Low-dose anti-thymocyte globulin (ATG) preserves β-cell function and improves HbA1c in new-onset type 1 diabetes

Michael J. Haller, Desmond A. Schatz, Jay S. Skyler, Jeffrey P. Krischer, Brian N. Bundy, Jessica L. Miller, Mark A. Atkinson, Dorothy J. Becker, David Baidal, Linda DiMeglio, Stephen E. Gitelman, Robin Goland, Peter A. Gottlieb, Kevan C. Herold, Jennifer B. Marks, Antoinette Moran, Henry Rodriguez, William Russell, Darrell M. Wilson, Carla J. Greenbaum

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

OBJECTIVE: A 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 β-cell function in patients with new-onset T1D (duration <100 days). RESEARCH DESIGN AND METHODS: A three-arm, randomized, double-masked, placebo-controlled trial was performed by the Type 1 Diabetes TrialNet Study Group in89 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. RESULTS: The 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). HbA1c was significantly reduced at 1 year in subjects treated with ATG and ATG/GCSF, P = 0.002 and 0.011, respectively. CONCLUSIONS: Low-dose ATG slowed decline of C-peptide and reduced HbA1c in new-onset T1D. Addition of GCSF did not enhance C-peptide preservation afforded by low-dose ATG. Futurestudies should be considered to determine wheth erlow-dose ATG aloneorin combination with other agents may prevent or delay the onset of the disease.

Original languageEnglish (US)
Pages (from-to)1917-1925
Number of pages9
JournalDiabetes Care
Volume41
Issue number9
DOIs
StatePublished - Sep 1 2018

Fingerprint

Antilymphocyte Serum
Type 1 Diabetes Mellitus
C-Peptide
Granulocyte Colony-Stimulating Factor
Placebos
Area Under Curve
Granulocyte-Macrophage Colony-Stimulating Factor
Meals
Research Design

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

Cite this

Haller, M. J., Schatz, D. A., Skyler, J. S., Krischer, J. P., Bundy, B. N., Miller, J. L., ... Greenbaum, C. J. (2018). Low-dose anti-thymocyte globulin (ATG) preserves β-cell function and improves HbA1c in new-onset type 1 diabetes. Diabetes Care, 41(9), 1917-1925. https://doi.org/10.2337/dc18-0494

Low-dose anti-thymocyte globulin (ATG) preserves β-cell function and improves HbA1c in new-onset type 1 diabetes. / Haller, Michael J.; Schatz, Desmond A.; Skyler, Jay S.; Krischer, Jeffrey P.; Bundy, Brian N.; Miller, Jessica L.; Atkinson, Mark A.; Becker, Dorothy J.; Baidal, David; DiMeglio, Linda; Gitelman, Stephen E.; Goland, Robin; Gottlieb, Peter A.; Herold, Kevan C.; Marks, Jennifer B.; Moran, Antoinette; Rodriguez, Henry; Russell, William; Wilson, Darrell M.; Greenbaum, Carla J.

In: Diabetes Care, Vol. 41, No. 9, 01.09.2018, p. 1917-1925.

Research output: Contribution to journalArticle

Haller, MJ, Schatz, DA, Skyler, JS, Krischer, JP, Bundy, BN, Miller, JL, Atkinson, MA, Becker, DJ, Baidal, D, DiMeglio, L, Gitelman, SE, Goland, R, Gottlieb, PA, Herold, KC, Marks, JB, Moran, A, Rodriguez, H, Russell, W, Wilson, DM & Greenbaum, CJ 2018, 'Low-dose anti-thymocyte globulin (ATG) preserves β-cell function and improves HbA1c in new-onset type 1 diabetes', Diabetes Care, vol. 41, no. 9, pp. 1917-1925. https://doi.org/10.2337/dc18-0494
Haller, Michael J. ; Schatz, Desmond A. ; Skyler, Jay S. ; Krischer, Jeffrey P. ; Bundy, Brian N. ; Miller, Jessica L. ; Atkinson, Mark A. ; Becker, Dorothy J. ; Baidal, David ; DiMeglio, Linda ; Gitelman, Stephen E. ; Goland, Robin ; Gottlieb, Peter A. ; Herold, Kevan C. ; Marks, Jennifer B. ; Moran, Antoinette ; Rodriguez, Henry ; Russell, William ; Wilson, Darrell M. ; Greenbaum, Carla J. / Low-dose anti-thymocyte globulin (ATG) preserves β-cell function and improves HbA1c in new-onset type 1 diabetes. In: Diabetes Care. 2018 ; Vol. 41, No. 9. pp. 1917-1925.
@article{51bf2d2d15f444debb230691b1158cb3,
title = "Low-dose anti-thymocyte globulin (ATG) preserves β-cell function and improves HbA1c in new-onset type 1 diabetes",
abstract = "OBJECTIVE: A 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 β-cell function in patients with new-onset T1D (duration <100 days). RESEARCH DESIGN AND METHODS: A three-arm, randomized, double-masked, placebo-controlled trial was performed by the Type 1 Diabetes TrialNet Study Group in89 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. RESULTS: The 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). HbA1c was significantly reduced at 1 year in subjects treated with ATG and ATG/GCSF, P = 0.002 and 0.011, respectively. CONCLUSIONS: Low-dose ATG slowed decline of C-peptide and reduced HbA1c in new-onset T1D. Addition of GCSF did not enhance C-peptide preservation afforded by low-dose ATG. Futurestudies should be considered to determine wheth erlow-dose ATG aloneorin combination with other agents may prevent or delay the onset of the disease.",
author = "Haller, {Michael J.} and Schatz, {Desmond A.} and Skyler, {Jay S.} and Krischer, {Jeffrey P.} and Bundy, {Brian N.} and Miller, {Jessica L.} and Atkinson, {Mark A.} and Becker, {Dorothy J.} and David Baidal and Linda DiMeglio and Gitelman, {Stephen E.} and Robin Goland and Gottlieb, {Peter A.} and Herold, {Kevan C.} and Marks, {Jennifer B.} and Antoinette Moran and Henry Rodriguez and William Russell and Wilson, {Darrell M.} and Greenbaum, {Carla J.}",
year = "2018",
month = "9",
day = "1",
doi = "10.2337/dc18-0494",
language = "English (US)",
volume = "41",
pages = "1917--1925",
journal = "Diabetes Care",
issn = "1935-5548",
publisher = "American Diabetes Association Inc.",
number = "9",

}

TY - JOUR

T1 - Low-dose anti-thymocyte globulin (ATG) preserves β-cell function and improves HbA1c in new-onset type 1 diabetes

AU - Haller, Michael J.

AU - Schatz, Desmond A.

AU - Skyler, Jay S.

AU - Krischer, Jeffrey P.

AU - Bundy, Brian N.

AU - Miller, Jessica L.

AU - Atkinson, Mark A.

AU - Becker, Dorothy J.

AU - Baidal, David

AU - DiMeglio, Linda

AU - Gitelman, Stephen E.

AU - Goland, Robin

AU - Gottlieb, Peter A.

AU - Herold, Kevan C.

AU - Marks, Jennifer B.

AU - Moran, Antoinette

AU - Rodriguez, Henry

AU - Russell, William

AU - Wilson, Darrell M.

AU - Greenbaum, Carla J.

PY - 2018/9/1

Y1 - 2018/9/1

N2 - OBJECTIVE: A 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 β-cell function in patients with new-onset T1D (duration <100 days). RESEARCH DESIGN AND METHODS: A three-arm, randomized, double-masked, placebo-controlled trial was performed by the Type 1 Diabetes TrialNet Study Group in89 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. RESULTS: The 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). HbA1c was significantly reduced at 1 year in subjects treated with ATG and ATG/GCSF, P = 0.002 and 0.011, respectively. CONCLUSIONS: Low-dose ATG slowed decline of C-peptide and reduced HbA1c in new-onset T1D. Addition of GCSF did not enhance C-peptide preservation afforded by low-dose ATG. Futurestudies should be considered to determine wheth erlow-dose ATG aloneorin combination with other agents may prevent or delay the onset of the disease.

AB - OBJECTIVE: A 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 β-cell function in patients with new-onset T1D (duration <100 days). RESEARCH DESIGN AND METHODS: A three-arm, randomized, double-masked, placebo-controlled trial was performed by the Type 1 Diabetes TrialNet Study Group in89 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. RESULTS: The 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). HbA1c was significantly reduced at 1 year in subjects treated with ATG and ATG/GCSF, P = 0.002 and 0.011, respectively. CONCLUSIONS: Low-dose ATG slowed decline of C-peptide and reduced HbA1c in new-onset T1D. Addition of GCSF did not enhance C-peptide preservation afforded by low-dose ATG. Futurestudies should be considered to determine wheth erlow-dose ATG aloneorin combination with other agents may prevent or delay the onset of the disease.

UR - http://www.scopus.com/inward/record.url?scp=85052680633&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85052680633&partnerID=8YFLogxK

U2 - 10.2337/dc18-0494

DO - 10.2337/dc18-0494

M3 - Article

VL - 41

SP - 1917

EP - 1925

JO - Diabetes Care

JF - Diabetes Care

SN - 1935-5548

IS - 9

ER -