![]() Lipodystrophy resulting from insulin injections refers to two conditions: lipoatrophy and lipohypertrophy. Immunological insulin resistance can develop in patients with very high titers of IgG- antibodies. Insulin therapy can rarely result in the production of insulin antibodies of the IgG class, which inactivate insulin. Delayed, IgG-mediated allergic reactions also develop with animal insulins ( 19). Patients who experience a true allergic reaction to insulin have typically received insulin in the past, and experience the reaction after insulin is restarted. Rare hypersensitivity responses to insulin can be immediate-type, local or systemic IgE- mediated reactions ( 19). Because of the availability of human insulin and the increased potential for animal source insulin to be immunogenic, animal source insulins are no longer available in the United States. Components of insulin preparations (e.g., zinc, protamine) and subcutaneous insulin aggregates are also thought to contribute to antibody formation ( 19). Older formulations of insulin were less pure, containing islet-cell peptides, proinsulin, C-peptide, pancreatic polypeptides, glucagon, and somatostatin, which contributed to the immunogenicity of insulin ( 19). The long-term clinical significance of differences in IGF- 1 binding among available insulins is not known.īecause pork and beef insulin differ from human insulin by 1 and 3 amino acids respectively, they are more immunogenic than exogenous human insulin. An in vitro study showed that insulin degludec had a low IGF-1 receptor binding affinity compared to human insulin ( 18). Insulin detemir was found to be more than 5-fold less potent than human insulin in binding to IGF-1 ( 12). Observational studies with up to 7 years of follow up have also not shown an association of cancer with insulin glargine or detemir use ( 17). A review of large epidemiologic studies did not find evidence of an increased risk of malignancy among glargine-treated patients when compared with other insulin therapies ( 14). However, there are inherent limitations to such analyses. In human studies, meta-analyses comparing exogenous insulin to non-insulin antihyperglycemic therapies have shown associations of insulin with several cancers ( 15, 16). The predominant metabolite M1 has been shown to have a 0.4-fold binding affinity to the IGF-1 receptor compared with human insulin ( 14). However, glargine is rapidly degraded to metabolites. Insulin glargine was found to have a 6- to 8-fold increase in mitogenic potency and IGF- 1 receptor affinity compared to human insulin. Insulin lispro and aspart are similar to human insulin on all of the above parameters, except insulin lispro was found to be 1.5-fold more potent in binding to the IGF-1 receptor compared to human insulin. ![]() Insulin and IGF-1 receptor binding affinities, and the metabolic and mitogenic potencies of insulin analogs relative to human insulin have been assessed. ![]() Because insulin analogs are modified human insulin, the safety and efficacy profiles of these insulins have been compared to human insulin ( 12). Subcutaneously administered insulin bypasses the usual 80% hepatic first pass clearance of pancreatic islet cell-secreted insulin, and therefore contributes to systemic hyperinsulinemia in insulin-treated patients with diabetes ( 13). Suggesting that hyperinsulinemia may promote tumorigenesis. In vitro studies have demonstrated the mitogenic effects of insulin at high concentrations, as well as carcinogenic effects of insulin binding to the insulin like growth factor-1 (IGF-1) receptor, ![]()
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