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22296077 10.1056/NEJMoa1107096 1:CAS:528:DC%2BC38XitVSjsr4%3D This large randomized trial of subcutaneous GAD65 with alum as adjuvant followed an earlier trial by the same investigators [ref. 29] that suggested that the vaccine reduced the decline in β-cell function after diagnosis. In the previous trial, 70 patients 10-18 years of age with T1D for less than 18 months were treated with two 20-μg doses of either GAD-alum or placebo a month apart. Changes in fasting and meal-stimulated C-peptide secretion were similar after 15 months but declined less in those treated with GAD-alum within 6 months of diagnosis. Here, 334 patients of similar age but diagnosed less than 3 months were randomized to two doses of GAD-alum or placebo. GAD65-alum induced antibodies to GAD65 and was not associated with major side effects, as previously, but did not alter the decline in β-cell function
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•• Ludvigsson J, Krisky D, Casas R, et al. GAD65 antigen therapy in recently diagnosed type 1 diabetes mellitus. N Engl J Med. 2012;366:433-42. This large randomized trial of subcutaneous GAD65 with alum as adjuvant followed an earlier trial by the same investigators [ref. 29] that suggested that the vaccine reduced the decline in β-cell function after diagnosis. In the previous trial, 70 patients 10-18 years of age with T1D for less than 18 months were treated with two 20-μg doses of either GAD-alum or placebo a month apart. Changes in fasting and meal-stimulated C-peptide secretion were similar after 15 months but declined less in those treated with GAD-alum within 6 months of diagnosis. Here, 334 patients of similar age but diagnosed less than 3 months were randomized to two doses of GAD-alum or placebo. GAD65-alum induced antibodies to GAD65 and was not associated with major side effects, as previously, but did not alter the decline in β-cell function.
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21714999 10.1016/S0140-6736(11)60895-7 1:CAS:528:DC%2BC3MXpt1Ons7c%3D This well-powered randomized controlled trial in 145 people with recent-onset T1D (<3 months) showed that subcutaneous GAD65-alum did not arrest the decline in age-adjusted meal-stimulated C-peptide secretion after 1 year. This finding conclusively demonstrates that the GAD-alum vaccine is ineffective in people with clinical T1D but does not exclude possible efficacy in people with subclinical disease or those genetically at risk
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•• Wherrett DK, Bundy B, Becker DJ, et al. Antigen-based therapy with glutamic acid decarboxylase (GAD) vaccine in patients with recent-onset type 1 diabetes: a randomised double-blind trial. Lancet. 2011;378:319-27. This well-powered randomized controlled trial in 145 people with recent-onset T1D (<3 months) showed that subcutaneous GAD65-alum did not arrest the decline in age-adjusted meal-stimulated C-peptide secretion after 1 year. This finding conclusively demonstrates that the GAD-alum vaccine is ineffective in people with clinical T1D but does not exclude possible efficacy in people with subclinical disease or those genetically at risk.
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22362174 10.2337/db11-1304 1:CAS:528:DC%2BC38XotlGqurY%3D The authors demonstrate synergy between treatment with anti-CD3 monoclonal antibody and oral insulin in reversing hyperglycemia at diagnosis in NOD mice. This is a rationale for combining autoantigen-specific vaccination with conventional immune suppression. In addition, they show that a high serum concentration of insulin autoantibody (IAA) predicts response to combination treatment. This echoes the post-DPT-1 oral insulin trial finding [ref. 23] that slower progression to diabetes after oral insulin was associated with higher IAA at entry. How insulin autoimmunity relates to a tolerogenic response to insulin requires an answer; meanwhile, IAA could be a useful biomarker
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