Decreased Alu methylation in type 2 diabetes mellitus patients increases HbA1c levels

Abstract

IntroductionAlu hypomethylation is a common epigenetic process that promotes genomic instability with aging phenotypes, which leads to type 2 diabetes mellitus (type 2 DM). Previously, our results showed significantly decreased Alu methylation levels in type 2 DM patients. In this study, we aimed to investigate the longitudinal changes in Alu methylation levels in these patients.ResultsWe observed significantly decreased Alu methylation levels in type 2 DM patients compared with normal (p = 0.0462). Moreover, our findings demonstrated changes in Alu hypomethylation over a follow‐up period within the same individuals (p < 0.0001). A reduction in Alu methylation was found in patients with increasing HbA1c levels (p = 0.0013) and directly correlated with increased HbA1c levels in type 2 DM patients (r = −0.2273, p = 0.0387).ConclusionsAlu methylation in type 2 DM patients progressively decreases with increasing HbA1c levels. This observation suggests a potential association between Alu hypomethylation and the underlying molecular mechanisms of elevated blood glucose. Furthermore, monitoring Alu methylation levels may serve as a valuable biomarker for assessing the clinical outcomes of type 2 DM.

Alu Methylation Patterns in Type 1 Diabetes: A Case-Control Study

“…Also, Alu methylation in patients with T2D progressively decreased with increasing HbA1c levels during a 4-year follow-up period. The authors proposed that this observation suggested a potential link between Alu hypomethylation and the underlying molecular processes, as prolonged hyperglycemia may cause an imbalance in oxidative production and suppression, also induces p53 and may contribute to impaired insulin signaling [43].…”

“…Laboratory methods: COBRA-interspersed repetitive sequence PCR is a highly accurate semi-quantitative methylation measurement, able to detect more than one CpG site, even when pyrosequencing cannot demonstrate a DNA methylation pattern [15,43]. DNA extraction and bisulfate DNA modification: DNA was extracted from peripheral blood cells using the DNA Blood Mini kit (Qiagen, Hilden, Germany) according to the manufacturer's protocol.…”

“…To assess methylation levels of Alu, the sodium-bisulfite-treated DNA in each sample was amplified by PCR using 0.2 mM of deoxynucleotide triphosphate, 1 mM of magnesium chloride, 1 U of HotStarTaq DNA Polymerase (Qiagen, Germany) and 0.3 µM primer pairs (Alu-F: 5 -GGCGCGGTGGTTTACGTTTGTAA-3 and Alu-R: 5 -TTAATAAAAACGAAATTTCACCAT ATTAACCAAAC-3 ) (Figure 1). Laboratory methods: COBRA-interspersed repetitive sequence PCR is a highly accurate semi-quantitative methylation measurement, able to detect more than one CpG site, even when pyrosequencing cannot demonstrate a DNA methylation pattern [15,43]. DNA extraction and bisulfate DNA modification: DNA was extracted from peripheral blood cells using the DNA Blood Mini kit (Qiagen, Hilden, Germany) according to the manufacturer's protocol.…”