Accurately diagnosing T1D, identifying biomarkers

Comparing Type 1 and Type 2 Diabetes

First, it is crucial to understand the differences between T1D and T2D. This provides context for misconceptions contributing to the broader challenges of accurately diagnosing T1D in adulthood.

Type 1 diabetes, historically called juvenile diabetes or insulin-dependent diabetes, is a chronic autoimmune disease that causes the pancreas to make little or no insulin. This prevents individuals with the condition from processing glucose for energy correctly. Type 1 diabetes is characterized by excessive thirst, urination, unintended weight loss, blurry vision, and other issues.

Casu explained that T1D was previously called juvenile diabetes because it predominantly affected children; however, as research and science have advanced, the name changed to indicate the mechanism of the disease rather than the age bracket because new discoveries suggested that the condition could be diagnosed at any age, not just in childhood.

“There is a peak of incidents in childhood, but there are cases described at the age of 93 onset of T1D.”

Conversely, T2D is a chronic condition that occurs when an individual cannot use insulin to convert food into energy properly.

“Type 1 diabetes accounts for approximately 10% of all diabetes cases. However, this percentage varies by age. In children, 90% of diabetes cases are type 1, while the remaining 10% are type 2. In adults, the prevalence is reversed, with T2D becoming more common as age increases,” began Casu.

While both are insulin-related endocrine disorders, these conditions have differing pathophysiologies and, thus, are treated differently.

Misdiagnosis of T1D

Casu explained to LifeSciencesIntelligence that T1D cases as T2D are often misdiagnosed among older patients.

“Many cases of T1D are diagnosed later in life. Because this is not well known, physicians often automatically label diabetes in adults as type 2. Some characteristics of the patients can suggest that it might not be type 2 at all, such as a lean figure or not being overweight,” she explained. “However, with the current obesity epidemic, where 75% of people in the US are overweight or obese, this is not always accurate. If a diagnosis of type 1 occurs in an overweight person, there might have been some weight loss, but it may not be dramatic.”

Part of the reason for misdiagnosis in adulthood is the ongoing obesity epidemic that makes it difficult for providers to see symptoms that may be linked to T1D accurately. Casu told LifeSciencesIntelligence that data from the Type 1 Diabetes Registry found that adults over the age of 40 with T1D were often treated with oral agents before an accurate diagnosis of T1D was made.

“In those with later onset, the disease is milder; that's probably why it takes longer to manifest clinically, but because it's milder, it's easier to misdiagnose it,” added Casu.

ACCESS-T1D

According to Casu, the ACCESS-T1D study has two primary goals: expanding access to screening for T1D and identifying better biomarkers for T1D. AdventHealth and the Florida Department of Health sponsor the study.

Researchers are recruiting participants over two years old who have a close relative with T1D, have another autoimmune disease diagnosis, or have been diagnosed with another form of diabetes and are suspected to have T1D.

After 20–30 years of research, providers can assess the probability of a patient developing T1D from the presence of islet-related autoantibodies in the blood. Using a blood draw, the researchers can identify whether a participant has T1D, even if the disease is not fully manifested at stage 3.

Casu highlighted the critical importance of screening and identifying T1D risk early.

“There is a medication that is being approved by the FDA that can delay the onset of type 1 diabetes. So now we have a goal for screening.”

In November 2022, the FDA approved TZIELD,  an anti-CD3 monoclonal antibody manufactured by Provention Bio that delays the onset of stage 3 T1D in people eight years and older diagnosed with stage 2  T1D. While this medication does not offer a cure for T1D, the ability to delay onset can improve quality of life, reduce the risk of complications, and provide more time to prepare for the physical and financial implications of T1D.

“The other reason for the screening is that it prevents, in a large proportion of cases, the onset of diabetes ketoacidosis that is a potentially deadly condition or can cause brain damage.”

Patients with a positive test result are referred for additional blood samples and treatment by a physician or endocrinologist to manage the condition.

In addition to improving T1D diagnosis, the study also offers a route for identifying new biomarkers from positive blood samples. While the study is ongoing, Casu explained that some trends have already emerged.

"Extracellular vesicles in the blood are being studied," explained Casu. "Extracellular vesicles are tiny vesicles released by every cell type. A preliminary study comparing people showed that some of the proteins carried by these extracellular vesicles differ in T1D patients versus those without the condition. These proteins were correlated with 151 clinical characteristics. Some were found to be associated with pancreas size, indicating a pathogenic mechanism, while others were linked to immune mechanisms, which are also relevant in T1D."

As the understanding of T1D evolves, tools and biomarkers for accurate disease diagnosis will be critical for improving patient outcomes.