What is the significance of insulin antibodies (IA) in diabetes?

From the Guidelines

Insulin antibodies should be suspected in diabetic patients with erratic glucose control despite adherence to treatment, and testing is recommended when patients experience unexplained glucose variability, sudden changes in insulin requirements, or allergic reactions to insulin, as identifying and addressing this issue can significantly improve glycemic management and patient outcomes. The presence of insulin antibodies can be an indicator of an immune response to exogenous insulin therapy, which can affect the efficacy of insulin treatment 1. When insulin antibodies form, they may cause unpredictable blood glucose fluctuations by binding to insulin and either delaying its action or releasing it unpredictably, leading to unexplained hypoglycemia or insulin resistance requiring higher doses 2. Some key points to consider when evaluating insulin antibodies include:

• Testing for insulin antibodies is recommended in patients with unexplained glucose variability, sudden changes in insulin requirements, or allergic reactions to insulin 3
• Management of insulin antibodies typically involves switching to a different insulin formulation, adjusting dosing regimens, or considering immunosuppressive therapy in severe cases 4
• Clinicians should be aware of the potential for insulin antibodies to develop in patients receiving exogenous insulin therapy, particularly with animal-derived insulins, although this is less common with modern human insulin analogs 5
• The presence of insulin antibodies can be associated with a higher likelihood of lifelong insulin requirement, although clinical judgment using a patient's phenotype, history, presentation, and selective laboratory testing is still necessary for diagnosis and management 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 HUMALOG (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. The antibody levels peaked by 12 months and declined over the remaining years of the study These antibodies do not appear to cause deterioration in glycemic control or necessitate an increase in insulin dose

Insulin Antibody Formation: The formation of anti-insulin antibodies, including insulin lispro-specific antibodies, insulin-specific antibodies, and cross-reactive antibodies, was evaluated in clinical trials with HUMALOG.

• The largest increase in antibody levels occurred in patients new to insulin therapy.
• Antibody levels peaked by 12 months and declined over the remaining years of the study.
• These antibodies do not appear to cause deterioration in glycemic control or necessitate an increase in insulin dose 6.

From the Research

Insulin Antibody Overview

• Insulin antibodies are proteins produced by the immune system in response to insulin, which can affect the body's ability to regulate blood sugar levels 7, 8.
• These antibodies can be found in individuals with insulin-naive individuals (insulin autoimmune syndrome) and in patients with insulin-treated diabetes, although they are rarely of clinical significance in the latter group 7.

Clinical Significance of Insulin Antibodies

• In some cases, insulin antibodies can cause severe insulin resistance, leading to poor glycemic control despite high doses of insulin 7, 8.
• Patients with high levels of insulin antibodies may experience uncontrolled hyperglycemia or frequent episodes of hypoglycemia, and may require changes to their insulin regimen or treatment with glucocorticoids 8.

Treatment and Management of Insulin Antibodies

• Plasma exchange and immunosuppressive therapy have been shown to be effective in reducing insulin antibody levels and improving glycemic control in patients with severe insulin resistance due to anti-insulin antibodies 7.
• Changing insulin formulations or discontinuing insulin and switching to oral antidiabetic agents may also be effective in reducing insulin antibody levels and improving glycemic control 8.

Insulin Analogues and Insulin Antibodies

• The development of insulin analogues has improved the treatment of type 2 diabetes, with benefits including reduced hypoglycemia and improved postprandial glucose control 9, 10, 11.
• Insulin analogues such as insulin aspart and insulin lispro have been shown to have a more rapid absorption and better postprandial glucose control compared to human insulin 9, 10, 11.