Nodular amyloidosis at the sites of insulin injections

Amyloid is characterized by its fibrillary ultrastructure, and more than 20 proteins have been described to date as possible precursors. Among them, insulin and enfuvirtide represent the only medications described as amyloidogenic substances. We describe two diabetic patients, who were undergoing long-standing subcutaneous insulin treatment, who developed subcutaneous nodules at the sites of insulin injections. Histopathologic examination showed the presence of eosinophilic and amorphous masses in deep dermis, which stained positive with Congo red, amyloid P substance and anti-human insulin antibody. Whether the type of injected insulin played a role or not in the pathogenesis of the process is still uncertain, because all described patients used both fast-acting and slow-acting insulins at the same injection sites. Our second case showed nodular insulin-derived amyloid tumors only at the sites where exclusively fast-acting insulin was injected, which supports the notion that fast-acting insulin may also be the cause of this disorder. Insulin-derived nodular amyloidosis is probably underdiagnosed because of the small body of literature in comparison with the prevalence of insulin dependent diabetic patients. This underdiagnosis probably is because of its clinical similarity with the lesions of lipohypertrophy at the sites of insulin injections, which is rarely biopsied.