title: GAD65 antigen therapy in recently diagnosed type 1 diabetes mellitus.
abstract: BACKGROUND
  The 65-kD isoform of glutamic acid decarboxylase (GAD65) is a major autoantigen in type 1 diabetes. We hypothesized that alum-formulated GAD65 (GAD-alum) can preserve beta-cell function in patients with recent-onset type 1 diabetes.
  
  
  METHODS
  We studied 334 patients, 10 to 20 years of age, with type 1 diabetes, fasting C-peptide levels of more than 0.3 ng per milliliter (0.1 nmol per liter), and detectable serum GAD65 autoantibodies. Within 3 months after diagnosis, patients were randomly assigned to receive one of three study treatments: four doses of GAD-alum, two doses of GAD-alum followed by two doses of placebo, or four doses of placebo. The primary outcome was the change in the stimulated serum C-peptide level (after a mixed-meal tolerance test) between the baseline visit and the 15-month visit. Secondary outcomes included the glycated hemoglobin level, mean daily insulin dose, rate of hypoglycemia, and fasting and maximum stimulated C-peptide levels.
  
  
  RESULTS
  The stimulated C-peptide level declined to a similar degree in all study groups, and the primary outcome at 15 months did not differ significantly between the combined active-drug groups and the placebo group (P=0.10). The use of GAD-alum as compared with placebo did not affect the insulin dose, glycated hemoglobin level, or hypoglycemia rate. Adverse events were infrequent and mild in the three groups, with no significant differences.
  
  
  CONCLUSIONS
  Treatment with GAD-alum did not significantly reduce the loss of stimulated C peptide or improve clinical outcomes over a 15-month period. (Funded by Diamyd Medical and the Swedish Child Diabetes Foundation; ClinicalTrials.gov number, NCT00723411.).
authors.affiliation: Division of Pediatrics, Department of Clinical and Experimental Medicine, Linköping University, 58185 Linköping, Sweden. johnny.ludvigsson@liu.se
authors.forename: Johnny
authors.initials: J
authors.lastname: Ludvigsson
authors.forename: David
authors.initials: D
authors.lastname: Krisky
authors.forename: Rosaura
authors.initials: R
authors.lastname: Casas
authors.forename: Tadej
authors.initials: T
authors.lastname: Battelino
authors.forename: Luis
authors.initials: L
authors.lastname: Castaño
authors.forename: James
authors.initials: J
authors.lastname: Greening
authors.forename: Olga
authors.initials: O
authors.lastname: Kordonouri
authors.forename: Timo
authors.initials: T
authors.lastname: Otonkoski
authors.forename: Paolo
authors.initials: P
authors.lastname: Pozzilli
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Robert
authors.forename: Henk J
authors.initials: HJ
authors.lastname: Veeze
authors.forename: Jerry
authors.initials: J
authors.lastname: Palmer
authors.forename: Ulf
authors.initials: U
authors.lastname: Samuelsson
authors.forename: Helena
authors.initials: H
authors.lastname: Elding Larsson
authors.forename: Jan
authors.initials: J
authors.lastname: Åman
authors.forename: Gunilla
authors.initials: G
authors.lastname: Kärdell
authors.forename: Jan
authors.initials: J
authors.lastname: Neiderud Helsingborg
authors.forename: Göran
authors.initials: G
authors.lastname: Lundström
authors.forename: Eva
authors.initials: E
authors.lastname: Albinsson
authors.forename: Annelie
authors.initials: A
authors.lastname: Carlsson
authors.forename: Maria
authors.initials: M
authors.lastname: Nordvall
authors.forename: Hans
authors.initials: H
authors.lastname: Fors
authors.forename: Carl-Göran
authors.initials: CG
authors.lastname: Arvidsson
authors.forename: Stig
authors.initials: S
authors.lastname: Edvardson
authors.forename: Ragnar
authors.initials: R
authors.lastname: Hanås
authors.forename: Karin
authors.initials: K
authors.lastname: Larsson
authors.forename: Björn
authors.initials: B
authors.lastname: Rathsman
authors.forename: Henrik
authors.initials: H
authors.lastname: Forsgren
authors.forename: Helena
authors.initials: H
authors.lastname: Desaix
authors.forename: Gun
authors.initials: G
authors.lastname: Forsander
authors.forename: Nils-Östen
authors.initials: NÖ
authors.lastname: Nilsson
authors.forename: Carl-Göran
authors.initials: CG
authors.lastname: Åkesson
authors.forename: Päivi
authors.initials: P
authors.lastname: Keskinen
authors.forename: Riitta
authors.initials: R
authors.lastname: Veijola
authors.forename: Timo
authors.initials: T
authors.lastname: Talvitie
authors.forename: Klemens
authors.initials: K
authors.lastname: Raile
authors.forename: Thomas
authors.initials: T
authors.lastname: Kapellen
authors.forename: Walter
authors.initials: W
authors.lastname: Burger
authors.forename: Andreas
authors.initials: A
authors.lastname: Neu
authors.forename: Ilse
authors.initials: I
authors.lastname: Engelsberger
authors.forename: Bettina
authors.initials: B
authors.lastname: Heidtmann
authors.forename: Suzanne
authors.initials: S
authors.lastname: Bechtold
authors.forename: David
authors.initials: D
authors.lastname: Leslie
authors.forename: Francesco
authors.initials: F
authors.lastname: Chiarelli
authors.forename: Alesandro
authors.initials: A
authors.lastname: Cicognani
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Chiumello
authors.forename: Franco
authors.initials: F
authors.lastname: Cerutti
authors.forename: Gian Vincenzo
authors.initials: GV
authors.lastname: Zuccotti
authors.forename: Ana
authors.initials: A
authors.lastname: Gomez Gila
authors.forename: Itxaso
authors.initials: I
authors.lastname: Rica
authors.forename: Raquel
authors.initials: R
authors.lastname: Barrio
authors.forename: Maria
authors.initials: M
authors.lastname: Clemente
authors.forename: Maria José
authors.initials: MJ
authors.lastname: López Garcia
authors.forename: Mercedes
authors.initials: M
authors.lastname: Rodriguez
authors.forename: Isabel
authors.initials: I
authors.lastname: Gonzalez
authors.forename: Juan Pedro
authors.initials: JP
authors.lastname: Lopez
authors.forename: Mirentxu
authors.initials: M
authors.lastname: Oyarzabal
authors.forename: H M
authors.initials: HM
authors.lastname: Reeser
authors.forename: Roos
authors.initials: R
authors.lastname: Nuboer
authors.forename: Pauline
authors.initials: P
authors.lastname: Stouthart
authors.forename: Natasa
authors.initials: N
authors.lastname: Bratina
authors.forename: Nina
authors.initials: N
authors.lastname: Bratanic
authors.forename: Marc
authors.initials: M
authors.lastname: de Kerdanet
authors.forename: Jacques
authors.initials: J
authors.lastname: Weill
authors.forename: Nicole
authors.initials: N
authors.lastname: Ser
authors.forename: Pascal
authors.initials: P
authors.lastname: Barat
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Bertrand
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Carel
authors.forename: Rachel
authors.initials: R
authors.lastname: Reynaud
authors.forename: Regis
authors.initials: R
authors.lastname: Coutant
authors.forename: Sabine
authors.initials: S
authors.lastname: Baron
mesh_terms: D000293:Adolescent; D001323:Autoantibodies / Q000097:blood; D002096:C-Peptide / Q000097:blood*; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D005968:Glutamate Decarboxylase / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D020033:Protein Isoforms; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D002096:C-Peptide; D020033:Protein Isoforms; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2