecules. The intensity of this fluorescence provides information about the concentration in the skin. In all participants of the EPIC-DZD study – 642 people with diabetes, 805 people with prediabetes and 2088 people with normal metabolism – the researchers determined the HbA1c value in addition to the AGE value, which provides information about the average glucose content of the blood over the past weeks. The research team also assessed various parameters to determine vascular elasticity, including pulse wave velocity and the ankle brachial index (ABI).
The evaluation of the data clearly shows that increased AGE levels correlate with reduced elasticity of the arteries – regardless of whether the subjects have diabetes or not.
Epidemiological evidence of a link between elevated AGE levels and arterial stiffness that is independent of glucose metabolism disorders could potentially open up new possibilities in the early detection of cardiovascular diseases in the future: For example, doctors could use an AGE reader to determine non-invasively and within a few seconds whether a patient has an increased risk of arteriosclerosis. The measurement of AGEs based on skin fluorescence could also have future potential in interventional studies, for example to evaluate the effects of dietary changes on AGE concentration and reduction of the risk of atherosclerosis.
The European Prospective Investigation into Cancer and Nutrition (EPIC) study is a European collaborative project of prospective cohort studies in ten European countries with a total of around 521,000 study participants. There are two study centres in Germany: the German Cancer Research Center (DKFZ) supervises the EPIC-Heidelberg cohort and the DIfE is participating in the cohort with the EPIC-Potsdam Study.