insulin--isophane and Drug-Hypersensitivity

Insulin allergy is a rare yet severe side effect of exogenous insulin use. Management typically involves use of alternative antihyperglycaemic agents, symptom control with antihistamines, use of different insulin formulations, and induction of tolerance with incremental doses of insulin. This treatment regimen is not always successful, and the use of omalizumab, an anti-IgE monoclonal antibody, has been used to induce tolerance to insulin.. G.M. is a 62-year-old man with Type 2 diabetes mellitus. His condition was not optimized on oral agents, and insulin therapy was required. G.M. had anaphylaxis to insulin NPH, and subsequent skin-prick testing was positive to insulin aspart, insulin NPH, insulin glulisine, insulin detemir, regular insulin, insulin glargine 100 units/ml and insulin glargine 300 units/ml. He received incremental doses of several insulin formulations; however, he experienced diffuse urticaria preventing optimal glycaemic control. Three successful cases have been described in the literature of omalizumab inducing tolerance to exogenous insulin; therefore, G.M. was started on omalizumab. He subsequently tolerated treatment doses of insulin glulisine and insulin detemir with no allergic reactions and with improvement in glycaemic control.. To our knowledge, this is the first described case of allergy to insulin glargine 300 units/ml and reiterates the potential use of omalizumab in insulin allergy. Further research is warranted to determine if omalizumab should be considered standard of care in difficult-to-treat insulin hypersensitivity.

Topics: Anaphylaxis; Anti-Allergic Agents; Diabetes Mellitus, Type 2; Drug Hypersensitivity; Humans; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Male; Middle Aged; Omalizumab

The objective of this study was to compare the efficacy and safety of insulin glargine, a long-acting insulin analog, with NPH insulin in children and adolescents with type 1 diabetes mellitus (T1DM). In a multicenter, open-label, randomized, 6-month study, 349 patients with TIDM, aged 5-16 years, received insulin glargine once daily or NPH insulin either once or twice daily, based on their prior treatment regimen. Although there was no significant difference between the NPH insulin and insulin glargine treatment groups with respect to baseline to endpoint change in HbA1c levels, fasting blood glucose (FBG) levels decreased significantly more in the insulin glargine group (-1.29 mmol/l) than in the NPH insulin group (-0.68 mmol/L, p = 0.02). The percentage of symptomatic hypoglycemic events was similar between groups; however, fewer patients in the insulin glargine group reported severe hypoglycemia (23% vs 29%) and severe nocturnal hypoglycemia (13% vs 18%), although these differences were not statistically significant (p = 0.22 and p = 0.19, respectively). Fewer serious adverse events occurred in the insulin glargine group than in the NPH insulin group (p < 0.02). A once-daily subcutaneous dose of insulin glargine provides effective glycemic control and is well tolerated in children and adolescents with T1DM.

Topics: Adolescent; Age of Onset; Blood Glucose; Child; Child, Preschool; Diabetes Mellitus, Type 1; Double-Blind Method; Drug Hypersensitivity; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Multicenter Studies as Topic; Puberty

Allergy to insulin became a rare complication due to the introduction of recombinant human insulin preparations. Nevertheless, allergic reactions to components of such preparations can occur. We report a case of a 61-year-old man with an atopic background and affected by diabetes mellitus type 2 since 27 years, who experienced generalized allergy to insulin at the moment of switching oral anti-diabetics to insulin. Prick tests revealed an allergy specifically to zinc, and the patient was treated with zinc-free glulisine insulin. After 8 months of such treatment, patient's glucose is stable and he never experienced allergic reactions to insulin injections. Even insulin allergy due specifically to zinc is rare, such complication must be assessed especially in a patient suffering from multiple allergies.

Topics: Diabetes Mellitus, Type 2; Drug Hypersensitivity; Humans; Hypoglycemic Agents; Insulin; Insulin, Isophane; Male; Middle Aged; Zinc

This is a case report of a patient with allergy to the rapid acting insulins and rapid acting analogs. Before trying insulin desensitization the treatment was changed to a basal-bolus regimen with glargine and glulisine with no signs of insulin allergy during the months after the start of the treatment.

Topics: Aged; Diabetes Mellitus, Type 2; Drug Hypersensitivity; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male

The patient was a 56-year-old man with type 2 diabetes and insulin allergy. He was administered glargine, which did not produce any allergic reactions, except for a small non-pruritic wheal. Thereafter, other insulin preparation could be administered. We consider this the first case of successful insulin desensitization by glargine administration.

Topics: Desensitization, Immunologic; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Hypersensitivity; Glycated Hemoglobin; Humans; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged

Allergic reaction to insulin preparations seemed to have decreased since the introduction of contaminant-free, human preparations. The role of protamine sulfate in decreasing the prevalence of allergy is unclear. This study examines the causative components of insulin allergy along with the value of skin tests for diagnosis. Eleven patients with insulin allergy and 53 patients receiving insulin but without an insulin allergy were included as controls. Intradermal skin tests were conducted using preparations containing various concentrations of insulin [Neutral protamine Hagedorn (NPH) insulin, regular insulin (RI)] and protamine sulfate. Of the 11 patients studied, 3 had anaphylaxis and 8 displayed localized reactions. All of the patients reacted positively during skin testing. Five patients showed positive intradermal skin test reactions to protamine sulfate, and 4 reacted to insulin. Two patients that were not tested with protamine sulfate reacted positively to NPH insulin. In the case of protamine sulfate, 4 patients with localized symptoms displayed positive reactions at concentrations of 10 microg/ml, 3 microg/ml or 0.3 microg/ml. One patient with anaphylaxis reacted positively to a concentration as low as 0.03 ng/ml. In the case of insulin protein, 3 patients reacted positively to a 100-fold dilution (1 UI/ml). Eight of the 53 controls experienced pruritus and/or skin lesions. However, none of the controls reacted at a concentration of NPH insulin of less than 10 U/ml or to protamine sulfate at less than 30 microg/ml. Allergic reactions to protamine sulfate are common and should not be ignored. This study shows a good correlation between clinical manifestations and skin test reactions for insulin allergy.

Topics: Adult; Aged; Anaphylaxis; Drug Eruptions; Drug Hypersensitivity; Female; Humans; Insulin; Insulin, Isophane; Intradermal Tests; Male; Middle Aged; Protamines

Although most patients receiving insulin produce insulin-specific IgE, significant allergic symptoms develop in very few of them. Patients receiving neutral protamine Hagedorn (NPH) insulin are at increased risk for the development of protamine hypersensitivity. The case of a 19-year-old woman with insulin-dependent diabetes and regular and NPH insulin hypersensitivity is presented.. The purpose of this study was to determine whether desensitization to NPH insulin, as well as standard insulin desensitization, could control allergic symptoms in a patient allergic to both NPH and regular insulin.. The patient required insulin desensitization for severe urticaria, angioedema, and occasional wheezing resulting from her insulin dose. She underwent a standard protocol for insulin desensitization twice in a 2-month period, with persistence in her symptoms. She was found to have high protamine-specific, as well as insulin-specific, IgE levels, and because of her poor response to regular insulin desensitization, she was desensitized to both regular and NPH insulin.. Dual desensitization resulted in marked improvement in her symptoms. The patient had recurrence of urticaria and angioedema a year and a half later, at which point the NPH was stopped and she was desensitized to regular insulin. She continued to receive regular insulin 4 times per day over the following 3 years with only occasional hives.. Patients with insulin allergy may not have complete resolution of their symptoms after standard desensitization, particularly those patients with concomitant protamine allergy. These patients may require protamine/NPH desensitization, an alternative insulin preparation, or both.

Topics: Adult; Diabetes Mellitus, Type 1; Drug Hypersensitivity; Female; Humans; Hypersensitivity, Immediate; Immunoglobulin E; Insulin; Insulin, Isophane; Protamines

Topics: Anaphylaxis; Angioedema; Diabetes Mellitus; Drug Hypersensitivity; Female; Heparin Antagonists; Humans; Hypoglycemic Agents; Immunoglobulin E; Insulin, Isophane; Intraoperative Complications; Middle Aged; Protamines; Urticaria; Vascular Surgical Procedures

We report an insulin-treated diabetic patient who suffered, in a 2-month period, three severe anaphylactic reactions immediately after self-administered subcutaneous injections of neutral protamine Hagedorn (NPH) human recombinant-DNA insulin. These reactions consisted of local and systemic symptoms, including dyspnea and hypotension. A simultaneous sensitization to human insulin and to protamine was demonstrated, both by skin tests and by the determination of serum specific IgE. Suspecting protamine allergy, we performed a test dose to human lente insulin with perfect tolerance. After a 1-year follow-up with lente-insulin treatment, no reactions have occurred, despite treatment interruptions. Therefore, protamine IgE-mediated allergy probably caused our patient's reactions. In conclusion, protamine sensitization should be ruled out in any patient with a history of reactions to subcutaneous protamine-containing insulins, even if insulin sensitization is present.

Topics: Adult; Anaphylaxis; Diabetes Mellitus, Type 1; Drug Hypersensitivity; Humans; Hypoglycemic Agents; Immunoglobulin E; Insulin, Isophane; Insulin, Long-Acting; Male; Protamines; Skin Tests

Reactions to intravenous protamine include rash, urticaria, bronchospasm, hypotension, and/or pulmonary artery pressure elevation. We have previously shown that in diabetic patients receiving daily protamine-insulin injections, the presence of anti-protamine IgE or IgG antibodies are significant risk factors for acute, life-threatening reactions when protamine is given intravenously. To study protamine reactions further, we measured serum anti-protamine IgE and IgG antibody levels, in-vitro basophil histamine release and intracutaneous skin testing to protamine serially in an NPH-insulin dependent diabetic who had a severe, protracted anaphylactic reaction to protamine. At the time of his protamine reaction, his serum contained 8.5 ng/ml of anti-protamine IgE and 1.3 micrograms/ml of anti-protamine IgG antibody. One month following the reaction both anti-protamine IgE and IgG increased to 16 ng/ml (twofold rise) and 90.5 micrograms/ml (70-fold rise), respectively. With time, both anti-protamine IgE and IgG antibody declined. Serial intradermal skin tests using protamine sulphate did not discriminate between the protamine reactor and nine normal control subjects who had no prior exposure nor any demonstrable serum IgE antibody to protamine. In-vitro basophil histamine release to protamine sulphate was inconclusive in discriminating between the protamine reactor and normal control subjects. We postulate that protamine may be an incomplete or univalent antigen that must first combine with a tissue macromolecule or possibly heparin to become a complete multivalent antigen capable of eliciting IgE antibody-dependent mediator release.

Topics: Aged; Basophils; Diabetes Mellitus, Type 1; Drug Hypersensitivity; Histamine Release; Humans; Immunoglobulin E; Immunoglobulin G; In Vitro Techniques; Infusions, Intravenous; Insulin, Isophane; Intradermal Tests; Male; Protamines

Protamine is widely used for reversing systemic heparinization after cardiac catheterization. Although rare, major reactions to protamine that simulate anaphylaxis occasionally occur and have previously been associated only with an allergic reaction to fish. Because neutral protamine Hagedorn (NPH) insulin includes protamine, it might be anticipated that NPH insulin-dependent diabetic patients would develop sensitivity to protamine. Of 866 consecutive patients undergoing cardiac catheterization over a 20 month period, 651 received protamine for reversal of heparinization. Of these, 8.5% (56/651) were diabetics and 2.3% (15/651) were NPH insulin-dependent diabetics. During this period seven patients were observed immediately after administration of protamine to have major adverse reactions that required the administration of catecholamines. One death ensued. Of the seven major reactions, four occurred in NPH insulin-dependent diabetics and one occurred in a patient with an allergy to fish. The incidence of major protamine reactions was 27% (4/15) in the NPH insulin-dependent diabetics vs 0.5% (3/636) in those with no history of NPH insulin use (p less than .001). This represents a 50-fold increased risk of a major reaction to protamine if the patient was receiving NPH insulin. Accordingly, we recommend that diabetics on NPH insulin and patients with allergies to fish undergo cardiac catheterization without the use of protamine or, when necessary, that protamine be administered cautiously in anticipation of a major adverse reaction.

Topics: Anaphylaxis; Blood Pressure; Cardiac Catheterization; Diabetes Mellitus, Type 1; Drug Hypersensitivity; Epinephrine; Female; Humans; Injections, Intravenous; Insulin, Isophane; Male; Middle Aged; Prospective Studies; Protamines

Topics: Adult; Animals; Blood Glucose; Diabetes Mellitus; Double-Blind Method; Drug Hypersensitivity; Female; Humans; Insulin, Isophane; Kinetics; Male; Swine

Topics: Adolescent; Animals; Cattle; Diabetes Mellitus, Type 1; Drug Hypersensitivity; Humans; Insulin, Isophane; Male; Protamines

A 56-year-old man developed shock and skin flush minutes after the slow administration of 25 mg of protamine sulfate. Prior protamine exposure from treatment of his diabetes with isophane insulin (NPH insulin) was believed to have sensitized this patient to protamine. A review of three other cases of reaction to low doses of protamine revealed that in each, the patient had previously been exposed to protamine. If heparin is used in a patient with a history of treatment of diabetes with isophane insulin, the heparin should be allowed to spontaneously reverse, without pharmacological assistance if possible. If protamine must be used, the patient should be pretreated with glucocorticoid and vasopressors should be immediately available.

Topics: Diabetes Mellitus; Drug Hypersensitivity; Humans; Insulin, Isophane; Male; Middle Aged; Protamines; Shock

A young woman with diabetes mellitus developed chronic urticaria after changing from isophane been insulin suspension to isophane beef-pork insulin suspension. She reverted to treatment with her original insulin preparation, but urticaria failed to terminate. While in the hospital, her eruption began each afternoon at the site of insulin injection. Zinc single-peak beef insulin suspension, a purer preparation with different additives than isophane beef insulin, was substituted, and urticaria terminated rapidly. Intradermal skin testing using single-peak (purified) preparations indicated that the patient was sensitive to beef and pork forms of isophane insulin but not to beef and pork forms of zinc insulin. The patient later had a brief recurrence of urticaria following oral erythromycin and tetracycline therapy but did not develop lesions at sites of insulin injection.

Topics: Adult; Animals; Cattle; Chronic Disease; Diabetes Mellitus; Drug Combinations; Drug Hypersensitivity; Female; Humans; Insulin, Isophane; Recurrence; Suspensions; Swine; Urticaria