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- Title
Masked and overt autoantibodies specific to the DPD epitope of 65-kDa glutamate decarboxylase (GAD65-DPD) are associated with preserved β-cell functional reserve in ketosis-prone diabetes.
- Authors
Oak, Shilpa; Gaur, Lakshmi K; Radtke, Jared; Patel, Roshni; Iyer, Dinakar; Ram, Nalini; Gaba, Ruchi; Balasubramanyam, Ashok; Hampe, Christiane S
- Abstract
<bold>Context: </bold>Ketosis-prone diabetes (KPD), defined by presentation with diabetic ketoacidosis (DKA), comprises 4 subgroups based on the presence or absence of islet cell autoantibodies (A(-) or A(+)) and β-cell functional reserve (β(-) or β(+)). Among A(+) KPD, autoantibody epitope reactivity to 65-kDa glutamate decarboxylase (GAD65), defined by monoclonal GAD65Ab(DPD), was associated with greater β-cell functional reserve. In a majority of healthy individuals, GAD65Ab are present in the sera but are masked by anti-idiotypic antibodies; in contrast, overtly GAD65Ab-positive patients with autoimmune type 1 diabetes patients lack these anti-idiotypic antibodies.<bold>Objective: </bold>Our objective was to determine the presence of masked and overt GAD65Ab(DPD) in relation to β-cell function and genetic risk factors in KPD patients.<bold>Design: </bold>We investigated the associations of masked and overt GAD65Ab(DPD) with β-cell functional reserve, and their relationship with human leukocyte antigen (HLA) class II haplotypes linked to autoimmune diabetes susceptibility or resistance, in a large KPD cohort.<bold>Patients: </bold>Adult KPD patients (n = 384) were followed longitudinally in a research clinic.<bold>Main Outcome Measures: </bold>β-Cell function, autoantibody status, GAD65Ab epitopes, and HLA class II haplotypes were evaluated.<bold>Results: </bold>Overall, KPD patients with β-cell functional reserve (β(+) subgroups) showed significantly higher frequency of masked GAD65Ab(DPD) than patients without β-cell functional reserve (β(-) subgroups): 112 of 144 (79%) compared with 59 of 100 (59%), respectively (P = .002). Masked or overt GAD65Ab(DPD) were also more frequent among autoantibody-positive patients with preserved β-cell functional reserve (A(+)β(+) KPD) than those lacking β-cell function (A(+)β(-) KPD): 77% compared with 55% (P = .01). The susceptibility HLA haplotypes DQA1*0301/DQB1*0302 and DQA1*0301/DQB1*0201 were associated with absence of overt or masked GAD65Ab(DPD) (odds Ratios 2.3 and 2.2, respectively).<bold>Conclusions: </bold>Masked GAD65Ab(DPD) are strongly associated with preserved β-cell functional reserve among patients with KPD. Absence of GAD65Ab(DPD) reactivity is associated with 2 HLA class II susceptibility haplotypes for autoimmune type 1 diabetes.
- Publication
Journal of Clinical Endocrinology & Metabolism, 2014, Vol 99, Issue 6, pE1040
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/jc.2013-4189