From the Guidelines
LADA antibodies are autoantibodies, specifically islet-associated autoantibodies such as anti-GAD, that aid in the identification of Latent Autoimmune Diabetes in Adults, a slowly progressive form of type 1 diabetes. These antibodies are crucial in diagnosing LADA, which presents with mild hyperglycemia initially responsive to oral agents but eventually requires intensive insulin regimens 1. The presence of these antibodies indicates an autoimmune destruction of pancreatic beta cells, distinguishing LADA from typical type 2 diabetes. Key characteristics that may suggest LADA include adult-onset diabetes with a relatively low BMI, personal or family history of autoimmune conditions, or a poor response to oral diabetes medications.
- Commonly tested LADA antibodies include:
- Glutamic acid decarboxylase antibodies (GADA or anti-GAD)
- Islet cell antibodies (ICA)
- Insulin autoantibodies (IAA)
- Zinc transporter 8 antibodies (ZnT8) Testing for these antibodies is essential for early identification and appropriate treatment planning, which may involve starting with oral medications but transitioning to insulin therapy earlier than in typical type 2 diabetes 1.
- The clinical implications of LADA antibodies include:
- Slower progression to insulin dependence compared to classic type 1 diabetes
- Eventual requirement for insulin therapy
- Importance of early identification for tailored treatment approaches
- Distinction from typical type 2 diabetes due to the autoimmune nature of the disease Given the information from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) position statement in 2012 1, measuring titres of islet-associated autoantibodies, such as anti-GAD, is recommended for identifying LADA patients, thereby encouraging a more rapid transition to insulin therapy when necessary.
From the Research
Definition and Characteristics of LADA Antibodies
- Latent Autoimmune Diabetes in Adults (LADA) is a disorder characterized by the presence of islet antibodies at diagnosis of diabetes, with a slow progression of autoimmune beta-cell failure 2.
- LADA patients are not insulin requiring, at least during the first 6 months after diagnosis of diabetes, and it may take up to 12 years until beta-cell failure occurs in some patients 2.
- The disease is characterized by β-cell failure and slow progression to insulin dependence, with autoantibodies against β-cells being critical diagnostic biomarkers 3.
Types of LADA Antibodies
- Glutamic acid decarboxylase antibodies (GADA) and/or islet cell antibodies (ICA) are detected in LADA patients 2, 4.
- Patients with multiple islet antibodies develop beta-cell failure within 5 years, whereas those with only GAD antibodies (GADAs) or only islet cell antibodies (ICAs) mostly develop beta-cell failure after 5 years 2.
- GADA-positive patients display lower stimulated C-peptide levels and progress more frequently to insulin treatment 4.
Diagnostic Biomarkers
- C-peptide levels and autoantibodies against β-cells are the most critical diagnostic biomarkers in LADA 3.
- Mixed Meal Tolerance Test and i.v. Glucagon Stimulation Test are used for estimation of beta cell function 5.
Treatment Approaches
- Insulin is the treatment of choice for LADA patients, with early diagnosis being significant in limiting disease progression 2, 3.
- Metformin and the addition of low doses of insulin are commonly used in the management of LADA, with newer oral hypoglycaemic agents also being used 3.
- Intra-lymphatic GAD-alum treatment has shown encouraging results in preserving beta cell function in LADA patients 5.