scholarly journals Maternal dysglycaemia, changes in the infant’s epigenome modified with a diet and physical activity intervention in pregnancy: Secondary analysis of a randomised control trial

PLoS Medicine ◽  
2020 ◽  
Vol 17 (11) ◽  
pp. e1003229
Author(s):  
Elie Antoun ◽  
Negusse T. Kitaba ◽  
Philip Titcombe ◽  
Kathryn V. Dalrymple ◽  
Emma S. Garratt ◽  
...  
Keyword(s):  
Physical Activity ◽  
Dna Methylation ◽  
Cord Blood ◽  
Pregnant Women ◽  
Lifestyle Intervention ◽  
Standard Care ◽  
Physical Activity Intervention ◽  
Randomised Control Trial ◽  
Oral Glucose ◽  
In Pregnancy

Background Higher maternal plasma glucose (PG) concentrations, even below gestational diabetes mellitus (GDM) thresholds, are associated with adverse offspring outcomes, with DNA methylation proposed as a mediating mechanism. Here, we examined the relationships between maternal dysglycaemia at 24 to 28 weeks’ gestation and DNA methylation in neonates and whether a dietary and physical activity intervention in pregnant women with obesity modified the methylation signatures associated with maternal dysglycaemia. Methods and findings We investigated 557 women, recruited between 2009 and 2014 from the UK Pregnancies Better Eating and Activity Trial (UPBEAT), a randomised controlled trial (RCT), of a lifestyle intervention (low glycaemic index (GI) diet plus physical activity) in pregnant women with obesity (294 contol, 263 intervention). Between 27 and 28 weeks of pregnancy, participants had an oral glucose (75 g) tolerance test (OGTT), and GDM diagnosis was based on diagnostic criteria recommended by the International Association of Diabetes and Pregnancy Study Groups (IADPSG), with 159 women having a diagnosis of GDM. Cord blood DNA samples from the infants were interrogated for genome-wide DNA methylation levels using the Infinium Human MethylationEPIC BeadChip array. Robust regression was carried out, adjusting for maternal age, smoking, parity, ethnicity, neonate sex, and predicted cell-type composition. Maternal GDM, fasting glucose, 1-h, and 2-h glucose concentrations following an OGTT were associated with 242, 1, 592, and 17 differentially methylated cytosine-phosphate-guanine (dmCpG) sites (false discovery rate (FDR) ≤ 0.05), respectively, in the infant’s cord blood DNA. The most significantly GDM-associated CpG was cg03566881 located within the leucine-rich repeat-containing G-protein coupled receptor 6 (LGR6) (FDR = 0.0002). Moreover, we show that the GDM and 1-h glucose-associated methylation signatures in the cord blood of the infant appeared to be attenuated by the dietary and physical activity intervention during pregnancy; in the intervention arm, there were no GDM and two 1-h glucose-associated dmCpGs, whereas in the standard care arm, there were 41 GDM and 160 1-h glucose-associated dmCpGs. A total of 87% of the GDM and 77% of the 1-h glucose-associated dmCpGs had smaller effect sizes in the intervention compared to the standard care arm; the adjusted r2 for the association of LGR6 cg03566881 with GDM was 0.317 (95% confidence interval (CI) 0.012, 0.022) in the standard care and 0.240 (95% CI 0.001, 0.015) in the intervention arm. Limitations included measurement of DNA methylation in cord blood, where the functional significance of such changes are unclear, and because of the strong collinearity between treatment modality and severity of hyperglycaemia, we cannot exclude that treatment-related differences are potential confounders. Conclusions Maternal dysglycaemia was associated with significant changes in the epigenome of the infants. Moreover, we found that the epigenetic impact of a dysglycaemic prenatal maternal environment appeared to be modified by a lifestyle intervention in pregnancy. Further research will be needed to investigate possible medical implications of the findings. Trial registration ISRCTN89971375.

scholarly journals Lifestyle Intervention in Pregnant Women With Obesity Impacts Cord Blood DNA Methylation Which Associates With Body Composition in the Offspring

2021 ◽  
Author(s):  
Josefine Jönsson ◽  
Kristina M. Renault ◽  
Sonia García-Calzón ◽  
Alexander Perfilyev ◽  
Angela C. Estampador ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Body Composition ◽  
Cord Blood ◽  
Pregnant Women ◽  
Lifestyle Intervention ◽  
Lean Mass ◽  
Maternal Obesity ◽  
Standard Of Care ◽  
Dietary Advice ◽  
Lifestyle Interventions

Maternal obesity may lead to epigenetic alterations in the offspring and might thereby contribute to disease later in life. We investigated whether a lifestyle intervention in pregnant women with obesity is associated with epigenetic variation in cord blood and body composition in the offspring.<b> </b>Genome-wide DNA methylation was analyzed in cord blood from 208 offspring from the TOP-study, which includes pregnant women with obesity randomized to lifestyle interventions comprised of physical activity with or without dietary advice versus controls (standard of care). DNA methylation was altered at 379 sites, annotated to 370 genes, in cord blood from offspring of mothers following a lifestyle intervention versus controls (<i>FDR</i><5%) when using the Houseman reference-free method to correct for cell composition and three of these sites were significant based on Bonferroni correction. These 370 genes are overrepresented in gene ontology terms including response to fatty acids and adipose tissue development. Offspring of mothers included in a lifestyle intervention were born with more lean mass compared to controls. Methylation at 17 sites, annotated to e.g. <i>DISC1</i>, <i>GBX2</i>, <i>HERC2</i> and <i>HUWE1</i>, partially mediates the effect of the lifestyle intervention on lean mass in the offspring (FDR<5%). Moreover, 22 methylation sites were associated with offspring BMI z-scores during the first 3 years of life (<i>p</i><0.05). Overall,<b> </b>lifestyle interventions in pregnant women with obesity are associated with epigenetic changes in offspring, potentially influencing the offspring’s lean mass and early growth.

Associations between an integrated component of maternal glycemic regulation in pregnancy and cord blood DNA methylation

Epigenomics ◽  
2021 ◽  
Author(s):  
Diana L Juvinao-Quintero ◽  
Andres Cardenas ◽  
Patrice Perron ◽  
Luigi Bouchard ◽  
Sharon M Lutz ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cord Blood ◽  
Principal Component ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Characterization Methods ◽  
Abnormal Glucose Metabolism ◽  
Glycemic Regulation ◽  
The Life Course ◽  
In Pregnancy

Background: Previous studies suggest that fetal programming to hyperglycemia in pregnancy is due to modulation of DNA methylation (DNAm), but they have been limited in their maternal glycemic characterization. Methods: In Gen3G, we used a principal component analysis to integrate multiple glucose and insulin values measured during the second trimester oral glucose tolerance test. We investigated associations between principal components and cord blood DNAm levels in an epigenome-wide analysis among 430 mother–child pairs. Results: The first principal component was robustly associated with lower DNAm at cg26974062 ( TXNIP; p = 9.9 × 10-9) in cord blood. TXNIP is a well-known DNAm marker for type 2 diabetes in adults. Conclusion: We hypothesize that abnormal glucose metabolism in pregnancy may program dysregulation of TXNIP across the life course.

scholarly journals Lifestyle Intervention in Pregnant Women With Obesity Impacts Cord Blood DNA Methylation Which Associates With Body Composition in the Offspring

2021 ◽  
Author(s):  
Josefine Jönsson ◽  
Kristina M. Renault ◽  
Sonia García-Calzón ◽  
Alexander Perfilyev ◽  
Angela C. Estampador ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Body Composition ◽  
Cord Blood ◽  
Pregnant Women ◽  
Lifestyle Intervention ◽  
Lean Mass ◽  
Maternal Obesity ◽  
Standard Of Care ◽  
Dietary Advice ◽  
Lifestyle Interventions

Maternal obesity may lead to epigenetic alterations in the offspring and might thereby contribute to disease later in life. We investigated whether a lifestyle intervention in pregnant women with obesity is associated with epigenetic variation in cord blood and body composition in the offspring.<b> </b>Genome-wide DNA methylation was analyzed in cord blood from 208 offspring from the TOP-study, which includes pregnant women with obesity randomized to lifestyle interventions comprised of physical activity with or without dietary advice versus controls (standard of care). DNA methylation was altered at 379 sites, annotated to 370 genes, in cord blood from offspring of mothers following a lifestyle intervention versus controls (<i>FDR</i><5%) when using the Houseman reference-free method to correct for cell composition and three of these sites were significant based on Bonferroni correction. These 370 genes are overrepresented in gene ontology terms including response to fatty acids and adipose tissue development. Offspring of mothers included in a lifestyle intervention were born with more lean mass compared to controls. Methylation at 17 sites, annotated to e.g. <i>DISC1</i>, <i>GBX2</i>, <i>HERC2</i> and <i>HUWE1</i>, partially mediates the effect of the lifestyle intervention on lean mass in the offspring (FDR<5%). Moreover, 22 methylation sites were associated with offspring BMI z-scores during the first 3 years of life (<i>p</i><0.05). Overall,<b> </b>lifestyle interventions in pregnant women with obesity are associated with epigenetic changes in offspring, potentially influencing the offspring’s lean mass and early growth.

scholarly journals Lifestyle Intervention in Pregnant Women With Obesity Impacts Cord Blood DNA Methylation Which Associates With Body Composition in the Offspring

Diabetes ◽  
2021 ◽  
pp. db200487
Author(s):  
Josefine Jönsson ◽  
Kristina M. Renault ◽  
Sonia García-Calzón ◽  
Alexander Perfilyev ◽  
Angela C. Estampador ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Body Composition ◽  
Cord Blood ◽  
Pregnant Women ◽  
Lifestyle Intervention

scholarly journals Lifestyle Intervention in Pregnant Women With Obesity Impacts Cord Blood DNA Methylation Which Associates With Body Composition in the Offspring

2021 ◽  
Author(s):  
Josefine Jönsson ◽  
Kristina M. Renault ◽  
Sonia García-Calzón ◽  
Alexander Perfilyev ◽  
Angela C. Estampador ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Body Composition ◽  
Cord Blood ◽  
Pregnant Women ◽  
Lifestyle Intervention ◽  
Lean Mass ◽  
Maternal Obesity ◽  
Standard Of Care ◽  
Dietary Advice ◽  
Lifestyle Interventions

Maternal obesity may lead to epigenetic alterations in the offspring and might thereby contribute to disease later in life. We investigated whether a lifestyle intervention in pregnant women with obesity is associated with epigenetic variation in cord blood and body composition in the offspring.<b> </b>Genome-wide DNA methylation was analyzed in cord blood from 208 offspring from the TOP-study, which includes pregnant women with obesity randomized to lifestyle interventions comprised of physical activity with or without dietary advice versus controls (standard of care). DNA methylation was altered at 379 sites, annotated to 370 genes, in cord blood from offspring of mothers following a lifestyle intervention versus controls (<i>FDR</i><5%) when using the Houseman reference-free method to correct for cell composition and three of these sites were significant based on Bonferroni correction. These 370 genes are overrepresented in gene ontology terms including response to fatty acids and adipose tissue development. Offspring of mothers included in a lifestyle intervention were born with more lean mass compared to controls. Methylation at 17 sites, annotated to e.g. <i>DISC1</i>, <i>GBX2</i>, <i>HERC2</i> and <i>HUWE1</i>, partially mediates the effect of the lifestyle intervention on lean mass in the offspring (FDR<5%). Moreover, 22 methylation sites were associated with offspring BMI z-scores during the first 3 years of life (<i>p</i><0.05). Overall,<b> </b>lifestyle interventions in pregnant women with obesity are associated with epigenetic changes in offspring, potentially influencing the offspring’s lean mass and early growth.

scholarly journals A Physical Activity Intervention Feasibility Study for Kidney Inpatients: A Basic Research Protocol

2021 ◽  
Vol 8 ◽  
pp. 205435812098705
Author(s):  
Kathryn Wytsma-Fisher ◽  
Stefan Mustata ◽  
Theresa Cowan ◽  
Manuel Ester ◽  
S. Nicole Culos-Reed
Keyword(s):  
Quality Of Life ◽  
Physical Activity ◽  
Physical Function ◽  
Kidney Failure ◽  
Standard Care ◽  
Physical Activity Intervention ◽  
Clinical Care ◽  
Activity Promotion ◽  
Cardiovascular Morbidity And Mortality

Background: Low physical activity levels and poor physical functioning are strongly associated with poor clinical outcomes and mortality in adult kidney failure patients, regardless of treatment modality. Compared with the general population, individuals with chronic kidney disease are physically inactive, have reduced physical abilities and difficulties performing routine daily tasks, lower health-related quality of life, and higher cardiovascular morbidity and mortality. In addition, frail kidney failure patients have higher hospitalization and mortality rates as compared with other kidney failure patients. Evidence suggests that assessment and recommendations for physical activity should be part of standard care for kidney failure patients. Structured exercise can improve physical function and quality of life in frail older adults and may be used specifically for management of frailty in kidney failure. However, research is needed to determine best practices for implementation of physical function measurements and physical activity promotion in standard kidney failure care. Objective: The proposed Move More study will assess the feasibility of a physical activity intervention offered to the kidney failure inpatients in Calgary, Alberta. Specifically, this study is designed to examine the effects of an early physical activity/mobility intervention led by a kinesiologist, and supported by the clinical care team including physiotherapists (PT) and nurse clinicians. Methods: The Move More study is a single-arm pilot intervention examining feasibility and optimal improvement in real-world conditions. Kidney failure inpatients at the Foothills Medical Centre will be recruited to participate. Patients will receive an individualized in-hospital physical activity/mobility intervention. Frailty and physical function will be assessed at baseline and postintervention prior to hospital discharge. The goal is to recruit 24 to 36 patients. Conclusions: Evidence needed to support the inclusion of mobility and physical activity as part of standard care will be gathered, with knowledge gained used to help direct future physical activity programming for kidney failure inpatients.

scholarly journals Acceptability of the “MOVEdiabetes” physical activity intervention in diabetes primary care settings in Oman: findings from participants and practitioners

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Thamra S. Alghafri ◽  
Saud M. Al Harthi ◽  
Fatma Al-Ajmi ◽  
Yahya Al-Farsi ◽  
Angela M. Craigie ◽  
...  
Keyword(s):  
Physical Activity ◽  
Primary Care ◽  
Diabetes Management ◽  
Physical Activity Intervention ◽  
Retention Rate ◽  
Intervention Group ◽  
Randomised Control Trial ◽  
Dietary Advice ◽  
Intervention Programme ◽  
Randomised Controlled

Abstract Background Adequate physical activity (PA) is considered essential in diabetes management. However, evidence on the best method of promoting PA within diabetes care is inconclusive. The current work identifies perceptions on the acceptability of Intervention Group Participants (IGP) and Project Officers (POs) about the “MOVEdiabetes” intervention programme aimed at increasing PA in adults with type 2 diabetes in Oman (a retrospectively registered trial). Methods The “MOVEdiabetes” programme (PA consultations, pedometers and WhatsApp messages) was delivered by the POs (primary health care practitioners) in four primary care centres within a one-year cluster randomised control trial. Recruitment and retention were measured from trial attendance records. Programme satisfaction, appropriateness, and content suitability were assessed using exit surveys for both the IGP (interview based) and POs (self-administered). Open text questions on perceptions to the study programme were also included. Results Participants were randomised to an intervention group (IG, n = 122) or comparison group (CG, n = 110). The overall retention rate at three and 12 months was 92.7% [110(90.2%) IG vs 105(95.5%) CG] and 75% [82(67.2%) IG vs 92(83.6%) CG] respectively. Most (n = 14, 87.5%) POs and more than half (n = 49, 59.8%) IGP perceived the programme as very appropriate and many reported that they were “quite/ very satisfied” with the programme (n = 16, 100% PO’s and n = 71, 86.6% IGP). Two thirds (n = 55, 66.0%) of IGP were very/quite likely to recommend the programme to others. PA consultations, use of pedometers and Whatsapp messages were well perceived by all. Participants recommended the inclusion of dietary advice and PA promotion for the general public. Exploring PA facilities within the community was suggested by POs. Conclusions The “MOVEdiabetes” programme achieved a high retention rate and was perceived as satisfactory and appropriate. Results from this study suggest that it is worthwhile exploring the use of the “MOVEdiabetes” programme in clinical practice and further community links. Trial registration International Standard Randomised Controlled Trials No: ISRCTN14425284. Registered retrospectively on 12th April 2016.

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