The Influence of Advanced Glycation End Products (AGEs)

Abstract

INTRODUCTION. The coexistence of diabetes mellitus (DM) and
pulmonary tuberculosis (TB) represents a major global public health
challenge, with diabetes being recognized as an important risk factor for the
development and progression of TB. Chronic hyperglycemia promotes the
formation and accumulation of advanced glycation end products (AGE),
which contribute to oxidative stress, persistent inflammation, and immune
dysfunction. In patients with TB-DM comorbidity, elevated AGE levels may
impair innate and adaptive immune responses by reducing phagocytic
activity, altering macrophage function, and delaying antigen presentation,
thereby favoring the persistence and severity of Mycobacterium tuberculosis
infection.
OBJECTIVE. To evaluate the influence of advanced glycation end
products (AGE) in patients with pulmonary tuberculosis and diabetes mellitus
and to determine their role in the inflammatory and immune response
associated with TB-DM comorbidity.
MATERIAL AND METHODS. The prospective observational study was
conducted at the “Chiril Draganiuc” Institute of Pneumology during the
period 2019–2024 and included 118 patients. The study population was
divided into two subgroups: group L1, consisting of 59 patients with
pulmonary tuberculosis and diabetes mellitus, and group L2, comprising 59
patients with pulmonary tuberculosis without diabetes mellitus. All
participants were assessed before and after in-hospital treatment. The
diagnosis of pulmonary tuberculosis was confirmed by acid-fast bacilli (AFB)
smear microscopy and the molecular-genetic method Xpert MTB/RIF. In
order to evaluate the influence of advanced glycation end products (AGEs) in
TB-DM comorbidity, serum AGE levels, biomarkers of systemic inflammation
like Ceruloplasmin and C-reactive protein were determined and
comparatively analyzed between the study groups.
RESULTS. In the study, we demonstrated importance of AGEs and
systemic inflammatory markers Ceruloplasmin and C-reactive protein (CRP)
showed distinct dynamics during treatment. In the TB-DM group,
ceruloplasmin exhibited a more moderate increase of 19.3%, compared to
30.8% in group 1. Diabetes mellitus was also associated with a lower overall
rise in serum AGE levels, reaching 153% by the end of therapy. Regarding
bacteriological outcomes, the proportion of patients with negative AFB
results decreased 2.3-fold in the study group during treatment, whereas in
group 1 the reduction was more pronounced, reaching 5.4-fold, with a decline
from 62.7% to 27.1%. A similar trend was observed for Xpert MTB/RIF, with
a decrease in the number of negative patients in both groups throughout
therapy.
Overall, the coexistence of these two conditions is characterized by a
more pronounced attenuation of the immune–inflammatory response during
anti-tuberculosis treatment.
CONCLUSION. Overall, these findings indicate that AGEs,
ceruloplasmin, and C-reactive protein collectively represent valuable
biomarkers reflecting the complex interaction between oxidative stress,
inflammation, and immune dysfunction in pulmonary tuberculosis associated
with type II diabetes mellitus, and may serve as useful indicators for disease
severity, progression, and therapeutic response.