Identification of epigenetic biomarkers associated with the development of diabetic kidney disease in individuals with type 2 diabetes: a nested cohort study
(2023) MPHN40 20231Social Medicine and Global Health
- Abstract
- Introduction. Type 2 diabetes (T2D) is the most common type of diabetes, and it can cause complications such as diabetic kidney disease (DKD), the main cause of end-stage renal disease worldwide. There is an urgent need to develop new biomarkers that would improve DKD’s risk prediction in patients with T2D. This research aimed at identifying novel epigenetic biomarkers associated with future DKD in patients with T2D. Methods. Nested cohort study of 487 newly diagnosed individuals with T2D within the ANDIS and ANDIU cohorts, followed-up over a period of 11.5 years. Genome-wide DNA methylation analysis was performed in blood samples taken at registration in the cohorts, and its association with future DKD was assessed through weighted-cox... (More)
- Introduction. Type 2 diabetes (T2D) is the most common type of diabetes, and it can cause complications such as diabetic kidney disease (DKD), the main cause of end-stage renal disease worldwide. There is an urgent need to develop new biomarkers that would improve DKD’s risk prediction in patients with T2D. This research aimed at identifying novel epigenetic biomarkers associated with future DKD in patients with T2D. Methods. Nested cohort study of 487 newly diagnosed individuals with T2D within the ANDIS and ANDIU cohorts, followed-up over a period of 11.5 years. Genome-wide DNA methylation analysis was performed in blood samples taken at registration in the cohorts, and its association with future DKD was assessed through weighted-cox regression models. Results. DNA methylation of 37 CpG sites was found to be significantly associated with future DKD in the sample, with an effect size of 5% (q<0.05). The HR ranged from 0.0005 (95% CI 0 - 0.07) to 37.05 (95% CI 4.88 - 281.28) per 1% of methylation increase. 20 CpG sites (54%) were hypermethylated in patients with diabetes who developed DKD, in relation to those who did not develop DKD. Some of these 37 CpG sites are annotated to genes with important reported biological processes, such as ADAMTS16, involved in regulation of arterial blood pressure; RPH3AL in positive regulation of insulin secretion, and EHMT1 in methylation of histones. Discussion. Our study found that DNA methylation in blood taken at baseline is associated with future DKD in the study’s population, indicating that DNA methylation markers can be potential valuable biomarkers for predicting DKD in T2D. Conclusions. To the author’s knowledge, no study has investigated the association between DNA methylation and future DKD. There is a need, however, to refine the study design and to validate the results in different populations. (Less)
- Popular Abstract
- Diabetes is a global health crisis, with over 537 million people diagnosed worldwide, causing 6.7 million deaths in 2021 alone. Type 2 diabetes (T2D) is the most common type and can lead to serious complications such as diabetic kidney disease (DKD), the main cause of end-stage renal disease globally. DKD is a significant health and economic burden. To improve DKD’s prediction in T2D patients, there is a critical need to develop new biomarkers. Our study aimed to identify novel epigenetic biomarkers associated with the development of DKD in 487 newly diagnosed T2D patients who were followed up for 11.5 years. Epigenetic biomarkers, such as DNA methylation, refer to modifications on DNA molecules that affect how genes are expressed, which... (More)
- Diabetes is a global health crisis, with over 537 million people diagnosed worldwide, causing 6.7 million deaths in 2021 alone. Type 2 diabetes (T2D) is the most common type and can lead to serious complications such as diabetic kidney disease (DKD), the main cause of end-stage renal disease globally. DKD is a significant health and economic burden. To improve DKD’s prediction in T2D patients, there is a critical need to develop new biomarkers. Our study aimed to identify novel epigenetic biomarkers associated with the development of DKD in 487 newly diagnosed T2D patients who were followed up for 11.5 years. Epigenetic biomarkers, such as DNA methylation, refer to modifications on DNA molecules that affect how genes are expressed, which can be used to predict an individual's risk of developing certain diseases. Genome-wide DNA methylation analysis, which analyses 850,000 methylation markers, was performed for all patients at baseline, and its association with the development of DKD was assessed. 37 differentially methylated CpGs (regions of DNA) significantly associated with the
development of DKD were found. Hypermethylation in 20 of these CpGs was observed in patients who developed DKD. These CpGs are annotated to genes involved in critical biological processes, including ADAMTS16, involved in the regulation of systemic arterial blood pressure; RPH3AL in positive regulation of insulin secretion, and EHMT1 in DNA methylation. The results suggest that DNA methylation can be a potential valuable biomarker in predicting DKD for T2D patients. This study is the first to investigate the association between DNA methylation and future DKD. While the findings are promising, the study design needs to be refined and validated in different populations. The identification of epigenetic biomarkers could help to improve the risk prediction of DKD in T2D patients, ultimately leading to earlier diagnosis and better management of this debilitating condition. (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9127369
- author
- Paiva Marchiori, Marian LU
- supervisor
- organization
- course
- MPHN40 20231
- year
- 2023
- type
- H2 - Master's Degree (Two Years)
- subject
- language
- English
- id
- 9127369
- date added to LUP
- 2023-08-24 13:15:54
- date last changed
- 2023-08-24 13:16:09
@misc{9127369,
abstract = {{Introduction. Type 2 diabetes (T2D) is the most common type of diabetes, and it can cause complications such as diabetic kidney disease (DKD), the main cause of end-stage renal disease worldwide. There is an urgent need to develop new biomarkers that would improve DKD’s risk prediction in patients with T2D. This research aimed at identifying novel epigenetic biomarkers associated with future DKD in patients with T2D. Methods. Nested cohort study of 487 newly diagnosed individuals with T2D within the ANDIS and ANDIU cohorts, followed-up over a period of 11.5 years. Genome-wide DNA methylation analysis was performed in blood samples taken at registration in the cohorts, and its association with future DKD was assessed through weighted-cox regression models. Results. DNA methylation of 37 CpG sites was found to be significantly associated with future DKD in the sample, with an effect size of 5% (q<0.05). The HR ranged from 0.0005 (95% CI 0 - 0.07) to 37.05 (95% CI 4.88 - 281.28) per 1% of methylation increase. 20 CpG sites (54%) were hypermethylated in patients with diabetes who developed DKD, in relation to those who did not develop DKD. Some of these 37 CpG sites are annotated to genes with important reported biological processes, such as ADAMTS16, involved in regulation of arterial blood pressure; RPH3AL in positive regulation of insulin secretion, and EHMT1 in methylation of histones. Discussion. Our study found that DNA methylation in blood taken at baseline is associated with future DKD in the study’s population, indicating that DNA methylation markers can be potential valuable biomarkers for predicting DKD in T2D. Conclusions. To the author’s knowledge, no study has investigated the association between DNA methylation and future DKD. There is a need, however, to refine the study design and to validate the results in different populations.}},
author = {{Paiva Marchiori, Marian}},
language = {{eng}},
note = {{Student Paper}},
title = {{Identification of epigenetic biomarkers associated with the development of diabetic kidney disease in individuals with type 2 diabetes: a nested cohort study}},
year = {{2023}},
}