A case of slowly progressive type 1 diabetes with unstable glycemic control caused by unusual insulin antibody and successfully treated with steroid therapy

Abstract 

A 75-year-old man with type 1 diabetes and history of insulin therapy for previous 3 years using only human recombinant ones was suffering from unstable glycemic control. He had a high level of total insulin and a high titer of insulin antibodies (IA) (bound/total ratio: 89.8%). Low affinity constant (k₁: 0.0312×10⁸M⁻¹) and high binding capacity (b₁: 51.8×10⁻⁸M) of IA in the patient detected by the Scatchard analysis were not compatible with those of IA associated with exogenous insulin injections in the diabetic patients, but compatible with those of the insulin autoantibodies found in patients with insulin autoimmune syndrome (IAS), although he had DRB1*0405, which may have protection against IAS development. The glucose infusion rate during hyperinsulinemic euglycemic clamp was 2.84mg/kg/min, suggesting a high level of insulin resistance. Steroid pulse therapy (1000mg for 3 days) aimed at reducing the possible effect of the IA on his insulin resistance and glycemic instability successfully decreased IA titer (from 89.8 to 58.3%), lowered its binding capacity (51.8–9.8×10⁻⁸M), increased glucose infusion rate (from 2.84 to 5.55mg/kg/min) and improved glycemic control (HbA_1c: from 10.0 to 7.4%) with reduced blood glucose excursion. In conclusion, the alteration in insulin pharmacokinetics induced by IA seemed to be the cause of the brittle diabetes of the present case. Steroid treatment might be useful for the improvement of glycamic control in such patients with high IA levels and unstable blood glucose.

Keywords: Insulin antibody, Insulin autoimmune antibody, Steroid pulse therapy, Insulin autoimmune syndrome (IAS)