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Glutamic acid decarboxylase immunotherapy for type 1 diabetes
Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.ORCID iD: 0000-0003-1695-5234
2022 (English)In: Current Opinion in Endocrinology, Diabetes & Obesity, ISSN 1752-296X, E-ISSN 1752-2978, Vol. 29, no 4, p. 361-369Article, review/survey (Refereed) Published
Abstract [en]

Purpose of review To describe recent development of an autoantigen (GAD) treatment towards well tolerated and efficacious precision medicine in type 1 diabetes. Recent findings Although subcutaneous GAD-alum treatment failed to reach primary endpoint in a phase III trial, metanalyses showed a 97% probability of efficacy, and clear efficacy in patients carrying Hyman Leucoycte Antigen (HLA) DR3DQ2. Efforts have been made to improve efficacy by trying combination therapies with vitamin D + Ibuprofen resp vitamin D + Etanercept (TNF-alpha inhibition), without any breakthrough until the administration of GAD-alum was changed from subcutaneous to intralymphatic. With a very small dose of GAD-alum (4 mu g) given into an inguinal lymph three times with 1 month interval, the efficacy in patients with HLADR3DQ2 has been impressive, with significantly better beta cell preservation than patients who got placebo in a double-blind randomized trial, and clinical efficacy with more patients in partial remission (IDAA1c < 9) and larger proportion of patients with CGM-measured blood glucose Time In Range (TIR), significantly correlated to the C-peptide values. The treatment has been easy for patients and healthcare without treatment-related risk or adverse events. Intralymphatic GAD-alum treatment in type 1 diabetes patients carrying HLA DR3DQ2 seems to be an attractive immune intervention.

Place, publisher, year, edition, pages
LIPPINCOTT WILLIAMS & WILKINS , 2022. Vol. 29, no 4, p. 361-369
Keywords [en]
C-peptide; glutamic acid decarboxylase-alum; Hyman Leucoycte Antigen; intralymphatic; time in range; type 1 diabetes
National Category
Hematology
Identifiers
URN: urn:nbn:se:liu:diva-187322DOI: 10.1097/MED.0000000000000748ISI: 000825476000009PubMedID: 35776501OAI: oai:DiVA.org:liu-187322DiVA, id: diva2:1688434
Note

Funding Agencies|Barndiabetesfonden (The Swedish Child diabetes Foundation); Diabetesfonden (Swedish Diabetes Association); Juvenile Diabetes Research Foundation; Diamyd Medical; Research Council of southeast Sweden

Available from: 2022-08-18 Created: 2022-08-18 Last updated: 2022-08-18

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Ludvigsson, Johnny
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Division of Children's and Women's HealthFaculty of Medicine and Health SciencesH.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus
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