Exploring the Role of Metabolic Memory in Diabetes Complications

Metabolic Memory

As the immune system slowly destroys insulin-producing pancreatic beta cells, a hallmark sign of type 1 diabetes, the body has an increasingly difficult time controlling blood glucose levels. These cells are no longer available to naturally secrete insulin in response to rising blood sugar, meaning individuals must control this process manually or through the use of continuous glucose monitors (CGM) and/or insulin pumps.

Poor glycemic control can contribute to a multitude of diabetes complications and health concerns. It is critical for individuals who are newly diagnosed with the disease to learn how to manage their diabetes and keep blood glucose levels within the target range. A recent study found that incidences of poor glycemic control can have a lasting impact, potentially triggering complications later on in life, even if blood sugar is well-managed now.

This occurrence may be due to the body’s metabolic memory. When hyperglycemia occurs, it may lead to DNA methylation or changes in gene expression. These epigenetic changes may be ongoing, lasting for years to come, even though they do not actually alter the person’s genetic code. Researchers at the Diabetes & Metabolism Research Institute at City of Hope analyzed blood samples from more than 500 participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) clinical trial involving patients with type 1 diabetes.

They used the samples to profile DNA methylation, then compared that to the participants’ glycemic history and any complications that had developed over the past 18 years. Their findings showed that “prior history of hyperglycemia may induce persistent DNA methylation changes in blood and stem cells at key loci, which are epigenetically retained in certain cells to facilitate metabolic memory, likely through modifying enhancer activity at nearby genes.”

By matching these key factors, researchers may be able to uncover biomarkers that could help predict the risk of complications in the future. Recognizing signs early on could help initiate interventions to reduce complications or prevent the progression of these issues. There is still a lot that researchers do not yet understand about metabolic memory, but this is a start. While the research team at City of Hope is currently looking at DNA methylation and metabolic memory as it relates to retinopathy and nephropathy complications, they would like to expand this to include other regions where complications can occur through whole-genome bisulfite sequencing.

In the past, it was more difficult for individuals with type 1 diabetes to maintain glycemic control following diagnosis due to inferior technology, but over the years, technology has greatly improved. This has allowed individuals to minimize complications by using devices that have empowered them to improve their care and better manage their blood glucose levels. These advancements have also helped people with more recent diagnoses achieve better glycemic control earlier on, which may impact metabolic memory and the risk of future complications.

The Diabetes Research Connection is interested to see how this study advances understanding of metabolic memory and the role of DNA methylation in diabetes management. Developing complications is an ongoing concern for individuals living with T1D. The DRC is committed to providing funding for early-career scientists pursuing novel research studies focused on prevention, treatment, and a cure for the disease, as well as improving quality of life and minimizing complications. Check out current projects and how to support these efforts by visiting https://diabetesresearchconnection.org.

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