Visit to visit transition in TXNIPgene methylation and the risk of type 2 diabetes mellitus: a nested case-control study

Our study aimed to investigate the association between the transition of the TXNIPgene methylation level and the risk of incident type 2 diabetes mellitus (T2DM). This study included 263 incident cases of T2DM and 263 matched non-T2DM participants. According to the methylation levels of five loci (CpG1–5; chr1:145441102-145442001) on the TXNIPgene, the participants were classified into four transition groups: maintained low, low to high, high to low, and maintained high methylation levels. Compared with individuals whose methylation level of CpG2–5 at the TXNIPgene was maintained low, individuals with maintained high methylation levels showed a 61–87% reduction in T2DM risk (66% for CpG2 [OR: 0.34, 95% CI: 0.14, 0.80]; 77% for CpG3 [OR: 0.23, 95% CI: 0.07, 0.78]; 87% for CpG4 [OR: 0.13, 95% CI: 0.03, 0.56]; and 61% for CpG5 [OR: 0.39, 95% CI: 0.16, 0.92]). Maintained high methylation levels of four loci of the TXNIPgene are associated with a reduction of T2DM incident risk in the current study. Our study suggests that preserving hypermethylation levels of the TXNIPgene may hold promise as a potential preventive measure against the onset of T2DM.