Anti-thymocyte globulin/G-CSF treatment preserves β cell function in patients with established type 1 diabetes

BACKGROUND. Previous efforts to preserve beta cell function in individuals with type 1 diabetes (T1D) have focused largely on the use of single immunomodulatory agents administered within 100 days of diagnosis. Based on human and preclinical studies, we hypothesized that a combination of low-dose anti-thymocyte globulin (ATG) and pegylated granulocyte CSF (G-CSF) would preserve beta cell function in patients with established T1D (duration of T1D >4 months and <2 years). METHODS. A randomized, single-blinded, placebo-controlled trial was performed on 25 subjects: 17 subjects received ATG (2.5 mg/kg intravenously) followed by pegylated G-CSF (6 mg subcutaneously every 2 weeks for 6 doses) and 8 subjects received placebo. The primary outcome was the 1-year change in AUC C-peptide following a 2-hour mixed-meal tolerance test (MMTT). At baseline, the age (mean +/- SD) was 24.6 +/- 10 years; mean BMI was 25.4 +/- 5.2 kg/m(2); mean A1c was 6.5% +/- 1.1%; insulin use was 0.31 +/- 0.22 units/kg/d; and length of diagnosis was 1 +/- 0.5 years. RESULTS. Combination ATG/G-CSF treatment tended to preserve beta cell function in patients with established T1D. The mean difference in MMTT-stimulated AUC C-peptide between treated and placebo subjects was 0.28 nmol/l/min (95% CI 0.001-0.552, P = 0.050). A1c was lower in ATG/G-CSF-treated subjects at the 6-month study visit. ATG/G-CSF therapy was associated with relative preservation of Tregs. CONCLUSIONS. Patients with established T1D may benefit from combination immunotherapy approaches to preserve p cell function. Further studies are needed to determine whether such approaches may prevent or delay the onset of the disease.