Department of Medicine, Division of Pulmonary Allergy and Critical Care Medicine
Endocrinology, Diabetes, and Metabolism | Immunology of Infectious Disease | Immunopathology | Integrative Biology | Systems Biology
Comorbid diabetes mellitus (DM) increases tuberculosis (TB) risk and adverse outcomes but the pathological interactions between DM and TB remain incompletely understood. We performed an integrative analysis of whole blood gene expression and plasma analytes, comparing South Indian TB patients with and without DM to diabetic and non-diabetic controls without TB. Luminex assay of plasma cytokines and growth factors delineated a distinct biosignature in comorbid TBDM in this cohort. Transcriptional profiling revealed elements in common with published TB signatures from cohorts that excluded DM. Neutrophil count correlated with the molecular degree of perturbation, especially in TBDM patients. Body mass index and HDL cholesterol were negatively correlated with molecular degree of perturbation. Diabetic complication pathways including several pathways linked to epigenetic reprogramming were activated in TBDM above levels observed with DM alone. Our data provide a rationale for trials of host-directed therapies in TBDM, targeting neutrophilic inflammation and diabetic complication pathways to address the greater morbidity and mortality associated with this increasingly prevalent dual burden of communicable and non-communicable diseases.
Diabetes complications, Tuberculosis
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DOI of Published Version
Sci Rep. 2017 May 17;7(1):1999. doi: 10.1038/s41598-017-01767-4. Link to article on publisher's site
Prada-Medina, Cesar A.; Fukutani, Kiyoshi F.; Pavan Kumar, Nathella; Gil-Santana, Leonardo; Babu, Subash; Lichtenstein, Flavio; West, Kim; Sivakumar, Shanmugam; Menon, Pradeep A.; Viswanathan, Vijay; Andrade, Bruno B.; Nakaya, Helder I.; and Kornfeld, Hardy, "Systems Immunology of Diabetes-Tuberculosis Comorbidity Reveals Signatures of Disease Complications" (2017). Open Access Articles. 3155.
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