title: High levels of antigen-specific islet antibodies predict future beta-cell failure in patients with onset of diabetes in adult age.
abstract: It is unclear whether high levels of antigen-specific islet antibodies [GADA (glutamic acid decarboxylase 65 antibodies) and IA2-ab (protein tyrosine phosphatase-like protein antibodies)] predict beta-cell failure in patients with onset of diabetes in adult age. Therefore, GADA and IA2-ab levels at the diagnosis of diabetes were related to fasting plasma C-peptide levels 5 yr later in 148 patients with diabetes onset in adult age (age at onset, 20-77 yr; median, 57 yr). Classical islet cell antibodies (ICA) were also determined. Complete beta-cell failure (undetectable fasting plasma C-peptide) was only present in 4 patients at diagnosis of diabetes, but in 21 patients 5 yr thereafter. At diagnosis, ICA were detected in 20 of 21 (95%) patients with beta-cell failure after 5 yr and in only 7 of 127 (5%) without, whereas GADA and/or IA2-ab (>97.5 percentile of healthy controls) were detected in all 21 (100%) with but also in 23 of 127 (18%) patients without beta-cell failure after 5 yr. Thus, ICA had a higher positive predictive value (74%) than GADA and/or IA2-ab (47%; P < 0.05). With high cutoff values for GADA and IA2-ab, however, GADA and/or IA2-ab were detected in 19 of 21 (90%) patients with beta-cell failure vs. only in 5 of 127 (4%) without, giving a positive predictive value of 79%. Slightly elevated GADA levels in IA2-ab-negative patients were associated with progressive but not complete beta-cell failure within the study period. Hence, high GADA and/or IA2-ab levels predict a future complete beta-cell failure, whereas low GADA levels predict slowly progressive beta-cell insufficiency.
authors.affiliation: Department of Endocrinology, University of Lund, Malmö University Hospital, SE-205 02 Malmö, Sweden. Henrik.Borg@endo.mas.lu.se
authors.forename: H
authors.initials: H
authors.lastname: Borg
authors.forename: A
authors.initials: A
authors.lastname: Gottsäter
authors.forename: M
authors.initials: M
authors.lastname: Landin-Olsson
authors.forename: P
authors.initials: P
authors.lastname: Fernlund
authors.forename: G
authors.initials: G
authors.lastname: Sundkvist
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D002096:C-Peptide / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000503:physiopathology; D005215:Fasting; D005260:Female; D005934:Glucagon; D005951:Glucose Tolerance Test; D005968:Glutamate Decarboxylase / Q000276:immunology; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology* / Q000503:physiopathology*; D007700:Kinetics; D008297:Male; D008565:Membrane Proteins / Q000276:immunology; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000276:immunology; D011446:Prospective Studies; D012372:ROC Curve; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D012680:Sensitivity and Specificity
chemical_list: D001323:Autoantibodies; D002096:C-Peptide; D005934:Glucagon; D005968:Glutamate Decarboxylase; D006442:Glycated Hemoglobin; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; C516864:Ptprn protein, rat