Human Milk: Understanding the Mechanisms Linked to the Prevention of Obesity and Diabetes in Children Exposed in Utero to Gestational Diabetes

Abstract Context Gestational diabetes (GDM) has profound effects on the intrauterine metabolic milieu and is linked to obesity and diabetes in offspring, but the mechanisms driving these effects remain largely unknown. Alterations in DNA methylation and gene expression in amniocytes exposed to GDM in utero represent a potential mechanism leading to metabolic dysfunction later in life. Objective To profile changes in genome-wide DNA methylation and expression in human amniocytes exposed to GDM. Design A nested case-control study (n = 14 pairs) was performed in amniocytes matched for offspring sex, maternal race/ethnicity, maternal age, gestational age at amniocentesis, and gestational age at birth. Sex-specific genome-wide DNA methylation analysis and RNA-sequencing were completed and differentially methylated regions (DMRs) and gene expression changes were identified. Ingenuity pathway analysis identified biologically relevant pathways enriched after GDM exposure. In silico high-throughput chromosome conformation capture (Hi-C) analysis identified potential chromatin interactions with DMRs. Results Expression of interferon-stimulated genes was increased in GDM amniocytes, accounting for 6 of the top 10 altered genes (q < 0.05). Enriched biological pathways in GDM amniocytes included pathways involving inflammation, the interferon response, fatty liver disease, monogenic diabetes, and atherosclerosis. Forty-two DMRs were identified in male GDM-exposed amniocytes and 20 in female amniocyte analysis (q < 0.05). Hi-C analysis identified interactions between DMRs and 11 genes with significant expression changes in male amniocytes and 9 in female amniocytes (P < .05). Conclusion In a unique repository of human amniocytes exposed to GDM in utero, transcriptome analysis identified enrichment of inflammation and interferon-related pathways and novel DMRs with potential distal regulatory functions.

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Epigenetic programming of obesity and diabetes by in utero exposure to gestational diabetes mellitus

Nutrition Reviews ◽

10.1111/nure.12057 ◽

2013 ◽

Vol 71 ◽

pp. S88-S94 ◽

Cited By ~ 72

Author(s):

Stephanie-May Ruchat ◽

Marie-France Hivert ◽

Luigi Bouchard

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

In Utero ◽

In Utero Exposure ◽

Epigenetic Programming ◽

Obesity And Diabetes

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Selective morphological and volumetric alterations in the hippocampus of children exposed in utero to gestational diabetes mellitus

Human Brain Mapping ◽

10.1002/hbm.25390 ◽

2021 ◽

Author(s):

Kirsten M. Lynch ◽

Jasmin M. Alves ◽

Ting Chow ◽

Kristi A. Clark ◽

Shan Luo ◽

...

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

In Utero

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Gestational microbiome: metabolic perturbations and developmental programming

Reproduction ◽

10.1530/rep-21-0241 ◽

2021 ◽

Vol 162 (6) ◽

pp. R85-R98

Author(s):

Sophia Han ◽

Charlotte C Ellberg ◽

Isoken N Olomu ◽

Arpita K Vyas

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Gestational Diabetes ◽

Human Microbiome ◽

Disease States ◽

Microbial Dysbiosis ◽

Obesity And Diabetes ◽

Growing Body

A growing body of research suggests that alterations to the human microbiome are associated with disease states, including obesity and diabetes. During pregnancy, these disease states are associated with maternal microbial dysbiosis. This review discusses the current literature regarding the typical maternal and offspring microbiome as well as alterations to the microbiome in the context of obesity, type 2 diabetes mellitus, and gestational diabetes mellitus. Furthermore, this review outlines the proposed mechanisms linking associations between the maternal microbiome in the aforementioned disease states and offspring microbiome. Additionally, this review highlights associations between alterations in offspring microbiome and postnatal health outcomes.

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In Utero Exposure to Maternal Tobacco Smoke and Subsequent Obesity, Hypertension, and Gestational Diabetes Among Women in The MoBa Cohort

Environmental Health Perspectives ◽

10.1289/ehp.1103789 ◽

2012 ◽

Vol 120 (3) ◽

pp. 355-360 ◽

Cited By ~ 54

Author(s):

Lea A. Cupul-Uicab ◽

Rolv Skjaerven ◽

Kjell Haug ◽

Kari K. Melve ◽

Stephanie M. Engel ◽

...

Keyword(s):

Gestational Diabetes ◽

Tobacco Smoke ◽

In Utero ◽

In Utero Exposure ◽

Obesity Hypertension

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Associations between exposure to gestational diabetes mellitus in utero and daily energy intake, brain responses to food cues, and adiposity in children

Yearbook of Paediatric Endocrinology ◽

10.1530/ey.18.11.13 ◽

2021 ◽

Author(s):

Luo S ◽

Angelo BC ◽

Chow T ◽

Monterosso JR ◽

Thompson PM ◽

...

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Energy Intake ◽

In Utero ◽

Food Cues ◽

Daily Energy Intake ◽

Brain Responses ◽

Daily Energy

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Cardiovascular risk factors in offspring exposed to gestational diabetes mellitus in utero: systematic review and meta-analysis

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174419000850 ◽

2020 ◽

Vol 11 (6) ◽

pp. 599-616 ◽

Cited By ~ 8

Author(s):

Maleesa M. Pathirana ◽

Zohra S. Lassi ◽

Claire T. Roberts ◽

Prabha H. Andraweera

Keyword(s):

Diabetes Mellitus ◽

Risk Factors ◽

Systematic Review ◽

Blood Pressure ◽

Cardiovascular Risk ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Systolic Blood Pressure ◽

Meta Analysis ◽

In Utero

AbstractGestational diabetes mellitus (GDM) is a pregnancy complication that affects one in seven pregnancies. Emerging evidence demonstrates that children born of pregnancies complicated by GDM may be at increased risk of cardiovascular disease (CVD) in adulthood. Therefore, the aim of this study was to determine cardiovascular risk factors in offspring exposed to GDM in utero. PubMed, CINAHL, SCOPUS, and EMBASE databases were searched. Information was extracted on established CVD risk factors including blood pressure, lipids, blood glucose, fasting insulin, body mass index (BMI), and endothelial/microvascular function. The review protocol is registered in PROSPERO (CRD42018094983). Prospective and retrospective studies comparing offspring exposed to GDM compared to controls (non-GDM pregnancies) were considered. We included studies that defined GDM based on the International Association of Diabetes and Pregnancy Study Groups (IADPSG) definition, or prior definitions. The PRISMA guidelines were followed in conducting this systematic review. Methodological quality was assessed using the Newcastle–Ottawa Quality Assessment Scale. Study selection, data extraction, and quality assessment were done by two independent reviewers. The data were pooled using a random-effects model. Of 59 eligible studies, 24 were included in the meta-analysis. Offspring exposed to GDM had higher systolic blood pressure (mean difference (MD): 1.75 mmHg, 95% CI 0.57–2.94; eight studies, 7264 participants), BMI z-score (MD 0.11, 95% CI 0.02–0.20; nine studies, 8759 participants), and glucose (standard MD 0.43, 95% CI 0.08–0.77; 11 studies, 6423 participants) than control participants. In conclusion, offspring exposed to GDM have elevated systolic blood pressure, BMI, and glucose. Those exposed to GDM in utero may benefit from early childhood blood pressure measurements.

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Chemerin and Dermcidin in Human Milk and Their Alteration in Gestational Diabetes

Journal of Human Lactation ◽

10.1177/0890334419837523 ◽

2019 ◽

Vol 35 (3) ◽

pp. 550-558 ◽

Cited By ~ 2

Author(s):

Sefer Ustebay ◽

Yakup Baykus ◽

Rulin Deniz ◽

Kader Ugur ◽

Seyda Yavuzkir ◽

...

Keyword(s):

Gestational Diabetes ◽

Human Milk ◽

Antimicrobial Properties ◽

Enzyme Linked Immunosorbent Assay ◽

Mature Milk ◽

Diabetes Group ◽

Blood Samples ◽

Mature Period ◽

Convenience Sampling ◽

Human Milk And Blood

Background: Chemerin and dermcidin, which have antimicrobial properties, are molecules that are also related to insulin resistance and inflammation. Research aims: The aims were to determine the amounts of chemerin and dermcidin in the milk and blood of mothers with gestational diabetes, and to compare the amounts of chemerin and dermcidin in the milk and blood of mothers with and without diabetes. Methods: This was a two-group nonrandomized longitudinal study with a convenience sampling of mothers without gestational diabetes ( n = 27) and mothers with gestational diabetes ( n = 26). Human milk and blood samples were obtained from these mothers during colostrum, transitional, and mature milk periods. The amount of chemerin and dermcidin in these samples was measured by enzyme-linked immunosorbent assay. Results: The presence of chemerin and dermcidin was first detected in human milk. The amounts of chemerin and dermcidin in the blood of all the mothers were greater in the colostrum period and lowest in the mature period. The amount of chemerin and dermcidin in the milk of all the mothers was greater than that in the blood. The amounts of chemerin and dermcidin were significantly increased in both blood and human milk within the gestational age samples. Conclusions: Chemerin and dermcidin may contribute to the protection of infants from infections during infancy. Increased amounts of these molecules found within the gestational diabetes group may also prevent adverse maternal and fetal outcomes.

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