Context: Latentautoimmunediabetes in adults(LADA)includesaheterogeneous population wherein, based on glutamic acid decarboxylase antibody (GADA) titer, different subgroups of subjects can be identified. Objective: The aim of the present study was to evaluateGADAtiter-related risk for-cell and other organ-specific autoimmunity in LADA subjects. Methods: Adult-onsetautoimmunediabetes subjects (n236)andtype 2 diabetes (T2DM) subjects (n 450) were characterized for protein tyrosine phosphatase (IA-2IC and IA-2256–760), zinc transporter 8 (ZnT8), thyroid peroxidase, (TPO), steroid 21-hydroxylase (21-OH), tissue transglutaminase (tTG), and antiparietal cell (APC) antibodies. Results: High GADA titer compared to low GADA titer showed a significantly higher prevalence of IA-2IC, IA-2256–760, ZnT8, TPO, and APC antibodies (P 0.04 for all comparison). 21-OH antibodies were detected in 3.4% of high GADA titer. A significant decreasing trend was observed from high GADA to low GADA and to T2DM subjects for IA-2256–760, ZnT8, TPO, tTG, and APC antibodies (P for trend0.001).TPOwas the only antibody showing a different prevalence between gender; low GADA titer and T2DM female patients had a higher frequency of TPO antibody compared to males (P0.0004 and P0.0006, respectively), where the presence of highGADAtiter conferred an odds ratio of 8.6 for TPO compared to low GADA titer. After subdividing high and low GADA titer subjects according to the number of antibodies, we observed that 73.3% of high GADA titer subjects were positive for at least one or more antibodies, compared to 38.3% of low GADA titer (P 0.0001). Conclusions: In LADA subjects, high GADA titer was associated with a profile of more severe autoimmunity and, in male gender, specifically predisposed to thyroid autoimmunity. A regular screening for other antibodies is recommended in LADA patients according to GADA titer and gender.
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