Tuberculosis in poorly controlled type 2 diabetes: altered cytokine expression in peripheral white blood cells

Abstract

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.

Figure 1

Scatter plots of glycosylated hemoglobin (HbA_1c) level, expressed as percentage of total hemoglobin, versus cytokine response to PPD for selected cytokines. Each circle represents 1 patient, with black circles representing patients with diabetes and open circles representing patients without diabetes. The horizontal line indicates the median cytokine level. The vertical line at the HbA_1c level of 6.2% of total hemoglobin indicates the upper limits of normal (left) and elevated (right) HbA_1c level. Cytokine values are provided in natural log (Ln) scale. P values for the association between cytokine values (above vs. below median value) and HbA_1c levels (normal vs. high) are indicated.