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Circulating biomarkers of upstream kynurenine pathway and brain-derived neurotropic factor in the diagnosis of type 2 and gestational diabetes mellitus with depression

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Abstract

The kynurenine pathway (KP) is the main catabolic pathway for the essential amino acid tryptophan (TRP). The imbalance between beneficial and harmful kynurenines was concerned with the pathogenesis and biological mechanisms of various disorders such as diabetes mellitus (DM), obesity, dyslipidemia, hypertension, depression, and schizophrenia. The present study aimed to determine the levels of biomarkers—TRP, indoleamine-2,3-dioxygenase (IDO), kynurenine (KYN) and brain-derived neurotrophic factor (BDNF) in type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM) to find their association with relevant clinical parameters. Further, aimed to shed light on how coordination amongst the metabolites of KP and BDNF may influence the diagnosis of T2DM and GDM comorbid with depression. One hundred eighty participants were divided into six groups based on glycemic index and depression state. TRP, IDO, KYN and BDNF were determined using enzyme-linked immunosorbent assay (ELISA), and their association was examined. The biochemical parameters were analysed by fully automated equipment. The levels of TRP, IDO and KYN were significantly higher in diabetic patients when compared to non-diabetic, whereas the BDNF level was lower. Correlation analyses showed that TRP, IDO and KYN were positively associated, whereas BDNF was negatively associated with glycemic index (p < 0.01). Our study correlated the overall association between KYN metabolites and BDNF in the aetiology of T2DM and GDM with depression as a cofactor. According to our findings, TRP, IDO, KYN and BDNF either individually or in combination have the potential to be an effective diagnostic tool for both diabetes and depression.

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Abbreviations

BDNF:

Brain-derived neurotrophic factor

IDO:

Indoleamine-2,3-dioxygenase

FBS:

Fasting blood sugar

KP:

Kynurenine pathway

KYN:

Kynurenine

MDD:

Major depressive disorder

PPBS:

Post prandial blood sugar

TDO:

Tryptophan-2,3-dioxygenase

TRP:

Tryptophan

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Authors and Affiliations

  1. Department of Medical Research, SRM Medical College Hospital and Research Centre, SRMIST, Chennai, Kattankulathur, Tamil Nadu, India

    Prasanth Subramanian & Venkataraman Prabhu

  2. Department of General Medicine, SRM Medical College Hospital and Research Centre, SRMIST, Chennai, Kattankulathur, Tamil Nadu, India

    Kumar J. S

  3. Department of Obstetrics and Gynaecology, SRM Medical College Hospital and Research Centre, SRMIST, Chennai, Kattankulathur, Tamil Nadu, India

    Anuradha M

  4. Department of Psychiatry, SRM Medical College Hospital and Research Centre, SRMIST, Chennai, Kattankulathur, Tamil Nadu, India

    Arul Saravanan Ramachandran

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  1. Prasanth Subramanian
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  2. Venkataraman Prabhu
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  3. Kumar J. S
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  4. Anuradha M
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  5. Arul Saravanan Ramachandran
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Contributions

Concept or design: P.S; acquisition, analysis or interpretation of data: P.S; supervision and support: V.P, K.J.S, A.M and A.S.R; drafting the work or revising: P.S and V.P; final approval of the manuscript: P.S and V.P. All co-authors have seen and agree with the contents of the manuscript.

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Correspondence to Venkataraman Prabhu.

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This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

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Ethical approval

This study was approved by the Institutional Ethical Committee of the SRM Medical College Hospital and Research Centre (SRM MCH & RC) IEC no: 3065/IEC/2022.

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Informed consent was obtained from all participants involved in the study.

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Subramanian, P., Prabhu, V., S, K.J. et al. Circulating biomarkers of upstream kynurenine pathway and brain-derived neurotropic factor in the diagnosis of type 2 and gestational diabetes mellitus with depression. Comp Clin Pathol 33, 247–255 (2024). https://doi.org/10.1007/s00580-023-03546-2

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