AGEs Are Risk Factors for Vascular Stiffness Also in People Without Diabetes
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," said last author Matthias Schulze, summarizing the results.
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 EPIC-DZD study is a follow-up study to the EPIC-Potsdam Study, which has been possible since 2014 thanks to funding from the German Center for Diabetes Research (DZD). The subjects are invited to the study center at the German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE) on a limited basis, where they are comprehensively examined and interviewed. This includes a detailed nutritional survey, anthropometric measurements, recording of physical performance characteristics and testing of physical and mental functions. The collection of biological samples is also part of the process. The EPIC-Potsdam Study, also known as the Brandenburg Nutrition and Cancer Study (BEK), is a population-based prospective cohort study and part of the international EPIC study. It includes about 27,500 participants. At the beginning of the study in 1994, the women were aged 35 to 64 years and the men 40 to 64 years. With its extensive database, the EPIC-Potsdam Study serves as the basis for population-based epidemiological research at the DIfE. The research results help to create the scientific basis for possible preventive measures and for improving the health of the population. https://www.dife.de/forschung/kooperationen/epic-studie/
Birukov A, et al.: Advanced glycation end‑products, measured as skin autofluorescence, associate with vascular stiffness in diabetic, pre‑diabetic and normoglycemic individuals: a cross‑sectional study. Cardiovasc Diabetol, https://doi.org/10.1186/s12933-021-01296-5
Dr. Anna Birukov
Prof. Dr. Matthias Schulze
Department of Molecular Epidemiology
German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE)
Arthur-Scheunert-Allee 114 - 116
phone: +49 33200 88 2431
e-mail: Anna.Birukov(at)dife.de / mschulze(at)dife.de
The German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE) is a member of the Leibniz Association. It investigates the causes of nutrition-associated diseases in order to develop new strategies for prevention, treatment and nutritional recommendations. Its research interests include the causes and consequences of the metabolic syndrome, a combination of obesity, hypertension (high blood pressure), insulin resistance and lipid metabolism disorder, the role of nutrition for healthy aging and the biological bases of food choices and dietary behavior. DIfE is also a partner of the German Center for Diabetes Research (DZD), which has been funded by the Federal Ministry of Education and Research (BMBF) since 2009. www.dife.de/en
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