PMID- 35665810 OWN - NLM STAT- MEDLINE DCOM- 20220822 LR - 20221208 IS - 1945-7197 (Electronic) IS - 0021-972X (Print) IS - 0021-972X (Linking) VI - 107 IP - 9 DP - 2022 Aug 18 TI - Intralymphatic GAD-Alum (Diamyd(R)) Improves Glycemic Control in Type 1 Diabetes With HLA DR3-DQ2. PG - 2644-2651 LID - 10.1210/clinem/dgac343 [doi] AB - 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 mug 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. CI - (c) The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. FAU - Nowak, Christoph AU - Nowak C AUID- ORCID: 0000-0001-8435-3978 AD - Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, 14183 Huddinge, Sweden. AD - Diamyd Medical AB, 11135 Stockholm, Sweden. FAU - Lind, Marcus AU - Lind M AD - Department of Molecular and Clinical Medicine, University of Gothenburg, 41345 Gothenburg, Sweden, Sahlgrenska University Hospital, Gothenburg and NU-Hospital Group, S41553, Uddevalla, Sweden. FAU - Sumnik, Zdenek AU - Sumnik Z AD - Department of Pediatrics, 2nd Faculty of Medicine, Charles University and Motol University Hospital, 15000 Prague, Czech Republic. FAU - Pelikanova, Terezie AU - Pelikanova T AD - Diabetes Centre of the Institute of Clinical and Experimental Medicine, 14000 Prague, Czech Republic. FAU - Nattero-Chavez, Lia AU - Nattero-Chavez L AD - Department of Endocrinology and Nutrition, Hospital Universitario Ramon y Cajal, 28034 Madrid, Spain. FAU - Lundberg, Elena AU - Lundberg E AD - Institution of Clinical Science, Department of Pediatrics, Umea University, Norrland University Hospital, 93451 Umea, Sweden. FAU - Rica, Itxaso AU - Rica I AD - Department of Pediatric Endocrinology, Cruces University Hospital, 48902 Bilbao, Ciberdem, Spain. FAU - Martinez-Brocca, Maria A AU - Martinez-Brocca MA AD - Department of Endocrinology, Virgen Macarena Hospital, Department of Endocrinology and Nutrition, Virgen Macarena University Hospital, 41009 Sevilla, Spain. FAU - Ruiz de Adana, MariSol AU - Ruiz de Adana M AD - Diabetes Unit, Department of Endocrinology and Nutrition, Ibima, Ciberdem, General University Hospital, 29010 Malaga, Spain. FAU - Wahlberg, Jeanette AU - Wahlberg J AUID- ORCID: 0000-0001-9456-2044 AD - Department of Endocrinology in Linkoping and Department of Health, Medicine and Caring Sciences, Linkoping University, 58183 Linkoping, Sweden. AD - Department of Internal Medicine, School of Health and Medical Sciences, Orebro University, 70281 Orebro, Sweden. FAU - Hanas, Ragnar AU - Hanas R AD - Department of Pediatrics, NU Hospital Group, 45153 Uddevalla, Sweden. FAU - Hernandez, Cristina AU - Hernandez C AD - Department of Endocrinology and Nutrition, Vall d'Hebron Hospital, 08035 Barcelona, Ciberdem, Spain. FAU - Clemente-Leon, Maria AU - Clemente-Leon M AD - Department of Endocrinology, Pediatric Service, Vall d'Hebron Hospital, 08035 Barcelona, CibererSpain. FAU - Gomez-Gila, Ana AU - Gomez-Gila A AD - Pediatric Endocrinology Service, Virgen del Rocio University Hospital, 41013 Sevilla, Spain. FAU - Ferrer Lozano, Marta AU - Ferrer Lozano M AD - Department of Pediatric Endocrinology, Miguel Servet University Hospital, 50009 Zaragoza, Spain. FAU - Sas, Theo AU - Sas T AD - Diabeter, National Treatment and Research Center for Children, Adolescents and Young Adults with type 1 diabetes, and Department of Pediatric Endocrinology, Erasmus University Medical Center, 3015 Rotterdam, The Netherlands. FAU - Pruhova, Stepanka AU - Pruhova S AD - Department of Pediatrics, 2nd Faculty of Medicine, Charles University and Motol University Hospital, 15000 Prague, Czech Republic. FAU - Dietrich, Fabricia AU - Dietrich F AD - Division of Pediatrics, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Linkoping University, 58183 Linkoping, Sweden. FAU - Puente-Marin, Sara AU - Puente-Marin S AD - Division of Pediatrics, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Linkoping University, 58183 Linkoping, Sweden. FAU - Hannelius, Ulf AU - Hannelius U AD - Diamyd Medical AB, 11135 Stockholm, Sweden. FAU - Casas, Rosaura AU - Casas R AD - Division of Pediatrics, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences and Crown Princess Victoria Children s Hospital, Linkoping University, 58183 Linkoping, Sweden. FAU - Ludvigsson, Johnny AU - Ludvigsson J AUID- ORCID: 0000-0003-1695-5234 AD - Division of Pediatrics, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences and Crown Princess Victoria Children s Hospital, Linkoping University, 58183 Linkoping, Sweden. LA - eng SI - ClinicalTrials.gov/NCT03345004 PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 0 (Alum Compounds) RN - 0 (Blood Glucose) RN - 0 (C-Peptide) RN - 0 (HLA-DR3 Antigen) RN - 1406-16-2 (Vitamin D) RN - 34S289N54E (aluminum sulfate) RN - EC 4.1.1.15 (Glutamate Decarboxylase) SB - IM CIN - J Clin Endocrinol Metab. 2022 Jul 26;:. PMID: 35881553 MH - Adolescent MH - Alum Compounds MH - Blood Glucose MH - Blood Glucose Self-Monitoring MH - C-Peptide MH - Child MH - *Diabetes Mellitus, Type 1 MH - Glutamate Decarboxylase MH - Glycemic Control MH - HLA-DR3 Antigen MH - Humans MH - Vitamin D/therapeutic use MH - Young Adult PMC - PMC9721339 OTO - NOTNLM OT - C-peptide OT - Diamyd OT - GAD-alum OT - GAD65 OT - HLA DR3-DQ2 OT - HbA1c OT - antigen-specific immune therapy OT - continuous glucose monitoring OT - type 1 diabetes EDAT- 2022/06/07 06:00 MHDA- 2022/08/23 06:00 PMCR- 2022/06/06 CRDT- 2022/06/06 15:00 PHST- 2022/02/25 00:00 [received] PHST- 2022/06/07 06:00 [pubmed] PHST- 2022/08/23 06:00 [medline] PHST- 2022/06/06 15:00 [entrez] PHST- 2022/06/06 00:00 [pmc-release] AID - 6602344 [pii] AID - dgac343 [pii] AID - 10.1210/clinem/dgac343 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2022 Aug 18;107(9):2644-2651. doi: 10.1210/clinem/dgac343.