The Link Between Red Blood Cells and Cardiovascular Risks in Long-Term Type 2 Diabetes
Long-standing type 2 diabetes significantly elevates the risk of cardiovascular diseases, highlighting the need for early intervention and preventive strategies through potential biomarkers.
Recent research from the esteemed Karolinska Institutet has unveiled a concerning trend: the longer an individual lives with type 2 diabetes (T2D), the greater their likelihood of developing cardiovascular issues. The authors of this study, whose results were published in the journal Disease, pointed out that this heightened risk may stem from alterations in red blood cells, specifically identifying a particular molecule as a promising biomarker.
Why Is Cardiovascular Risk Elevated in Type 2 Diabetes?
According to the American Heart Association, diabetes stands out as a significant modifiable risk factor for cardiovascular diseases. Individuals with T2D are not only more likely to develop heart-related conditions, such as heart attacks and strokes, but they also face an increased risk of mortality from these issues compared to those without diabetes.
While diabetes can be managed and blood glucose levels regulated, the condition continues to pose a serious threat to heart health, particularly in T2D patients, due to various coexisting factors that enhance cardiovascular risk. These include high blood pressure, irregular cholesterol levels, elevated triglycerides, obesity, insufficient physical activity, smoking habits, and poorly controlled blood sugar levels.
The underlying cause of this increased risk appears to be endothelial dysfunction, which worsens over time as the disease progresses; however, the precise mechanisms remain elusive.
How Does the Duration of Diabetes Influence Endothelial Function?
In previous studies, researchers found that red blood cells from individuals living with T2D negatively affect endothelial function by reducing the levels of microRNA (miRNA)-210-3p. This small regulatory RNA is crucial for gene expression control, especially under low-oxygen conditions, and it plays an integral role in metabolism, oxidative stress management, and blood vessel functionality.
Building on this foundation, scientists aimed to determine whether the duration of diabetes impacts the degree of endothelial dysfunction induced by red blood cells and its relationship with miR-210-3p. Their investigation included both mice of differing ages with T2D and human subjects diagnosed with either newly onset or long-term T2D, categorized based on the duration of their condition.
The findings revealed that red blood cells from older diabetic mice and those with long-term T2D significantly impaired endothelial function, unlike samples from younger mice or newly diagnosed patients. This vascular dysfunction correlated with lower levels of miR-210-3p, increased oxidative stress, and heightened expression of glycerol-3-phosphate dehydrogenase 2. Remarkably, this damage was reversible with the restoration of miR-210-3p levels.
Zhichao Zhou, an associate professor at the Department of Medicine, Solna, Karolinska Institutet, and the lead author of the study, emphasized, "What truly differentiates our findings is the realization that it is not merely the presence of type 2 diabetes that is significant, but rather the length of time one has been affected by the disease. It's only after several years that red blood cells begin to exert a detrimental influence on blood vessels."
These revelations underscore the importance of disease duration as a critical factor in red blood cell-mediated vascular damage and position miR-210-3p as a prospective biomarker for cardiovascular complications associated with diabetes. However, the researchers noted that further exploration is needed to assess the application of these findings in larger population studies.
Eftychia Kontidou, a doctoral student involved in the research and the first author of the paper, stated, "Identifying patients at the highest risk before vascular damage occurs could enhance our ability to prevent serious complications."
References
- Eftychia Kontidou, Aida Collado, Rawan Humoud, Kesavan Manickam, John Tengbom, Tong Jiao, Michael Alvarsson, Jiangning Yang, Linda Mellbin, Ali Mahdi, John Pernow, Zhichao Zhou; Long Duration of Type 2 Diabetes Drives Erythrocyte-Induced Vascular Endothelial Dysfunction: A Link to miRNA-210-3p. Diabetes 2026; db250463. https://doi.org/10.2337/db25-0463
- A new study explains the link between long-term diabetes and vascular damage. News release. EurekAlert. January 9, 2026. Accessed January 9, 2025. https://www.eurekalert.org/news-releases/1111963
- Cardiovascular Disease and Diabetes. American Heart Association. Updated April 2, 2024. Accessed January 9, 2026. https://www.heart.org/en/health-topics/diabetes/diabetes-complications-and-risks/cardiovascular-disease--diabetes
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