PRELIMIANRY REPORT Glycerophospholipid Metabolism Alterations in Patients with Type 2 Diabetes Mellitus and Tuberculosis Comorbidity Yamile L opez-Hern andez, a Edgar E. Lara-Ram  ırez, b Mariana Salgado-Bustamante, c Jes us Adri  an L opez, d Juan J. Oropeza-Valdez, b Elena Jaime-S anchez, b Julio E. Casta~ neda-Delgado, e Mart  ın Maga~ na-Aquino, f Michael Murgu, g and Jos e A. Enciso-Moreno b a Laboratorio de Metabol omica y Prote omica, CONACyT-Universidad Aut onoma de Zacatecas, Zacatecas, Mexico b Unidad de Investigaci on Biom edica de Zacatecas, Instituto Mexicano de Seguro Social, Zacatecas, Mexico c Biochemistry Department, Medicine Faculty, Universidad Aut onoma de San Luis Potos  ı, San Luis Potos  ı, Mexico d MicroRNAs Laboratory, Unidad Acad emica de Ciencias Biol ogicas, Universidad Aut onoma de Zacatecas, Zacatecas, Mexico e C atedras-CONACyT, Unidad de Investigaci on Biom edica de Zacatecas, Instituto Mexicano de Seguro Social, Zacatecas, Mexico f Hospital Central ‘‘Dr. Ignacio Morones Prieto’’, San Luis Potos  ı, Mexico g Waters Technologies of Brazil, Barueri, Brazil Received for publication February 20, 2019; accepted May 20, 2019 (ARCMED_2019_88). Available online xxx Type-2 Diabetes (T2D) is a predisposing cause for developing tuberculosis (TB) in low- and middle-income countries. TB-T2D comorbidity worsens clinical control and prognosis of the affected individuals. The underlying metabolic alterations for this infectious-metabolic dis- ease are still largely unknown. Possible mediators of the increased susceptibility to TB in dia- betic patients are lipids levels, which are altered in individuals with T2D. To evaluate the modulation of glycerophospholipids in patients with TB-T2D, an untargeted lipidomic approach was developed by means of ultra-performance liquid chromatography (UPLC) coupled to electrospray ionization/quadrupole time-of-flight mass spectrometry (ESI-QToF). In addition, tandem mass spectrometry was performed to determine the identity of the differ- entially expressed metabolites. We found that TB infected individuals with or without T2D share a common glycerophospholipid profile characterized by a decrease in phosphatidylcho- lines. A total of 14 glycerophospholipids were differentially deregulated in TB and TB-T2D patients and could potentially be considered biomarkers. It is necessary to further validate these identified lipids as biomarkers, focusing on the anticipate diagnosis for TB development in T2D predisposed individuals. Ó 2019 IMSS. Published by Elsevier Inc. Key Words: Tuberculosis, Diabetes, Glycerophospholipids, Biomarkers, Metabolomics. Introduction Tuberculosis (TB) is the ninth leading cause of death world- wide and the leading cause from a single infectious agent. In 2017, there were an estimated 1.3 million TB deaths (1). One third of the world population is considered to be in- fected with the causal agent, M. tuberculosis. However, it is estimated that only 10% could develop the active disease during their lifetime. Some risk factors (undernutrition, smoking, alcoholism, HIV infections and diabetes mellitus (T2D), among others) might increase the risk of developing TB, thus contributing to the dissemination of the disease (2). TB is an infectious disease that spreads from person to person through the air and it prevails in endemic countries with low- and middle-incomes. T2D is a chronic and non- communicable metabolic disease historically seen as a sign of development of high-income countries. The World Health Organization (WHO) considers TB as a re- emergent health problem in Mexico, reporting an incidence of 22 cases per 100,000 habitants in 2017. On the other hand, according to the Mexican Diabetes Federation, Mexico was ranked fifth in worldwide prevalence of T2D in 2017. It is well known that T2D increases susceptibility to TB by three times (on average) (3e5). In fact, T2D is considered one of the most important risk factors for the Address reprint requests to: Dr. Jose A. Enciso-Moreno, Unidad de In- vestigaci on Biom edica de Zacatecas, Instituto Mexicano de Seguro Social, Zacatecas, Mexico; Phone/FAX: þ52 4929226019; E-mail: enciso_2000@ yahoo.com 0188-4409/$ - see front matter. Copyright Ó 2019 IMSS. Published by Elsevier Inc. https://doi.org/10.1016/j.arcmed.2019.05.006 Archives of Medical Research 50 (2019) 71e78