Low-Dose Anti-Thymocyte Globulin (ATG) Preserves -Cell Function and Improves HbA1c in New-Onset Type 1 Diabetes

被引：135

作者：

Haller, Michael J. ^{[1
]}

Schatz, Desmond A. ^{[1
]}

Skyler, Jay S. ^{[2
]}

Krischer, Jeffrey P. ^{[3
]}

Bundy, Brian N. ^{[3
]}

Miller, Jessica L. ^{[3
]}

Atkinson, Mark A. ^{[1
]}

Becker, Dorothy J. ^{[4
]}

Baidal, David ^{[2
]}

DiMeglio, Linda A. ^{[5
]}

Gitelman, Stephen E. ^{[6
]}

Goland, Robin ^{[7
]}

Gottlieb, Peter A. ^{[8
]}

Herold, Kevan C. ^{[9
]}

Marks, Jennifer B. ^{[2
]}

Moran, Antoinette ^{[10
]}

Rodriguez, Henry ^{[3
]}

Russell, William ^{[11
]}

Wilson, Darrell M. ^{[12
]}

Greenbaum, Carla J. ^{[13
]}

机构：

[1] Univ Florida, Gainesville, FL 32611 USA

[2] Univ Miami, Miller Sch Med, Diabet Res Inst, Miami, FL 33136 USA

[3] Univ S Florida, Tampa, FL USA

[4] Univ Pittsburgh, Pittsburgh, PA USA

[5] Indiana Univ, Indianapolis, IN 46204 USA

[6] Univ Calif San Francisco, San Francisco, CA 94143 USA

[7] Columbia Univ, New York, NY USA

[8] Univ Colorado, Barbara Davis Ctr Childhood Diabet, Aurora, CO USA

[9] Yale Univ, New Haven, CT USA

[10] Univ Minnesota, Minneapolis, MN USA

[11] Vanderbilt Univ, 221 Kirkland Hall, Nashville, TN 37235 USA

[12] Stanford Univ, Palo Alto, CA 94304 USA

[13] Benaroya Res Inst, Seattle, WA USA

来源：

DIABETES CARE | 2018年 / 41卷 / 09期

基金：

美国国家卫生研究院;

关键词：

PLACEBO-CONTROLLED TRIAL; B-LYMPHOCYTE DEPLETION; DOUBLE-BLIND; MONOCLONAL-ANTIBODY; COMBINATION THERAPY; PHASE-2; TRIAL; MELLITUS; PREDNISONE; MODULATION; RESPONDERS;

D O I：

10.2337/dc18-0494

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

OBJECTIVEA pilot study suggested that combination therapy with low-dose anti-thymocyte globulin (ATG) and pegylated granulocyte colony-stimulating factor (GCSF) preserves C-peptide in established type 1 diabetes (T1D) (duration 4 months to 2 years). We hypothesized that 1) low-dose ATG/GCSF or 2) low-dose ATG alone would slow the decline of -cell function in patients with new-onset T1D (duration <100 days).RESEARCH DESIGN AND METHODSA three-arm, randomized, double-masked, placebo-controlled trial was performed by the Type 1 Diabetes TrialNet Study Group in 89 subjects: 29 subjects randomized to ATG (2.5 mg/kg intravenously) followed by pegylated GCSF (6 mg subcutaneously every 2 weeks for 6 doses), 29 to ATG alone (2.5 mg/kg), and 31 to placebo. The primary end point was mean area under the curve (AUC) C-peptide during a 2-h mixed-meal tolerance test 1 year after initiation of therapy. Significance was defined as one-sided P value < 0.025.RESULTSThe 1-year mean AUC C-peptide was significantly higher in subjects treated with ATG (0.646 nmol/L) versus placebo (0.406 nmol/L) (P = 0.0003) but not in those treated with ATG/GCSF (0.528 nmol/L) versus placebo (P = 0.031). HbA(1c) was significantly reduced at 1 year in subjects treated with ATG and ATG/GCSF, P = 0.002 and 0.011, respectively.CONCLUSIONSLow-dose ATG slowed decline of C-peptide and reduced HbA(1c) in new-onset T1D. Addition of GCSF did not enhance C-peptide preservation afforded by low-dose ATG. Future studies should be considered to determine whether low-dose ATG alone or in combination with other agents may prevent or delay the onset of the disease.

引用

页码：1917 / 1925

页数：9