Association of early pregnancy telomere length and mitochondrial copy number with gestational diabetes mellitus and depressive symptoms.

AIM: A bidirectional link exists between depression and gestational diabetes mellitus (GDM). While telomere length (TL) and mitochondrial DNA copy number (mtDNA-CN) alterations have been reported either in GDM or depression, their predictive ability of GDM with coexisting depression remains unexplored. We, therefore, prospectively investigated the relationship of TL and mtDNA-CN in blood leukocytes during early pregnancy and explored their potential as predictive biomarkers for identifying the risk of developing GDM with depressive symptoms later in pregnancy.

METHODS

A nested cohort of 301 women with normal fasting glucose and without depressive symptoms in early pregnancy (<16 weeks) were selected from the STratification of Risk of Diabetes in Early Pregnancy (STRiDE) study. At 24-28 weeks (OGTT visit), a 75 g OGTT and PHQ-9 were performed. Women were categorized into four groups: NGT without depressive symptoms (n = 80), NGT with depressive symptoms (n = 105), GDM without depressive symptoms (n = 75), and GDM with depressive symptoms (n = 41). Blood leukocyte TL and mtDNA-CN were assessed using qRT-PCR.

RESULTS

TL and mtDNA-CN at early pregnancy were lower in women with GDM, depressive symptoms or both, compared to NGT without depressive symptoms at OGTT visit. TL and mtDNA-CN at early pregnancy were negatively associated with PHQ-9 score and OGTT blood glucose levels at OGTT visit after adjusting for age, pre-pregnancy BMI and family history of diabetes. Higher levels of both TL and mtDNA-CN in early pregnancy were associated with lower adjusted Relative Risk (aRR) (TL; aRR: 0.34; 95 % CI: 0.28, 0.41, mtDNA-CN; aRR: 0.83; 95 % CI: 0.74, 0.93) of GDM with depressive symptoms at OGTT visit.

CONCLUSION

Lower levels of TL and mtDNA-CN in early pregnancy are significantly associated with the later development of GDM and depressive symptoms at OGTT visit. Our findings indicate that early trimester TL and mtDNA-CN could be potential predictive biomarkers for predicting GDM with depressive symptoms and emphasize their potential for improved risk assessment so as to adopt preventive strategies targeting these conditions.