Telomere length is reduced in 9- to 16-year-old girls exposed to gestational diabetes in utero
Shortened telomere length is a marker of cell damage and is associated with oxidative stress, chronic inflammation and metabolic disease. We hypothesised that the offspring of women with gestational diabetes mellitus (GDM) with increased risk of cardiovascular and metabolic diseases might exhibit shorter telomere length.
We investigated telomere length in 439 GDM and 469 control group offspring, aged between 9 and 16 years, recruited from the Danish National Birth Cohort. Relative telomere length was measured in peripheral blood DNA (n = 908) using a quantitative PCR approach. Multivariate regression analysis was used to investigate the association between mothers’ GDM status and telomere length in the offspring.
Female offspring had longer telomeres than males. Offspring of mothers with GDM had significantly shorter telomere length than control offspring, but this difference was observed only in girls. There was a negative association between telomere length and GDM exposure among the female offspring (14% shorter telomeres, p = 0.003) following adjustment for the age of the offspring. Telomere length in female offspring was negatively associated with fasting insulin levels and HOMA-IR (p = 0.03). Maternal age, smoking, gestational age, birthweight and the offspring’s anthropometric characteristics were not associated with telomere length (p ≥ 0.1).
The 9- to 16-year-old girls of mothers with GDM had shorter telomeres than those from the control population. Further studies are needed to understand the extent to which shortened telomere length predicts and/or contributes to the increased risk of disease later in life among the offspring of women with GDM.
KeywordsDevelopmental programming Gestational diabetes Inflammation Offspring Oxidative stress Telomere length Type 2 diabetes
Body fat percentage
Danish National Birth Cohort
Gestational diabetes mellitus
High-sensitivity C-reactive protein
We greatly appreciate all the children and their mothers who participated in the study. Additional GDM study team members include F. Bach Kampmann, M. Egholm, A.-C. Baun Thuesen, C. Møller Madsen, C. Fau Brinkløv and student assistants, who did tremendous work assisting in collecting data (Department of Endocrinology, Copenhagen University Hospital, Denmark). Additionally, we want to acknowledge the great collaboration with Staten’s Serum Institute DNBC study members S. Hansen, M. Strøm, K. Agerskov, C. Granström and A. Ahrendt in the planning and organisation of the GDM study (Centre for Fetal Programming, Statens Serum Institut, Copenhagen, Denmark) and C. Zhang for the collaboration on the Diabetes and Women’s Health (DWH) study (Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA). We also kindly thank the clinics across Denmark’s regions for providing housing facilities for the clinical study.
LH, RV and RS designed the telomere study, and LGG, SFO and AV designed the GDM subcohort study. LH and LGG, together with the GDM/DNBC study team, collected the in vivo data. LH processed the blood samples and extracted DNA, and LH and RV performed the telomere length measurements. LH, RV and RS analysed the data, and LH, RV, LGG, DB, RS and AV interpreted the results of the experiments. LH wrote the manuscript, with contributions from RV, LGG, DB and RS. All co-authors revised the manuscript and approved the final version. AV is the guarantor of this work and takes responsibility for the contents and integrity of the data in this article.
This study was funded by the Danish Council for Strategic Research, the Innovation Fund Denmark (09-067124 and 11-115923), the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (contract #HHSN275201000020C), The European Commission (FP7-289346-EarlyNutrition), Rigshospitalet/The Copenhagen University Hospital, the faculty of Health and Medical Sciences, Copenhagen University and the Danish Diabetes Academy supported by the Novo Nordisk Foundation.
Duality of interest
AV is employed by AstraZeneca, Mölndal, Sweden and is shareholder of Novo Nordisk A/S. All other authors declare no potential conflict of interest relevant to this study.
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