Insulin Allergy and Extensive Lipoatrophy in Child with Type 1 Diabetes

Abstract

Insulin allergy and lipoatrophy in type 1 diabetic patients have been previously reported but the mechanisms are not well documented. Here, we report a case emphasizing the role of abnormal local immune reaction associated with cytokine hyper production. The patient is a 7-year-old boy with a familial history of common variable immunodeficiency. Eight months after the diagnosis of type 1 diabetes, he developed signs of insulin allergy expressed as continuously extensive and profound lipoatrophy contrasting with a well-preserved metabolic control. Specific insulin allergy was confirmed by skin prick tests that showed lymphoid activated cells in the subcutaneous tissue at the site of insulin injection. All therapies reported in the literature (antihistaminic, local steroid, change to lispro insulin, immunosuppressive treatment, subcutaneous insulin pump, peritoneal insulin infusion) were not efficient. It is suggested that familial disorders of immune cell functions with abnormal and excessive cytokine production might explain these adverse effects triggered by insulin with severe allergic reactions and lipoatrophy.

Skin signs in diabetes mellitus

“…An immunologic reaction in the development of lipoatrophy is strongly suspected. Immunofluorescence analysis of affected skin has shown abnormal accumulation of immunoglobulins and complement in dermal blood vessels initiating a signaling cascade that results in inhibition of adipocyte differentiation 101,102 . The likelihood of lipoatrophy decreases with regular rotation of the infection area.…”

“…Immunofluorescence analysis of affected skin has shown abnormal accumulation of immunoglobulins and complement in dermal blood vessels initiating a signaling cascade that results in inhibition of adipocyte differentiation. 101,102 The likelihood of lipoatrophy decreases with regular rotation of the infection area. In contrast, lipohypertrophy is characterized by increase of local subcutaneous fat.…”

Allergic reactions to human insulin: a review of current knowledge and treatment options

“…Geldof et al [61] reported a patient who developed hand eczema associated with CSII. In another paper, Beltrand et al [62] reported a 7-year-old boy who developed insulin allergy and extensive lipoatrophy although his insulin treatment switched to CSII after first signs of insulin allergy had appeared. Durand-Gonzalez et al [63] reported that insulin allergy reappeared 7 weeks after the initiation of CSII in a patient with gestational diabetes who had first developed insulin allergy while using insulin injections.…”

Early-onset, severe lipoatrophy in a patient with permanent neonatal diabetes mellitus secondary to a recessive mutation in the INS gene

“…Thus, we hypothesize that the complete absence of endogenous insulin protein in our patient prevented induction of immune tolerance resulting in antibody production against the exogenous insulin followed by progressive immune-mediated lipoatrophy at injection sites. Indeed, Beltrand et al (16) previously suggested that immune insulin-induced lipodystrophy involves the local formation of immune complexes, complement fixation, and release of cytokines. The latter causes a loss of differentiation of subcutaneous fat tissue, the inhibition of the differentiation of adipocyte precursors and the delipidation of mature cells, as described in our patient's pathology report.…”