Insulin hypersensitivity in type 1 diabetes: investigation and treatment with immunodepletion

Abstract

A 12-year-old girl presented with type 1 diabetes which was well controlled for the first two years. Glycaemic control then markedly deteriorated with a very large increase in insulin requirement and the appearance of inflammatory nodules at injection sites. Immunoprecipitation studies showed this to be due to a type 3 hypersensitivity reaction with the generation of IgG autoantibodies binding to insulin itself. Trials of a wide range of different insulins and treatment with a hyposensitisation protocol provided no benefit. Following treatment with rituximab, antibody generation subsided. Since the clinical response was only partial she also received intravenous immunoglobulin. A reduced insulin requirement and better glycaemic control were achieved over time. These parameters have subsequently deteriorated again.

Insulin Allergy to Detemir Followed by Rapid Onset of Diabetic Ketoacidosis: A Case Report and Literature Review

“…However, her pre-existing diagnosis of T2DM was not in line with the current definition of “fulminant type 1 diabetes” ( 10 ). To our knowledge, this is the first case report of insulin-dependent DM presenting with DKA which occurred after exposure to an exogenous insulin (detemir), and another rare report of a case of exogenous insulin allergy with concomitant immunological form of insulin resistance ( 11 ).…”

“…Detemir is an insulin analogue which differ from native insulin by the deletion of amino acid threonine B30 and addition of the saturated long-chain fatty acid myristic acid residue at B29 ( 12 ). Although all insulin analogues resemble human insulin, insulin analogues can cause immunogenicity leading to antibodies against insulin ( 2 , 3 ) and insulin allergy ( 1 , 5 , 6 , 11 , 13 ). Among the long-acting insulin analogues, there are more reports of insulin detemir causing severe allergy ( 5 , 6 , 12 ), raising the question whether detemir is particularly immunogenic.…”

“…Management of patients with T1DM with insulin allergy varies, with 7 cases switching the insulin type used ( 7 , 8 , 19 , 25 , 30 – 32 ), and 8 cases adopting the use of anti-histamines ( 7 , 26 – 30 , 32 , 33 ). Where anti-histamines did not work or insulin therapy could not be switched, other measures are explored, with 5 cases adopting the use of insulin desensitisation with continuous subcutaneous insulin infusion ( 7 , 11 , 24 , 28 , 29 ), and 6 cases adopting the use of immunosuppression via steroids ( 7 , 8 , 23 , 26 , 29 , 33 ), tacrolimus ( 30 ), rituximab (anti-CD20 monoclonal antibody) and IV immunoglobulin ( 11 ). Matheu et al.…”

A case report and systematic literature review: insulin-induced type III hypersensitivity reaction

“…Both TPE and IVIg have been utilized in the treatment of insulin-induced type III HSRs. TPE was effective in 3 cases, including ours, while IVIg's effectiveness varied, with an initial positive response reported in one case (4)(5)(6)(7)(8). Immunosuppressive agents targeting B and T cells, such as rituximab, methotrexate, azathioprine, and MMF, have yielded varying effectiveness results (Table 1).…”

“…However, the patient needed escalating IV insulin doses, up to 10 units/h, along with frequent boluses (total daily doses of up to 230-240 units/24 h), to sustain euglycemia. Based on previously reported clinical responses to IVIg and TPE, a combination of both was pursued (5)(6)(7)(8). She completed 5 sessions of TPE followed by 2 g/kg IVIg administered over two days.…”