Cell-Mediated Immunity to Insulin and its Polypeptide Chains in Insulin-Treated Diabetics

Wp, Faulk; Jp, Girard; Hd, Welscher

doi:10.1159/000231321

Cited by 13 publications

(3 citation statements)

References 2 publications

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“…The most commonly used assay to measure insulinresponsive T cells involves coincubating peripheral blood mononuclear cells with or without insulin for 6 to 10 d. The proliferative response is measured by the incorporation of radio-labeled nucleotide (357). T cell responses in patients with type 1 diabetes treated with porcine and bovine insulin or porcine-bovine mixtures were first reported in 1975 (358,359). Patients with recent-onset diabetes (32%) and those with long-standing illness (47%) were found to have positive T cell responses to human insulin (360).…”

Section: Cellular Immune Response To Exogenous Insulinmentioning

confidence: 99%

Immunological Responses to Exogenous Insulin

et al. 2007

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Regardless of purity and origin, therapeutic insulins continue to be immunogenic in humans. However, severe immunological complications occur rarely, and less severe events affect a small minority of patients. Insulin autoantibodies (IAAs) may be detectable in insulin-naive individuals who have a high likelihood of developing type 1 diabetes or in patients who have had viral disorders, have been treated with various drugs, or have autoimmune disorders or paraneoplastic syndromes. This suggests that under certain circumstances, immune tolerance to insulin can be overcome. Factors that can lead to more or less susceptibility to humoral responses to exogenous insulin include the recipient's immune response genes, age, the presence of sufficient circulating autologous insulin, and the site of insulin delivery. Little proof exists, however, that the development of insulin antibodies (IAs) to exogenous insulin therapy affects integrated glucose control, insulin dose requirements, and incidence of hypoglycemia, or contributes to beta-cell failure or to long-term complications of diabetes. Studies in which pregnant women with diabetes were monitored for glycemic control argue against a connection between IAs and fetal risk. Although studies have shown increased levels of immune complexes in patients with diabetic microangiopathic complications, these immune complexes often do not contain insulin or IAs, and insulin administration does not contribute to their formation. The majority of studies have shown no relationship between IAs and diabetic angiopathic complications, including nephropathy, retinopathy, and neuropathy. With the advent of novel insulin formulations and delivery systems, such as insulin pumps and inhaled insulin, examination of these issues is increasingly relevant.

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Section: Cellular Immune Response To Exogenous Insulinmentioning

confidence: 99%

Immunological Responses to Exogenous Insulin

et al. 2007

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“…Type IV reactions are lymphocyte-mediated reactions. Such reactions have been described using in vitro stimulation of lymphocytes of patients treated with insulin and may be involved in some local reactions in humans treated with insulin (7). Local reactions of this type attributable to zinc have also been reported (8).…”

mentioning

confidence: 94%

Immunogenicity and Allergenic Potential of Animal and Human Insulins

1993

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Immunological complications of insulin therapy have been evident since animal insulins became available for the treatment of diabetes mellitus in 1922. Insulin allergy has been particularly common, with local symptoms still occurring in approximately 5% of all patients. Insulin antibodies of high titers were observed in many patients treated with early insulin preparations containing proinsulin, C-peptide, and other peptide contaminants. Immunoglobulin G-insulin antibodies of very high levels can lead to immune-mediated insulin resistance, which is now extremely rare because of the widespread use of highly purified porcine insulin and human insulin preparations. Lipoatrophy, which was reported in 10-55% of patients treated with nonpurified bovine/porcine insulin preparations, has almost disappeared in patients since the advent of exclusive human insulin treatment. In view of the wide spectrum of immune-mediated complications of insulin therapy, much attention has been directed to the reduced immunogenicity and allergenicity of highly purified porcine insulins and the more recently available recombinant and semisynthetic human insulin preparations. Insulin antibodies of the immunoglobulin G and immunoglobulin E type can develop, however, in very low titers in patients treated exclusively with human insulin. Frequency and levels of immunoglobulin G insulin antibodies are identical in patients treated either with biosynthetic or semisynthetic human insulin preparations. Allergic symptoms to human insulin are now found in < 1% of de novo-treated patients, but still may occur when human insulin is used in the insulin-allergic patient. In summary, immunological complications of insulin therapy have decreased significantly during the last two decades and are now predominantly observed in patients with interrupted insulin therapy.

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“…The results of one study have been interpreted as showing that such complexes can pass into the fetal circulation (Bauman and Yalow, 1981); an unlikely event when viewed within the context of the placental sink. Type IV reactions have been shown to occur by virtue of the demonstrated cell-mediated immunity to insulin and its potypeptide chains (Faulk et al, 1975). The presently speculative type V reactions have not been sought in diabetes, but it is reasonable to speculate that such immunostimulating reactions could be mediated through some of the constellation of auto-antibodies found in diabetic sera (for review, see Galbraith, 1979).…”

mentioning

confidence: 99%

Fetoplacental physiology in relation to metabolic diseases

Faulk¹

1984

J of Inher Metab Disea

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Cell-Mediated Immunity to Insulin and its Polypeptide Chains in Insulin-Treated Diabetics

Cited by 13 publications

References 2 publications

Immunological Responses to Exogenous Insulin

Immunological Responses to Exogenous Insulin

Immunogenicity and Allergenic Potential of Animal and Human Insulins

Fetoplacental physiology in relation to metabolic diseases

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