Absence of telomere shortening and oxidative DNA damage in the young adult offspring of women with pre-gestational type 1 diabetes

Abstract

Aims/hypothesis The offspring of mothers with pre-gestational type 1 diabetes (PGDM) may be at increased risk of glucose intolerance and cardiovascular disease in childhood. The underlying causes of these observations, and whether they persist into adulthood, are unknown. The aim of the present study was to test the hypothesis that fetal chromosomal telomere oxidative DNA damage resulting from maternal PGDM programmes the offspring towards a senescent phenotype that is detectable in young adulthood. Methods We studied 21 young adult offspring (age 16-23 years) with a maternal history of PGDM and 23 age-and weight-matched controls with no maternal history of diabetes. All participants underwent anthropometric assessments, a standard 75 g OGTT, measurement of peripheral blood mononuclear cell and skin fibroblast telomere length, fibroblast senescence, cell DNA damage (by determination of 8-oxoguanine levels using flow cytometry), plasma lipoprotein profiles (determined by nuclear magnetic resonance) and plasma levels of soluble adhesion molecules and inflammatory markers. ResultsThe groups did not differ significantly with respect to anthropometric measures, glucose tolerance, fasting and 2 h plasma insulin levels during OGTT, estimated peripheral insulin resistance, peripheral blood mononuclear cell or fibroblast telomere length, DNA damage or senescence in vitro, plasma NMR lipoprotein profiles or levels of highsensitivity C-reactive protein. Plasma concentrations of soluble intercellular adhesion molecule 1 (sICAM-1; p< 0.05) and IL-6 (p=0.08) were higher in the PGDM offspring. Conclusions/interpretation Young adult offspring of mothers with PGDM do not differ in terms of glucose tolerance, DNA damage or telomere length from controls of the same weight and BMI. This does not preclude such abnormalities at an earlier age, but there is no evidence of telomere damage as a pre-programming mechanism in the young adults enrolled in this study.

Cord blood telomere length, telomerase activity and inflammatory markers in pregnancies in women with diabetes or gestational diabetes

“…As with the telomere data, the lack of difference in this study in hs‐CRP and sICAM‐1 concentrations could reflect the good glycaemic control in the diabetes populations [24]. We and others have previously shown that the young adult offspring of mothers with Type 1 diabetes do have elevated plasma sICAM‐1 levels, although they do not differ in venous nucleated blood cell telomere length, glucose tolerance, insulin sensitivity or nuclear magnetic resonance lipoprotein profiles [25].…”

Telomere length, pre-eclampsia, and gestational diabetes

“…Fifty per group gives us 80% power to see an odds ratio of 3.2 for top vs. bottom quartile, lower than the hazard ratio of 3.5 seen in previous studies of telomere length and cancer [37]. Several studies of this size looking at telomere length and reproductive outcomes have been published[22,30,32]…”

“…In addition, telomere length has been associated with oxidative stress, [16,27] and markers of oxidative stress are raised in pre-eclampsia[28] A recent article found lower telomere length in the placentas of women with pre-eclampsia and intrauterine growth retardation[29] We are unaware of other previous studies of telomere length in pre-eclampsia and gestational diabetes. For studies related to reproductive outcomes, no difference in telomere lengths was found in young adults whose mothers had pre-gestational type 1 diabetes[30], while another study of newborns did not find statistically significant differences in telomere lengths between newborns whose mothers had pre-eclampsia, hypertension, or diabetes[31]. However, these studies dealt with the child rather than the mothers.…”

Telomeres and human health

“… demonstrated that the very strong associations between telomere length and chronic obstructive pulmonary disease and lung function indices were reduced to almost insignificance after adjusting for age, gender, smoking habits, body mass index and other lifestyle factors. Risk of diabetes has also been examined; the combined evidence does not suggest a strong association with telomere length , although it might be predictive of late complications of diabetes .…”