From the Guidelines
GAD65 antibody testing alone is not sufficient to refute a diagnosis of type 1 diabetes, as a negative result does not exclude the diagnosis, and a comprehensive approach including clinical presentation, laboratory findings, and other autoantibody tests is required for accurate diagnosis. According to the 2024 standards of care in diabetes, GAD65 antibodies are present in approximately 70-80% of newly diagnosed type 1 diabetes patients, but 5-10% of people with type 1 diabetes do not have antibodies 1. The diagnosis of type 1 diabetes should be made by healthcare providers considering the complete clinical picture, including age of onset, body mass index, family history, presence of other autoimmune conditions, and response to treatment 1.
Some key points to consider in the diagnosis of type 1 diabetes include:
- Clinical presentation, such as symptoms like polyuria, polydipsia, weight loss
- Laboratory findings, such as elevated blood glucose levels, low C-peptide levels indicating decreased insulin production
- Other autoantibody tests beyond GAD65, such as islet cell antibodies, insulin autoantibodies, IA-2 antibodies, and ZnT8 antibodies
- Genetic testing for monogenic forms of diabetes may also be considered in atypical cases where the diagnosis remains unclear despite antibody testing 1.
It is essential to note that some patients with type 1 diabetes may be antibody-negative at diagnosis or may have antibodies that decrease over time, highlighting the need for a comprehensive approach to diagnosis. The flow chart for investigation of suspected type 1 diabetes in newly diagnosed adults, based on data from White European populations, provides a useful guide for healthcare providers to make a clinical decision about treatment 1. In summary, GAD65 antibody testing alone is not enough to refute a diagnosis of type 1 diabetes, and a comprehensive approach is required for accurate diagnosis and treatment.
From the Research
Autoantibodies in Type 1 Diabetes
- Autoantibodies against Glutamic Acid Decarboxylase (GADA), insulinoma antigen-2 (IA-2A), insulin (IAA), and Zinc Transporter 8 (ZnT8A) are reliable biomarkers for autoimmune diabetes 2.
- GAD65 autoantibodies (GADA) are the most common in adult-onset autoimmune diabetes, especially Latent Autoimmune Diabetes in Adults (LADA) 2.
- The presence of multiple autoantibodies has a high predictive value of childhood type 1 diabetes, but autoantibody levels can fluctuate and transient autoantibody positivity in adult-onset autoimmune diabetes have been reported to affect the phenotype 2, 3.
GAD65 Autoantibodies in Diagnosis
- GADA is a valuable marker for autoimmune diabetes, but it may not be enough to refute diabetes type 1 on its own 4, 5.
- A multiplex assay combining GADA with other autoantibodies, such as IA-2A and ZnT8A, can improve the diagnosis of type 1 diabetes and identify patients with a higher risk of rapid progression to clinical onset 4, 3, 6.
- The combination of GADA, IA-2A, and ZnT8A allows for a stratification of clinical phenotype and can differentiate clinical phenotypes in adult-onset autoimmune diabetes 6.
Limitations of GAD65 Autoantibodies
- GADA alone may not be sufficient to diagnose type 1 diabetes, as some patients may have low levels of autoantibody positivity or fluctuating autoantibody levels 2, 3.
- The presence of GADA does not necessarily confirm type 1 diabetes, as it can also be present in other forms of diabetes, such as LADA 2.
- Further testing and evaluation of multiple autoantibodies are necessary to confirm the diagnosis of type 1 diabetes and to identify patients with a higher risk of rapid progression to clinical onset 4, 5, 3, 6.