What are the differences in antibodies between Type 1 Diabetes Mellitus (Type 1 DM) and Type 2 Diabetes Mellitus (Type 2 DM)?

From the Guidelines

Type 1 Diabetes Mellitus (Type 1 DM) is characterized by the presence of autoantibodies, while Type 2 Diabetes Mellitus (Type 2 DM) typically does not involve autoantibodies. In Type 1 DM, the immune system produces several specific autoantibodies that attack pancreatic beta cells, including glutamic acid decarboxylase antibodies (GADA or anti-GAD65), islet cell antibodies (ICA), insulin autoantibodies (IAA), insulinoma-associated-2 autoantibodies (IA-2A), and zinc transporter 8 antibodies (ZnT8A) 1. These antibodies can be detected in the blood years before clinical symptoms appear and are used for diagnostic purposes, especially in ambiguous cases. The presence of multiple antibodies indicates a higher risk of developing Type 1 DM. Some key points to consider are:

• The presence of two or more autoantibodies is associated with a higher risk of developing Type 1 DM, with a 5-year risk of 44% and a 10-year risk of 70% 1.
• The absence of diabetes-related autoantibodies helps distinguish Type 2 DM from Type 1 DM, which is important for determining appropriate treatment approaches.
• Type 1 DM is primarily characterized by an autoimmune component, while Type 2 DM is characterized by insulin resistance and relative insulin deficiency without an autoimmune component.
• The diagnosis of Type 1 DM can be made using a combination of clinical features, laboratory tests, and autoantibody screening, as outlined in the flowchart for investigation of suspected Type 1 DM in newly diagnosed adults 1. In contrast, Type 2 DM is primarily characterized by insulin resistance and relative insulin deficiency without an autoimmune component. This fundamental difference reflects the distinct pathophysiological mechanisms underlying these two forms of diabetes. It is essential to accurately diagnose and distinguish between Type 1 and Type 2 DM to provide appropriate treatment and management, as the presence of autoantibodies can indicate a higher risk of developing complications and requiring insulin therapy 1.

From the Research

Differences in Antibodies between Type 1 and Type 2 Diabetes Mellitus

The main difference in antibodies between Type 1 Diabetes Mellitus (Type 1 DM) and Type 2 Diabetes Mellitus (Type 2 DM) lies in the presence of specific autoantibodies.

• Type 1 DM is characterized by the presence of autoantibodies such as:
  • Glutamic acid decarboxylase antibodies (GADA) 2
  • Insulinoma-associated protein 2 antibodies (IA-2A) 2, 3, 4
  • Zinc transporter 8 antibodies (ZnT8A) 5, 3, 4, 6
  • Insulin autoantibodies (IAA) 2, 4
• Type 2 DM is not typically associated with these autoantibodies, but some patients may test positive for one or more of them, particularly those with latent autoimmune diabetes in adults (LADA) 2, 6

Clinical Implications

The presence of these autoantibodies can help identify patients with Type 1 DM, even among those initially diagnosed with Type 2 DM 2.

• Screening for GADA, IA-2A, and ZnT8A can help identify patients with Type 1 DM who may require insulin therapy 2, 4
• The presence of multiple autoantibodies can indicate a higher risk of rapid progression to clinical onset of Type 1 DM 4

Research Findings

Studies have shown that:

• ZnT8A is a reliable biomarker for the identification and characterization of Type 1 DM 5, 6
• IA-2A and ZnT8A can identify rapid progressors to clinical onset of Type 1 DM, regardless of age 4
• The presence of thyroid autoantibodies is more common in patients with Type 1 DM who are positive for GADA, IA-2A, and ZnT8A 3