Increased reduction in fasting C-peptide is associated with islet cell antibodies in Type 1 (insulin-dependent) diabetic patients

Abstract

A cohort of 82 patients with Type 1 (insulin-dependent) diabetes was followed prospectively for 24 months, and 54 of them for 30 months, to study the relationship between fasting levels of immunoreactive C-peptide and titres of islet cell antibodies. After diagnosis, fasting C-peptide rose temporarily for 1-6 months of insulin therapy and declined continuously thereafter. While islet cell antibodies were present among 55% of the newly diagnosed patients, only 31% remained positive at 30 months. Their antibody titres decreased from 1:81 at diagnosis to 1:3. Only 3 patients (4%) who were islet cell antibody negative at diagnosis became positive later. The median C-peptide values among the persistently islet cell antibody positive patients decreased from 0.11 pmol/ml at 18 months, to 0.09 pmol/ml at 24 months, to 0.06 pmol/ml at 30 months compared to 0.18 (p = 0.04), 0.15 (p = 0.05) and 0.16 (p less than 0.003) pmol/ml, respectively, for the islet cell antibody negative patients. The median slope for the latter was -0.09 compared to -0.19 for the islet cell antibody positive patients (p = 0.01). These differences were reflected in increasing dosages of insulin, since patients remaining antibody-positive for 30 months were given 1.3-1.4 times more insulin (p = 0.01-0.004) than the antibody negative patients. This study demonstrates that islet cell antibodies may be a useful marker for predicting an increased rate by which endogenous B cell function is lost in Type 1 diabetes.

An Association of Autoantibody Status and Serum Cytokine Levels in Type 1 Diabetes

“…Evidence has been accumulating that the islet autoantibody status at diagnosis of type 1 diabetes reflects disease quality, in that patients with islet autoantibodies exhibit faster loss of endogenous ␤-cell function during the next years (12)(13)(14)(15)(16)(17)(18)(19)(20). In addition, multiple autoantibody positivity and titer seem relevant (21)(22)(23)(24)(25)(26).…”

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

“…Conflicting observations have been published in various studies, showing either no correlation (18)(19)(20), a positive correlation (21-23), or a negative correlation (24)(25)(26)(27). These conflicting results may be due to differences in patient selection criteria (e.g., age at diagnosis) and in the type and methodology of the biologic markers used.…”

“…The assay depends on the quality of the donor organ used, is difficult to standardize, and yields, at best, semiquantitive results (4,39). Interlaboratory differences in ICA technology and the use of small or selected patient groups are factors that may help explain previous conflicting reports on the relationship between ICA and C-peptide levels (18)(19)(20)(21)(22)(23)(24)(25)(26)(27). ICA are made up of a mix of autoantibodies with different specificities, including IA-2A and GADA.…”

Assessment of precision, concordance, specificity, and sensitivity of islet cell antibody measurement in 41 assays

“…Precise quantitative assays have been identified and reference standards and common units established. [7,8], or undergoing therapeutic trials with cyclosporine [9,10]. Since ICA were first described [11], numerous methodological modifications to the standard indirect immunofluorescent (IFL) assay have been proposed [12][13][14][15][16][17][18].…”

“…Islet cell antibody (ICA) determinations have been used as a serological marker for the identification of individuals at risk of developing Type 1 (insulin-dependent) diabetes mellitus [1][2][3]; the diagnosis of Type 1 diabetes in cases of secondary failure, or unusual presentation [4][5][6]; and * S.Assa, Perah-Tiqua, Israel; A.Arnaiz-Villena, Madrid, Spain; J. Barbosa, Minneapolis, Minnesota, USA; C. Betterle, Padua, Italy, E. Beutner, Buffalo, New York, USA; G. Bright, Charleston, South Carolina, USA; H.Chapel, Oxford, U.K.; M.Codina, Barcelona, Spain; R. Dawkins, Perth, Western Australia; E. Deitsch, Vienna, Austria; U.Di Mario, Rome, Italy; G.Eisenbarth, Boston, Massachusetts, USA; R. Elliot, Auckland, New Zealand; R. Gomis de Barbara, Barcelona, Spain; T. Hanafusa, Osaka, Japan; L. Harrison, Victoria, Australia; K.Helmke, Giessen, FRG; C.Howard, Oregon, USA; P. In't Veld, Brussels, Belgium; D. Kawathara, Orange, California, USA; T. Kobayashi, Tokyo, Japan; M. Landin, Malm6, Sweden; A.Lernmark, Gentoft, Denmark; N.Maclaren, Gainesville, Florida, USA; T. Mandrup-Poulsen, Gentofte, Denmark; R. Manna, Rome, Italy; A. Miettinen, Finland; J. Palmer, Seattle, Washington, USA; R Panczel, Budapest, Hungary, J. Peter, Los Angeles, California, USA; K. Pirich, Vienna, Austria; L. Quenette, La Jolla, California, USA; G.Reeves, Nottingham, UK; K.Reinauer, Tt~bingen, FRG; W. Scherbaum, Ulm FRG; L. Scott-Morgan, Southampton, UK; D. Vergani, London, U. K.; B. Vialettes, Marseille, France monitoring patients on insulin therapy [7,8], or undergoing therapeutic trials with cyclosporine [9,10]. Since ICA were first described [11], numerous methodological modifications to the standard indirect immunofluorescent (IFL) assay have been proposed [12][13][14][15][16][17][18].…”