Intralymphatic GAD-alum (Diamyd(R)) improves glycaemic control in Type 1 diabetes with HLA DR3-DQ2

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F22%3A10444306" target="_blank" >RIV/00064203:_____/22:10444306 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11130/22:10444306

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=eu~QKAuJEK" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=eu~QKAuJEK</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1210/clinem/dgac343" target="_blank" >10.1210/clinem/dgac343</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Intralymphatic GAD-alum (Diamyd(R)) improves glycaemic control in Type 1 diabetes with HLA DR3-DQ2

Popis výsledku v původním jazyce

AIMS: Residual beta cell function in Type 1 diabetes (T1D) is associated with lower risk of complications. Autoantigen therapy with GAD-alum (Diamyd(R)) given in three intralymphatic injections with oral Vitamin D has shown promising results in persons with T1D carrying the HLA DR3-DQ2 haplotype in the phase IIb 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 12-24 years with GAD65 antibodies and fasting C-peptide &gt;0.12 nmol/L, which randomized patients to three 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, % time in range (TIR, 3.9-10 mmol/L) declined less between baseline and Month 15 in GAD-alum-treated compared to placebo-treated patients (-5.1% and -16.7%, respectively, p=0.0075), with reduced time &gt;13.9 mmol/L (p=0.0036), and significant benefits on the glucose management indicator (p=0.0025). No differences were detected for hypoglycaemia. GAD-alum compared to placebo lowered the increase in glycaemic 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 glycaemic control in recently diagnosed T1D patients carrying HLA DR3-DQ2.

Název v anglickém jazyce

Intralymphatic GAD-alum (Diamyd(R)) improves glycaemic control in Type 1 diabetes with HLA DR3-DQ2

Popis výsledku anglicky

AIMS: Residual beta cell function in Type 1 diabetes (T1D) is associated with lower risk of complications. Autoantigen therapy with GAD-alum (Diamyd(R)) given in three intralymphatic injections with oral Vitamin D has shown promising results in persons with T1D carrying the HLA DR3-DQ2 haplotype in the phase IIb 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 12-24 years with GAD65 antibodies and fasting C-peptide &gt;0.12 nmol/L, which randomized patients to three 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, % time in range (TIR, 3.9-10 mmol/L) declined less between baseline and Month 15 in GAD-alum-treated compared to placebo-treated patients (-5.1% and -16.7%, respectively, p=0.0075), with reduced time &gt;13.9 mmol/L (p=0.0036), and significant benefits on the glucose management indicator (p=0.0025). No differences were detected for hypoglycaemia. GAD-alum compared to placebo lowered the increase in glycaemic 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 glycaemic control in recently diagnosed T1D patients carrying HLA DR3-DQ2.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30202 - Endocrinology and metabolism (including diabetes, hormones)

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

The Journal of Clinical Endocrinology &amp; Metabolism

ISSN

0021-972X

e-ISSN

1945-7197

Svazek periodika

107

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

8

Strana od-do

2644-2651

Kód UT WoS článku

000818061200001

EID výsledku v databázi Scopus

2-s2.0-85134420398