Published on 15 November 2022

A recently published DRWF-funded study looked at usefulness of the islet autoantibody test in adults and young people suspected to have type 1 diabetes.

Autoantibodies are immune proteins that mistakenly target and react with a person’s own tissues or organs. The test is available in routine clinic practice across the UK. However, the additional benefit of measuring these antibodies when someone have strong clinical suspicion of type 1 diabetes, particularly in adult-onset, is not known. Currently, it is performed more widely when there is diagnostic uncertainty.  

Researchers aimed to explore this by assessing the genetic risk of type 1 diabetes in a large number of autoantibody-negative and -positive children and adults.

The results of the study were recently published in Diabetologia.

Researchers measured type 1 diabetes genetic risk by genotyping (investigating the genetic constitution of, for example, an individual organism) 30 different type 1 diabetes-associated genetic changes as well as three islet autoantibodies at diagnosis in 1,814 people with clinician-diagnosed type 1 diabetes (1,112 adult-onset, 702 childhood-onset).

Image of DNA strands.

Benefit of autoantibodies

Dr Kashyap Patel, Wellcome Trust Fellow and Consultant Physician at the University of Exeter, who led the study, said: “We found that nearly 13% of adults with clinically suspected type 1 diabetes were estimated not to have type 1 diabetes. This misclassification greatly increased to 20% in adults diagnosed after 30 years of age.”

He added: “More importantly, all of these misclassifications were in the autoantibody negative group. We estimated that adults who were clinically suspected with type 1 diabetes due to their severe clinical presentation but lack the autoantibodies have 67% chance of having non-type 1 diabetes.”

These results strongly suggest that lack of islet autoantibodies greatly changes the diagnosis in the adult/late-onset clinically suspected type 1 diabetes thus, highlighting the importance of routine testing for islet autoantibodies at diagnosis in all patients suspected to have adult/late-onset type 1 diabetes.

Dr Patel said: “In line with these results, the National Institute for Health and Care Excellence (NICE) has recently changed the guideline which suggests testing these antibodies in all clinical cases.”

Research samples and a pipette.

Unmasking the phenotype of adult-onset type 1 diabetes

Dr Patel added: “Once we discovered the misclassification of type 1 diabetes in our clinically suspected type 1 diabetes study, it became clear that all the previous studies that used the clinical judgment to define type 1 diabetes at diagnosis inadvertently included non-autoimmune diabetes.

“This may have resulted in masking the true phenotype of late-onset type 1 diabetes. Indeed, when we removed the misclassified type 1 diabetes, we uncovered novel biology of late-onset type 1 diabetes and diversity of type 1 diabetes; for example, we found that adult-onset type 1 diabetes has the same rate of positive autoantibodies as children but the pattern of autoantibodies are very different.”

The study concluded: “The high rate of misclassification in adults who are clinically suspected of having type 1 diabetes strongly supports the routine measurement of autoantibodies in all individuals and not just when there is diagnostic uncertainty.”

Dr Patel said: “Our study results have improved our understanding of the late-onset type 1 diabetes which accounts for nearly half of all type 1 diabetes.

“Our results strongly suggest that clinical suspicion is not enough to accurately diagnose type 1 diabetes. Nearly one in five patients who are clinically thought to have late-onset type 1 diabetes (diabetes onset after 30 years of age) actually have type 2 diabetes. We went on and showed that measuring islet autoantibodies, which are easily accessible in routine clinical practice, greatly minimise this misdiagnosis.

“Based on our work, we recommend that all patients, despite the very high clinical suspicion, should have islet autoantibodies to support the clinical diagnosis.

“Our study also provides important new information that adult/late type 1 diabetes is different from childhood-onset diabetes. We showed that people living with adult/late-onset type 1 diabetes have a different combination of islet autoantibodies compared to childhood-onset type 1 diabetes.

“We also showed that nearly 92% of adult/late-onset type 1 diabetes have islet antibodies similar to childhood-onset type 1 diabetes. This has challenged the current understanding that fewer people with adult-onset type 1 diabetes have these antibodies.”

Sarah Tutton, Chief Executive of DRWF, said: “DRWF awarded Dr Patel a Pump Priming award in 2018 to support the implementation of a genetic risk score, as part of a wider body of research that sought to define heterogeneity in patients with clinically diagnosed adult-onset type 1 diabetes using islet autoantibodies and genetics. This work has ultimately identified clinically useful new information about type 1 diabetes which will have a clinical implication in routine clinical care of type 1 diabetes.

“This is a fantastic outcome and just goes to show that relatively small amounts of funding can have a significant impact and result in tangible benefits for diagnosis and treatment of diabetes.”

Read the report in Diabetologia
Find out more about type 1 diabetes
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