Patients with concurrent tuberculosis and diabetes have a pro-atherogenic plasma lipid profile

Vrieling, Frank ; Ronacher, Katharina ; Kleynhans, Leanie ; Van Den Akker, Erik ; Walzl, Gerhard ; Ottenhoff, Tom H. M. ; Joosten, Simone A. (2018)

CITATION: Vrieling, F., et al. 2018. Patients with concurrent tuberculosis and diabetes have a pro-atherogenic plasma lipid profile. EBioMedicine, 32:192–200, doi:10.1016/j.ebiom.2018.05.011.

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Background: Type 2 diabetes mellitus (DM) is a major risk factor for development of tuberculosis (TB), however the underlyingmolecular foundations are unclear. Since lipids play a central role in the development of both DM and TB, lipid metabolism may be important for TB-DM pathophysiology. Methods: A 1H NMR spectroscopy-based platform was used to determine 225 lipid and other metabolic intermediates in plasma samples of healthy controls (n=50) and patients with TB (n=50), DM(n=50) or TB-DM (n = 27). Results: TB patients presented with wasting disease, represented by decreased amino acid levels including histidine and alanine. Conversely, DM patients were dyslipidemic as evidenced by high levels of very lowdensity lipoprotein triglycerides and low high-density lipoprotein cholesterol. TB-DM patients displayed metabolic characteristics of both wasting and dyslipidemia combined with disease interaction-specific increases in phospholipid metabolites (e.g. sphingomyelins) and atherogenic remnant-like lipoprotein particles. Biomarker analysis identified the ratios of phenylalanine/histidine and esterified cholesterol/ sphingomyelin as markers for TB classification regardless of DM-status. Conclusions: TB-DM patients possess a distinctive plasma lipid profile with pro-atherogenic properties. These findings support further research on the benefits of improved blood lipid control in the treatment of TB-DM.

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