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Intralymphatic GAD-Alum (Diamyd®) Improves Glycemic Control in Type 1 Diabetes With HLA DR3-DQ2
C. Nowak, M. Lind, Z. Sumnik, T. Pelikanova, L. Nattero-Chavez, E. Lundberg, I. Rica, MA. Martínez-Brocca, M. Ruiz de Adana, J. Wahlberg, R. Hanas, C. Hernandez, M. Clemente-León, A. Gómez-Gila, M. Ferrer Lozano, T. Sas, S. Pruhova, F. Dietrich,...
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, multicentrická studie, randomizované kontrolované studie, práce podpořená grantem
PubMed
35665810
DOI
10.1210/clinem/dgac343
Knihovny.cz E-zdroje
- MeSH
- C-peptid MeSH
- diabetes mellitus 1. typu * MeSH
- dítě MeSH
- glutamát dekarboxyláza MeSH
- HLA-DR3 antigen MeSH
- kamencové sloučeniny MeSH
- krevní glukóza MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- regulace glykemie MeSH
- selfmonitoring glykemie MeSH
- vitamin D terapeutické užití MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
AIMS: Residual beta cell function in type 1 diabetes (T1D) is associated with lower risk of complications. Autoantigen therapy with GAD-alum (Diamyd) given in 3 intralymphatic injections with oral vitamin D has shown promising results in persons with T1D carrying the human leukocyte antigen (HLA) DR3-DQ2 haplotype in the phase 2b trial DIAGNODE-2. We aimed to explore the efficacy of intralymphatic GAD-alum on blood glucose recorded by continuous glucose monitoring (CGM). METHODS: DIAGNODE-2 (NCT03345004) was a multicenter, randomized, placebo-controlled, double-blind trial of 109 recent-onset T1D patients aged 12 to 24 years with GAD65 antibodies and fasting C-peptide > 0.12 nmol/L, which randomized patients to 3 intralymphatic injections of 4 μg GAD-alum and oral vitamin D, or placebo. We report results for exploratory endpoints assessed by 14-day CGM at months 0, 6, and 15. Treatment arms were compared by mixed-effects models for repeated measures adjusting for baseline values. RESULTS: We included 98 patients with CGM recordings of sufficient quality (DR3-DQ2-positive patients: 27 GAD-alum-treated and 15 placebo-treated). In DR3-DQ2-positive patients, percent of time in range (TIR, 3.9-10 mmol/L) declined less between baseline and month 15 in GAD-alum-treated compared with placebo-treated patients (-5.1% and -16.7%, respectively; P = 0.0075), with reduced time > 13.9 mmol/L (P = 0.0036), and significant benefits on the glucose management indicator (P = 0.0025). No differences were detected for hypoglycemia. GAD-alum compared to placebo lowered the increase in glycemic variability (standard deviation) observed in both groups (P = 0.0219). Change in C-peptide was correlated with the change in TIR. CONCLUSIONS: Intralymphatic GAD-alum improves glycemic control in recently diagnosed T1D patients carrying HLA DR3-DQ2.
Department of Endocrinology and Nutrition Hospital Universitario Ramón y Cajal 28034 Madrid Spain
Department of Endocrinology and Nutrition Vall d'Hebron Hospital 08035 Barcelona Ciberdem Spain
Department of Endocrinology Pediatric Service Vall d'Hebron Hospital 08035 Barcelona CibererSpain
Department of Neurobiology Care Sciences and Society Karolinska Institutet 14183 Huddinge Sweden
Department of Pediatric Endocrinology Cruces University Hospital 48902 Bilbao Ciberdem Spain
Department of Pediatric Endocrinology Miguel Servet University Hospital 50009 Zaragoza Spain
Department of Pediatrics NU Hospital Group 45153 Uddevalla Sweden
Diabetes Centre of the Institute of Clinical and Experimental Medicine 14000 Prague Czech Republic
Diamyd Medical AB 11135 Stockholm Sweden
Pediatric Endocrinology Service Virgen del Rocío University Hospital 41013 Sevilla Spain
Citace poskytuje Crossref.org
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- $a Nowak, Christoph $u Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, 14183 Huddinge, Sweden $u Diamyd Medical AB, 11135 Stockholm, Sweden $1 https://orcid.org/0000000184353978
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