The Treatment for Anti-insulin Antibody-mediated Immunological Insulin Resistance

Abstract

Anti-insulin antibody is sometimes observed in diabetic patients treated by exogenous insulin. Anti-insulin antibody induces immunological insulin resistance and poor glycemic control. We previously reported a type 1 diabetic patient who showed severe insulin resistance due to insulin analog aspart-induced anti-insulin antibody [1]. He has been treated by using insulin aspart and insulin glargine. We treated him with the use of the newest insulin analog, insulin glulisine. This treatment significantly ameliorated his glycemic control and anti-insulin antibody 125I-binding rate, suggesting insulin glulisine as a possible treatment for other insulin analogmediated immunological insulin resistance [1]. We also reported a type 2 diabetic patient (patient A) who developed severe insulin resistance due to anti-insulin antibody after 2 years of use of insulin lispro and insulin detemir [2]. Switching to the treatment with insulin glulisine and insulin glargine improved glycemic control, however, anti-insulin antibody binding rate was still high. Finally, three pre-meal injections of insulin glulisine and discontinuation of insulin glargine (4 weeks) decreased anti-insulin antibody 125I-binding rate [2]. Basal insulin therapy using long-acting insulin analogs may be necessary for type 1 diabetic patient or type 2 diabetic patients who have no endogenous insulin secretion capacity. How can we treat these patients with long-acting insulin analogs-mediated anti-insulin antibody? Here, we will show the changes in HbA1c and anti-insulin antibody 125I-binding rate following the change in dose of insulin glulisine and insulin glargine in patient A (Fig. 1). Increased dose of insulin glulisine and 10 weeks-discontinuation of insulin glargine significantly decreased anti-insulin antibody 125I-binding rate, however, fasting blood glucose level (more than 200 mg/dl) and HbA1c level showed deterioration. After 10 weeks-discontinuation of insulin glargine, we re-started the use of low dose of insulin glargine. Fasting blood glucose and HbA1c levels were promptly decreased, and interestingly, anti-insulin antibody 125I-binding rate has been also continuously reduced. As the treatments for anti-insulin antibody-mediated insulin resistance or hypoglycemia, in addition to our reports [1, 2], cessation of insulin administration [3], glucocorticoids [4], the combination therapy using glucocorticoids, immunosuppressant and plasmapheresis [5, 6], and insulin lispro [7, 8] have been reported (Table 1). Increasing dose of insulin glulisine and the use of low dose of insulin glargine after the discontinuation of insulin glargine for a sufficient long period may be a new treatment for the anti-insulin antibodymediated immunological insulin resistance.