Gestational Diabetes Linked to Accelerated Aging in Offspring

Stephanie Shiau, PhD

New data by a team of researchers at Rutgers University is shedding light on a potential connection between gestational diabetes and biological age of offspring.

An analysis including more than 1100 children from Tianjin, China, researchers revealed children born to mothers with gestational diabetes mellitus had a higher epigenetic age than their counterparts born to mothers without gestational diabetes mellitus. Additionally, this increased epigenetic age was linked to increased risk of other comorbidities later in life, such as obesity and increased blood pressure.

"These findings suggest that gestational diabetes may have long-term effects on epigenetic aging in offspring and lead to poorer cardiometabolic health outcomes," said lead author Stephanie Shiau, an instructor at the Rutgers School of Public Health, in a statement.

In an effort to further investigate the effects of gestational diabetes mellitus on offspring, Shiau and a team of colleagues from the US and China designed the current study. To do so, they designed their study as an analysis of estimated DNA methylation (DNAm) age in offspring born to mothers with and without gestational diabetes mellitus from the Tianjin GDM Observational Study.

Of note, the Tianjin GDM Observational Study was conducted between 2005-2009 and sought to compare risks of early postpartum diabetes and prediabetes in Chinese women with and without gestational diabetes mellitus during pregnancy. Ultimately, the trial contained cohorts of 1263 women with a history of gestational diabetes mellitus and 705 women without gestational diabetes mellitus. With a mean follow-up time of 3.53 years postpartum, Shiau and team used this study to identify data related to 1156 children between the ages of 3-10 years born to mothers within the study.

Of the 1156 children included, 758 were born to mothers with gestational diabetes and 758 were born to mothers without gestational diabetes. All children included in the study underwent an exam at a median age of 5.9 years (3.1-10.2) that included anthropometric measurements and a blood draw for DNAm analysis. For the purpose of analysis, DNAm age was calculated using Horvath and Hannum epigenetic clock algorithms and the residual resulting from regressing DNAm age on chronological age was used as the metric for age acceleration.

Upon analysis, results indicated chronological age strongly correlated with both the Horvath DNAm age (r=.53; P <.0001) and the Hannum DNAm age (r=.38; P <.0001). Results also indicated offspring age acceleration was higher among those born to mothers with gestational diabetes mellitus compared to their counterparts who had mother without gestational diabetes mellitus when adjusting for potential confounders (Horvath, 4.96 months higher, P=.0002; Hannum, 11.2 months higher, P <.0001). Investigators noted the Horvath algorith was adjusted for sex, pre-pregnancy BMI, cell-type proportions, and technical bias while the Hannum algorithm adjusted for cell-type proportions and technical bias.

Results of the analyses suggest increased offspring DNAm age acceleration was associated with increased offspring weight-for-age Z-score, BMI-for-age-Z-score, waist circumference, body fat percentage, subscapular skinfold, suprailiac skinfold, upper-arm circumference, and blood pressure. Investigators pointed out these associations were strong among offspring born to mothers with gestational diabetes mellitus.

“We found that offspring of women with gestational diabetes mellitus exhibit accelerated epigenetic age compared to control participants, independent of other maternal factors. Epigenetic age in offspring was associated with cardiometabolic risk factors, suggesting that gestational diabetes mellitus and gestational diabetes mellitus-associated factors may have long-term effects on offspring epigenetic age and contribute to health outcomes,” wrote investigators.

This study, “Prenatal gestational diabetes mellitus exposure and accelerated offspring DNA methylation age in early childhood,” was published in Epigenetics.