Association of early pregnancy telomere length and mitochondrial copy number with gestational diabetes mellitus and depressive symptoms
Thirumoorthy, Chinnasamy Rekha, Ravikumar Pavithra Deepa, Mohan Ram, Uma Shalu, Durai Venkatesan, Ulagamadesan Srikumar, Bettadapura N. Anjana, Ranjit Mohan Balasubramanyam, Muthuswamy Mohan, Viswanathan
Thirumoorthy, Chinnasamy
Rekha, Ravikumar Pavithra
Deepa, Mohan
Ram, Uma
Shalu, Durai
Venkatesan, Ulagamadesan
Srikumar, Bettadapura N.
Anjana, Ranjit Mohan
Balasubramanyam, Muthuswamy
Mohan, Viswanathan
Affiliation
National Institute of Mental Health and Neuro Sciences (NIMHANS), Bangalore, India; Madras Diabetes Research Foundation (MDRF), Chennai, India; Seethapathy Clinic & Hospital, Chennai, India; University of Warwick, Coventry; George Eliot Hospital NHS Trust, Nuneaton
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Publication date
2025-03-18
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Abstract
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.
Keywords: Asian Indians; Depressive symptoms; Gestational diabetes mellitus; Mitochondrial copy number; Pregnancy; Prospective study; Telomere length.
Citation
Thirumoorthy C, Rekha RP, Deepa M, Ram U, Shalu D, Venkatesan U, Srikumar BN, Anjana RM, Balasubramanyam M, Mohan V, Saravanan P, Govindaraj P, Gokulakrishnan K. Association of early pregnancy telomere length and mitochondrial copy number with gestational diabetes mellitus and depressive symptoms. Psychoneuroendocrinology. 2025 Jun;176:107431. doi: 10.1016/j.psyneuen.2025.107431. Epub 2025 Mar 18.
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Article