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Results for “INSULIN ANTIBODIES”

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At least 19 recordsLinked to original sources
PubMed1987

Prevalence of islet cell antibodies, insulin antibodies and hyperglycaemia in 2291 schoolchildren.

Islet cell antibodies, insulin antibodies and hyperglycaemia were investigated in 2291 healthy schoolchildren. Eight of the subjects had islet cell antibodies and eight had insulin antibodies. However, no schoolchild who was positive for islet cell antibodies also had insulin antibodies present. Hyperglycaemia was observed in five children but neither islet cell antibodies nor insulin antibodies could be detected in the sera from these particular subjects.

Adolescent↗
PubMed1978

The relationship between circulating free and bound insulin, insulin antibodies, insulin dosage and diabetic control in insulin treated diabetics.

Free and bound insulin concentrations, blood glucose and anti-insulin antibody binding characteristics have been determined in 100 insulin treated diabetics; medium serum free insulin was 11 mU/l when fasting and rose to 30 mU/l after the mid-day meal. Significant correlation between blood glucose and serum free (but not bound) insulin was found. No relationship between insulin antibodies and daily insulin dose or diabetic control were found, nor a relationship between free insulin and antibody characteristics.

Adolescent↗
PubMed1990

Lack of predictive value of islet cell antibodies, insulin antibodies, and HLA-DR phenotype for remission in cyclosporin-treated IDDM patients. The Canadian-European Randomized Control Trial Group.

The effect of immunosuppression on the humoral immune response to islet autoantigens and exogenously administered insulin and the predictive value of islet cell cytoplasmic antibodies (ICAs), insulin antibodies (IAs), and HLA-DR phenotype for remission during immunosuppression were studied in a prospective randomized double-blind trial of cyclosporin administration in 98 newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients. HLA-DR phenotype and glycosylated hemoglobin were determined at study entry, and insulin requirement, glucagon-stimulated C-peptide, ICAs, and IAs were measured at entry and after 1, 3, 6, 9, and 12 mo of follow-up. Cyclosporin therapy caused significant suppression of the prevalence and serum concentrations of ICAs and IAs. Cyclosporin-treated IDDM patients ICA+ at study entry had higher levels of stimulated C-peptide after 1 mo of study, but the increased beta-cell function was not associated with a higher frequency of insulin-free remission at 1 mo. ICA and IA status at entry did not predict cyclosporin-insulin-free remission as assessed by the prevalence of insulin-free remission or beta-cell function at 3-12 mo of study, and significant decrements in the titers or total disappearance of ICAs were not associated with an increased prevalence or duration of non-insulin-requiring remission or higher stimulated C-peptide values. There was no correlation between the serum levels of ICAs and IAs at entry and beta-cell function at 12 mo of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Receptor binding studies and clinical effects of human insulin (recombinant DNA): studies in patients with newly diagnosed type i diabetes, type II diabetes, insulin resistance (type A and type B), insulin antibodies, insulin allergy, and "brittle" diabetes.

Thirty-eight insulin-dependent diabetic subjects were treated for periods ranging from 1 to 14 mo with human insulin (recombinant DNA) in order to investigate the clinical effects of human insulin in comparison with pork insulin. Human insulin was well tolerated and no side effects were detected. The following differences between human and pork insulin were observed: reduced blood glucose oscillations associated with a reduction in hypoglycemic symptoms in patients with "brittle" diabetes and type I diabetes, decreased concentrations of antibodies against pork insulin related to a reduction of insulin requirement of approximately 15%, increased specific receptor binding in patients with type I diabetes and insulin resistance: type A, possibility for treating patients with pork insulin allergy, and an increased biologic activity in a patient with polyclonal antireceptor antibodies. No difference was detected between pork and human insulin treatment in patients with type II diabetes and in a patient with insulin resistance: type B with monoclonal antireceptor antibodies. Human insulin was used safely and successfully in the treatment of diabetic patients.

Adolescent↗
PubMed1979

Determination of insulin antibodies.

Insulin antibodies were determined as percentage binding of 125I-insulin in the sera of normal persons and of diabetic subjects treated and untreated with insulin. The effect of the dilution of the serum, circulating insulin and extraction of free and total insulin was evaluated. The determination of insulin antibodies in samples at a final dilution of 1:10 clearly discriminated between insulin-treated and untreated subjects. In insulin-treated subjects, the determination of insulin antibodies in samples at a final dilution of 1:100 gave false-negative results in 28 per cent. However, the determination of insulin antibodies at a final dilution of 1:100 discriminated between insulin-resistant and non-resistant diabetic subjects. Extraction of total insulin at pH 3.0 using 0.1 N HCl increased the percentage of 125I-insulin binding significantly. Extraction of free insulin by charcoal from the samples did not increase the binding of 125I-insulin. The injection of crystalline insulin 4 hours prior to withdrawing the samples did not decrease binding of 125I-insulin.

Diabetes Mellitus↗
PubMed2005

Impact of insulin antibodies on insulin aspart pharmacokinetics and pharmacodynamics after 12-week treatment with multiple daily injections of biphasic insulin aspart 30 in patients with type 1 diabetes.

OBJECTIVE: This study aimed to evaluate the impact of insulin antibodies on insulin aspart pharmaco-kinetics and pharmacodynamics after 12-week multiple daily injections of biphasic insulin aspart 30 (30% fast-acting and 70% protamine-crystallised insulin aspart, BIAsp30) in patients with type 1 diabetes. METHODS: Twenty-three patients (8 women, 15 men) aged 44.8 (20.6-62.5) years (median and range) with diabetes duration of 19.5 (1.6-44.6) years and haemoglobin (Hb)A(1C) of 9.2% (8.1-12.3%) participated in the study, which consisted of 12-week treatment with multiple injections of BIAsp30. At the end of the treatment period, all patients attended two 24-h profile days 1 week apart for pharmacokinetic and pharmacodynamic assessments. HbA(1C) and insulin antibodies were also determined. RESULTS: Patients were stratified into two groups depending on whether the level of insulin binding to insulin antibodies was below or above 75% (moderate vs high (%, median and range): 62 (15-74) vs 80 (75-89)). High levels of insulin antibodies resulted in about threefold increase in AUC((0 - 24 h)) (the area under the concentration-time curve during 24 h) for total insulin aspart (analysis of variance, P < 0.05). The differences in free insulin aspart pharmacokinetics, insulin pharmacodynamics and HbA(1C) were not statistically significant between patients with different levels of insulin antibodies. Total daily insulin dosage was significantly lower in patients with high than moderate levels of insulin antibodies. CONCLUSIONS: In type 1 diabetic patients, high levels of circulating insulin antibodies result in elevated total, but not free, insulin aspart profiles. Consistent with the finding of similar insulin pharmacodynamics, the long-term glycaemic control is not significantly different between patients with different levels of insulin antibodies.

Adult↗
PubMed2002

The interference of insulin antibodies in insulin immunometric assays.

We investigated the interference of insulin antibodies in two insulin immunometric assays (Bio-Rad and Elecsys) by measuring direct and free insulin in plasma from 30 patients without insulin antibodies (group 1), as screened by a sensitive radio-binding assay, and in plasma from 80 patients with insulin antibodies (group 2). In group 1, the direct/free insulin ratio did not differ from 1, showing the equivalence of free and direct insulin results in theses samples. In group 2, this ratio was markedly increased (mean: Bio-Rad 2.63, Elecsys 5.02) and correlated positively with the insulin antibody radio-binding assay result (r=0.92 for the correlation between Bio-Rad and Elecsys assays after log-transformation of the ratios). In samples containing insulin antibodies, direct insulin concentration was frequently lower than total (bound and unbound) insulin measured with the Bio-Rad and Elecsys assays. This study underlines the interference of insulin antibodies in insulin immunometric assays and the importance of assessing an insulin immunometric assay for sensitivity towards the presence of these antibodies.

Autoantibodies↗
PubMedDate not supplied

Comparison of liquid phase radiobinding assay and solid phase ELISA for the measurement of insulin antibodies and insulin autoantibodies in serum.

Sera containing insulin antibodies from 20 insulin-treated diabetic patients, sera containing insulin autoantibodies from 20 insulin-naive non-diabetic patients, and from 10 normal controls, were tested at 1:20 dilution in three different radioimmunoassays (RIA) and an enzyme linked immunosorbent assay (ELISA), using a highly purified human insulin ligand. The RIA using insulin radiolabelled at multiple sites detected insulin antibodies in 17/20 and insulin autoantibodies in 13/20 sera. The same RIA using A-14-monoiodinated insulin was sensitive to antibodies and autoantibodies in all the sera. The same RIA using sera after insulin extraction detected only 13/20 diabetic sera and 9/20 autoimmune sera as positive, owing to a substantial rise in non-specific binding of the control sera. ELISA was sensitive to insulin antibodies and autoantibodies in every case. When binding curves for ELISA and the most sensitive RIA were compared using serial dilutions of four insulin antibody containing sera and four insulin autoantibody containing sera, antibody titres varied from 1.1 to 3.8 times higher in ELISA, and autoantibody titres from 10.6 to 28.6 times higher in ELISA. These studies indicate that ELISA is more sensitive than RIA to insulin antibodies, and in particular to insulin autoantibodies.

Adolescent↗
PubMed1998

Influence of anti-insulin antibodies on insulin immunoassays in the autoimmune insulin syndrome.

The autoimmune insulin syndrome (AIS) is a rare, benign syndrome characterized by hyperinsulinaemia and hypoglycaemia associated with the presence of autoantibodies to insulin in patients who have not been treated with insulin. We report here the case of a 52-year-old patient with recurrent attacks of severe postprandial hypoglycaemia and we also present the effect of anti-insulin antibodies on insulin immunoassays. The patient was submitted to the following diagnostic tests: 5-h oral glucose tolerance test (OGTT), a prolonged 72-h fast and an insulin tolerance test (ITT). Serum glucose, total and free insulin, C-peptide, proinsulin, insulin antibodies and other autoantibodies were measured. Insulin concentrations were measured by two methods: a double antibody radioimmunoassay (RIA) and an immunoradiometric assay (IRMA). Insulin concentration measured by RIA was extremely high in the OGTT and 72-h fast. In contrast, insulin concentrations measured by IRMA were between 120 and 888 pmol/L in the OGTT and between 37 and 133 pmol/L during the 72-h fast. Fasting free-insulin concentrations measured by RIA were between 2224 and 2669 pmol/L, whereas free-insulin concentrations measured by IRMA ranged between 93 and 237 pmol/L. Total insulin concentrations measured by RIA and IRMA were 57,615 and 94,021 pmol/L, respectively. The C-peptide concentrations were moderately high in the three tests. Serum insulin antibody concentrations were extremely high (62-71%), compared with less than 3% in normal serum samples. In conclusion, the high insulin concentrations measured by RIA were caused by insulin autoantibodies. However, insulin concentrations measured by IRMA were not influenced by them. We conclude that IRMA is the more accurate method for measuring insulin concentrations in such cases.

Autoantibodies↗
PubMed1997

Anti-insulin antibodies in insulin immunometric assays: a still possible pitfall.

Insulin was assayed directly using radioimmunoassay and immunometric assay in 31 sera containing anti-insulin antibodies. Anti-insulin antibodies were determined by radio-binding-assay. Insulin measurements were compared with those of free (unbound to antibodies, polyethylene glycol precipitated) insulin measurements. Compared with free insulin concentrations, radioimmunoassay and immunometric assay yielded falsely increased insulin results. The degree of overestimation by radioimmunoassay and by immunometric assay correlated with the anti-insulin antibody value. Anti-insulin antibodies still remain a possible pitfall in the insulin-specific immunometric assays which are now being widely used.

False Positive Reactions↗
PubMed1987

Serum antibody-bound insulin as a measure of insulin antibodies in diabetic children.

The usefulness of the measurement of serum antibody-bound and total immunoreactive insulin (IRI) concentrations in the assessment of insulin antibodies was evaluated in a material comprising 49 insulin-dependent diabetic children with a mean age at onset of 8.6 years (range 0.8-16 years) treated with highly purified porcine insulins. Serum antibody-bound and total IRI concentrations of individual patients were compared with insulin antibody levels measured with 3 different insulin antibody assays. The correlation coefficients of insulin antibody levels with concentrations of serum antibody-bound IRI ranged from 0.75-0.79. In serum samples with moderate or high insulin antibody levels most of the insulin was in the form of insulin-insulin antibody immunocomplexes. Thereby a very close correlation was found between antibody-bound and total serum IRI concentrations (r = 0.98) in this material. Residual endogenous insulin secretion decreased with increasing duration of diabetes. No significant correlation was found between the duration of diabetes and serum antibody-bound IRI concentrations. High serum antibody-bound IRI concentrations were associated with low glucagon-stimulated plasma C-peptide levels. Although the determination of serum antibody-bound IRI concentrations does not characterize insulin antibodies with regard to binding capacity and affinity constants, it yields information of the actual degree of insulin binding in the circulation. This information may be useful in assessing the benefits of transferring diabetics with high insulin antibody titers from conventional to highly purified porcine or human insulin therapy.

Adolescent↗
PubMed1986

Effects of anti-insulin antibody on insulin binding to liver membranes: evidence against antibody-induced enhancement of insulin binding to the insulin receptor.

In the presence of anti-insulin antibody, 2-to 3-fold enhancement of 125I-insulin binding to liver membranes was observed when binding was estimated by the radioactivity of 125I-insulin bound to the membrane pellets. However, after 125I-insulin was covalently cross-linked to liver membranes using disuccinimidyl suberate in the presence of anti-insulin antibody, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography showed that 125I-insulin bound to the alpha-subunit of the insulin receptor was inhibited by anti-insulin insulin antibody in an dose-dependent manner. More importantly, at an anti-insulin antibody dilution range between 1:50 and 1:5,000, sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed two 125I-labelled bands of mol wt 62,000 and 27,000, while only one band of mol wt 130,000 was revealed in the absence of anti-insulin antibody. These Mr = 62,000 and Mr = 27,000 bands were found to be the heavy and the light chain of anti-insulin IgG molecules respectively. Pepsin digested anti-insulin serum had only an inhibitory effect on 125I-insulin binding to liver membranes. Non-immunized guinea pig serum or IgG completely abolished the enhanced effect of anti-insulin antibody. Further, this enhanced effect was inhibited by Fc fragment-specific anti-IgG serum or H&L-chain-specific anti-IgG serum in a dose-dependent manner. Protein A also inhibited the effect of anti-insulin antibody. In IM-9 lymphocytes and human red blood cell ghosts, which have no Fc gamma receptors, enhancement of insulin binding was not observed in the presence of anti-insulin antibody.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1996

Proinsulin immunoreactivity in recent-onset IDDM: the significance of insulin antibodies and insulin autoantibodies.

OBJECTIVE: To study the natural history of fasting proinsulin immunoreactivity (PIM) during the first 30 months of IDDM and its relationship to fasting C-peptide and insulin antibodies. RESEARCH DESIGN AND METHODS: An incidence cohort of 204 consecutive newly diagnosed IDDM patients were followed prospectively, having blood drawn for measurements at diagnosis and at 1, 3, 6, 9, 12, 18, 24, and 30 months. A sensitive enzyme-linked immunosorbent assay was used for the determination of PIM. RESULTS: All patients had detectable fasting PIM in plasma at diagnosis, with a median value and interquartile range of 3.5 pmol/l (2.2-6.2). The median PIM level increased during the first months of IDDM to reach a peak at 9-12 months (9.9-10.3 pmol/l). PIM then declined gradually to 5.6 pmol/l (1.9-13.5) at 30 months without reaching baseline. PIM at each time point was widely scattered in a skewed log-normal distribution without signs of bimodality. After the onset of insulin treatment, median insulin antibody level increased and declined in a similar pattern. Both PIM and antibody level were significantly higher in children and adolescents compared with adults. However, stepwise multiple regression analysis showed that age was only of minor importance for the PIM variation during the study period. Insulin antibody level and fasting C-peptide were the major determinants at 3-30 months, accounting for approximately 40% of the variation (R2). Blood glucose was of minor importance, and insulin dose, HbA1c, and BMI were of no importance. The correlation between fasting PIM and fasting C-peptide improved (R2 doubled) if the insulin antibody level was accounted for. Further, the slope of the correlation curve between PIM and C-peptide increased threefold when antibody binding was > 4%. At diagnosis, insulin autoantibodies could be detected in 19% of the patients. Their presence predicted higher proinsulin at 1-3 months, a higher insulin dose the 1st year, and higher levels of insulin antibodies later in the study. CONCLUSIONS: Circulating insulin antibodies may affect the level of PIM in IDDM, probably by adding a pool of IgG-bound PIM thereby increasing half-life and plasma concentration. This may explain why C-peptide and PIM levels do not change in concert during the 1st years of IDDM. Unlike C-peptide, PIM can not therefore quantitate beta-cell secretion unless the presence of insulin antibodies is ruled out.

Adolescent↗
PubMed1995

[Anti-insulin antibodies and insulin resistance].

The submitted review deals with the phenomenon of immunological insulin resistance in insulin dependent diabetics which develops as a result of the presence of circulating anti-insulin antibodies as a response of the organism to administered insulin. This phenomenon is a liminal situation when anti-insulin antibodies exceed as to their concentration and affinity a certain arbitrary limit and the increasingly impaired pharmacokinetics of insulin cause a clinically manifest metabolic decompensation of the disease with the necessity of large daily doses of exogenous insulin. The authors discuss factors ensuing from the type of the administered insulin preparation, as well as the biological predisposition of the patient which potentiates the production of anti-insulin antibodies. Some laboratory methods are discussed which are used for the assessment of anti-insulin antibodies in vitro and the authors summarize individual physical variables which characterize the antibody system and which can be extracted by special mathematical procedures from experimental radioimmunoanalytical data. Only a detailed characterization of the antibody system makes it possible to evaluate the influence of this system on the pharmacokinetics of insulin.

Diabetes Mellitus, Type 1↗
PubMed1986

The role of insulin antibodies in insulin treatment of type I diabetes.

We investigated equilibrium plasma binding patterns of insulin in 45 juvenile diabetics treated with conventional insulin preparations. Insulin binding parameters were evaluated by Scatchard analysis of the binding data. Stable diabetics had significantly lower equilibrium dissociation constants than labile, thus suggesting an enhanced insulin depot effect due to stronger insulin binding. Correlation of insulin binding data with a glycemic control index yielded a positive relationship between insulin antibody binding and the degree of glycemic control. Insulin neutralization as detected by a relationship between maximum binding capacity of high affinity antibodies and insulin requirement could only be found if patients with poor diabetes control were excluded. Similarly, the well-known promoting influence of residual beta-cell functional capacity (assessed by C-peptide levels) on diabetic stability was observed only after exclusion of patients with higher insulin antibody binding. These data suggest that insulin antibodies are influencing insulin treatment of diabetics in a dual way. They may neutralize therapeutic insulin but at the same time they exert an insulin-sparing action by improvement of diabetes control. Occasionally the latter effect may abolish the correlation between diabetes control and beta-cell functional capacity.

Adolescent↗
PubMed1995

Induction of insulin antibodies and insulin allergy under alpha-interferon treatment of renal cell carcinoma in a patient with insulin-treated diabetes mellitus--a case report.

The induction of insulin antibodies and the development of an insulin allergy were observed in a male diabetic patient treated with insulin during alpha-IFN therapy of renal cell carcinoma. Diabetes and renal cell carcinoma were diagnosed at the same time. The patient was treated with biosynthetic human insulin and nephrectomy was performed. Four months later, antineoplastic chemotherapy was started (alpha-IFN, vinblastin). Six weeks after initiation of alpha-IFN injections, the patient reported signs of insulin allergy. Significant titers of insulin antibodies of both the IgG and IgE subclasses were found in the serum at that time and during follow-up, but not before the treatment with alpha-IFN. None of the other autoantibodies investigated were positive.

Adult↗
PubMed1994

[The measurement of insulin antibodies and insulin autoantibodies by enzyme-linked immunosorbent assay using recombinant human insulin antigen and its clinical application].

Insulin antibodies (IA) are detectable in the sera of most insulin-treated patients with diabetes mellitus. Antibodies to exogenous insulin sometimes cause clinical symptoms of insulin resistance, allergy, and local lipoatrophy. Although the frequency of these complications has diminished with the use of highly purified porcine insulin or recombinant human insulin, there are some patients with high titer of IA. Autoantibodies to insulin (IAA) are also described. IAA has been reported to be in association with both insulin-dependent diabetes mellitus (IDDM) and polyendocrine autoimmune disease. For many years these antibodies have been measured by radiobinding assay (RBA) in which the complexes are precipitated non-specifically by polyethylene glycol. In the present study we developed a rapid and quantitative enzyme-linked immunosorbent assay (ELISA) method for measuring IA and IAA using recombinant human insulin antigen. We applied this method to the samples obtained from patients with diabetes mellitus and autoimmune thyroid disease and then compared the results with those obtained from the RBA method. The calibration curve for ELISA was derived from the dilution curve of a single serum from a patient positive for insulin antibody, and the results were expressed arbitrarily as ELISA UNIT. The calibration curve was approximately linear on the log-log scale within the range of 0.1-2.0 at optical density (OD)450nm, (6.25-200 ELISA UNIT). The intra-assay (CV = 2.3-3.1%) and inter-assay (CV = 2.8-7.2%) precisions were acceptable. Recovery rate varied from 74.5% to 118.5% and dilution experiments showed good linearity. Specificity was demonstrated by substituting purified human IgG for the test serum and glucagon for insulin. Except for hemoglobin, coexisting substances in serum had almost no effect on ELISA. The range of ELISA UNIT (Mean +/- SD) of 83 normal sera was 12.7 +/- 4.6. Positivity for IA by ELISA (> normal Mean + 3SD) was 11 out of 58 (19.0%) and 26 out of 55 (47.3%) in patients with IDDM and with non-insulin-dependent diabetes mellitus (NIDDM) who were treated with insulin, respectively. Positivity for IAA by ELISA was 5 out of 173 (2.8%) and 1 out of 20 (5.0%) in patients with NIDDM without insulin therapy and hyperthyroidism due to Graves' disease, respectively. However, by RBA, we detected 4 other cases positive for IAA in NIDDM without insulin therapy and one case in Graves' disease. The present study demonstrates that the newly developed method of ELISA using recombinant human insulin antigen is clinically useful for measuring IA and IAA.

Antigens↗