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

Abstract

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. 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. The 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 high-sensitivity 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. 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.