%0 Journal Article
%A Nowak, Christoph
%A Lind, Marcus
%A Sumnik, Zdenek
%A Pelikanova, Terezie
%A Nattero-Chavez, Lía
%A Lundberg, Elena
%A Rica, Itxaso
%A Martínez-Brocca, Maria A
%A Ruiz de Adana, MariSol
%A Wahlberg, Jeanette
%A Hanas, Ragnar
%A Hernandez, Cristina
%A Clemente-León, Maria
%A Gómez-Gila, Ana
%A Ferrer Lozano, Marta
%A Sas, Theo
%A Pruhova, Stepanka
%A Dietrich, Fabricia
%A Puente-Marin, Sara
%A Hannelius, Ulf
%A Casas, Rosaura
%A Ludvigsson, Johnny
%T Intralymphatic GAD-Alum (Diamyd®) Improves Glycemic Control in Type 1 Diabetes With HLA DR3-DQ2.
%D 2022
%U http://hdl.handle.net/10668/20398
%X 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). 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. 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. Intralymphatic GAD-alum improves glycemic control in recently diagnosed T1D patients carrying HLA DR3-DQ2.
%K C-peptide
%K Diamyd
%K GAD-alum
%K GAD65
%K HLA DR3-DQ2
%K HbA1c
%K antigen-specific immune therapy
%K continuous glucose monitoring
%K type 1 diabetes
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