Background and aims: Type 1 diabetes mellitus (T1DM) results from a severe autoimmune destruction of pancreatic beta cells, which renders patients insulin-dependent for life. The triggering of autoimmunity against beta cells is caused by a complex interaction between environmental, genetic and epigenetic risk factors. Although significant progress has been made in elucidating the genetic factors associated with T1DM, the non-genetic components have remained poorly understood. Recent evidence has suggested that epigenetic regulation is a key mechanism by which environmental factors interact with genetic factors to trigger T1DM. DNA methylation is an epigenetic modification that results in the addition of methyl groups to the cytosine residues of CpG dinucleotides, leading to repression of gene expression. Even though some studies have suggested that T1DM patients have global alterations in DNA methylation levels, little is known about the contribution of methylation to the etiology of T1DM. Therefore, the aim of this study was to investigate the global DNA methylation levels in T1DM patients and non-diabetic subjects from Southern Brazil.
Material and methods: This case-control study was carried out in 55 T1DM patients (cases) and 55 non-diabetic subjects (controls). Subjects were divided into two groups: Group 1: 39 patients with >5 years of T1DM paired to 39 controls, and Group 2: 16 patients with ≤5 years of T1DM paired to 16 controls. Case and control subjects from both groups were paired according to body mass index, age and sex. DNA was extracted from peripheral leukocytes, and global DNA methylation levels were quantified using a colorimetric kit (MDQ1, Imprint Methylated DNA Quantification Kit, Sigma-Aldrich). Percentages of global methylation were compared between paired case and control groups using generalized estimating Default (GEE), and are shown as estimated means (95% confidence interval).
Results: Global DNA methylation levels were higher in T1DM cases compared to non-diabetic controls from Group 1: 117.2% (95.9138.5) vs 74.7% (65.384.1); P=0.001. In contrast, in Group 2, global methylation levels did not differ between cases and controls 93.7% (57.9129.5) vs 99.6% (85.2113.9); P=0.753). Moreover, glycated hemoglobin levels were positively correlated with methylation levels in cases and controls from Group 1 (r=0.369; P=0,001), but not Group 2 (r=−0.335; P=0.065).
Conclusion: Our results indicate that global DNA methylation levels are associated with T1DM, which is dependent on the duration of this disease.
18 - 21 May 2019
European Society of Endocrinology