Heightened plasma levels of heme oxygenase-1 and tissue inhibitor of metalloproteinase-4 as well as elevated peripheral neutrophil counts are associated with TB-diabetes comorbidity.
BACKGROUND
The increased prevalence of type 2 diabetes mellitus (T2DM) in countries endemic for TB poses a serious complication in the clinical management of this major infectious disease. Understanding the impact of T2DM on TB and the determinants of comorbidity is critical in responding to this growing public health problem with better therapeutic approaches. Here, we performed an exploratory study assessing a series of biologic parameters that could serve as markers of pathogenesis in TB with T2DM.


METHODS
Cross-sectional analyses of levels of heme oxygenase-1 (HO-1), acute phase proteins, tissue metalloproteinases, and tissue inhibitors of metalloproteinase (TIMPs) as well as cytokines and chemokines were performed in plasma samples from individuals with active pulmonary TB or with coincident TB and T2DM from South India.


RESULTS
Compared with patients with TB without diabetes, those with coincident T2DM exhibited increased Mycobacterium tuberculosis bacillary loads in sputum. Plasma levels of HO-1 but not of other acute phase proteins were higher in patients with TB and T2DM than in patients without diabetes, independent of bacillary sputum loads. HO-1 concentrations also positively correlated with random plasma glucose, circulating glycosylated hemoglobin, and low-density lipoprotein levels. Moreover, patients with coincident TB and T2DM exhibited increased plasma levels of TIMP-4 and elevated peripheral blood neutrophil counts, which, when considered together with HO-1, resulted in increased power to discriminate individuals with active TB with and without T2DM.


CONCLUSIONS
Elevated plasma levels of HO-1 and TIMP-4 and peripheral blood neutrophil counts are potential single and combined markers of pathogenesis in TB and T2DM.
Immunobiology Section, Helminth Immunology Section, Laboratory of Parasitic Diseases, National Institutes of Health, Bethesda, MD. Electronic address: andradebd@niaid.nih.gov.
Bruno B
BB
Andrade
National Institutes of Health, International Center for Excellence in Research, Chennai, India; National Institute for Research in Tuberculosis, Chennai, India.
Nathella Pavan
NP
Kumar
Government Stanley Medical Hospital, Chennai, India.
Rathinam
R
Sridhar
National Institute for Research in Tuberculosis, Chennai, India.
Vaithilingam V
VV
Banurekha
National Institute for Research in Tuberculosis, Chennai, India.
Mohideen S
MS
Jawahar
Immunobiology Section, Helminth Immunology Section, Laboratory of Parasitic Diseases, National Institutes of Health, Bethesda, MD.
Thomas B
TB
Nutman
Immunobiology Section, Helminth Immunology Section, Laboratory of Parasitic Diseases, National Institutes of Health, Bethesda, MD.
Alan
A
Sher
Immunobiology Section, Helminth Immunology Section, Laboratory of Parasitic Diseases, National Institutes of Health, Bethesda, MD; National Institutes of Health, International Center for Excellence in Research, Chennai, India.
Subash
S
Babu
D000209:Acute-Phase Proteins / Q000378:metabolism; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002452:Cell Count; D018925:Chemokines / Q000097:blood; D015897:Comorbidity; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000209:etiology*; D005260:Female; D051547:Heme Oxygenase-1 / Q000097:blood*; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000473:pathology*; D015995:Prevalence; D019714:Tissue Inhibitor of Metalloproteinases / Q000097:blood*; D014376:Tuberculosis / Q000175:diagnosis / Q000209:etiology*; D000097792:Tissue Inhibitor of Metalloproteinase-4
D000209:Acute-Phase Proteins; D015415:Biomarkers; D018925:Chemokines; D016207:Cytokines; D051547:Heme Oxygenase-1; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4