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Low-Dose Anti-Thymocyte Globulin Preserves C-Peptide, Reduces HbA1c, and Increases Regulatory to Conventional T-Cell Ratios in New-Onset Type 1 Diabetes: Two-Year Clinical Trial Data
- Source :
- Diabetes
- Publication Year :
- 2019
- Publisher :
- American Diabetes Association, 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 HbA1c 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 HbA1c, 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). HbA1c 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+CD4+ T cells following low-dose ATG and ATG/GCSF. Low-dose ATG partially preserved β-cell function and reduced HbA1c 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.
- Subjects :
- 0301 basic medicine
Adult
Male
medicine.medical_specialty
Adolescent
Endocrinology, Diabetes and Metabolism
T cell
CD4-CD8 Ratio
030209 endocrinology & metabolism
Placebo
T-Lymphocytes, Regulatory
03 medical and health sciences
chemistry.chemical_compound
Young Adult
0302 clinical medicine
Double-Blind Method
Internal medicine
Diabetes mellitus
Granulocyte Colony-Stimulating Factor
Internal Medicine
medicine
Humans
Immunologic Factors
Child
Antilymphocyte Serum
Glycated Hemoglobin
Type 1 diabetes
C-Peptide
C-peptide
business.industry
Area under the curve
medicine.disease
Flow Cytometry
Anti-thymocyte globulin
030104 developmental biology
Endocrinology
medicine.anatomical_structure
Diabetes Mellitus, Type 1
chemistry
Female
Immunology and Transplantation
business
CD8
Subjects
Details
- Language :
- English
- ISSN :
- 1939327X and 00121797
- Volume :
- 68
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Diabetes
- Accession number :
- edsair.doi.dedup.....e408ecd37f3201a76d7f54cd07b1a446