Allergic reaction to insulin is a rare complication which may significantly impede achievement of optimal glycaemic control in patients with diabetes.
We present a case of an atopic, centrally obese, 41-year-old woman, with Type 2 Diabetes and persistent hyperglycemia (HbA1c 12.8%) despite multiple combinations of oral hypoglycemic agents (Metformin, Sitagliptin, Exanatide, Gliclazide, Dapagliflozin, Acarbose, and Pioglitazone).
Localised urticarial reactions occurred with all commercially available insulins, which persisted despite daily antihistamine use and topical hydrocortisone administration. Facial angioedema and airway compromise resulted from injection of aspart/ aspart protamine mix.
Desensitisation with small incremental doses of subcutaneous Aspart and using continuous subcutaneous insulin infusion (CSII) with Aspart, Lispro and Glulisine was unsuccessful and resulted in cutaneous wheals, 24-48 hours after administration.
Insulin desensitisation to Aspart was ultimately achieved using an intravenous insulin infusion, which was down-titrated as CSII was gradually up-titrated. Small meal boluses were introduced several weeks after successful introduction of basal CSII. CSII has remained in situ for the last 11 months without provoking any allergic reaction. Most recent measured HbA1c was at target at 7%.
The mechanism of insulin desensitisation may involve alteration of antigen / antibody concentrations leading to solubilisation of immune complexes; as well as induction of lymphocyte tolerance, depletion of specific T cells and induction of regulatory T cells. Longer term changes are proposed to involve switching from Th2 allergenic cytokines production (IL-4, IL-5) to a Th1 profile (IFNγ). The use of intravenous insulin may facilitate this process by preventing immune complex aggregation and depleting chemical mediators from mast cells in subcutaneous tissue, allowing subcutaneous insulin to be continued in the longer term.
Similar protocols have been reported in paediatric patients with Type 1 diabetes, however to our knowledge this is the first reported case in a patient with Type 2 Diabetes.