Tuberculosis in poorly controlled type 2 diabetes: altered cytokine expression in peripheral white blood cells.
BACKGROUND
Although the biological basis for the increased susceptibility of diabetic patients to tuberculosis remains unclear, the world is undergoing a type 2 diabetes pandemic. We hypothesize that chronic hyperglycemia leads to immunocompromise that facilitates progression to active tuberculosis. To assess this possibility, we determined whether patients with tuberculosis and diabetes (particularly those with chronic hyperglycemia), compared with patients with tuberculosis who did not have diabetes, presented altered cytokine responses to a mycobacterial antigen.


METHODS
Samples of whole blood from patients with tuberculosis and diabetes and from patients with tuberculosis who did not have diabetes was stimulated in vitro with purified protein derivative from Mycobacterium tuberculosis. We then determined whether there was an association between the levels of innate and adaptive cytokines secreted in response to the antigen and diabetes status, or diabetes with chronic hyperglycemia (measured by glycosylated hemoglobin level), after controlling for possible confounders.


RESULTS
Innate and type 1 cytokine responses were significantly higher in patients with tuberculosis who had diabetes than in nondiabetic control subjects. The effect was consistently and significantly more marked in diabetic patients with chronic hyperglycemia.


CONCLUSIONS
These data provide preliminary evidence that type 2 diabetes, especially type 2 diabetes involving chronic hyperglycemia, is associated with an altered immune response to M. tuberculosis. More-detailed knowledge of the underlying mechanisms should focus on the effect of chronic hyperglycemia on the immune response to help in understanding the enhanced susceptibility of diabetic patients to tuberculosis.
Restrepo
Blanca I
BI
Division of Epidemiology, University of Texas Health Science Center at Houston, School of Public Health, University of Texas at Brownsville, 80 Fort Brown, SPH Bldg., Brownsville, TX 78520, USA. blanca.i.restrepo@utb.edu
Fisher-Hoch
Susan P
SP
Pino
Paula A
PA
Salinas
Adrian
A
Rahbar
Mohammad H
MH
Mora
Francisco
F
Cortes-Penfield
Nicolas
N
McCormick
Joseph B
JB
D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D014373:Tuberculin / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology*; D055815:Young Adult
D016207:Cytokines; D014373:Tuberculin