Side Effects of Insulin Therapy and The Treatment In Diabetes Type 1

The side effects of insulin therapy include delayed local skin reactions to injected insulin, true or systemic insulin allergy, insulin resistance, insulin-induced lipoatrophy, and insulin-induced lipohypertrophy. Three other possible sequelae of insulin administration are considered therapeutic effects, not side effects. The most common effect is hypoglycemia.

The other two are weight gain and the development of insulin edema.Weight gain often occurs as high blood sugars become normalized, with a subsequent reduction of glycosuria. The calories once lost in the urine can account for 70–100% of the weight gained. Insulin edema occurs when a patient who was generally in very poor glycemic control begins to use insulin regularly, which, through its salt-retaining properties, causes the accumulation of fluid and an increase in plasma volume. This can lead to localized or even generalized edema.

Local Reaction at the Site of Injection

Localized reactions at the site of insulin injection have become much less frequent with the advent of more pure human insulin preparations. However, local reactions do still occur68 and have been associated with a hypersensitivity to non-insulin components, such as the latex in the insulin needle. Patients should be referred to an allergist for testing, so that the offending antigens can be avoided. Generally it is possible to switch from one type of insulin to another or to find products that do not cause the allergy.

Systemic Insulin Allergy

True allergy to insulin, also called systemic insulin allergy, is rare, occurring in approximately 0.1% of diabetic patients receiving insulin. The same sort of a reaction can occur to protamine, which is found in NPH insulin. It is much more common in patients with a history of interrupted insulin therapy than in those whose therapy has been continuous and in those who have received protamine in large doses previously (for instance to reverse anticoagulation following coronary artery bypass surgery). The manifestations of insulin allergy are usually seen within 1 or 2 weeks of the resumption of interrupted insulin therapy. The hallmark of true insulin allergy is an immediate local reaction (within 30–60 min) that gradually increases until large areas surrounding the injection site are involved. In approximately one half of the patients, the reaction soon spreads into a generalized urticarial pattern and is occasionally associated with angioneurotic edema or even anaphylactic shock. These systemic reactions are often preceded by gradual increases in the severity of an immediate local reaction, which may serve as a warning that serious difficulties lie ahead unless desensitization occurs. These immediate reactions seem to be allergic responses to the insulin molecule itself. They are rarely alleviated by the use of extremely pure insulin preparations. The clinical similarity to penicillin allergy is striking and the immunologic characteristics of true insulin allergy are almost identical to those of penicillin allergy. Both types of allergy involve 1 exquisite sensitivity to minute amounts of the antigen on conjunctival or intradermal testing, 2 passive transfer of an antibody (identified as IgE) that is capable of sensitizing normal skin to a subsequent challenge by the antigen, 3 high titers (as measured by direct assays) of IgE antibodies to the particular antigen in question, and 4 successful treatment by desensitization in almost all cases. Although true insulin allergy is mediated by the same antibody (IgE) that causes atopic disease (asthma, allergic rhinitis, and urticaria), patients allergic to insulin apparently have no greater predisposition to atopy than do other patients. On the other hand, one-third of patients with true insulin allergy had a history of penicillin allergy.

Treatment of Insulin Allergy

Skin testing by an allergist can be helpful – a variety of different types and species of insulin can be tested to determine if there are any that can be tolerated by the patient. To desensitize a patient, very small but gradually increasing amounts of insulin are injected after relatively short periods. These minute doses of the antigen bind to IgE, but the amount of histamine and other chemical mediators of inflammation released by the IgE–mast cell combination is too small to cause clinical symptoms. As the dose of injected insulin is gradually increased, the amount of insulin bound to IgE is thought to increase at a slow enough pace that the resultant mast cell degranulation causes no symptoms. Eventually, all of the IgE affixed to mast cells are bound to the increasing doses in insulin and the patient can tolerate the usual therapeutic doses of insulin. This desensitization should be undertaken by an allergist or someone experienced in performing the procedure.

Insulin-Induced Lipoatrophy

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