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Low-Dose Anti-Thymocyte Globulin Preserves C-Peptide, Reduces HbA 1c , and Increases Regulatory to Conventional T-Cell Ratios in New-Onset Type 1 Diabetes: Two-Year Clinical Trial Data.
- Source :
-
Diabetes [Diabetes] 2019 Jun; Vol. 68 (6), pp. 1267-1276. Date of Electronic Publication: 2019 Apr 09. - Publication Year :
- 2019
-
Abstract
- A three-arm, randomized, double-masked, placebo-controlled phase 2b trial performed by the Type 1 Diabetes TrialNet Study Group previously demonstrated that low-dose anti-thymocyte globulin (ATG) (2.5 mg/kg) preserved β-cell function and reduced HbA <subscript>1c</subscript> for 1 year in new-onset type 1 diabetes. Subjects ( N = 89) were randomized to 1 ) ATG and pegylated granulocyte colony-stimulating factor (GCSF), 2 ) ATG alone, or 3 ) placebo. Herein, we report 2-year area under the curve (AUC) C-peptide and HbA <subscript>1c</subscript> , prespecified secondary end points, and potential immunologic correlates. The 2-year mean mixed-meal tolerance test-stimulated AUC C-peptide, analyzed by ANCOVA adjusting for baseline C-peptide, age, and sex ( n = 82) with significance defined as one-sided P < 0.025, was significantly higher in subjects treated with ATG versus placebo ( P = 0.00005) but not ATG/GCSF versus placebo ( P = 0.032). HbA <subscript>1c</subscript> was significantly reduced at 2 years in subjects treated with ATG ( P = 0.011) and ATG/GCSF ( P = 0.022) versus placebo. Flow cytometry analyses demonstrated reduced circulating CD4:CD8 ratio, increased regulatory T-cell:conventional CD4 T-cell ratios, and increased PD-1 <superscript>+</superscript> CD4 <superscript>+</superscript> T cells following low-dose ATG and ATG/GCSF. Low-dose ATG partially preserved β-cell function and reduced HbA <subscript>1c</subscript> 2 years after therapy in new-onset type 1 diabetes. Future studies should determine whether low-dose ATG might prevent or delay the onset of type 1 diabetes.<br /> (© 2019 by the American Diabetes Association.)
- Subjects :
- Adolescent
Adult
C-Peptide metabolism
CD4-CD8 Ratio
Child
Diabetes Mellitus, Type 1 immunology
Diabetes Mellitus, Type 1 metabolism
Double-Blind Method
Female
Flow Cytometry
Glycated Hemoglobin metabolism
Granulocyte Colony-Stimulating Factor therapeutic use
Humans
Male
T-Lymphocytes, Regulatory immunology
Young Adult
Antilymphocyte Serum therapeutic use
Diabetes Mellitus, Type 1 drug therapy
Immunologic Factors therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1939-327X
- Volume :
- 68
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Diabetes
- Publication Type :
- Academic Journal
- Accession number :
- 30967424
- Full Text :
- https://doi.org/10.2337/db19-0057