المؤلفون: Lind, Alexander, Freyhult, Eva, 1979, de Jesus Cortez, Felipe, Ramelius, Anita, Bennet, Rasmus, Robinson, Peter V., Seftel, David, Gebhart, David, Tandel, Devangkumar, Maziarz, Marlena, Elding Larsson, Helena, Lundgren, Markus, Carlsson, Annelie, Nilsson, Anna-Lena, Fex, Malin, Törn, Carina, Agardh, Daniel, Tsai, Cheng-ting, Lernmark, Åke

المصدر: EBioMedicine. 104

مصطلحات موضوعية: Type 1 diabetes, Insulin autoantibodies, GAD65 autoantibodies, IA-2 autoantibodies, ZnT8 autoantibodies, Radiobinding assay, Antibody detection by agglutination PCR, Diagnostic sensitivity, Diagnostic specificity

الوصف: BackgroundTwo or more autoantibodies against either insulin (IAA), glutamic acid decarboxylase (GADA), islet antigen-2 (IA-2A) or zinc transporter 8 (ZnT8A) denote stage 1 (normoglycemia) or stage 2 (dysglycemia) type 1 diabetes prior to stage 3 type 1 diabetes. Automated multiplex Antibody Detection by Agglutination-PCR (ADAP) assays in two laboratories were compared to single plex radiobinding assays (RBA) to define threshold levels for diagnostic specificity and sensitivity.MethodsIAA, GADA, IA-2A and ZnT8A were analysed in 1504 (54% females) population based controls (PBC), 456 (55% females) doctor's office controls (DOC) and 535 (41% females) blood donor controls (BDC) as well as in 2300 (48% females) patients newly diagnosed (1–10 years of age) with stage 3 type 1 diabetes. The thresholds for autoantibody positivity were computed in 100 10-fold cross-validations to separate patients from controls either by maximizing the χ2-statistics (chisq) or using the 98th percentile of specificity (Spec98). Mean and 95% CI for threshold, sensitivity and specificity are presented.FindingsThe ADAP ROC curves of the four autoantibodies showed comparable AUC in the two ADAP laboratories and were higher than RBA. Detection of two or more autoantibodies using chisq showed 0.97 (0.95, 0.99) sensitivity and 0.94 (0.91, 0.97) specificity in ADAP compared to 0.90 (0.88, 0.95) sensitivity and 0.97 (0.94, 0.98) specificity in RBA. Using Spec98, ADAP showed 0.92 (0.89, 0.95) sensitivity and 0.99 (0.98, 1.00) specificity compared to 0.89 (0.77, 0.86) sensitivity and 1.00 (0.99, 1.00) specificity in the RBA. The diagnostic sensitivity and specificity were higher in PBC compared to DOC and BDC.InterpretationADAP was comparable in two laboratories, both comparable to or better than RBA, to define threshold levels for two or more autoantibodies to stage type 1 diabetes.

وصف الملف: electronic

الوصول الحر: https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-532277Test
https://doi.org/10.1016/j.ebiom.2024.105144Test
https://uu.diva-portal.org/smash/get/diva2:1873397/FULLTEXT01.pdfTest

المؤلفون: Alexander Lind, Eva Freyhult, Felipe de Jesus Cortez, Anita Ramelius, Rasmus Bennet, Peter V. Robinson, David Seftel, David Gebhart, Devangkumar Tandel, Marlena Maziarz, Helena Elding Larsson, Markus Lundgren, Annelie Carlsson, Anna-Lena Nilsson, Malin Fex, Carina Törn, Daniel Agardh, Cheng-ting Tsai, Åke Lernmark, Martina Persson, Gun Forsander, Johnny Ludvigsson, Ulf Samuelsson, Claude Marcus

المصدر: EBioMedicine, Vol 104, Iss , Pp 105144- (2024)

مصطلحات موضوعية: Type 1 diabetes, Insulin autoantibodies, GAD65 autoantibodies, IA-2 autoantibodies, ZnT8 autoantibodies, Radiobinding assay, Medicine, Medicine (General), R5-920

الوصف: Summary: Background: Two or more autoantibodies against either insulin (IAA), glutamic acid decarboxylase (GADA), islet antigen-2 (IA-2A) or zinc transporter 8 (ZnT8A) denote stage 1 (normoglycemia) or stage 2 (dysglycemia) type 1 diabetes prior to stage 3 type 1 diabetes. Automated multiplex Antibody Detection by Agglutination-PCR (ADAP) assays in two laboratories were compared to single plex radiobinding assays (RBA) to define threshold levels for diagnostic specificity and sensitivity. Methods: IAA, GADA, IA-2A and ZnT8A were analysed in 1504 (54% females) population based controls (PBC), 456 (55% females) doctor's office controls (DOC) and 535 (41% females) blood donor controls (BDC) as well as in 2300 (48% females) patients newly diagnosed (1–10 years of age) with stage 3 type 1 diabetes. The thresholds for autoantibody positivity were computed in 100 10-fold cross-validations to separate patients from controls either by maximizing the χ2-statistics (chisq) or using the 98th percentile of specificity (Spec98). Mean and 95% CI for threshold, sensitivity and specificity are presented. Findings: The ADAP ROC curves of the four autoantibodies showed comparable AUC in the two ADAP laboratories and were higher than RBA. Detection of two or more autoantibodies using chisq showed 0.97 (0.95, 0.99) sensitivity and 0.94 (0.91, 0.97) specificity in ADAP compared to 0.90 (0.88, 0.95) sensitivity and 0.97 (0.94, 0.98) specificity in RBA. Using Spec98, ADAP showed 0.92 (0.89, 0.95) sensitivity and 0.99 (0.98, 1.00) specificity compared to 0.89 (0.77, 0.86) sensitivity and 1.00 (0.99, 1.00) specificity in the RBA. The diagnostic sensitivity and specificity were higher in PBC compared to DOC and BDC. Interpretation: ADAP was comparable in two laboratories, both comparable to or better than RBA, to define threshold levels for two or more autoantibodies to stage type 1 diabetes. Funding: Supported by The Leona M. and Harry B. Helmsley Charitable Trust (grant number 2009-04078), the Swedish Foundation for Strategic Research (Dnr IRC15-0067) and the Swedish Research Council, Strategic Research Area (Dnr 2009-1039). AL was supported by the DiaUnion collaborative study, co-financed by EU Interreg ÖKS, Capital Region of Denmark, Region Skåne and the Novo Nordisk Foundation.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2352396424001798Test; https://doaj.org/toc/2352-3964Test

الوصول الحر: https://doaj.org/article/a4975652334e42b38b70cf638422fb61Test

المؤلفون: Strollo, Rocky, Vinci, Chiara, Man, Y. K. Stella, Bruzzaniti, Sara, Piemonte, Erica, Alhamar, Ghadeer, Briganti, Silvia Irina, Malandrucco, Ilaria, Tramontana, Flavia, Fanali, Chiara, Garnett, James, Buccafusca, Roberto, Guyer, Perrin, Mamula, Mark, James, Eddie A., Pozzilli, Paolo, Ludvigsson, Johnny, Winyard, Paul G., Galgani, Mario, Nissim, Ahuva

المصدر: Diabetologia. 66(1):132-146

مصطلحات موضوعية: Autoimmunity, Immune response, Insulin, Insulin autoantibodies, Insulin neoepitope peptide, Neoantigen, Neoepitope, Oxidative post-translational modifications, Post-translational modifications

الوصف: Aims/hypothesis Antibodies specific to oxidative post-translational modifications (oxPTM) of insulin (oxPTM-INS) are present in most individuals with type 1 diabetes, even before the clinical onset. However, the antigenic determinants of such response are still unknown. In this study, we investigated the antibody response to oxPTM-INS neoepitope peptides (oxPTM-INSPs) and evaluated their ability to stimulate humoral and T cell responses in type 1 diabetes. We also assessed the concordance between antibody and T cell responses to the oxPTM-INS neoantigenic peptides. Methods oxPTM-INS was generated by exposing insulin to various reactive oxidants. The insulin fragments resulting from oxPTM were fractionated by size-exclusion chromatography further to ELISA and LC-MS/MS analysis to identify the oxidised peptide neoepitopes. Immunogenic peptide candidates were produced and then modified in house or designed to incorporate in silico-oxidised amino acids during synthesis. Autoantibodies to the oxPTM-INSPs were tested by ELISA using sera from 63 participants with new-onset type 1 diabetes and 30 control participants. An additional 18 fresh blood samples from participants with recently diagnosed type 1 diabetes, five with established disease, and from 11 control participants were used to evaluate, in parallel, CD4(+) and CD8(+) T cell activation by oxPTM-INSPs. Results We observed antibody and T cell responses to three out of six LC-MS/MS-identified insulin peptide candidates: A:12-21 (SLYQLENYCN, native insulin peptide 3 [Nt-INSP-3]), B:11-30 (LVEALYLVCGERGFFYTPKT, Nt-INSP-4) and B:21-30 (ERGFFYTPKT, Nt-INSP-6). For Nt-INSP-4 and Nt-INSP-6, serum antibody binding was stronger in type 1 diabetes compared with healthy control participants (p <= 0.02), with oxidised forms of ERGFFYTPKT, oxPTM-INSP-6 conferring the highest antibody binding (83% binders to peptide modified in house by hydroxyl radical [(OH)-O-?] and >88% to in silico-oxidised peptide; p <= 0.001 vs control participants). Nt-INSP-4 induced the strongest T cell stimulation in type 1 diabetes compared with control participants for both CD4(+) (p<0.001) and CD8(+) (p=0.049). CD4(+) response to oxPTM-INSP-6 was also commoner in type 1 diabetes than in control participants (66.7% vs 27.3%; p=0.039). Among individuals with type 1 diabetes, the CD4(+) response to oxPTM-INSP-6 was more frequent than to Nt-INSP-6 (66.7% vs 27.8%; p=0.045). Overall, 44.4% of patients showed a concordant autoimmune response to oxPTM-INSP involving simultaneously CD4(+) and CD8(+) T cells and autoantibodies. Conclusions/interpretation Our findings support the concept that oxidative stress, and neoantigenic epitopes of insulin, may be involved in the immunopathogenesis of type 1 diabetes.

وصف الملف: electronic

الوصول الحر: https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-189307Test
https://liu.diva-portal.org/smash/get/diva2:1704649/FULLTEXT01.pdfTest

المؤلفون: Pop Andrada Raluca, Ruscanu Claudia Emanuela, Roman Gabriela, Pascanu Ionela Maria

المصدر: Acta Marisiensis - Seria Medica, Vol 68, Iss 2, Pp 89-92 (2022)

مصطلحات موضوعية: insulin autoimune syndrome, hirata’s disease, continuous monitoring system, insulin autoantibodies, Medicine

الوصف: Background: Insulin autoimune syndrome (IAS), also known as Hirata’s disease, is a rare cause of spontaneous hyperinsulinemic hypoglicemia characterised by the presence of autoantibodies directed against human insulin (IAA).

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2668-7763Test

الوصول الحر: https://doaj.org/article/72f999414c5541449cf9b91fe52b7ddbTest

المؤلفون: Grant, Bonnie, Ratnayake, Gowri, Williams, Claire L, Long, Anna, Halsall, David J, Semple, Robert K, Cavenagh, James D, Drake, William M, Church, David S

مصطلحات موضوعية: MGUS, hyperinsulinaemia, hypoglycaemia, insulin autoantibodies, lenalidomide, myeloma, plasma exchange, smouldering myeloma, Male, Humans, Aged, Monoclonal Gammopathy of Undetermined Significance, Paraproteinemias, Paraproteins, Endocrine System Diseases, Insulin, Hypoglycemia, Glucose, Multiple Myeloma

الوصف: In very rare cases of monoclonal gammopathy, insulin-binding paraprotein can cause disabling hypoglycaemia. We report a 67-year-old man re-evaluated for hyperinsulinaemic hypoglycaemia that persisted despite distal pancreatectomy. He had no medical history of diabetes mellitus or autoimmune disease but was being monitored for an IgG kappa monoclonal gammopathy of undetermined significance. On glucose tolerance testing, hyperglycaemia occurred at 60 min (glucose 216 mg/dL) and hypoglycaemia at 300 min (52 mg/dL) concurrent with an apparent plasma insulin concentration of 52 850 pmol/L on immunoassay. Laboratory investigation revealed an IgG2 kappa with very high binding capacity but low affinity (Kd 1.43 × 10-6 mol/L) for insulin. The monoclonal gammopathy was restaged as smouldering myeloma not warranting plasma cell-directed therapy from a haematological standpoint. Plasma exchange reduced paraprotein levels and improved fasting capillary glucose concentrations. Lenalidomide was used to treat disabling hypoglycaemia, successfully depleting paraprotein and leading to resolution of symptoms.

وصف الملف: application/pdf

العلاقة: https://www.repository.cam.ac.uk/handle/1810/362209Test

الإتاحة: https://www.repository.cam.ac.uk/handle/1810/362209Test

المؤلفون: Qiuping Zhu, Hanxin Zhao, Wei Qiu, Fang Wu, Chungen Qian, Yonghong Yang, Ye Kang, Fenping Zheng, Jiaqiang Zhou

المصدر: Frontiers in Immunology, Vol 13 (2022)

مصطلحات موضوعية: hypoglycemia, insulin autoimmune syndrome, insulin autoantibodies, clopidogrel, case report, Immunologic diseases. Allergy, RC581-607

الوصف: We present a case of recurrent autoimmune hypoglycemia induced by non-hypoglycemic agents. We review reported cases of autoimmune hypoglycemia related to non-hypoglycemic agents, and discuss the effects of different detection methods for insulin autoantibodies on the results obtained. We aim to provide information for clinicians and a warning for medication usage. Considering the increasing number of clopidogrel-induced AIH cases and the hypoglycemia-induced increase in the risk of cardiovascular events, we recommend that cardiovascular disease patients being treated with clopidogrel be informed of this rare side effect and that clinicians be vigilant for the possibility of autoimmune hypoglycemia in this patient population.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2022.855350/fullTest; https://doaj.org/toc/1664-3224Test

الوصول الحر: https://doaj.org/article/8af6ce4c6d754afe9cd8a58708a68c09Test

المؤلفون: Zuojun Li, Dan Yi, Lijuan Zheng, Shiran Li, Weijin Fang, Chunjiang Wang

المصدر: Diabetology & Metabolic Syndrome, Vol 13, Iss 1, Pp 1-8 (2021)

مصطلحات موضوعية: Insulin autoimmune syndrome, Exogenous insulin, Insulin autoantibodies, Hypoglycemia, Nutritional diseases. Deficiency diseases, RC620-627

الوصف: Abstract Background The exact incidence, clinical features and uniform diagnostic criteria of exogenous insulin autoimmune syndrome (EIAS) are still unclear. The purpose of this study is to explore the clinical characteristics of EIAS and to provide a structural approach for clinical diagnosis, treatment and prevention. Methods The literature on EIAS in Chinese and English from 1970 to 2020 was collected for retrospective analysis. Results A total of 122 patients (33 males and 73 females) were included in the study with a median age of 67 years (range 14–86) and a median HbA1c of 7.7%. EIAS mainly occurred in type 2 diabetes mellitus patients using premixed insulin. Symptoms manifested were hypoglycemia in 86.54%, recurrent episodes of symptomatic hypoglycemia in 35.58%, nocturnal hypoglycemia along with daytime hyperglycemia in 21.15% and recurrent hypoglycemia after discontinued insulin in 64.43%. The onset of symptoms occurred at night, in the early morning or during fasting, ranging from a few days to 78 months after the administration of insulin. The mean blood glucose level during the hypoglycemic phase was 2.21 mmol/L (range 1–3.4), and the serum insulin levels were mainly ≥ 100 U/mL and were associated with low C-peptide levels (≤ 10 ng/ml). Insulin autoantibodies (IAAs) were positive in all EIAS patients. The 75-g extended oral glucose tolerance test (OGTT) mainly showed a diabetic curve. Pancreatic imaging was unremarkable. Withdrawal of insulin alone or combination of oral hypoglycemic agents or replacement of insulin formulations or with corticosteroid treatment eliminated hypoglycemia in a few days to 3 months. IAA turned negative in 6 months (median, range 1–12). No hypoglycemia episodes were observed at a median follow-up of 6 months (range 0.5–60). Conclusions EIAS is an autoimmune disease caused by insulin-binding antibodies in susceptible subjects. Insulin antibodies change glucose dynamics and could increase the incidence of hypoglycemic episodes. Detection of insulin antibodies is the diagnostic test. Changing therapeutic modalities reduced the incidence of hypoglycemic episodes.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1758-5996Test

الوصول الحر: https://doaj.org/article/dd144c87d44c4c41bdf4b30665376243Test

المؤلفون: Kateřina Žibřidová, Barbora Havlínová, Eliška Svobodová, Pavel Žák, Jan Čáp, Filip Gabalec

المصدر: Acta Medica, Vol 64, Iss 1, Pp 50-54 (2021)

مصطلحات موضوعية: hyperinsulinemic hypoglycaemia, insulin autoantibodies, hirata’s disease, insulin autoimmune syndrome, Medicine

الوصف: Insulin autoimmune syndrome or Hirata’s disease is an extremely rare condition leading to hypoglycaemia of variable severity due to autoantibodies against insulin. We present the first case documented in the Czech Republic.

وصف الملف: electronic resource

العلاقة: https://actamedica.lfhk.cuni.cz/64/1/0050Test/; https://doaj.org/toc/1211-4286Test; https://doaj.org/toc/1805-9694Test

الوصول الحر: https://doaj.org/article/894e44d56f3f4ecb876e79b07ffc30deTest

المؤلفون: Sutkowska E, Ostrowska M, Sutkowska M

المصدر: Diabetes, Metabolic Syndrome and Obesity, Vol Volume 14, Pp 1557-1561 (2021)

مصطلحات موضوعية: autoimmune hypoglycemia, latent autoimmune diabetes, insulin autoantibodies, pre-clinical diabetes, Specialties of internal medicine, RC581-951

الوصف: Edyta Sutkowska,1 Malgorzata Ostrowska,2 Magdalena Sutkowska3 1Medical Division, Department and Division of Medical Rehabilitation, Wroclaw Medical University, Wroclaw, Poland; 2Clinical Department of Nephrology and Dialysis Station, Karol Marcinkowski University Hospital, Zielona Gora, Poland; 3Medical Division, Wroclaw Medical University, Wroclaw, PolandCorrespondence: Edyta SutkowskaDepartment and Division of Medical Rehabilitation, Wroclaw Medical University, Borowska 213, Wroclaw, 50-556, PolandTel +48 71 734 32 20Email edyta.sutkowska@umed.wroc.plAbstract: Hypoglycemia presents relatively typical symptoms. However, when it occurs spontaneously – like in insulin autoimmune syndrome – it is difficult to perform scheduled biochemical tests at the laboratory. The study presents the case of a 31-year-old Caucasian female whose recurrent hypoglycemia symptoms were the reason for further diagnostics. The final results revealed a positive test for insulin autoantibody and glutamic acid decarboxylase autoantibody. Therefore, not only the potential causes of hypoglycemia but also an active autoimmune process typical for latent autoimmune diabetes in adults were confirmed. It was concluded that autoimmune hypoglycemia can be a part of the autoimmune process associated with diabetes and pre-diabetes in adults.Keywords: autoimmune hypoglycemia, latent autoimmune diabetes, insulin autoantibodies, pre-clinical diabetes

وصف الملف: electronic resource

العلاقة: https://www.dovepress.comTest/insulin-autoimmune-syndrome-as-part-of-pre-clinical-lada-peer-reviewed-article-DMSO; https://doaj.org/toc/1178-7007Test

الوصول الحر: https://doaj.org/article/38768e12925f4b7090e39d1cc6a819c6Test

المؤلفون: Scarlette Garcia-Avila, MD, Anish Samuel, MD, Iqra Farooqi, MD, Rajapriya Manickam, MD, Mourad Ismail, MD, Saleh I. Khaddash, MD, Sandra Gibiezaite, MD

المصدر: AACE Clinical Case Reports, Vol 7, Iss 2, Pp 158-162 (2021)

مصطلحات موضوعية: diabetic ketoacidosis, Hirata disease, insulin autoantibodies, insulin receptor antibodies, type B insulin resistance syndrome, Diseases of the endocrine glands. Clinical endocrinology, RC648-665

الوصف: Objective: The main objective was to describe and review a unique case that presented with diabetic ketoacidosis, positive insulin autoantibodies (IAAbs, which are found in Hirata disease and are usually present with hypoglycemia), and laboratory findings characteristic of type B insulin resistance syndrome (TBIRS) and systemic lupus erythematosus. Confirmation of TBIRS was obtained in Germany as immunoassay for insulin receptor antibodies (IRAbs) is not available in the United States. Methods: A literature review on TBIRS and cases that present with IAAbs and IRAbs simultaneously was conducted. Results: We found 6 cases presenting with hypoglycemia, both antibodies, and treatment attempts with various management approaches that were different from the proposed National Institutes of Health (NIH) protocol for TBIRS. Our case is distinct because of the demographic background, presentation with diabetic ketoacidosis, comparatively lower insulin requirement, and no significant hypoglycemic episodes in the third phase. Conclusion: We propose that access to IRAb immunoassays may be important for diagnosing milder cases of TBIRS, while IAAbs may provide prognostic and therapeutic insights. Despite completely different presentation from other TBIRS patients reviewed, we observed that the proposed NIH protocol consisting of dexamethasone, rituximab, and cyclophosphamide was successfully employed in our patient. Thus, we propose that our case and the findings regarding antibody testing and the NIH treatment regimen may assist clinicians with earlier recognition and effective management of milder cases of TBIRS.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2376060520310518Test; https://doaj.org/toc/2376-0605Test

الوصول الحر: https://doaj.org/article/73add4c64792483e9a19577915931cadTest