What antibodies are associated with a new diagnosis of Diabetes Mellitus (DM)?

From the Guidelines

Antibody testing, specifically for glutamic acid decarboxylase (GAD) antibodies, islet cell antibodies (ICA), insulin autoantibodies (IAA), and zinc transporter 8 (ZnT8) antibodies, is crucial for diagnosing type 1 diabetes in newly diagnosed patients, as it helps differentiate between type 1 and type 2 diabetes and ensures prompt initiation of appropriate insulin therapy. The presence of one or more of these antibodies indicates autoimmune destruction of pancreatic beta cells, confirming type 1 diabetes 1. GAD antibodies are the most sensitive and commonly used test, present in about 70-80% of type 1 diabetes patients. Testing for multiple antibodies increases diagnostic accuracy, with the presence of two or more antibodies strongly supporting type 1 diabetes 1. These tests are particularly valuable in adults with ambiguous presentations, where distinguishing between type 1 and type 2 diabetes can be challenging. Some key points to consider when testing for antibodies include:

• The primary antibody to measure is GAD, and if negative, follow up with IA-2 and/or ZnT8 where available 1
• In individuals who have not been treated with insulin, antibodies against insulin may also be useful
• A negative result does not change the diagnosis of type 1 diabetes in those diagnosed at <35 years of age who have no clinical features of type 2 diabetes or monogenic diabetes, since 5-10% of people with type 1 diabetes do not have antibodies 1
• C-peptide testing may be useful in certain situations, such as in individuals receiving insulin treatment, but must be measured prior to insulin discontinuation to exclude severe insulin deficiency 1. Early identification of type 1 diabetes through antibody testing ensures appropriate insulin therapy is initiated promptly, preventing diabetic ketoacidosis and other complications, thus prioritizing morbidity, mortality, and quality of life as the outcome 1.

From the FDA Drug Label

Antibody Production In large clinical trials with patients with type 1 (n=509) and type 2 (n=262) diabetes mellitus, anti-insulin antibody (insulin lispro-specific antibodies, insulin-specific antibodies, cross-reactive antibodies) formation was evaluated in patients receiving both regular human insulin and Insulin Lispro (including patients previously treated with human insulin and naive patients). As expected, the largest increase in the antibody levels occurred in patients new to insulin therapy. In a 6-month study with a 6-month extension in adult subjects with type 1 diabetes, 99. 8% of patients who received NOVOLOG were positive for anti-insulin antibodies (AIA) at least once during the study, including 97.2% that were positive at baseline. A total of 92.1% of patients who received NOVOLOG were positive for anti-drug antibodies (ADA) at least once during the study, including 64. 6% that were positive at baseline.

Antibodies for new diabetic diagnosis:

• Patients new to insulin therapy experience the largest increase in antibody levels.
• The formation of anti-insulin antibodies and anti-drug antibodies has been observed in patients receiving insulin lispro and insulin aspart.
• These antibodies do not appear to cause deterioration in glycemic control or necessitate an increase in insulin dose 2, 3.
• The presence of antibodies may be influenced by several factors, including assay methodology and concomitant medications.
• It is essential to monitor patients for signs of immunogenicity and adjust treatment accordingly.

From the Research

Antibodies for New Diabetic Diagnosis

• The presence of islet autoantibodies in a person with diabetes indicates an autoimmune etiology, establishing the diagnosis of type 1 diabetes (T1D) 4.
• Five islet autoantibodies are available for routine clinical use: islet cell cytoplasmic autoantibodies (ICA), insulin autoantibodies (IAA), glutamic acid decarboxylase autoantibodies (GADA), insulinoma associated-2 autoantibodies (IA-2A), and zinc transporter-8 autoantibodies (ZnT8A) 4.
• Autoantibodies to glutamate decarboxylase, islet antigen-2, insulin, and zinc transporter-8 are characteristic of type 1 diabetes and can be detectable before clinical onset 5.
• Islet autoantibody testing allows prediction of type 1 diabetes and definition of the latent autoimmune diabetes in adults subgroup of non-insulin-treated patients 5.
• Screening for T1D autoantibodies has positive clinical consequences, including reduction of diabetic ketoacidosis events, improved glycemic control, and positive impact on short- and long-term complications 6.

Types of Antibodies

• Islet cell antibodies (ICA) and glutamic acid decarboxylase antibodies (GADAb) are useful in identifying patients with type 1(1/2) diabetes in patients presenting with type 2 diabetes 7.
• Insulin autoantibodies (IAA) and IA-2 antibodies occur less frequently in patients with type 2 diabetes 7.
• Autoantibodies to glutamic acid decarboxylase or ICA are of high diagnostic sensitivity in patients with type 1 diabetes and are better predictors for future insulin dependency than biochemical or clinical parameters 8.

Clinical Applications

• The determination of islet autoantibodies can greatly aid in the diagnosis and prediction of T1D 4.
• Autoantibody testing is useful in classifying diabetes of other types 5.
• Primary care clinicians can play a critical role in promoting islet autoantibody screening 6.
• Antibody testing can help identify patients with type 1 diabetes who may require insulin treatment, allowing for early intervention and improved management of the disease 8.