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Previous Volume 359:1909-1920 October 30, 2008 Number 18 Next

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ABSTRACT

Background The 65-kD isoform of glutamic acid decarboxylase (GAD) is a major autoantigen in patients with type 1 diabetes mellitus. This trial assessed the ability of alum-formulated GAD (GAD-alum) to reverse recent-onset type 1 diabetes in patients 10 to 18 years of age.

Methods We randomly assigned 70 patients with type 1 diabetes who had fasting C-peptide levels above 0.1 nmol per liter (0.3 ng per milliliter) and GAD autoantibodies, recruited within 18 months after receiving the diagnosis of diabetes, to receive subcutaneous injections of 20 µg of GAD-alum (35 patients) or placebo (alum alone, 35 patients) on study days 1 and 30. At day 1 and months 3, 9, 15, 21, and 30, patients underwent a mixed-meal tolerance test to stimulate residual insulin secretion (measured as the C-peptide level). The effect of GAD-alum on the immune system was also studied.

Results Insulin secretion gradually decreased in both study groups. The study treatment had no significant effect on change in fasting C-peptide level after 15 months (the primary end point). Fasting C-peptide levels declined from baseline levels significantly less over 30 months in the GAD-alum group than in the placebo group (–0.21 vs. –0.27 nmol per liter [–0.62 vs. –0.81 ng per milliliter], P=0.045), as did stimulated secretion measured as the area under the curve (–0.72 vs. –1.02 nmol per liter per 2 hours [–2.20 vs. –3.08 ng per milliliter per 2 hours], P=0.04). No protective effect was seen in patients treated 6 months or more after receiving the diagnosis. Adverse events appeared to be mild and similar in frequency between the two groups. The GAD-alum treatment induced a GAD-specific immune response.

Conclusions GAD-alum may contribute to the preservation of residual insulin secretion in patients with recent-onset type 1 diabetes, although it did not change the insulin requirement. (ClinicalTrials.gov number, NCT00435981 [ClinicalTrials.gov] .)

Source Information

From Linköping University, Linköping (J.L., M.F., M.H., S.A., M.C., M.P., O.V., R.C.); the Queen Silvia Children's Hospital, Gothenburg (G.F.); Malmö University Hospital, Malmö (S.I.); Regional Hospital Ryhov, Jönköping (C.J.); Southern Älvsborg Hospital, Borås (A.L.); Halmstad County Hospital, Halmstad (N.-Ö.N.); Örebro University Hospital, Örebro (J.Å.); Astrid Lindgrens Children's Hospital, Karolinska University Hospital, Stockholm (E.Ö.); and Diamyd Medical, Stockholm (P.Z.) — all in Sweden; and the National Public Health Institute, Helsinki (O.V.).

This article (10.1056/NEJMoa0804328) was published at www.nejm.org on October 8, 2008.

Address reprint requests to Dr. Ludvigsson at the Division of Pediatrics, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, SE-58185 Linköping, Sweden, or at johnny.ludvigsson{at}lio.se.

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