Insulin Allergy

Abstract

Insulin hypersensitivity reactions have been reported in both type 1 and type 2 diabetic patients. Some of these reactions stem from insulin itself, while some result from additive agents. Although reactions to all types of insulin can develop, reactions to human insulin and its analogues are rare. However, vital reactions can be observed. Previously used bovine and porcine insulins are known to be more immunogenic, and reactions to these types of insulin are more commonly observed. Due to the development of the purification process, the rate of these reactions has decreased considerably, from 30%-1% (1, 2). One-third of these reactions are associated with insulin, while the remaining reactions result from different substances that are added to the preparations. The allergic reaction types are named Type I, Type III, and Type IV (1-4). Skin reactions occurring at the injection site reduce the effects of exogenous insulin, stimulate insulin degradation, and/or impair insulin absorption. Thus, diabetes regulation also deteriorates (5).In addition to human insulins (NPH and regular insulins), analogues (lispro, aspart, glargine, detemir, glulisine, and degludec) may also induce allergic reactions. Stimulants may be an epitope of insulin itself and may also be changed by an antigenic epitope during production and purification. During subcutaneous degradation of insulin, different antigenic structures may be formed. Zinc and protamine are added to insulin to extend the duration of action, while metacresol and various contaminants are added as preservatives; these may cause reactions (1, 2). The commercially available insulin types and the additives they contain are presented in Table 1. Protamine is a cationic substance found in fish sperm; it is added to delay the release of insulin from the injection site. Exposure to protamine is a risk factor for allergy. Although fish allergies and vasectomy are believed to create risks in this regard, this situation was found to be only partly significant; no other relationships with other insulin types were observed, and no risk was found in a prospective study (3). However, protamine allergies and long-time use of insulin create risk for the production of insulin antibodies. In poorly controlled diabetes, this possibility should be considered. Although autoantibodies against protamine-heparin complex have been found, the relationship between insulin antibodies and protamine is not clear. This relationship is particularly significant in intermediate and rapid-acting insulins; the relationship between analogue insulins and autoantibodies was found to be contradictory. The time of insulin use, not the duration of diabetes, is significant. Protamine causes the formation of autoantibodies, probably by causing a change in the conformation of insulin. Also, cross-reactivity between human protamine and salmon protamine in insulin or the development of an immunologic response to salmon protamine can cause an allergic reaction. The amount of protamine found in NPH and insulin aspart is...

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