| 1. |
- Hjort, Line, et al.
(författare)
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Epigenetics of the non-coding RNA nc886 across blood, adipose tissue and skeletal muscle in offspring exposed to diabetes in pregnancy
- 2024
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Ingår i: Clinical Epigenetics. - 1868-7075. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Diabetes in pregnancy is associated with increased risk of long-term metabolic disease in the offspring, potentially mediated by in utero epigenetic variation. Previously, we identified multiple differentially methylated single CpG sites in offspring of women with gestational diabetes mellitus (GDM), but whether stretches of differentially methylated regions (DMRs) can also be identified in adolescent GDM offspring is unknown. Here, we investigate which DNA regions in adolescent offspring are differentially methylated in blood by exposure to diabetes in pregnancy. The secondary aim was to characterize the RNA expression of the identified DMR, which contained the nc886 non-coding RNA. Methods: To identify DMRs, we employed the bump hunter method in samples from young (9–16 yr, n = 92) offspring of women with GDM (O-GDM) and control offspring (n = 94). Validation by pyrosequencing was performed in an adult offspring cohort (age 28–33 years) consisting of O-GDM (n = 82), offspring exposed to maternal type 1 diabetes (O-T1D, n = 67) and control offspring (O-BP, n = 57). RNA-expression was measured using RT-qPCR in subcutaneous adipose tissue and skeletal muscle. Results: One significant DMR represented by 10 CpGs with a bimodal methylation pattern was identified, located in the nc886/VTRNA2-1 non-coding RNA gene. Low methylation status across all CpGs of the nc886 in the young offspring was associated with maternal GDM. While low methylation degree in adult offspring in blood, adipose tissue, and skeletal muscle was not associated with maternal GDM, adipose tissue nc886 expression was increased in O-GDM compared to O-BP, but not in O-T1D. In addition, adipose tissue nc886 expression levels were positively associated with maternal pre-pregnancy BMI (p = 0.006), but not with the offspring’s own adiposity. Conclusions: Our results highlight that nc886 is a metastable epiallele, whose methylation in young offspring is negatively correlated with maternal obesity and GDM status. The physiological effect of nc886 may be more important in adipose tissue than in skeletal muscle. Further research should aim to investigate how nc886 regulation in adipose tissue by exposure to GDM may contribute to development of metabolic disease.
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| 2. |
- Grunnet, Louise Groth, et al.
(författare)
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High Prevalence of Gestational Diabetes Mellitus in Rural Tanzania-Diagnosis Mainly Based on Fasting Blood Glucose from Oral Glucose Tolerance Test
- 2020
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1660-4601. ; 17:9
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Tidskriftsartikel (refereegranskat)abstract
- Gestational diabetes mellitus (GDM) is associated with poor pregnancy outcomes and increased long-term risk of metabolic diseases for both mother and child. In Tanzania, GDM prevalence increased from 0% in 1991 to 19.5% in 2016. Anaemia has been proposed to precipitate the pathogenesis of GDM. We aimed to examine the prevalence of GDM in a rural area of Tanzania with a high prevalence of anaemia and to examine a potential association between haemoglobin concentration and blood glucose during pregnancy. The participants were included in a population-based preconception, pregnancy and birth cohort study. In total, 538 women were followed during pregnancy and scheduled for an oral glucose tolerance test (OGTT) at week 32-34 of gestation. Gestational diabetes mellitus was diagnosed according to the WHO 2013 guidelines. Out of 392 women screened, 39% (95% CI: 34.2-44.1) had GDM, the majority of whom (94.1%) were diagnosed based solely on the fasting blood sample from the OGTT. No associations were observed between haemoglobin or ferritin and glucose measurements during pregnancy. A very high prevalence of GDM was found in rural Tanzania. In view of the laborious, costly and inconvenient OGTT, alternative methods such as fasting blood glucose should be considered when screening for GDM in low- and middle-income countries.
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| 3. |
- Grunnet, Louise Groth, et al.
(författare)
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The Triglyceride Content in Skeletal Muscle Is Associated with Hepatic But Not Peripheral Insulin Resistance in Elderly Twins.
- 2012
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X.
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Tidskriftsartikel (refereegranskat)abstract
- Context and Objective:Total muscle triglyceride (MT) content has been associated with insulin resistance. We investigated the predictors and impact of MT on relevant metabolic parameters including peripheral and hepatic insulin resistance in elderly twins.Design and Participants:Seventy-four elderly same-sex twins underwent hyperinsulinemic euglycemic clamps preceded by an iv glucose tolerance test. Aerobic capacity (VO(2max)) and body composition (dual-energy x-ray absorptiometry scan) were determined in all twins. A biopsy from the vastus lateralis muscle was excised in the fasting state. The muscle triacylglycerol content was analyzed by biochemical extraction from these biopsies.Results:The percentage of total body fat was the only independent predictor of MT content. After adjustment for trunk fat percentages and sex, MT level was significantly associated to fasting plasma levels of glucose and insulin as well as hepatic insulin resistance. However, the association was weakened after adjustment for total fat percentages. A 1 sd (34.5 mmol/kg dry weight) increase in MT content was associated with a 24% increase of hepatic insulin resistance. No association between MT content and peripheral insulin sensitivity was observed.Conclusion:MT content is associated with hepatic but not peripheral insulin resistance in elderly twins. We speculate that MT content may reflect the general ectopic accumulation of triglycerides, including fat in the liver.
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| 4. |
- Hatem, Gad, et al.
(författare)
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Mapping the cord blood transcriptome of pregnancies affected by early maternal anemia to identify signatures of fetal programming
- 2022
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 107:5, s. 1303-1316
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Anemia during early pregnancy (EP) is common in developing countries and is associated with adverse health consequences for both mother and children. Offspring of women with EP anemia often have low birth-weight, the latter being a risk factor for cardiometabolic diseases including type 2 diabetes (T2D) later in life. Mechanisms underlying developmental programming of adult cardiometabolic disease include epigenetic and transcriptional alterations potentially detectable in umbilical cord blood (UCB) at time of birth.METHODS: We leveraged global transcriptome- and accompanying epigenome-wide changes in 48 UCB from newborns of EP-anemic Tanzanian mothers and 50 controls to identify differentially expressed genes (DEG) in UCB exposed to maternal EP-anemia. DEGs were assessed for association with neonatal anthropometry and cord insulin levels. These genes were further studied in expression data from human fetal pancreas and adult islets to understand their role in beta-cell development and/or function.RESULTS: The expression of 137 genes was altered in UCB of newborns exposed to maternal EP anemia. These putative signatures of fetal programming which included the birth-weight locus LCORL, were potentially mediated by epigenetic changes in 27 genes and associated with neonatal anthropometry. Among the DEGs were P2RX7, PIK3C2B, and NUMBL which potentially influence beta-cell development. Insulin levels were lower in EP anemia exposed UCB, supporting the notion of developmental programming of pancreatic beta-cell dysfunction and subsequently increased risk of T2D in offspring of EP anemic mothers.CONCLUSIONS: Our data provide proof-of-concept on distinct transcriptional and epigenetic changes detectable in UCB from newborns exposed to maternal EP anemia.
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| 5. |
- Hjort, Line, et al.
(författare)
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FOETAL for NCD-FOetal Exposure and Epidemiological Transitions : the role of Anaemia in early Life for Non-Communicable Diseases in later life: a prospective preconception study in rural Tanzania
- 2019
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 9:5
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Low-income and middle-income countries such as Tanzania experience a high prevalence of non-communicable diseases (NCDs), including anaemia. Studying if and how anaemia affects growth, placenta development, epigenetic patterns and newborns' risk of NCDs may provide approaches to prevent NCDs.PARTICIPANTS: The FOETALforNCD (FOetal Exposure and Epidemiological Transitions: the role of Anaemia in early Life for Non-Communicable Diseases in later life) Study is a population-based preconception, pregnancy and birth cohort study (n=1415, n=538, n=427, respectively), conducted in a rural region of North-East Tanzania. All participants were recruited prior to conception or early in pregnancy and followed throughout pregnancy as well as at birth. Data collection included: maternal blood, screening for NCDs and malaria, ultrasound in each trimester, neonatal anthropometry at birth and at 1 month of age, cord blood, placental and cord biopsies for stereology and epigenetic analyses.FINDINGS TO DATE: At preconception, the average age, body mass index and blood pressure of the women were 28 years, 23 kg/m2 and 117/75 mm Hg, respectively. In total, 458 (36.7%) women had anaemia (haemoglobin Hb <12 g/dL) and 34 (3.6%) women were HIV-positive at preconception. During pregnancy 359 (66.7%) women had anaemia of which 85 (15.8%) women had moderate-to-severe anaemia (Hb ≤9 g/dL) and 33 (6.1%) women had severe anaemia (Hb ≤8 g/dL). In total, 185 (34.4%) women were diagnosed with malaria during pregnancy.FUTURE PLANS: The project will provide new knowledge on how health, even before conception, might modify the risk of developing NCDs and how to promote better health during pregnancy. The present project ended data collection 1 month after giving birth, but follow-up is continuing through regular monitoring of growth and development and health events according to the National Road Map Strategic Plan in Tanzania. This data will link fetal adverse event to childhood development, and depending on further grant allocation, through a life course follow-up.
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| 6. |
- Hjort, Line, et al.
(författare)
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Gestational diabetes and maternal obesity are associated with epigenome-wide methylation changes in children
- 2018
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Ingår i: JCI Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 3:17
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Tidskriftsartikel (refereegranskat)abstract
- Offspring of women with gestational diabetes mellitus (GDM) are at increased risk of developing metabolic disease, potentially mediated by epigenetic mechanisms. We recruited 608 GDM and 626 control offspring from the Danish National Birth Cohort, aged between 9 and 16 years. DNA methylation profiles were measured in peripheral blood of 93 GDM offspring and 95 controls using the Illumina HumanMethylation450 BeadChip. Pyrosequencing was performed for validation/replication of putative GDM-associated, differentially methylated CpGs in additional 905 offspring (462 GDM, 444 control offspring). We identified 76 differentially methylated CpGs in GDM offspring compared with controls in the discovery cohort (FDR, P < 0.05). Adjusting for offspring BMI did not affect the association between methylation levels and GDM status for any of the 76 CpGs. Most of these epigenetic changes were due to confounding by maternal prepregnancy BMI; however, 13 methylation changes were independently associated with maternal GDM. Three prepregnancy BMI-associated CpGs (cg00992687 and cg09452568 of ESM1 and cg14328641 of MS4A3) were validated in the replication cohort, while cg09109411 (PDE6A) was found to be associated with GDM status. The identified methylation changes may reflect developmental programming of organ disease mechanisms and/or may serve as disease biomarkers.
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