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New Evidence, Mindset Could Help Better Diagnose Adult-Onset T1D


Research supports markers like C-peptide not only for the diagnosis of type 1 diabetes (T1D), but also for patient management.

Type 1 diabetes (T1D) is often associated with childhood, even though it most often appears in adulthood. One possible reason is that many patients with T1D initially receive a type 2 diabetes (T2D) misdiagnosis.

In a new review article in European Journal of Internal Medicine, the authors outlined some of the latest findings related to T1D diagnosis and treatment.

They noted that globally, about 70% of T1D cases occur in people over the age of 30. One of the key differences between youth- and adult-onset cases is the genetic risk load. People younger than age 7 who receive a T1D diagnosis, for instance, have a higher risk of human leukocyte antigen (HLA) heterozygosity, HLA class I and class II genes, and gene risk scores, they said.

“In adult-onset T1D, HLA-associated risks are much lower than in childhood-onset disease,” they wrote.

When an adult develops T1D, some studies suggest the patient has a 40% chance of initially receiving a misdiagnosis. Three biomarkers—genetic risk, diabetes-associated antibodies, and C-peptide—can help lead to a more definitive diagnosis, but the investigators said the requisite testing is too expensive to be deployed on a population-level basis.

The authors said recent evidence suggests a combination of biomarkers and clinical factors can be used to correctly diagnose T1D in patients. Although no single clinical factor is sufficient to correctly deliver a diagnosis for a patient, factors such as age, family history, body mass index (BMI), and comorbidities, should factor into diagnosis.

Of the biomarkers, the authors said 3 recent efforts aimed at classifying T1D and T2D unanimously support C-peptide measurement.

“Unlike insulin, C-peptide is not confounded by the coincident injection of insulin as a therapy,” they wrote. “Improved assays that can read low levels of C-peptide with great accuracy have transformed our appreciation of the diagnostic and predictive capability of C-peptide.”

The recent papers in their review suggested collecting random serum C-peptide values along with co-incident blood glucose, although the authors said some controversy still remains. However, the investigators said C-peptide appears to be useful not just as a diagnostic measure, but also as a diabetes management tool.

“Unlike insulin, C-peptide is not substantially extracted on first pass through the liver and levels are not confounded by the coincident injection of insulin as a therapy,” they explained.

As with C-peptide as a diagnostic biomarker, however, the authors said questions remain that will need to be explored, such as at what stage of the disease C-peptide should be estimated, given the dynamism of the marker.

The authors closed by discussing diabetes-related complications, both in terms of traditional comorbidities and psychosocial challenges. They said the existing literature suggests a host of disease-related stressors and a significant degree of patient-to-patient variability.

“Adults identified a sense of powerlessness plus concerns about hypoglycemia, job security, driving, and the problems with being pregnant,” the authors said. “Because there is substantial variation in individual responses, care should be personalized with variable frequency of follow-up visits.”

About 5% of patients can be classified as reaching “Level 3” mental health concern, in which case the investigators said psychotropic medications would be justified to help improve the patients’ diabetes management.

In their conclusion, the study authors said the latest research gives clinicians a significant amount to consider, but also new tools to better classify patients with diabetes. However, they said it will take a mindset adjustment to take advantage of the new insights.

“Appreciating the frequency of adult-onset T1D, problems with diagnosing the disease, its different pathogenesis, natural history, and distinct psychosocial challenges, demands a change in our clinical perspective of adult-onset T1D,” he said.


Burahmah J, Zheng D, Leslie RD. Adult-onset type 1 diabetes: a changing perspective. Eur J Intern Med. Published online June 16, 2022. doi:10.1016/j.ejim.2022.06.003

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