Prospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Aug 10, 2015; 6(9): 1113-1121
Published online Aug 10, 2015. doi: 10.4239/wjd.v6.i9.1113
Epigenetic profiles of pre-diabetes transitioning to type 2 diabetes and nephropathy
Thomas A VanderJagt, Monica H Neugebauer, Marilee Morgan, Donald W Bowden, Vallabh O Shah
Thomas A VanderJagt, Monica H Neugebauer, Vallabh O Shah, Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, NM 87131, United States
Marilee Morgan, MIND Institute, Albuquerque, NM 87106, United States
Donald W Bowden, Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC 27157, United States
Author contributions: All authors contributed to this manuscript.
Supported by The grants from the National Center for Research Resources, No. 5P20RR016480-12; The National Institute of General Medical Sciences of the NIH, No. 8P20GM103451-12; the partial support from the National Center for Advancing Translational Sciences of the National Institutes of Health, No. 8UL1TR000041; the University of New Mexico Clinical and Translational Science Center; the cost for clinical phenotyping and payments to participants was supported under a UNM Health Sciences Center-based Cardiovascular and Metabolic Diseases Signature Program.
Institutional review board statement: The study protocol was approved by the Human Subject Research Review Committee of the University of New Mexico Health Sciences Center.
Clinical trial registration statement: The Clinical trial registration is not applicable for our study.
Informed consent statement: All participants rendered written informed consent.
Conflict-of-interest statement: No potential conflicts of interest relevant to this original article were reported by authors.
Data sharing statement: We will coordinate data sharing and make available both the raw data and analyzed data upon request.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Vallabh O Shah, PhD, FASN, Professor and Sr Fellow New Mexico Center for the Advancement of Research, Engagement, and Science on Health Disparities (NM CARES HD), Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, 2211 Lomas Blvd, NE, Albuquerque, NM 87131, United States. vshah@salud.unm.edu
Telephone: +1-505-2729615 Fax: +1-505-2722614
Received: February 27, 2015
Peer-review started: February 27, 2015
First decision: May 14, 2015
Revised: June 19, 2015
Accepted: July 11, 2015
Article in press: July 14, 2015
Published online: August 10, 2015
Processing time: 168 Days and 1.4 Hours
Abstract

AIM: To examine DNA methylation profiles in a longitudinal comparison of pre-diabetes mellitus (Pre-DM) subjects who transitioned to type 2 diabetes mellitus (T2DM).

METHODS: We performed DNA methylation study in bisulphite converted DNA from Pre-DM (n = 11) at baseline and at their transition to T2DM using Illumina Infinium HumanMethylation27 BeadChip, that enables the query of 27578 individual cytosines at CpG loci throughout the genome, which are focused on the promoter regions of 14495 genes.

RESULTS: There were 694 CpG sites hypomethylated and 174 CpG sites hypermethylated in progression from Pre-DM to T2DM, representing putative genes involved in glucose and fructose metabolism, inflammation, oxidative and mitochondrial stress, and fatty acid metabolism. These results suggest that this high throughput platform is able to identify hundreds of prospective CpG sites associated with diverse genes that may reflect differences in Pre-DM compared with T2DM. In addition, there were CpG hypomethylation changes associated with a number of genes that may be associated with development of complications of diabetes, such as nephropathy. These hypomethylation changes were observed in all of the subjects.

CONCLUSION: These data suggest that some epigenomic changes that may be involved in the progression of diabetes and/or the development of complications may be apparent at the Pre-DM state or during the transition to diabetes. Hypomethylation of a number of genes related to kidney function may be an early marker for developing diabetic nephropathy.

Keywords: Epigenetic changes; Pre-diabetes; Diabetes; Nephropathy

Core tip: Many independent predictors of diabetes including markers of metabolic dysfunction (high body mass index, hypertension, low HDL and smoking) were significantly increased early on in pre-diabetes mellitus (Pre-DM) and sustained in diabetes groups. The innovation in high-throughput epigenome of DNA methylation studies suggests that some epigenomic changes that may be involved in the progression of diabetes and/or the development of complications may be apparent at the Pre-DM state or during the transition to diabetes.