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High Levels of Antigen-Specific Islet Antibodies Predict Future ß-Cell Failure in Patients with Onset of Diabetes in Adult Age¹

Departments of Endocrinology (H.B., G.S.), Vascular Diseases (A.G.), and Clinical Chemistry (P.F.), University of Lund, Malmö University Hospital, SE-205 02 Malmö; and Department of Medicine (M.L.-O.), Lund University, Lund University Hospital, SE-221 85 Lund, Sweden

Address correspondence and requests for reprints to: Dr. H. Borg, Wallenberg Laboratory, Entrance 46 2nd floor, Malmö University Hospital, SE-205 02 Malmö, Sweden. E-mail: Henrik.Borg{at}endo.mas.lu.se

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 ß-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 ß-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 ß-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 ß-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 ß-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 ß-cell failure within the study period. Hence, high GADA and/or IA2-ab levels predict a future complete ß-cell failure, whereas low GADA levels predict slowly progressive ß-cell insufficiency.

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