GAD autoantibodies and epitope reactivities persist after diagnosis in latent autoimmune diabetes in adults but do not predict disease progression: UKPDS 77

M. Desai, C. A. Cull, V. A. Horton, M. R. Christie, E. Bonifacio, V. Lampasona, P. J. Bingley, J. C. Levy, I. R. Mackay, P. Zimmet, R. R. Holman, A. Clark

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Aims/hypothesis: Latent autoimmune diabetes in adults (LADA) is a slowly progressive form of autoimmune diabetes, with autoantibodies to islet proteins developing in older patients who have no immediate requirement for insulin therapy. Markers of its clinical course are uncharacterised. The aim of this study was to determine whether persistence of, or changes in, GAD65 autoantibodies (GADAs) in the LADA patients who participated in the United Kingdom Prospective Diabetes Study (UKPDS) were associated with disease progression or insulin requirement. Methods: GADA levels and their relative epitope reactivities to N-terminal, middle and C-terminal regions of human GAD65 were determined in 242 UKPDS patients who were GADA-positive at diagnosis; samples taken after 0.5, 3 and 6 years of follow-up were tested using a radiobinding assay. Comparisons were made of GADA status with clinical details and disease progression assessed by the requirement for intensified glucose-lowering therapy. Results: GADA levels fluctuated between 0.5 and 6 years but persisted in 225 of 242 patients. No association of GADA levels with disease progression or insulin requirement was observed. Antibody reactivity was directed to C-terminal and middle epitopes of GAD65 in >70% patients, and the N-terminal in <9%. There were no changes in epitope reactivity pattern over the 6 year follow-up period, nor any association between epitope reactivity and insulin requirement. Conclusions/interpretation: GADAs persist for 6 years after diagnosis of LADA, but levels and reactivity to different GAD65 epitopes are not associated with disease progression.

LanguageEnglish
Pages2052-2060
Number of pages9
JournalDiabetologia
Volume50
Issue number10
DOIs
Publication statusPublished - 1 Oct 2007

Keywords

  • Antibody persistence
  • Clinical progression
  • GAD antibodies
  • Latent autoimmune diabetes in adults
  • Type 1 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Desai, M. ; Cull, C. A. ; Horton, V. A. ; Christie, M. R. ; Bonifacio, E. ; Lampasona, V. ; Bingley, P. J. ; Levy, J. C. ; Mackay, I. R. ; Zimmet, P. ; Holman, R. R. ; Clark, A. / GAD autoantibodies and epitope reactivities persist after diagnosis in latent autoimmune diabetes in adults but do not predict disease progression : UKPDS 77. In: Diabetologia. 2007 ; Vol. 50, No. 10. pp. 2052-2060.
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abstract = "Aims/hypothesis: Latent autoimmune diabetes in adults (LADA) is a slowly progressive form of autoimmune diabetes, with autoantibodies to islet proteins developing in older patients who have no immediate requirement for insulin therapy. Markers of its clinical course are uncharacterised. The aim of this study was to determine whether persistence of, or changes in, GAD65 autoantibodies (GADAs) in the LADA patients who participated in the United Kingdom Prospective Diabetes Study (UKPDS) were associated with disease progression or insulin requirement. Methods: GADA levels and their relative epitope reactivities to N-terminal, middle and C-terminal regions of human GAD65 were determined in 242 UKPDS patients who were GADA-positive at diagnosis; samples taken after 0.5, 3 and 6 years of follow-up were tested using a radiobinding assay. Comparisons were made of GADA status with clinical details and disease progression assessed by the requirement for intensified glucose-lowering therapy. Results: GADA levels fluctuated between 0.5 and 6 years but persisted in 225 of 242 patients. No association of GADA levels with disease progression or insulin requirement was observed. Antibody reactivity was directed to C-terminal and middle epitopes of GAD65 in >70{\%} patients, and the N-terminal in <9{\%}. There were no changes in epitope reactivity pattern over the 6 year follow-up period, nor any association between epitope reactivity and insulin requirement. Conclusions/interpretation: GADAs persist for 6 years after diagnosis of LADA, but levels and reactivity to different GAD65 epitopes are not associated with disease progression.",
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Desai, M, Cull, CA, Horton, VA, Christie, MR, Bonifacio, E, Lampasona, V, Bingley, PJ, Levy, JC, Mackay, IR, Zimmet, P, Holman, RR & Clark, A 2007, 'GAD autoantibodies and epitope reactivities persist after diagnosis in latent autoimmune diabetes in adults but do not predict disease progression: UKPDS 77', Diabetologia, vol. 50, no. 10, pp. 2052-2060. https://doi.org/10.1007/s00125-007-0745-6

GAD autoantibodies and epitope reactivities persist after diagnosis in latent autoimmune diabetes in adults but do not predict disease progression : UKPDS 77. / Desai, M.; Cull, C. A.; Horton, V. A.; Christie, M. R.; Bonifacio, E.; Lampasona, V.; Bingley, P. J.; Levy, J. C.; Mackay, I. R.; Zimmet, P.; Holman, R. R.; Clark, A.

In: Diabetologia, Vol. 50, No. 10, 01.10.2007, p. 2052-2060.

Research output: Contribution to journalArticle

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T1 - GAD autoantibodies and epitope reactivities persist after diagnosis in latent autoimmune diabetes in adults but do not predict disease progression

T2 - Diabetologia

AU - Desai, M.

AU - Cull, C. A.

AU - Horton, V. A.

AU - Christie, M. R.

AU - Bonifacio, E.

AU - Lampasona, V.

AU - Bingley, P. J.

AU - Levy, J. C.

AU - Mackay, I. R.

AU - Zimmet, P.

AU - Holman, R. R.

AU - Clark, A.

PY - 2007/10/1

Y1 - 2007/10/1

N2 - Aims/hypothesis: Latent autoimmune diabetes in adults (LADA) is a slowly progressive form of autoimmune diabetes, with autoantibodies to islet proteins developing in older patients who have no immediate requirement for insulin therapy. Markers of its clinical course are uncharacterised. The aim of this study was to determine whether persistence of, or changes in, GAD65 autoantibodies (GADAs) in the LADA patients who participated in the United Kingdom Prospective Diabetes Study (UKPDS) were associated with disease progression or insulin requirement. Methods: GADA levels and their relative epitope reactivities to N-terminal, middle and C-terminal regions of human GAD65 were determined in 242 UKPDS patients who were GADA-positive at diagnosis; samples taken after 0.5, 3 and 6 years of follow-up were tested using a radiobinding assay. Comparisons were made of GADA status with clinical details and disease progression assessed by the requirement for intensified glucose-lowering therapy. Results: GADA levels fluctuated between 0.5 and 6 years but persisted in 225 of 242 patients. No association of GADA levels with disease progression or insulin requirement was observed. Antibody reactivity was directed to C-terminal and middle epitopes of GAD65 in >70% patients, and the N-terminal in <9%. There were no changes in epitope reactivity pattern over the 6 year follow-up period, nor any association between epitope reactivity and insulin requirement. Conclusions/interpretation: GADAs persist for 6 years after diagnosis of LADA, but levels and reactivity to different GAD65 epitopes are not associated with disease progression.

AB - Aims/hypothesis: Latent autoimmune diabetes in adults (LADA) is a slowly progressive form of autoimmune diabetes, with autoantibodies to islet proteins developing in older patients who have no immediate requirement for insulin therapy. Markers of its clinical course are uncharacterised. The aim of this study was to determine whether persistence of, or changes in, GAD65 autoantibodies (GADAs) in the LADA patients who participated in the United Kingdom Prospective Diabetes Study (UKPDS) were associated with disease progression or insulin requirement. Methods: GADA levels and their relative epitope reactivities to N-terminal, middle and C-terminal regions of human GAD65 were determined in 242 UKPDS patients who were GADA-positive at diagnosis; samples taken after 0.5, 3 and 6 years of follow-up were tested using a radiobinding assay. Comparisons were made of GADA status with clinical details and disease progression assessed by the requirement for intensified glucose-lowering therapy. Results: GADA levels fluctuated between 0.5 and 6 years but persisted in 225 of 242 patients. No association of GADA levels with disease progression or insulin requirement was observed. Antibody reactivity was directed to C-terminal and middle epitopes of GAD65 in >70% patients, and the N-terminal in <9%. There were no changes in epitope reactivity pattern over the 6 year follow-up period, nor any association between epitope reactivity and insulin requirement. Conclusions/interpretation: GADAs persist for 6 years after diagnosis of LADA, but levels and reactivity to different GAD65 epitopes are not associated with disease progression.

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KW - Clinical progression

KW - GAD antibodies

KW - Latent autoimmune diabetes in adults

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