RT Journal Article
T1 Intralymphatic GAD-Alum (Diamyd®) Improves Glycemic Control in Type 1 Diabetes With HLA DR3-DQ2.
A1 Nowak, Christoph
A1 Lind, Marcus
A1 Sumnik, Zdenek
A1 Pelikanova, Terezie
A1 Nattero-Chavez, Lía
A1 Lundberg, Elena
A1 Rica, Itxaso
A1 Martínez-Brocca, Maria A
A1 Ruiz de Adana, MariSol
A1 Wahlberg, Jeanette
A1 Hanas, Ragnar
A1 Hernandez, Cristina
A1 Clemente-León, Maria
A1 Gómez-Gila, Ana
A1 Ferrer Lozano, Marta
A1 Sas, Theo
A1 Pruhova, Stepanka
A1 Dietrich, Fabricia
A1 Puente-Marin, Sara
A1 Hannelius, Ulf
A1 Casas, Rosaura
A1 Ludvigsson, Johnny
K1 C-peptide
K1 Diamyd
K1 GAD-alum
K1 GAD65
K1 HLA DR3-DQ2
K1 HbA1c
K1 antigen-specific immune therapy
K1 continuous glucose monitoring
K1 type 1 diabetes
AB 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.
YR 2022
FD 2022
LK http://hdl.handle.net/10668/20398
UL http://hdl.handle.net/10668/20398
LA en
DS RISalud
RD Apr 6, 2025