Metabolite signatures of diabetes with cardiovascular disease

a pilot investigation

Lavanya Reddivari, Bishwa R. Sapkota, Apoorva Rudraraju, Yundi Liang, Christopher Aston, Evgeny Sidorov, Jairam K.P. Vanamala, Dharambir K. Sanghera

Research output: Contribution to journalArticle

Abstract

Introduction: Type 2 diabetes (T2D) is an independent risk factor in the development of cardiovascular disease. However, there are significant limitations in the detection of the metabolic disturbances in hyperglycemia that lead to vascular dysfunction. Objectives: The goals of the study were: (i) to identify circulating metabolites discriminating T2D and normoglycemia, and (ii) to assess phenotypic correlations of identified metabolites with other cardiometabolic risk traits (CMTs). Methods: We have generated global and targeted metabolomic profiles using AB Sciex TripleTOF 5600 and Thermo Scientific Q Exactive Plus using serum samples of patients and healthy controls from a Punjabi population from India. Results: In global profiling, we identified eight unknown molecules that currently do not match to any spectra in public databases. Additionally, serum levels of pyroglutamate, imidazole-4-acetate, tyramine-O-sulphate and 2,3-diphosphoglycerate were significantly elevated (2–5 fold) and betaine-aldehyde was reduced (fourfold) in patients. In targeted screening of amino acids and sugars, increased concentrations of serine, inositol, and threonine strongly correlated with T2D in both genders, while N-acetyl-l-alanine was reduced (58 fold) in men and glutamine was increased (fourfold) in women. Using random forest and ROC (AUC) analyses, we further cross-validated the predictive abilities of these molecules. Inositol, serine and threonine were among the top informative biomarkers in both genders while N-acetyl-l-alanine was highly confined to men. Conclusions: Our study has identified several metabolites whose concentrations were altered in T2D. Although further study is needed in larger datasets, the identified metabolites (unknown or known) point towards shared etiological pathways underlie diabetes and vascular disease which can be targeted for potential therapeutics or biomarkers discovery.

Original languageEnglish (US)
Article number154
JournalMetabolomics
Volume13
Issue number12
DOIs
StatePublished - Dec 1 2017

Fingerprint

Medical problems
Metabolites
Type 2 Diabetes Mellitus
Cardiovascular Diseases
Inositol
Threonine
Alanine
Serine
Biomarkers
Pyrrolidonecarboxylic Acid
Amino Sugars
2,3-Diphosphoglycerate
Metabolomics
Glutamine
Serum
Vascular Diseases
Molecules
ROC Curve
Hyperglycemia
Area Under Curve

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Clinical Biochemistry

Cite this

Reddivari, L., Sapkota, B. R., Rudraraju, A., Liang, Y., Aston, C., Sidorov, E., ... Sanghera, D. K. (2017). Metabolite signatures of diabetes with cardiovascular disease: a pilot investigation. Metabolomics, 13(12), [154]. https://doi.org/10.1007/s11306-017-1278-8
Reddivari, Lavanya ; Sapkota, Bishwa R. ; Rudraraju, Apoorva ; Liang, Yundi ; Aston, Christopher ; Sidorov, Evgeny ; Vanamala, Jairam K.P. ; Sanghera, Dharambir K. / Metabolite signatures of diabetes with cardiovascular disease : a pilot investigation. In: Metabolomics. 2017 ; Vol. 13, No. 12.
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Reddivari, L, Sapkota, BR, Rudraraju, A, Liang, Y, Aston, C, Sidorov, E, Vanamala, JKP & Sanghera, DK 2017, 'Metabolite signatures of diabetes with cardiovascular disease: a pilot investigation', Metabolomics, vol. 13, no. 12, 154. https://doi.org/10.1007/s11306-017-1278-8

Metabolite signatures of diabetes with cardiovascular disease : a pilot investigation. / Reddivari, Lavanya; Sapkota, Bishwa R.; Rudraraju, Apoorva; Liang, Yundi; Aston, Christopher; Sidorov, Evgeny; Vanamala, Jairam K.P.; Sanghera, Dharambir K.

In: Metabolomics, Vol. 13, No. 12, 154, 01.12.2017.

Research output: Contribution to journalArticle

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T2 - a pilot investigation

AU - Reddivari, Lavanya

AU - Sapkota, Bishwa R.

AU - Rudraraju, Apoorva

AU - Liang, Yundi

AU - Aston, Christopher

AU - Sidorov, Evgeny

AU - Vanamala, Jairam K.P.

AU - Sanghera, Dharambir K.

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Reddivari L, Sapkota BR, Rudraraju A, Liang Y, Aston C, Sidorov E et al. Metabolite signatures of diabetes with cardiovascular disease: a pilot investigation. Metabolomics. 2017 Dec 1;13(12). 154. https://doi.org/10.1007/s11306-017-1278-8