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Use of an islet cell antibody assay to identify type 1 diabetic patients with rapid decrease in C-peptide levels after clinical onset

(2000) DIABETES CARE. 23(8). p.1072-1078
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Abstract
OBJECTIVE - To investigate whether the presence of antibody markers at diagnosis could help predict the rapid decrease in residual beta-cell function noted in some, but not all, patients with recent-onset type 1 diabetes. RESEARCH DESIGN AND METHODS - We measured random C-peptide levels (radioimmunoassay); islet cell cytoplasmic antibodies (ICA) (indirect immunofluorescence); and antibodies against IA-2 protein, 65-kDa glutamate decarboxylase, and insulin (liquid-phase radiobinding assays) in 172 patients <40 years of age with type 1 diabetes. The patients had been consecutively recruited at diagnosis by the Belgian Diabetes Registry and were followed for 2 years. RESULTS - Two years after diagnosis, random C-peptide levels had decreased significantly (P < 0.001) in ICA(+) patients but not in ICA(-) patients. C-peptide values <50 pmol/l were noted in 88% of patients diagnosed before 7 years of age, in 45% of patients diagnosed between ages 7 and 15 years, and in 29% of patients diagnosed after 15 years of age (P < 0.001). In cases of clinical onset before age 15 years, a rapid decline in random C-peptide values was observed almost exclusively in patients with high-titer ICA (greater than or equal to 50 Juvenile Diabetes Foundation [JDF] units) at diagnosis (69 vs. 17% in patients with lower ICA titers, P < 0.001). In patients diagnosed after 15 years of age, 36% of patients with ICA titers greater than or equal to 12 JDF units developed low C-peptide levels compared with 14% of patients with ICA titers <12 JDF units (P < 0.03), Multivariate analysis confirmed that C-peptide levels after 2 years were inversely correlated with ICA levels (P < 0.001) and to a lesser degree positively correlated with age at diagnosis (P < 0.02), regardless of the levels or number of molecular autoantibodies. CONCLUSIONS - Young age at diagnosis and high-titer ICA identify a group of type 1 diabetic patients at high risk of rapidly losing residual beta-cell function. Using these selection criteria, it is possible to better target beta-cell-preserving interventions to patients with or without such rapid progression, depending on the nature of the tested substance. The ICA assay measures clinically relevant antibodies nor detected in antibody assays that use recombinant human autoantigens for substrate.
Keywords
IDDM PATIENTS, PANCREATIC BETA-CELLS, INSULIN AUTOANTIBODIES, MELLITUS, CHILDREN, GAD, RISK, IA-2-AUTOANTIBODIES, DESTRUCTION, PREDICTION

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Chicago
Decochez, Katelijn, Bart Keymeulen, Guido Somers, Harry Dorchy, Ivo H De Leeuw, Chantal Mathieu, Raoul Rottiers, et al. 2000. “Use of an Islet Cell Antibody Assay to Identify Type 1 Diabetic Patients with Rapid Decrease in C-peptide Levels After Clinical Onset.” Diabetes Care 23 (8): 1072–1078.
APA
Decochez, K., Keymeulen, B., Somers, G., Dorchy, H., De Leeuw, I. H., Mathieu, C., Rottiers, R., et al. (2000). Use of an islet cell antibody assay to identify type 1 diabetic patients with rapid decrease in C-peptide levels after clinical onset. DIABETES CARE, 23(8), 1072–1078. Presented at the 35th Annual meeting of the European Association for the Study of Diabetes.
Vancouver
1.
Decochez K, Keymeulen B, Somers G, Dorchy H, De Leeuw IH, Mathieu C, et al. Use of an islet cell antibody assay to identify type 1 diabetic patients with rapid decrease in C-peptide levels after clinical onset. DIABETES CARE. 2000;23(8):1072–8.
MLA
Decochez, Katelijn, Bart Keymeulen, Guido Somers, et al. “Use of an Islet Cell Antibody Assay to Identify Type 1 Diabetic Patients with Rapid Decrease in C-peptide Levels After Clinical Onset.” DIABETES CARE 23.8 (2000): 1072–1078. Print.
@article{172071,
  abstract     = {OBJECTIVE - To investigate whether the presence of antibody markers at diagnosis could help predict the rapid decrease in residual beta-cell function noted in some, but not all, patients with recent-onset type 1 diabetes. 
RESEARCH DESIGN AND METHODS - We measured random C-peptide levels (radioimmunoassay); islet cell cytoplasmic antibodies (ICA) (indirect immunofluorescence); and antibodies against IA-2 protein, 65-kDa glutamate decarboxylase, and insulin (liquid-phase radiobinding assays) in 172 patients {\textlangle}40 years of age with type 1 diabetes. The patients had been consecutively recruited at diagnosis by the Belgian Diabetes Registry and were followed for 2 years. 
RESULTS - Two years after diagnosis, random C-peptide levels had decreased significantly (P {\textlangle} 0.001) in ICA(+) patients but not in ICA(-) patients. C-peptide values {\textlangle}50 pmol/l were noted in 88\% of patients diagnosed before 7 years of age, in 45\% of patients diagnosed between ages 7 and 15 years, and in 29\% of patients diagnosed after 15 years of age (P {\textlangle} 0.001). In cases of clinical onset before age 15 years, a rapid decline in random C-peptide values was observed almost exclusively in patients with high-titer ICA (greater than or equal to 50 Juvenile Diabetes Foundation [JDF] units) at diagnosis (69 vs. 17\% in patients with lower ICA titers, P {\textlangle} 0.001). In patients diagnosed after 15 years of age, 36\% of patients with ICA titers greater than or equal to 12 JDF units developed low C-peptide levels compared with 14\% of patients with ICA titers {\textlangle}12 JDF units (P {\textlangle} 0.03), Multivariate analysis confirmed that C-peptide levels after 2 years were inversely correlated with ICA levels (P {\textlangle} 0.001) and to a lesser degree positively correlated with age at diagnosis (P {\textlangle} 0.02), regardless of the levels or number of molecular autoantibodies. 
CONCLUSIONS - Young age at diagnosis and high-titer ICA identify a group of type 1 diabetic patients at high risk of rapidly losing residual beta-cell function. Using these selection criteria, it is possible to better target beta-cell-preserving interventions to patients with or without such rapid progression, depending on the nature of the tested substance. The ICA assay measures clinically relevant antibodies nor detected in antibody assays that use recombinant human autoantigens for substrate.},
  author       = {Decochez, Katelijn and Keymeulen, Bart and Somers, Guido and Dorchy, Harry and De Leeuw, Ivo H and Mathieu, Chantal and Rottiers, Raoul and Winnock, Frederic and ver Elst, Kristien and Weets, Ilse and Kaufman, Leonard and Pipeleers, Daniel G and Gorus, Frans K},
  issn         = {0149-5992},
  journal      = {DIABETES CARE},
  keyword      = {IDDM PATIENTS,PANCREATIC BETA-CELLS,INSULIN AUTOANTIBODIES,MELLITUS,CHILDREN,GAD,RISK,IA-2-AUTOANTIBODIES,DESTRUCTION,PREDICTION},
  language     = {eng},
  location     = {Brussels, Belgium},
  number       = {8},
  pages        = {1072--1078},
  title        = {Use of an islet cell antibody assay to identify type 1 diabetic patients with rapid decrease in C-peptide levels after clinical onset},
  url          = {http://dx.doi.org/10.2337/diacare.23.8.1072},
  volume       = {23},
  year         = {2000},
}

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