Oxidative stress, senescence and mRNA decay in peripheral blood mononuclear cells of women with gestational diabetes mellitus-link to increased cardiovascular disease risk.

AIMS: Women who develop gestational diabetes mellitus (GDM) have a pancreatic β-cell defect that cannot compensate for the insulin resistance of pregnancy. The glucose intolerance may, in addition to direct effects, negatively impact lipid metabolism, promote vascular dysfunction and contribute to cardiovascular disease (CVD). We assessed associations between oxidative stress and senescence markers with indices of glucose and lipid metabolism in women developing GDM and with CVD risk after 5 years.

MATERIALS AND

METHODS

The oxidative stress and senescence markers NRF2, GPX4, TERC, XRN1 and DCP2 were assessed in peripheral blood mononuclear cells (PBMCs), advanced oxidation protein products (AOPP) and β-galactosidase in plasma, from healthy (n = 253) and women with GDM (n = 31) during pregnancy and at 5-year follow-up, from the STORK study. We investigated their associations with established markers of disease activity and later CVD.

RESULTS

Plasma AOPP and β-galactosidase were increased early in pregnancy in women developing GDM later and associated with indices of glucose metabolism and TG/HDL-Cholesterol. RNA levels of transcripts involved in telomer maintenance and antioxidant responses were decreased in women with GDM during pregnancy and at follow-up. DCP2 and XRN1 expression were positively associated with β-cell function at all timepoints and with pulse wave velocity at 5-year follow-up in women with previous GDM.

CONCLUSIONS

Markers of vascular oxidative stress and senescence are increased and correlate with indices of glucose and lipid metabolism early in pregnancy in women developing GDM. Cellular markers reflecting attenuated defence against oxidative stress and senescence decrease throughout pregnancy and at 5-year follow-up and correlate with aortic stiffness in women with previous GDM.