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Alan Krasner - One of the best experts on this subject based on the ideXlab platform.
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Insulin antibodies with pulmonary delivery of Insulin.
Diabetes Technology & Therapeutics, 2007Co-Authors: S. Edwin Fineberg, Alan Krasner, Thomas T Kawabata, Naomi S. FinebergAbstract:BACKGROUND AND METHODS: Delivery of Insulin to the deep lung presents unique challenges to the body's mucosal defense system. Pulmonary mucosal defense has the ability to discriminate between self and non-self antigens and has the potential for induction of immunologic tolerance. Published data concerning the immunogenicity of inhaled human Insulin in drug trials will be reviewed, and data regarding the possible adverse effects of anti-Insulin Antibody development will be presented. Examination of the immunologic safety of inhaled human Insulin will include discussion of comparator studies, factors affecting immunogenicity, the effects of Insulin immunity on glycemic control and pulmonary function, and the relationship of Insulin antibodies to dose requirements, pharmacodynamics, and hypoglycemia. CONCLUSIONS: Inhaled human Insulin, whether formulated as a powder or liquid, has been shown to be more immunogenic than comparator Insulins given by subcutaneous routes; however, adverse effects of Antibody formation have not been demonstrated.
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Insulin antibodies with pulmonary delivery of Insulin.
Diabetes Technology & Therapeutics, 2007Co-Authors: S. Edwin Fineberg, Alan Krasner, Thomas T Kawabata, Naomi S. FinebergAbstract:Background and Methods: Delivery of Insulin to the deep lung presents unique challenges to the body's mucosal defense system. Pulmonary mucosal defense has the ability to discriminate between self and non-self antigens and has the potential for induction of immunologic tolerance. Published data concerning the immunogenicity of inhaled human Insulin in drug trials will be reviewed, and data regarding the possible adverse effects of anti-Insulin Antibody development will be presented. Examination of the immunologic safety of inhaled human Insulin will include discussion of comparator studies, factors affecting immunogenicity, the effects of Insulin immunity on glycemic control and pulmonary function, and the relationship of Insulin antibodies to dose requirements, pharmacodynamics, and hypoglycemia. Conclusions: Inhaled human Insulin, whether formulated as a powder or liquid, has been shown to be more immunogenic than comparator Insulins given by subcutaneous routes; however, adverse effects of Antibody for...
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Insulin antibodies with pulmonary delivery of Insulin.
Diabetes technology & therapeutics, 2007Co-Authors: S. Edwin Fineberg, Alan Krasner, Thomas T Kawabata, Naomi S. FinebergAbstract:Delivery of Insulin to the deep lung presents unique challenges to the body's mucosal defense system. Pulmonary mucosal defense has the ability to discriminate between self and non-self antigens and has the potential for induction of immunologic tolerance. Published data concerning the immunogenicity of inhaled human Insulin in drug trials will be reviewed, and data regarding the possible adverse effects of anti-Insulin Antibody development will be presented. Examination of the immunologic safety of inhaled human Insulin will include discussion of comparator studies, factors affecting immunogenicity, the effects of Insulin immunity on glycemic control and pulmonary function, and the relationship of Insulin antibodies to dose requirements, pharmacodynamics, and hypoglycemia. Inhaled human Insulin, whether formulated as a powder or liquid, has been shown to be more immunogenic than comparator Insulins given by subcutaneous routes; however, adverse effects of Antibody formation have not been demonstrated.
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Antibody response to inhaled Insulin in patients with type 1 or type 2 diabetes an analysis of initial phase ii and iii inhaled Insulin exubera trials and a two year extension trial
The Journal of Clinical Endocrinology and Metabolism, 2005Co-Authors: Edwin S Fineberg, Tom Kawabata, Deborah Fincokent, Cameron Liu, Alan KrasnerAbstract:Objective: To compare Antibody responses to inhaled human Insulin vs. sc human Insulin and to determine whether Insulin Antibody binding is associated with adverse clinical consequences. Research Design and Methods: Insulin Antibody data from initial phase II/III trials were analyzed comparing the efficacy and safety of inhaled Insulin with various agents, including sc Insulin. Additionally, data from a 24-month extension of the phase III studies were examined. Data were pooled into the following three groups based on Insulin treatment status at baseline: patients with type 1 diabetes, and patients with type 2 diabetes using Insulin and not using Insulin at baseline. Ig class analysis was also performed on randomly selected sera from type 1 patients at the end of the initial trials. Results: In the initial trials, greater Insulin Antibody binding was observed in patients receiving inhaled Insulin vs. sc Insulin. The greatest Antibody responses to inhaled Insulin were observed in patients with type 1 diabe...
Mikael Knip - One of the best experts on this subject based on the ideXlab platform.
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impact of iddm2 on disease pathogenesis and progression in children with newly diagnosed type 1 diabetes reduced Insulin Antibody titres and preserved beta cell function
Diabetologia, 2006Co-Authors: L B Nielsen, Henrik B Mortensen, F Chiarelli, Reinhard W Holl, P Swift, C De Beaufort, Flemming Pociot, Philip Hougaard, Steen Gammeltoft, Mikael KnipAbstract:Aims/hypothesis The Insulin-dependent diabetes mellitus 2 gene (IDDM2) is a type 1 diabetes susceptibility locus contributed to by the variable number of tandem repeats (VNTR) upstream of the Insulin gene (INS). We investigated the association between INS VNTR class III alleles (–23HphIA/T) and both Insulin Antibody presentation and residual beta cell function during the first year after diagnosis in 257 children with type 1 diabetes.
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severe Antibody mediated human Insulin resistance successful treatment with the Insulin analog lispro a case report
Diabetes Care, 1997Co-Authors: Jorma Lahtela, Mikael Knip, Robert Paul, Jaakko Antonen, Jorma SalmiAbstract:OBJECTIVE To evaluate the efficacy of the Insulin analog lispro (Lys B28, Pro B29) in severe Insulin resistance caused by human Insulin antibodies. CASE: A 27-year-old man with a history of diabetes treated with human Insulin for 3 years developed severe immunological Insulin resistance caused by human Insulin antibodies. Throughout follow-up (12 months) the Insulin analog lispro was administered with an infusion pump as the only Insulin therapy. The Insulin dose decreased from an average of 300 U/day to 58 U/day, HbA1c decreased from 12.6 to 7.4%, and human Insulin antibodies decreased from 8,057 to 1,860 nU/ml. Hypoglycemic episodes during early morning disappeared. CONCLUSIONS The Insulin analog lispro might be suitable for the treatment of diabetic patients with substantially increased Insulin Antibody levels Apparently, the structural difference between the lispro and human Insulin molecules prevented lispro from binding to the human Insulin antibodies in this patient and consequently was nonimmunogenic.
Jean C Sodoyez - One of the best experts on this subject based on the ideXlab platform.
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Polymorphism of Insulin antibodies in six patients with Insulin-immune hypoglycaemic syndrome
Clinical & Experimental Immunology, 2008Co-Authors: Nicoletta Dozio, F. Sodoyez-goffaux, M. Koch, B. Ziegler, Jean C SodoyezAbstract:Insulin antibodies in six patients with immune hypoglycaemic syndrome were studied. The antibodies displayed a higher affinity for bovine Insulin in two patients, were specific for human Insulin in one patient and non-species specific in the other three patients. The predominant IgG subclass of the Insulin antibodies was IgG4 in two patients, IgG3 in two and IgG1 in two. In one of these, the other three subclasses were also detectable. Insulin autoantibodies of four patients were homogeneous with regard to light chains (kappa), and those of the other two contained both kappa and gamma light chains. Analysis of Insulin immune complex size by fast protein liquid chromatography was possible in three patients and demonstrated immune complexes with elution profile close to that of IgG, although not exactly superimposable to the one obtained with a mouse monoclonal Insulin Antibody. In two patients, avidity was too low to permit chromatography of the immune complexes, and, moreover, in these two cases Insulin antibodies were of the IgG3 isotype and spontaneously formed aggregates independently of Insulin binding. We conclude that Insulin antibodies of the Insulin immune syndrome are polymorphic but different from those generated by Insulin therapy.
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imaging of the buffering effect of Insulin antibodies in the autoimmune hypoglycemic syndrome
The Journal of Clinical Endocrinology and Metabolism, 1998Co-Authors: Nicoletta Dozio, Angelo Beretta, Elena Sarugeri, Stefano Sartori, Cristina Belloni, Alexander Savi, Franco Dosio, Marina Scavini, Ferruccio Fazio, Jean C SodoyezAbstract:Insulin autoimmune hypoglycemia is characterized by recurrent hypoglycemia and high levels of immunoreactive Insulin in the presence of Insulin autoantibodies. The mechanisms inducing hypoglycemia are largely unknown. An [123I]Insulin scintigraphic scanning was performed to directly demonstrate the effect of antibodies on Insulin biodistribution in one patient with this syndrome both before and after treatment. The patient had Insulin autoantibodies IgG3 λ, which had a single site dissociation constant (Kd = 10−7 mol/L, by Scatchard analysis), a very fast dissociation rate of immune complexes, and a very rapid association of[ 125I]Insulin. Insulin receptors on red blood cells were down-regulated. The [123I]Insulin scintigraphic study imaged the buffering effect of antibodies on Insulin bioavailability.[ 123I]Insulin was not removed from the blood, and no liver or kidney uptake of the hormone occurred. The frequency and severity of hypoglycemic episodes required treatment. Insulin Antibody levels decreased...
Christiane S Hampe - One of the best experts on this subject based on the ideXlab platform.
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animal Insulin therapy induces a biased Insulin Antibody response that persists for years after introduction of human Insulin
Acta Diabetologica, 2010Co-Authors: Shilpa Oak, Thanh Hien Thi Phan, Lisa K Gilliam, Irl B Hirsch, Christiane S HampeAbstract:Administration of exogenous Insulin for the treatment of diabetes is often accompanied by the development of Insulin antibodies (IA). These antibodies may affect the patient’s requirement for Insulin by acting as an Insulin binding reservoir. The improvement of Insulin purification in the 1970s and the development of human recombinant Insulin both reduced the incidence of IA and their binding levels. This study investigates the parameters affecting IA frequency and binding levels in a cohort of type 1 diabetes (T1D) patients. All patients were treated with human recombinant Insulin. About half of the patients had received animal Insulin prior to the introduction of human recombinant Insulin. We tested the IA frequency and binding level for all serum samples. IA were further analyzed for their epitope specificity comparing human and porcine Insulin binding. We found that T1D patients who received animal Insulin in the past show significantly higher IA binding levels as compared to patients treated exclusively with human recombinant Insulin (IA binding level of 0.9 and 0.25 index, respectively, P = 0.005). T1D patients who received animal Insulin in the past showed a relative bias towards porcine Insulin, as compared to T1D patients who were treated with human recombinant Insulin exclusively (P < 0.0001). We conclude that IA binding level and epitope specificity are biased by treatment with animal Insulin. This bias remains for over 20 years after animal Insulin treatment is terminated.
Naomi S. Fineberg - One of the best experts on this subject based on the ideXlab platform.
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Insulin antibodies with pulmonary delivery of Insulin.
Diabetes Technology & Therapeutics, 2007Co-Authors: S. Edwin Fineberg, Alan Krasner, Thomas T Kawabata, Naomi S. FinebergAbstract:BACKGROUND AND METHODS: Delivery of Insulin to the deep lung presents unique challenges to the body's mucosal defense system. Pulmonary mucosal defense has the ability to discriminate between self and non-self antigens and has the potential for induction of immunologic tolerance. Published data concerning the immunogenicity of inhaled human Insulin in drug trials will be reviewed, and data regarding the possible adverse effects of anti-Insulin Antibody development will be presented. Examination of the immunologic safety of inhaled human Insulin will include discussion of comparator studies, factors affecting immunogenicity, the effects of Insulin immunity on glycemic control and pulmonary function, and the relationship of Insulin antibodies to dose requirements, pharmacodynamics, and hypoglycemia. CONCLUSIONS: Inhaled human Insulin, whether formulated as a powder or liquid, has been shown to be more immunogenic than comparator Insulins given by subcutaneous routes; however, adverse effects of Antibody formation have not been demonstrated.
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Insulin antibodies with pulmonary delivery of Insulin.
Diabetes Technology & Therapeutics, 2007Co-Authors: S. Edwin Fineberg, Alan Krasner, Thomas T Kawabata, Naomi S. FinebergAbstract:Background and Methods: Delivery of Insulin to the deep lung presents unique challenges to the body's mucosal defense system. Pulmonary mucosal defense has the ability to discriminate between self and non-self antigens and has the potential for induction of immunologic tolerance. Published data concerning the immunogenicity of inhaled human Insulin in drug trials will be reviewed, and data regarding the possible adverse effects of anti-Insulin Antibody development will be presented. Examination of the immunologic safety of inhaled human Insulin will include discussion of comparator studies, factors affecting immunogenicity, the effects of Insulin immunity on glycemic control and pulmonary function, and the relationship of Insulin antibodies to dose requirements, pharmacodynamics, and hypoglycemia. Conclusions: Inhaled human Insulin, whether formulated as a powder or liquid, has been shown to be more immunogenic than comparator Insulins given by subcutaneous routes; however, adverse effects of Antibody for...
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Insulin antibodies with pulmonary delivery of Insulin.
Diabetes technology & therapeutics, 2007Co-Authors: S. Edwin Fineberg, Alan Krasner, Thomas T Kawabata, Naomi S. FinebergAbstract:Delivery of Insulin to the deep lung presents unique challenges to the body's mucosal defense system. Pulmonary mucosal defense has the ability to discriminate between self and non-self antigens and has the potential for induction of immunologic tolerance. Published data concerning the immunogenicity of inhaled human Insulin in drug trials will be reviewed, and data regarding the possible adverse effects of anti-Insulin Antibody development will be presented. Examination of the immunologic safety of inhaled human Insulin will include discussion of comparator studies, factors affecting immunogenicity, the effects of Insulin immunity on glycemic control and pulmonary function, and the relationship of Insulin antibodies to dose requirements, pharmacodynamics, and hypoglycemia. Inhaled human Insulin, whether formulated as a powder or liquid, has been shown to be more immunogenic than comparator Insulins given by subcutaneous routes; however, adverse effects of Antibody formation have not been demonstrated.