Telomere length is reduced in 9- to 16-year-old girls exposed to gestational diabetes in utero

Hjort, Line; Vryer, Regan; Grunnet, Louise Groth; Burgner, David; Olsen, Sjúrður F.; Saffery, Richard; Vaag, Allan

doi:10.1007/s00125-018-4549-7

Cited by 30 publications

(29 citation statements)

References 54 publications

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“…This is important to study, since TL at birth is a main predictor for TL throughout life ( 6 , 9 , 10 ), and TL later in life is associated with the risk of several outcomes, such as cancer and cardiovascular diseases ( 11 , 12 ). There is emerging evidence that factors such as maternal stress ( 13 , 14 ), inflammation ( 15 ), gestational diabetes ( 16 ), exposure to air pollution ( 17 , 18 ), tobacco smoke ( 19 ), and toxic metals ( 20 ) may influence offspring TL.…”

Section: Introductionmentioning

confidence: 99%

Placental and Cord Blood Telomere Length in Relation to Maternal Nutritional Status

Vahter

Broberg

Harari

2020

The Journal of Nutrition

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Background The uterine environment may be important for the chromosomal telomere length (TL) at birth, which, in turn, influences disease susceptibility throughout life. However, little is known about the importance of specific nutritional factors. Objectives We assessed the impact of multiple maternal nutritional factors on TL in placenta and cord blood. Methods In a population-based mother–child cohort in northwestern Argentina, we measured maternal weight, BMI, body fat percentage (BFP), and several nutrients [selenium, magnesium, calcium, zinc, manganese, iodine, vitamin B-12, folate, 25-hydroxycholecalciferol (25(OH)D3)], hemoglobin, and homocysteine in maternal whole blood, serum, plasma, or urine during pregnancy (mean gestational week 27). We measured the relative TL (rTL) in placenta (n = 99) and cord blood (n = 98) at delivery by real-time PCR. Associations were evaluated by multivariable-adjusted linear regression. Results The women's prepregnancy BMI (kg/m2; mean ± SD: 23.7 ± 4.1), body weight (55.4 ± 9.9 kg), and BFP (29.9 ± 5.5%), but not height (153 ± 5.3 cm), were inversely associated with placental rTL (P < 0.01 for all), with ∼0.5 SD shorter rTL for an IQR increase in prepregnancy body weight, BMI, or BFP. Also, impedance-based BFP, but not lean body mass, in the third trimester was associated with shorter placental rTL. In addition, serum vitamin B-12 (232 ± 96 pmol/L) in pregnancy (P = 0.038), but not folate or homocysteine, was associated with shorter placental rTL (0.2 SD for an IQR increase). In contrast, plasma 25(OH)D3 (46 ± 15 nmol/L) was positively associated with placental rTL (P < 0.01), which increased by 0.4 SD for an IQR increase in 25(OH)D3. No clear associations of the studied maternal nutritional factors were found with cord blood rTL. Conclusions Maternal BMI, BFP, and vitamin B-12 were positively associated, whereas 25(OH)D3 was inversely associated, with placental TL. No association was observed with cord blood TL. Future studies should elucidate the role of placental TL for child health.

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Section: Introductionmentioning

confidence: 99%

Placental and Cord Blood Telomere Length in Relation to Maternal Nutritional Status

Vahter

Broberg

Harari

2020

The Journal of Nutrition

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“…There is less information on maternal exposures in pregnancy and telomere length in children. A recent study (n = 439) demonstrated 14% shorter telomeres in 12-year-old children of mothers who had GDM, driven by shorter telomeres in female but not male children [38]. We demonstrated no effect modification with fetal sex, when assessing the metabolic syndrome and child telomere Table 3 Association between individual components of the metabolic syndrome in women during pregnancy, and increasing number of components, and child telomere length a length, though our sample size was small.…”

Section: Discussionmentioning

confidence: 51%

The metabolic syndrome in pregnancy and its association with child telomere length

et al. 2020

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Aims/hypothesis The aim of this study was to determine whether presence of the metabolic syndrome in pregnancy associates with child telomere length or child anthropometry (weight, BMI) and BP, measured at 10 years of age. Methods The Screening for Pregnancy Endpoints study (SCOPE) was a multicentre, international prospective cohort of nulliparous pregnant women recruited from Australia, New Zealand, Ireland and the UK (N = 5628). The current analysis is a 10 year follow-up of SCOPE pregnant women and their children, from the Australian cohort. Clinical data collected at 14-16 weeks' gestation during the SCOPE study were used to diagnose the metabolic syndrome using IDF criteria. Telomere length, a biomarker of ageing, was assessed by quantitative PCR from children's saliva collected at 10 years of age. Results In women who completed follow-up (n = 255), 20% had the metabolic syndrome in pregnancy. After adjusting for a range of confounders, children of mothers who had the metabolic syndrome in pregnancy had 14% shorter telomeres than children of mothers without the metabolic syndrome in pregnancy (mean difference −0.36 [95% CI −0.74, 0.01]). Height-and weight-forage , and BMI z scores were similar in children of mothers who did and did not have the metabolic syndrome during pregnancy. Conclusions/interpretation Children of mothers who had the metabolic syndrome in pregnancy have shorter telomeres, a biomarker of accelerated ageing. These findings warrant further studies in larger cohorts of children, as well as investigations into whether telomere length measured in cord blood associates with telomere length in childhood.

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“…We have not shown, in this study, whether the shortened telomeres were inherited by the offspring. While some studies suggest that this is the case [16, 17], other studies find no such association [18–20]. This may be due to the technical challenges imposed by the use of leukocyte DNA.…”

Section: Discussionmentioning

confidence: 99%

“…Conversely, individuals may start life with shorter than normal telomeres that then play a role in the disease progression of diabetes [14], contributing to impaired glucose management and insulin secretion [15]. The latter possibility is indicated by the observation that diabetes during pregnancy, is linked to shortened telomere length in blood leukocytes from exposed children [16, 17], although not all studies report such a link [18–20]. If individuals exposed in utero to GDM start life with shorter telomeres, this may explain why they are at higher risk of adverse outcomes such as T2DM later in life.…”

Section: Introductionmentioning

confidence: 99%

Metformin and insulin treatment prevent placental telomere attrition in boys exposed to maternal diabetes

et al. 2018

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Shortened leukocyte and placental telomeres associated with gestational diabetes mellitus (GDM) suggest this exposure triggers telomere attrition contributing to adverse outcomes. We applied high resolution Single Telomere Length Analysis (STELA) to placenta from GDM pregnancies with different treatment pathways to determine their effectiveness at preventing telomere attrition. Differences in telomere length between control (N = 69), GDM lifestyle intervention (n = 14) and GDM treated with metformin and/or insulin (n = 17) was tested by Analysis of Covariance (ANCOVA) followed by group comparisons using Fisher’s least significant difference. For male placenta only, there were differences in mean telomere length (F(2,54) = 4.98, P = 0.01) and percentage of telomeres under 5 kb (F(2,54) = 4.65, P = 0.01). Telomeres were shorter in the GDM lifestyle intervention group compared to both controls (P = 0.02) and medically treated pregnancies (P = 0.003). There were more telomeres under 5 kb in the GDM lifestyle intervention group compared to the other two groups (P = 0.03 and P = 0.004). Although further work is necessary, we suggest that early adoption of targeted medical treatment of GDM pregnancies where the fetus is known to be male may be an effective strategy for ameliorating adverse outcomes for children.

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Telomere length is reduced in 9- to 16-year-old girls exposed to gestational diabetes in utero

Cited by 30 publications

References 54 publications

Placental and Cord Blood Telomere Length in Relation to Maternal Nutritional Status

Placental and Cord Blood Telomere Length in Relation to Maternal Nutritional Status

The metabolic syndrome in pregnancy and its association with child telomere length

Metformin and insulin treatment prevent placental telomere attrition in boys exposed to maternal diabetes

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