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Intralymphatic GAD-Alum (Diamyd (R)) Improves Glycemic Control in Type 1 Diabetes With HLA DR3-DQ2
Karolinska Inst, Sweden; Diamyd Med AB, Sweden.
Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden; NU Hosp Grp, Sweden.
Charles Univ Prague, Czech Republic; Motol Univ Hosp, Czech Republic.
Inst Clin & Expt Med, Czech Republic.
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2022 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 107, no 9, p. 2644-2651Article in journal (Refereed) Published
Abstract [en]

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 mu g 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.

Place, publisher, year, edition, pages
ENDOCRINE SOC , 2022. Vol. 107, no 9, p. 2644-2651
Keywords [en]
type 1 diabetes; GAD-alum; GAD65; Diamyd; HLA DR3-DQ2; continuous glucose monitoring; C-peptide; HbA1c; antigen-specific immune therapy
National Category
Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:liu:diva-187540DOI: 10.1210/clinem/dgac343ISI: 000818061200001PubMedID: 35665810OAI: oai:DiVA.org:liu-187540DiVA, id: diva2:1690292
Note

Funding Agencies|Diamyd Medical AB; Barndiabetesfonden (Swedish Child Diabetes Foundation); Diabetesfonden (Swedish Diabetes Association)

Available from: 2022-08-25 Created: 2022-08-25 Last updated: 2023-02-21Bibliographically approved

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Wahlberg, JeanetteDietrich, FabriciaCasas, RosauraLudvigsson, Johnny

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Wahlberg, JeanetteDietrich, FabriciaPuente Marin, SaraCasas, RosauraLudvigsson, Johnny
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Division of Diagnostics and Specialist MedicineFaculty of Medicine and Health SciencesDepartment of EndocrinologyDivision of Children's and Women's HealthH.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus
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