Dataset Information

Integrative analysis reveals novel associations between DNA methylation and the serum metabolome of adolescents with type 2 diabetes: A cross-sectional study.

ABSTRACT:

Objective

Rates of type 2 diabetes (T2D) among adolescents are on the rise. Epigenetic changes could be associated with the metabolic alterations in adolescents with T2D.

Methods

We performed a cross sectional integrated analysis of DNA methylation data from peripheral blood mononuclear cells with serum metabolomic data from First Nation adolescents with T2D and controls participating in the Improving Renal Complications in Adolescents with type 2 diabetes through Research (iCARE) cohort study, to explore the molecular changes in adolescents with T2D.

Results

Our analysis showed that 43 serum metabolites and 36 differentially methylated regions (DMR) were associated with T2D. Several DMRs were located near the transcriptional start site of genes with established roles in metabolic disease and associated with altered serum metabolites (e.g. glucose, leucine, and gamma-glutamylisoleucine). These included the free fatty acid receptor-1 (FFAR1), upstream transcription factor-2 (USF2), and tumor necrosis factor-related protein-9 (C1QTNF9), among others.

Conclusions

We identified DMRs and metabolites that merit further investigation to determine their significance in controlling gene expression and metabolism which could define T2D risk in adolescents.

SUBMITTER: Agarwal P

PROVIDER: S-EPMC9593237 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Integrative analysis reveals novel associations between DNA methylation and the serum metabolome of adolescents with type 2 diabetes: A cross-sectional study.

Agarwal Prasoon P Wicklow Brandy A BA Dart Allison B AB Hizon Nikho A NA Sellers Elizabeth A C EAC McGavock Jonathan M JM Talbot Charlotte P J CPJ Fonseca Mario A MA Xu Wayne W Davie James R JR Jones Meaghan J MJ Acharjee Animesh A Dolinsky Vernon W VW

Frontiers in endocrinology 20221010

<h4>Objective</h4>Rates of type 2 diabetes (T2D) among adolescents are on the rise. Epigenetic changes could be associated with the metabolic alterations in adolescents with T2D.<h4>Methods</h4>We performed a cross sectional integrated analysis of DNA methylation data from peripheral blood mononuclear cells with serum metabolomic data from First Nation adolescents with T2D and controls participating in the Improving Renal Complications in Adolescents with type 2 diabetes through Research (iCARE) ...[more]

PMID: 36303872

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Project description:IntroductionSocial risks (e.g., food/transportation insecurity) can hamper type 2 diabetes mellitus (T2DM) self-management, leading to poor outcomes. To determine the extent to which high-quality care can overcome social risks' health impacts, this study assessed the associations between reported social risks, receipt of guideline-based T2DM care, and T2DM outcomes when care is up to date among community health center patients.MethodsA cross-sectional study of adults aged ≥18 years (N=73,484) seen at 186 community health centers, with T2DM and ≥1 year of observation between July 2016 and February 2020. Measures of T2DM care included up-to-date HbA1c, microalbuminuria, low-density lipoprotein screening, and foot examination, and active statin prescription when indicated. Measures of T2DM outcomes among patients with up-to-date care included blood pressure, HbA1c, and low-density lipoprotein control on or within 6‒12 months of an index encounter. Analyses were conducted in 2021.ResultsIndividuals reporting transportation or housing insecurity were less likely to have up-to-date low-density lipoprotein screening; no other associations were seen between social risks and clinical care quality. Among individuals with up-to-date care, food insecurity was associated with lower adjusted rates of controlled HbA1c (79% vs 75%, p<0.001), and transportation insecurity was associated with lower rates of controlled HbA1c (79% vs 74%, p=0.005), blood pressure (74% vs 72%, p=0.025), and low-density lipoprotein (61% vs 57%, p=0.009) than among those with no reported need.ConclusionsCommunity health center patients received similar care regardless of the presence of social risks. However, even among those up to date on care, social risks were associated with worse T2DM control. Future research should identify strategies for improving HbA1c control for individuals with social risks.Trial registrationThis study is registered at www.Clinicaltrialsgov NCT03607617.

Project description:Evidence supports a complex interplay of gut microbiome and host metabolism as regulators of obesity. The metabolic phenotype and microbial metabolism of host diet may also contribute to greater obesity risk in children early in life. This study aimed to identify features that discriminated overweight/obese from normal weight infants by integrating gut microbiome and serum metabolome profiles. This prospective analysis included 50 South Asian children living in Canada, selected from the SouTh Asian biRth cohorT (START). Serum metabolites were measured by multisegment injection-capillary electrophoresis-mass spectrometry and the relative abundance of bacterial 16S rRNA gene amplicon sequence variant was evaluated at 1 year. Cumulative body mass index (BMIAUC) and skinfold thickness (SSFAUC) scores were calculated from birth to 3 years as the total area under the growth curve (AUC). BMIAUC and/or SSFAUC >85th percentile was used to define overweight/obesity. Data Integration Analysis for Biomarker discovery using Latent cOmponent (DIABLO) was used to identify discriminant features associated with childhood overweight/obesity. The associations between identified features and anthropometric measures were examined using logistic regression. Circulating metabolites including glutamic acid, acetylcarnitine, carnitine, and threonine were positively, whereas γ-aminobutyric acid (GABA), symmetric dimethylarginine (SDMA), and asymmetric dimethylarginine (ADMA) were negatively associated with childhood overweight/obesity. The abundance of the Pseudobutyrivibrio and Lactobacillus genera were positively, and Clostridium sensu stricto 1 and Akkermansia were negatively associated with childhood overweight/obesity. Integrative analysis revealed that Akkermansia was positively whereas Lactobacillus was inversely correlated with GABA and SDMA, and Pseudobutyrivibrio was inversely correlated with GABA. This study provides insights into metabolic and microbial signatures which may regulate satiety, energy metabolism, inflammatory processes, and/or gut barrier function, and therefore, obesity trajectories in childhood. Understanding the functional capacity of these molecular features and potentially modifiable risk factors such as dietary exposures early in life may offer a novel approach for preventing childhood obesity.

Dataset Information

Integrative analysis reveals novel associations between DNA methylation and the serum metabolome of adolescents with type 2 diabetes: A cross-sectional study.

Objective

Methods

Results

Conclusions

Publications

Integrative analysis reveals novel associations between DNA methylation and the serum metabolome of adolescents with type 2 diabetes: A cross-sectional study.

Similar Datasets

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