The association between GAD65 antibody levels and incident Type 2 Diabetes Mellitus in an adult population: A meta-analysis

Antibodies to the 65 kD isoform of glutamic acid decarboxylase (GAD65) have been associated with incident Type 2 Diabetes Mellitus, however results are inconsistent. 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. A systematic literature search was conducted in Pubmed (MEDLINE) and Embase until January 14th, 2019. 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 To strengthen the review, unpublished data from 1302 Hoorn Study participants were included.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 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. 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 I2 statistic of 79% (p