From the Guidelines
In Latent Autoimmune Diabetes in Adults (LADA), glutamic acid decarboxylase antibodies (GADA or anti-GAD) should be the primary antibody measured, and if negative, islet tyrosine phosphatase 2 (IA-2) and/or zinc transporter 8 (ZnT8) should be considered, as recommended by the most recent guidelines 1.
Key Autoantibodies in LADA
The following autoantibodies are typically checked to confirm LADA diagnosis:
- Glutamic acid decarboxylase antibodies (GADA or anti-GAD)
- Islet cell antibodies (ICA)
- Insulin autoantibodies (IAA)
- Zinc transporter 8 antibodies (ZnT8A)
- Insulinoma-associated-2 antibodies (IA-2A) Testing for multiple antibodies increases diagnostic sensitivity, as some patients may be positive for only one type 1.
Importance of Early Detection
Early antibody detection is crucial as it helps identify patients who will likely progress more rapidly to insulin dependence and may benefit from earlier insulin therapy to preserve remaining beta cell function 1.
Diagnostic Approach
The presence of these autoantibodies indicates an ongoing autoimmune process targeting pancreatic beta cells, distinguishing LADA from type 2 diabetes despite similar adult-onset presentation 1.
Recommendations
Based on the most recent guidelines, GADA should be the primary antibody measured, and if negative, IA-2 and/or ZnT8 should be considered 1. This approach helps to identify patients with LADA and provides a basis for early intervention and management.
From the Research
Antibodies Checked in LADA
The following antibodies are checked in Latent Autoimmune Diabetes in Adults (LADA):
- Glutamic acid decarboxylase autoantibodies (GADA) 2, 3, 4, 5, 6
- Insulin autoantibody (IAA) 2, 3, 5
- Cytoplasmic islet cell autoantibodies (ICA) 2, 4, 6
- IA-2A (antibodies to insulinoma-associated antigen-2) 2, 3, 5
- Zinc Transporter 8 (ZnT8A) autoantibodies 3, 5
Importance of Antibody Testing
Antibody testing is necessary to correctly classify the type of diabetes and to identify LADA patients 6. The presence of these autoantibodies can distinguish LADA from type 2 diabetes mellitus (T2DM) 2, 3, 4.
Combination of Antibodies
The combination of multiple antibodies can improve the diagnosis rate of LADA 2, 3. For example, the combination of IAA, GADA, and IA-2A can improve the diagnosis rate by 2.39% compared to using GADA and IA-2A alone 2.
Clinical Significance
The presence and levels of these autoantibodies can provide information about the clinical characteristics and progression of LADA 4, 5. For example, high levels of GADA and/or GAD65-CAb can identify a subgroup of LADA patients with clinical characteristics similar to those of typical type 1 diabetes and at high risk of progression towards insulin dependency 4.