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Original investigation
Camilla Vavruch
Corresponding Author
ORCiD: https://orcid.org/0000-0001-6187-8827
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
We used a multiplex proteomics assay with the aim to discover novel associations between leptin and 88 circulating proteins in order to provide additional insights into the role of leptin in the development of CVD in patients with type 2 diabetes (T2DM).
Material and methods
In a discovery phase, we investigated associations between 88 plasma proteins, assessed with a proximity extension assay, and plasma leptin in a cohort of middle-aged patients with T2DM (CARDIPP, n=661). Associations that passed the significance threshold of a False discovery rate of 5% (corresponding to p <0.0017) were replicated in diabetes patients in an independent cohort (PIVUS, n=116). We also investigated if proteins mediated the longitudinal association between plasma leptin and the incidence of major cardiovascular events (MACE).
Results
Two proteins were significantly associated with leptin in the discovery phase, adipocyte fatty acid binding protein (A-FABP) (regression coefficient .118, 95% CI (.064, .173) p =0.000024) and adrenomedullin ( p =0.000002) but only A-FABP was significantly associated with leptin in the replication cohort (regression coefficient .0254, 95% CI (.119, .39) p =0.0003). Multiplicative interaction analyses in the two cohorts suggest a stronger association between A-FABP and leptin in men than in women. In longitudinal analyses, the association between leptin and MACE was slightly attenuated after adding A-FABP to the multivariate model.
Conclusions
Our analysis identified a consistent association between leptin and A-FABP in two independent cohorts of patients with T2DM, particularly in men. Our data encourage future large-scale proteomics analyses for additional insights into leptin biology.
Keywords
Leptin, A-FABP, multiplex proteomics assay, diabetes, cardiovascular disease
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A new preprint design is coming!
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Original investigation
Camilla Vavruch
Corresponding Author
ORCiD: https://orcid.org/0000-0001-6187-8827
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 18 Mar, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
We used a multiplex proteomics assay with the aim to discover novel associations between leptin and 88 circulating proteins in order to provide additional insights into the role of leptin in the development of CVD in patients with type 2 diabetes (T2DM).
Material and methods
In a discovery phase, we investigated associations between 88 plasma proteins, assessed with a proximity extension assay, and plasma leptin in a cohort of middle-aged patients with T2DM (CARDIPP, n=661). Associations that passed the significance threshold of a False discovery rate of 5% (corresponding to p <0.0017) were replicated in diabetes patients in an independent cohort (PIVUS, n=116). We also investigated if proteins mediated the longitudinal association between plasma leptin and the incidence of major cardiovascular events (MACE).
Results
Two proteins were significantly associated with leptin in the discovery phase, adipocyte fatty acid binding protein (A-FABP) (regression coefficient .118, 95% CI (.064, .173) p =0.000024) and adrenomedullin ( p =0.000002) but only A-FABP was significantly associated with leptin in the replication cohort (regression coefficient .0254, 95% CI (.119, .39) p =0.0003). Multiplicative interaction analyses in the two cohorts suggest a stronger association between A-FABP and leptin in men than in women. In longitudinal analyses, the association between leptin and MACE was slightly attenuated after adding A-FABP to the multivariate model.
Conclusions
Our analysis identified a consistent association between leptin and A-FABP in two independent cohorts of patients with T2DM, particularly in men. Our data encourage future large-scale proteomics analyses for additional insights into leptin biology.
Figure 1
Figure 2
This is a list of supplementary files associated with this preprint. Click to download.
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