A Case of Type 1 Diabetes With Nocturnal Hypoglycemia After Desensitization Therapy for Insulin Allergy

A ntibodies against exogenously injected insulin are common with insulin treatment but seldom have serious effects on blood glucose (1). In insulin autoimmune syndrome (IAS), however, the insulin antibody causes hy-poglycemia (2) in the absence of exoge-nous insulin treatment. Here, we report a case of type 1 diabetes with insulin antibody, whereby the patient developed nocturnal hypogly-cemia after desensitization therapy for an insulin allergy. After receiving insulin therapy for 1 year, a 61-year-old man was admitted to our hospital because of an insulin allergy and poor control of diabetes. He had an itchy eruption at the insulin injection site. At the time of admission, the patient presented with an HbA 1c level of 16.2% (154 mmol/mol); anti-GAD antibody 80.0 U/L (,1.5 U/mL); serum C-peptide level 0.01 ng/mL after glucagon injection (fasting 0.67–2.48 ng/mL); and insulin-specific IgE 41.5 UA/mL (,0.34 UA/mL). He tolerated three daily injections of NPH insulin because it produced a lesser reaction than other insulin or its analogs. In fact, almost all human insulin or insulin analogs caused a skin reaction during the skin test, whereas protamine, zinc, and glycerol did not. We therefore diagnosed him with an insulin allergy and initiated desensitization using an increasing dose of human regular insulin, according to the procedure reported by Hayashi et al. (3). Following desensitiza-tion with up to 4.0 U of regular insulin, the patient's skin reaction to insulin improved and he was able to tolerate insulin injections four times daily. However , at the same time, he developed nocturnal hypoglycemia. We subsequently reduced his bed-time dose of NPH insulin and finally stopped the treatment. We examined the binding kinetics of his insulin antibody using serum samples before and after desensitization. Scatchard analysis revealed two binding components (high [K 1 ] and low [K 2 ] affinity), although the former (i.e., K 1) principally reflects each antibody's affinity as reported previously (4). Before de-sensitization, the affinity constants (K 1) and binding capacities (b 1) for the high-affinity components were K 1 9.19 3 10 22 (1/10 28 M) (insulin antibodies in patients with diabetes who are treated with insulin , 1.45–7.11) and b 1 199 (10 28 M) (insulin antibodies in patients with diabetes who are treated with insulin , 0.08–1.1) (4), suggesting that the antibody had relatively low affinity (i.e., smaller K 1) but high capacity (i.e., larger b 1) for insulin binding. Interestingly, after the desensiti-zation therapy, K …