Reduced Fetal Telomere Length in Gestational Diabetes

Abstract

Gestational diabetes mellitus (GDM) is an important complication of pregnancy that poses significant threats to women and their offspring. Telomere length shortens as cellular damage increases and is associated with metabolic diseases. Telomere length in fetal leucocytes was determined in 82 infants of women with GDM (N = 82) and 65 normal pregnant women (N = 65). Women with preeclampsia (N = 45) and gestational hypertension (N = 23) were also studied. In the GDM group, telomere length was significantly shorter than normal pregnancy (P = 0.028), but there were no significant differences in fetal telomere length between preeclampsia and normal pregnancy (P = 0.841) and between gestational hypertension and normal pregnancy (P = 0.561). Regression analysis revealed that fetal telomere length was significantly associated with intrauterine exposure to GDM (P = 0.027 after adjustment for maternal age, gestational age at delivery, birth weight and fetal gender). Shortened telomere length may increase the risk of metabolic diseases in adulthood of GDM offspring.

A short leucocyte telomere length is associated with development of insulin resistance

“…In unadjusted analyses the skinfold values were associated with BMI and insulin resistance but not with LTL. Previously we reported tracking and fixed ranking of LTL in adults [18]. We replicated these findings in the GEMINAKAR participants.…”

“…However, this concept has now been challenged by showing that LTL is largely determined early in life [4,15]. Thus, genetic factors [16] and the intrauterine environment [17][18][19] might play a role in fashioning TL, which, in turn, may have a major impact on the risk of metabolic diseases in adulthood. A recent clinical study in American Indians showed that short LTL was associated with the incidence of type 2 diabetes mellitus [20] and obesity [21].…”

Telomere length change plateaus at 4 years of age in Latino children: associations with baseline length and maternal change

“…Studies have reported loss rates in leukocytes from 27 base pairs/year in adults 18-76 years of age (Valdes et al 2005), 31 base pairs/year (2-94 years of age) (Slagboom et al 1994) and up to 62-66 base pairs/year in a group spanning 0-100 years of age (Mayer et al 2006). However, as there is a wide variation in telomere length already present at birth based on ethnicity and race (Drury et al 2015) and due to in utero exposures such as gestational diabetes (Xu et al 2014), cross-sectional studies of telomere length using multi-age groups can be confounded by a myriad of factors. Additionally, as studies have reported telomere lengthening processes in individuals in addition to attrition (Aviv et al 2009;Nordfjall et al 2009;Farzaneh-Far et al 2010), longitudinal studies of telomere length in children with repeat measures are needed to provide accurate rates of telomere change at different ages.…”

The functional polymorphism rs73598374:G>A (p.Asp8Asn) of the ADA gene is associated with telomerase activity and leukocyte telomere length

“…Notably, ADA rs73598374-A carriers displayed a stronger age-dependent crosssectional decrease of LTL compared to G/G carriers, a finding in line with the association of ADA rs73598374-A allele with reduced life expectancy. 8,9 Interestingly, it has been demonstrated in gestional diabetes that the telomere length of fetal leukocytes is shorter than normal pregnancy, 14 and that the proportion of ADA rs73598374-A carrier newborns delivered by rs73598374 G/G mothers is significantly higher than would be expected on the basis of random mating. 15 In this context, it is also remarkable that our results suggest a more prominent effect of ADA rs73598374 on telomere biology at younger ages rather than later in life.…”