Context: Antibodies to the 65 kD isoform of glutamic acid decarboxylase (GAD65) have been associated with incident Type 2 Diabetes Mellitus, however results are inconsistent. Objective: To assess the association between GAD65 antibody positivity and incident Type 2 Diabetes Mellitus in a non-diabetic adult (≥18 years) population, in a systematic review and meta-analysis. Data Sources: A systematic literature search was conducted in Pubmed (MEDLINE) and Embase until January 14th, 2019. Study Selection: Included studies were 1) prospective studies on the association between GAD65 antibodies and incident Type 2 Diabetes Mellitus; 2) in a non-diabetic adult (≥18 years) population. To strengthen the review, unpublished data from 1302 Hoorn Study participants were included. Data Extraction: Data extraction and quality assessment were performed independently by two observers. Ten studies were rated for methodological quality and seven were pooled using a random-effects meta-analysis, of which 2 strong, 2 moderate and 3 of low methodological quality. Data Synthesis: The pooled risk estimate of incident Type 2 Diabetes Mellitus for GAD65 antibody positivity, compared to GAD65 antibody negativity was 3.36 (95% CI: 1.9–5.9). This result was robust to sensitivity analyses. Heterogeneity between studies was significant with I 2 statistic of 79% (p < 0.0001). However, excluding one study showed a decrease of I 2 to 19% (p < 0.0001), explaining a large part of the heterogeneity. Conclusion: GAD65 antibody positivity was associated with an increased risk of future Type 2 Diabetes Mellitus in adults.
Koopman, A. D. M., Beulens, J. W., Voerman, E., Rauh, S. P., van der Heijden, A. A., McDonald, T. J., ... Rutters, F. (2019). The association between GAD65 antibody levels and incident Type 2 Diabetes Mellitus in an adult population: A meta-analysis. Metabolism: Clinical and Experimental, 95, 1-7. https://doi.org/10.1016/j.metabol.2019.03.001