DNA Methylation and Type 2 Diabetes: Novel Biomarkers for Risk Assessment?

Abstract

Diabetes is a severe threat to global health. Almost 500 million people live with diabetes worldwide. Most of them have type 2 diabetes (T2D). T2D patients are at risk of developing severe and life-threatening complications, leading to an increased need for medical care and reduced quality of life. Improved care for people with T2D is essential. Actions aiming at identifying undiagnosed diabetes and at preventing diabetes in those at high risk are needed as well. To this end, biomarker discovery and validation of risk assessment for T2D are critical. Alterations of DNA methylation have recently helped to better understand T2D pathophysiology by explaining differences among endophenotypes of diabetic patients in tissues. Recent evidence further suggests that variations of DNA methylation might contribute to the risk of T2D even more significantly than genetic variability and might represent a valuable tool to predict T2D risk. In this review, we focus on recent information on the contribution of DNA methylation to the risk and the pathogenesis of T2D. We discuss the limitations of these studies and provide evidence supporting the potential for clinical application of DNA methylation marks to predict the risk and progression of T2D.

Epigenetics of type 2 diabetes and diabetes-related outcomes in the Strong Heart Study

“…However, to our knowledge, this is the first study that investigates the association between blood DNA methylation with type 2 diabetes prospectively. According to the meta-analysis conducted by Raciti et al [ 16 ], which was published by the end of 2021, all the previous studies in blood DNA methylation were either cross-sectional [ 10 , 44 , 47 – 50 ], focused on targeted genes rather than epigenome-wide [ 46 , 51 , 52 ], or focused on global DNA methylation, rather than site-specific methylation [ 53 ]. Although an EWAS conducted in a European population [ 45 ] evaluated incident diabetes, they did not account for time to event in the EWAS models, which were conducted using a logistic regression (with a dichotomous outcome) rather than survival analysis.…”

“…As the prediabetes period is long and the diabetes diagnostic criteria are established in advanced phases, DNA methylation dysregulations might be a powerful biomarker for early detection [ 15 ], which might help with early treatment and to reduce healthcare costs. In addition, DNA methylation has been suggested to have a higher predictive ability than genetics for type 2 diabetes in high-risk subjects [ 16 ].…”

Serological and Oncoinformatic Analysis of HbA1c as a Prognostic Biomarker in Screening the Risks of Different Cancers among the Male T2D Patients of Bangladesh

“…But in patients with cancers in all age groups, it was downregulated. Though in the case of the 3 younger people aged (21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) years tpm was around 35 while in older people (81-100) it was much less (Figure 5E). Similarly surveying nodal metastasis, we found that the HbA1 value decreases as nodal stages (N0, N1, and so on) advance, but it's higher in people without the disease (Figure 5F).…”

“…It is necessary to take steps to find undiagnosed diabetes and prevent it in people who are at high risk. More recent research indicates that changes in DNA methylation may even more significantly contribute to the risk of T2D than genetic variability and may be a useful indicator of T2D risk [22]. In many human cancers, including bladder cancer, abnormal promoter methylation (also known as hypermethylation) is a key mechanism for suppressing tumor suppressor genes and other cancer-associated genes.…”

Molecular Neuropathology versus Histopathology in the Diagnosis of Central Nervous System Tumors: Review Article about Novel Diagnostic and Investigative Technologies

“…DNA methylation may affect gene expression without affecting DNA sequencing and consequently alter various normal biological functions. Moreover, DNA methylation has been linked to the etiology of many diseases, including cancer [31], kidney disease [32], diabetes type 2 [33], psychiatric disorders [34], and sepsis [35]. Additionally, it has been reported that DNA methylation could be affected by estrogen treatment and is considered an explanation for gene expression changes by treatment in experimental models [36].…”