Type 2 diabetes mellitus (T2DM) is one of the most prevalent chronic metabolic disorders worldwide and is strongly associated with an increased risk of cardiovascular disease. Heart attacks, strokes, and other vascular complications remain the leading causes of morbidity and mortality among individuals living with diabetes. While elevated blood glucose, insulin resistance, and chronic inflammation have long been recognized as major contributors to this risk, emerging research suggests that less obvious cellular mechanisms may also play a crucial role. A recent study conducted by researchers at Karolinska Institutet and published in the journal Diabetes provides new insight into how changes in red blood cells over time may contribute to the rising cardiovascular danger faced by people with long-standing type 2 diabetes.
One of the most striking aspects of cardiovascular risk in diabetes is its progressive nature. The longer a person lives with the disease, the greater the likelihood of developing vascular complications. This temporal dimension has often been overlooked in favor of static risk factors such as glucose levels or lipid profiles. The new study addresses this gap by demonstrating that the duration of diabetes itself fundamentally alters red blood cell function, transforming these cells from passive oxygen carriers into active contributors to blood vessel damage.
Red blood cells, or erythrocytes, have traditionally been viewed as relatively simple cells whose primary role is to transport oxygen throughout the body. However, recent research has revealed that they are far more biologically active than once thought. In diabetes, red blood cells can influence vascular tone, nitric oxide signaling, and endothelial health. The Karolinska Institutet study builds on this knowledge by showing that these effects evolve over time and worsen as diabetes progresses.
To investigate these changes, the researchers conducted a series of experiments using both animal models and human subjects with type 2 diabetes. This dual approach allowed them to explore the underlying mechanisms in controlled laboratory conditions while also confirming their relevance in real-world clinical settings. Red blood cells were collected from mice with diabetes as well as from human patients at different stages of the disease. These cells were then studied for their effects on blood vessel function.
The results revealed a clear and compelling pattern. Red blood cells taken from individuals and animals with long-standing diabetes significantly impaired normal blood vessel function. They disrupted the ability of blood vessels to relax properly, a key feature of endothelial dysfunction and an early step in the development of atherosclerosis. In contrast, red blood cells obtained from newly diagnosed patients showed no such harmful effects. This finding highlights that it is not merely the presence of diabetes that matters, but the length of time the body has been exposed to the diabetic environment.
Perhaps even more revealing was the longitudinal aspect of the study. Patients who initially had newly diagnosed diabetes were followed over a period of seven years. At the start of the study, their red blood cells did not damage blood vessels. However, after several years of living with diabetes, those same patients developed red blood cells with properties similar to those seen in long-term diabetes. This observation provides strong evidence that red blood cell dysfunction develops gradually and parallels the increasing cardiovascular risk observed clinically.
At the molecular level, the researchers identified a key factor that may explain these changes: microRNA-210. MicroRNAs are small, non-coding RNA molecules that regulate gene expression and play important roles in cellular adaptation and stress responses. MicroRNA-210, in particular, is known to be involved in hypoxia signaling and vascular biology. The study found that levels of microRNA-210 were reduced in red blood cells from individuals with long-standing diabetes.
Importantly, when the researchers experimentally restored microRNA-210 levels in red blood cells, blood vessel function improved. This finding suggests that the loss of microRNA-210 is not merely a marker of disease progression but may be a direct contributor to vascular damage. By influencing signaling pathways within red blood cells, reduced microRNA-210 appears to impair their interaction with blood vessels, ultimately promoting endothelial dysfunction.
The implications of these findings are significant for both clinical practice and future research. First, they provide a novel explanation for why cardiovascular risk increases steadily with the duration of type 2 diabetes, even in patients whose glucose levels are relatively well controlled. Red blood cells, which circulate continuously throughout the body, may act as chronic stressors on the vascular system once they acquire harmful properties.
Second, the identification of microRNA-210 as a potential biomarker opens new possibilities for early risk detection. Measuring microRNA-210 levels in red blood cells could help identify patients who are entering a high-risk phase for cardiovascular complications, even before overt vascular damage occurs. As lead author Zhichao Zhou emphasizes, the timing of these changes is critical. It is only after several years of diabetes that red blood cells become actively harmful, suggesting a window of opportunity for early intervention.
From a preventive perspective, this research supports a more personalized and time-sensitive approach to diabetes management. Rather than treating all patients with type 2 diabetes as having the same cardiovascular risk, clinicians may one day be able to stratify risk based on disease duration and cellular biomarkers such as microRNA-210. This could lead to earlier and more aggressive preventive strategies for those most at risk, including targeted therapies aimed at preserving red blood cell function.
The study also raises intriguing questions for future investigation. Researchers are now exploring whether these findings can be replicated in larger population studies and whether interventions that restore or maintain microRNA-210 levels can reduce cardiovascular events. Additionally, understanding how metabolic factors such as glucose variability, oxidative stress, and inflammation interact with red blood cell biology over time could further refine our understanding of diabetic complications.
In conclusion, the Karolinska Institutet study offers a compelling new perspective on cardiovascular disease in type 2 diabetes. By showing that red blood cell dysfunction develops gradually and is strongly influenced by disease duration, the research highlights an underappreciated mechanism linking diabetes to vascular damage. The identification of microRNA-210 as both a functional regulator and a potential biomarker represents an important step toward earlier detection and prevention of cardiovascular complications. As diabetes continues to affect millions worldwide, such insights are essential for improving long-term outcomes and reducing the burden of cardiovascular disease.
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