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Could There Be More than One Form of Type 1 Diabetes?

Researchers know that there are significant differences between type 1 diabetes (T1D) and type 2 diabetes (T2D), but now they are digging a little deeper. When it comes to T1D, the disease may not affect everyone in the same way. According to a recent study, there may be more than one endotype, and a major differentiator could be age of diagnosis.

The study looked at a small sample of 19 children diagnosed with T1D within the past two years and compared age of diagnosis against amount of beta cell destruction and levels of proinsulin and C-peptides. They also compared these ratios in a group of 171 adults with T1D based on their age of diagnosis. Their results showed that children who were diagnosed before the age of 7 had much higher levels of proinsulin-insulin co-localization than those diagnosed after age 13. Individuals between ages 7 and 13 were divided and fell into one group or the other.

The researchers also compared results against CD20Hi and CD20Lo immune profile designations for each participant. Children age 7 or younger tended to be CD20Hi, while those age 13 or older were CD20Lo, and the children in between were aligned with their respective groups based on whether they were CD20Hi or CD20Lo.

These differences in proinsulin and C-peptide concentrations demonstrate a distinction in how individuals are impacted by T1D, leading to at least two separate endotypes. Understanding whether an individual has T1D endotype 1 (T1DE1) or T1D endotype 2 (T1DE2) could enable more targeted and effective treatment of the disease based on how each group responds. Individuals with T1DE1 are identified as having higher levels of beta cell loss, therefore may have more difficulty regulating blood glucose. Those with T1DE2 may retain more beta cells, and determining ways to activate and protect these cells could support improved natural insulin production.

Recognizing that T1D affects people differently is a step in the right direction toward more personalized medicine and targeted therapies. Therapeutic trials could be aimed at groups depending on age of diagnosis and specific endotype in the future as larger studies are conducted to determine the significance of these findings.

Diabetes Research Connection (DRC) is committed to supporting advances in research around type 1 diabetes and provides early-career scientists with critical funding for their studies. Research is focused on preventing and curing type 1 diabetes, minimizing complications, and improving quality of life for those living with the disease. Learn more and support these efforts by visiting https://diabetesresearchconnection.org.

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Exploring C-Peptide Persistence in Type 1 Diabetes

In diagnosing diabetes, be it type 1 or type 2, one of the key factors doctors look for is C-peptide levels. Traditionally, scientists have believed that low C-peptide levels indicated type 1 diabetes as the body is unable to produce an adequate supply (if any) of insulin, while higher C-peptide levels were associated with type 2 diabetes as the body made insulin but was unable to effectively use it.

However, a recent study shows that this may not be entirely accurate. In a large cohort study in Scotland, there was a broad range of variability in C-peptide persistence across individuals of different ages and duration of disease. Individuals who were older when diagnosed and were close to age of diagnosis had higher C-peptide levels than those who were adolescents when diagnosed and had been living with the disease for a longer period of time. Scientists believe this may point toward there being multiple genetic networks that impact diabetes risk.

The findings also showed that similar C-peptide levels may be present in individuals with adult-onset type 1 diabetes who did not immediately require insulin treatment as those who were diagnosed with type 2 diabetes. Many people with higher C-peptide levels also have increased amounts of proinsulin, which is a prohormone precursor to insulin. However, the cells do not respond to primary stimuli which could mean that they are in a stunned state. If this is the case, there is a potential that they could recover and once again play an active role in insulin production.

The ratio of proinsulin to C-peptide may also be influenced by genetic risk of diabetes. Both genetics and environmental factors may come into play regarding damage to beta cells and their ability or inability to produce insulin.

This study challenges previous understanding about the differences in type 1 and type 2 diabetes when it comes to diagnosis and treatment. There may be the potential to stimulate pancreatic beta cell function in individuals with type 1 diabetes depending on their levels of proinsulin, insulin, and C-peptide.

Diabetes Research Connection (DRC) is interested to see how this may impact the future of diagnosis and treatment of diabetes. It could certainly lead the way to more in-depth research opportunities, and the DRC provides critical funding to support these types of initiatives. Early career scientists can receive up to $75K from the DRC to pursue novel research projects focused on type 1 diabetes. To learn more, visit http://diabetesresearchconnection.org.

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