1. Introduction

Among the many problems in otorhinolaryngology, pathologies of the nose and paranasal sinuses (PNS) occupy a leading place. Chronic rhinosinusitis (CRS) accounts for 2.74% of all ENT pathologies annually, with higher rates in hospital populations. [1]

CRS is one of the most common diseases of the upper respiratory tract, affecting up to 10% of the general population. This pathology significantly impairs quality of life and daily activities, and can lead to severe complications. The inflammatory process most often localizes in the maxillary sinuses. [2]

A particularly important subgroup is formed by patients with concomitant somatic diseases that contribute to chronicity and recurrence of the process and increase the risk of complications. Type 2 diabetes mellitus (T2DM) is one such condition and represents not only a major medical problem, but also a significant socioeconomic challenge worldwide. [3]

According to the World Health Organization (WHO), the global number of patients with T2DM aged 20–79 years reached 537 million by the end of 2021, exceeded 588 million in 2023, and is projected to rise to 1.5 billion by 2050. In 98% of cases, this corresponds to T2DM. Approximately 49.6% of this growth is explained by obesity, while the remaining 50.4% is due to demographic changes. [4]

Research from Uzbekistan demonstrated that patients with T2DM account for 32% of all nasal pathologies, with CRS representing 15.1% of cases, purulent CRS – 4.15%, and purulent-hyperplastic CRS – 3.5%. [5]

T2DM significantly reduces the barrier and immune functions of the body. In this group of patients, chronic ENT diseases are more frequent, and the presence of T2DM accelerates the development and worsens the course of inflammatory processes. This is related to microvascular and metabolic disorders, as well as increased levels of free radicals and oxidative stress. [6]

2. Materials and Methods

The increased susceptibility to infections and their chronicity in T2DM patients is associated with impaired immune defenses, enhanced microbial adhesion, macro- and microangiopathy, and repeated conservative and surgical interventions. Patients with T2DM and purulent-inflammatory diseases of the PNS are not only prone to rapid progression of the process, but also to the development of extra- and intracranial complications. [7]

The clinical picture of purulent CRS in such patients is characterized by a prolonged and sluggish course, involvement of multiple paranasal sinuses in destructive processes, atypical radiological findings, and frequent development of complications with systemic spread of infection. [8]

Different forms of CRS occur in T2DM patients with the following frequencies: productive (35%), exudative (32.5%), alterative (15%), mixed (10%), and odontogenic (7.5%). [5,9,10] Microbiological studies of sinus secretions in CRS with T2DM often reveal Pseudomonas aeruginosa (22.5%), Staphylococcus aureus (18.75%), and fungal pathogens such as Candida (13.75%), Actinomyces (11.25%), and Mucor (8.75%). [5,10,11]

These circumstances highlight the complexity of managing CRS in T2DM patients, where “ideal conditions” for oxidative stress are created. Oxidative stress is regarded as a universal basis for the development of destructive processes and complications due to endothelial dysfunction. [12]

The mechanisms underlying both T2DM and its complications are largely similar. Correcting these mechanisms can halt disease progression and prevent complications. A distinctive feature of CRS in combination with T2DM is the impaired ability of neutrophils to adequately respond to cytokine stimulation. In CRS patients without T2DM, exposure to granulocyte-macrophage colony-stimulating factor (GM-CSF) significantly enhances phagocytic and biocidal activity, whereas in patients with T2DM, these functions remain impaired. [13]

3. Result and Discussion

Neutrophils in CRS with T2DM also demonstrate impaired cytokine production and responsiveness, related to metabolic disturbances and changes in the physicochemical properties of their biomembranes. Chronic inflammation in CRS acts as a constant irritant for neutrophilic granulocytes, inducing the release of biologically active substances such as peroxide radicals, nitric oxide, and proteolytic enzymes. These mediators can lead to degenerative-destructive changes in the sinus mucosa, while in the bloodstream they may cause stasis and thrombosis of small vessels, involving the orbit and cranial cavity in the inflammatory process. [14]

Hypoxia plays a major role in CRS with T2DM, as all immune components are compromised under such conditions. This limits the body’s ability to effectively combat disease and necessitates the development of new treatment approaches based on comprehensive patient evaluation. [15]

One of the most promising agents is dapagliflozin (Forxiga, 10 mg), a potent (Ki = 0.55 nM), selective, reversible inhibitor of the sodium-glucose cotransporter 2 (SGLT2). It belongs to the gliflozin class, which also possesses cardioprotective and nephroprotective properties. Dapagliflozin has been shown to reduce all-cause mortality in T2DM patients by 38.6%. [16]

Beyond improving glycemic control, SGLT2 inhibitors contribute to moderate reductions in body weight and blood pressure, enhance tissue sensitivity to insulin, and improve β-cell function. Due to their insulin-independent mechanism of action, these drugs are associated with a minimal risk of hypoglycemia. [17]

Long-term dapagliflozin therapy significantly improves clinical outcomes in T2DM patients, including reduced risk of death from any cause, heart failure, and cardiovascular disease, as well as reduced major cardiovascular risk compared to standard therapy without SGLT2 inhibitors. [18]

In routine practice, dapagliflozin not only improves glycemic control but also slows the progression of chronic kidney disease. The combination of efficacy and favorable safety profile allows for its broad use in initiating and intensifying therapy for T2DM in CRS patients. [19]

4. Conclusions

The coexistence of CRS and T2DM presents significant challenges due to the complex interplay between metabolic dysfunction, impaired immune responses, and microvascular complications. Understanding the epidemiological, microbiological, and immunological aspects of this comorbidity is essential for developing effective diagnostic and therapeutic strategies. The use of dapagliflozin represents an important step toward improving outcomes by addressing both metabolic control and systemic complications in this high-risk patient group. [20]