From the Guidelines
Zinc transporter 8 (ZnT8) antibodies are autoantibodies that target the zinc transporter 8 protein found in pancreatic beta cells and are important diagnostic markers for type 1 diabetes mellitus. These antibodies are particularly useful when used alongside other diabetes-related autoantibodies such as glutamic acid decarboxylase (GAD), insulin autoantibodies (IAA), and islet antigen-2 (IA-2) antibodies 1. The presence of ZnT8 antibodies indicates an ongoing autoimmune process targeting pancreatic beta cells, which leads to insulin deficiency. Key points to consider include:
- Testing for ZnT8 antibodies is recommended when evaluating patients with suspected autoimmune diabetes, especially in cases where other antibody tests are negative but clinical suspicion remains high.
- ZnT8 antibody testing has improved diagnostic sensitivity, helping to reduce the number of patients classified as having idiopathic or type 2 diabetes when they actually have autoimmune diabetes.
- The test is particularly useful in adult-onset autoimmune diabetes cases, where traditional antibody markers may be less frequently positive.
- No specific treatment targets ZnT8 antibodies themselves; management focuses on addressing the underlying diabetes through appropriate insulin therapy and blood glucose monitoring 2, 3. It's also important to note that ZnT8 antibodies can be detected before clinical symptoms appear, making them valuable for identifying individuals at risk of developing type 1 diabetes 1. In clinical practice, the diagnosis and classification of diabetes, including the use of ZnT8 antibodies, should follow the standards of care in diabetes as outlined in recent guidelines 1, 2, 3.
From the Research
Definition and Role of ZnT8 Antibodies
- Zinc Transporter 8 (ZnT8) antibodies, also known as ZnT8 autoantibodies (ZnT8A), are among the most recently discovered and least-characterized islet autoantibodies 4.
- ZnT8A are detectable in a proportion of patients with adult-onset autoimmune diabetes and seem to be a valuable marker to differentiate clinical phenotypes 5.
- ZnT8A are associated with younger age and a high GADA titer, and their presence can help predict the risk of future type 1 diabetes 4, 5.
Prediction and Diagnosis of Type 1 Diabetes
- ZnT8A can be used in combination with autoantibodies to several other islet antigens to predict the risk of future type 1 diabetes 4, 6.
- The addition of ZnT8A improved prediction of type 1 diabetes in a well-characterized cohort of islet cell antibody (ICA)-positive first-degree relatives, particularly in those at low genetic risk of diabetes and older individuals 6.
- ZnT8A testing requires age-related cut-offs to ensure high clinical specificity in islet autoantibody testing 7.
Association with Type 1 Diabetes Mellitus
- ZnT8A is identified as another major biomarker for type 1 diabetes mellitus (T1DM), expanding the panel of diagnostic autoantibodies 8.
- The frequency of ZnT8A was found higher in T1DM patients compared to controls, and ZnT8A concentrations were significantly higher in cases compared to controls 8.
- ZnT8A was found significantly associated with T1DM, and subjects with ZnT8A values ≥ 9 ng/ml are 10 times more at risk to develop T1DM 8.