Diabetes mellitus refers to a chronic metabolic disorder, where there is constant hyperglycemia due to abnormalities in insulin secretion, insulin action, or both.[1] It has become a serious health issue in the world, and the trend of increasing prevalence of the health issue in both developed and developing nations is alarming.[2] The International Diabetes Federation estimates that there were 537 million adults with diabetes in 2021, and this number is expected to increase to 643 million by 2030.[3] Pakistan is one of the top countries with a high burden of diabetes, as almost one out of every four adults has diabetes, which is a major health issue in the population.[4]

Diabetes is connected with a broad spectrum of systemic complications, microvascular and macrovascular disorders.[5] Notably, it also impacts oral health significantly. Chronic hyperglycemia causes dysfunction of the immune response, decreased salivary flow, and changes in oral microflora, predisposing diabetic patients to infections.[6] Among them, fungus, especially that of Candida species, is common in the oral cavity.[7] Oral candidiasis, angular cheilitis, and denture stomatitis are conditions commonly reported among diabetic patients, and this is often seen as opportunistic infections since the host defenses are compromised.[8]

Candida species are normal flora of the mouth cavity, yet they may turn pathogenic in an optimal environment.[9] Candida albicans has been the most common species linked to oral infections, but there has been a significant rise in the non-albicans ones like Candida glabrata, Candida tropicalis, and Candida krusei.[10] These species are of special clinical interest because they differ in the levels of virulence factors and antifungal resistance. This change in species distribution has important implications in terms of diagnosis, treatment, and general disease management.

Oral Candida prevalence in diabetic patients is rather variable and varies between 30% and 80% of the patients, based on glycemic control, oral health level, and risk factors associated with oral candida, including smoking, dentures, and duration of diabetes.[11] Candidal infection severity and colonization have been strongly associated with poor glycemic control. Moreover, clinical manifestations can be insidious or uncharacteristic of diabetic patients, which frequently results in underdiagnosis and late treatment.[7]

Since the prevalence of diabetes is rising and has affected the oral health, there has been an urgent need to further understand the association between Candida species and oral lesions in diabetic patients. Determination of the Candida spectrum and its relationship with the clinical expression will not only bolster the diagnostic approach but also inform specific antifungal treatment, particularly in the face of new drug resistance. The proposed study thus aims at filling this gap between the clinical and the microbiological perspective by offering a comprehensive study of Candida prevalence in diabetic oral lesions. The current study aimed to identify the prevalence and distribution of Candida species in the oral lesions of diabetic patients and to examine their relationship with clinical manifestations and the risk factors involved.

The research was a one year cross-sectional analytical study from June 2025 to December 2025. The objective was to assess the commonality and distribution of Candida species in oral lesions in diabetic patients and to compare microbiological results with clinical manifestations. The OpenEpi sample size calculator (version 3.01) was used to determine the size of the sample with an expected prevalence of the oral Candida infection among diabetic patients as 56.7% based on a prior study that established a significant relationship between diabetes mellitus and oral candidal colonization.[12] The minimum required sample size was estimated to be about 400 patients with a 95% confidence interval and a 5% margin of error.

An outpatient department of the hospital was sampled in a non-probability consecutive manner to select the eligible patients who attended the outpatient department within the study period. All the patients who met the inclusion criteria and who reported within the data collection period were recruited until the necessary sample size was reached.

The study was limited to patients with type 1 or type 2 diabetes mellitus of at least 1 year of duration, aged between 30 and 70 years, with oral lesions including erythematous patches, pseudomembranous plaques, angular cheilitis, or burning mouth symptoms. Both the controlled and uncontrolled diabetic patients were taken into consideration. The patients were not allowed to participate in the study due to immunocompromised conditions other than diabetes (including HIV infections, chemotherapy, long-term corticosteroid therapy, and edentulous patients without oral lesions), patients who had taken systemic or topical antifungal therapy within four weeks before the study, and those who were not willing to participate.

Following the informed consent, demographic/clinical data such as age, gender, duration of diabetes, glycemic control, judged by the last HbA1c level, oral hygiene, denture usage, and presenting oral symptoms, were gathered on a pre-structured proforma. Proper intraoral inspection was done with aseptic conditions using disposable materials, torchlight, and mouth mirrors. Standard diagnostic criteria were used to clinically diagnose the oral lesions.

In order to conduct microbiological analysis, the samples of the affected sites of the oral mucosa were collected using sterile cotton swabs. Immediately, the samples were taken to the microbiology lab in sterile transport media. Gram staining and potassium hydroxide (KOH) preparation were used as direct microscopic tests to detect budding yeast cells and pseudohyphae. The cultures were then inoculated on the Sabouraud Dextrose Agar (SDA) and incubated at 37 °C for 24-48 hours. The members of Candida were first classified using colony morphology, germ tube test, and chromogenic media. Additional speciation was tested with biochemical tests like carbohydrate assimilation and fermentation tests.

The IBM SPSS version 26 was used to enter and analyze the data. Quantitative variables (age and duration of diabetes) were given descriptive statistics (mean and standard deviation), whereas the qualitative variables (gender, Candida species, and types of oral lesions) were given as frequencies and percentages. The chi-square test was used to measure the relationship between Candida infection and such clinical variables as glycemic control, diabetes duration, and the state of oral hygiene. The p-value of  ≤0.05 was considered significant.

The participants of the study were 400 diabetic patients with oral lesions. The average age distribution was characterized by a large number of people in the middle to old age range, with a relatively higher number of females than males. The majority of the participants were urban residents, and a significant number of participants were illiterate. In clinical terms, most patients were diabetic type 2, with more than half exhibiting poor glycemic control. The high prevalence of long-term diabetes and poor oral health was observed, and a significant share of the patients were also smoking and using dentures. The given features demonstrate that the population of the study was mostly comprised of people who have many systemic and behavioral risk factors that predispose them to oral opportunistic infections (Table 1).

It was discovered that the prevalence of oral Candida infection was generally high in diabetic patients with oral lesions, and over half of the study population had been colonized or infected by fungi. This is indicative of the close relationship between diabetes mellitus and opportunistic fungal overgrowth in the oral cavity, especially in patients with compromised immunity and unregulated metabolic conditions. The results indicate that oral candidiasis is a common clinical issue in diabetic groups, and frequently it is not even diagnosed until clinical lesions occur (Table 2).

Candida albicans was the most commonly isolated microbe, and a significant percentage of non-albicans Candida species were also detected, including C. glabrata, C. tropicalis, and C. krusei. This change in species is clinically important, with the organisms frequently being less susceptible to antifungal agents available. The existence of more than one Candida species implies a complex microorganism profile in oral lesions of diabetes, and demands a species-level identification to be effectively managed (Table 3).

A close relationship between poor glycemic control and high prevalence of Candida infection was observed, indicating that the unregulated level of blood glucose is a significant factor that leads to the colonization of the fungi in the mouth. In the same way, smoking, use of dentures, and poor oral hygiene were closely associated with increased infection rates, which suggests that both systemic and local factors have a synergistic effect on the development of the disease. These results indicate that behavioral patterns and metabolic management are key predictors of oral fungal diseases among diabetics (Table 4).

Further comparison revealed that Candida infection was more common with the longer period of diabetes experience, which indicates that chronic hyperglycemia may have a cumulative impact on host immunity. Also, the poor educational level and rural residence were found to be related to the increased rates of infections as indicators of lower socioeconomic status and the lack of health awareness and care access. Even though the burden of infection was higher in type 2 diabetes patients than in type 1, both groups were significantly impacted, which implies that diabetes in itself is a significant predisposing factor irrespective of the type of diabetes (Table 5). Pseudomembranous candidiasis was the most frequent clinical presentation amongst infected patients, then erythematous candidiasis and angular cheilitis. A lower percentage of the patients indicated that they had burning mouth symptoms, which are usually related to chronic irritation of the mucosa and fungal colonization. These results indicate that Candida infections in diabetic individuals have a variety of clinical presentations, both with typical lesions and minor symptomatic problems, which highlights the significance of a meticulous oral examination in this high-risk group (Table 6).

Table 1: Demographic, Behavioral, and Clinical Characteristics of Study Participants (n = 400)

Table 2: Prevalence of Oral Candida Infection in Diabetic Patients (n = 400)

Table 3: Distribution of Candida Species Isolated from Oral Lesions (n = 248)

Table 4: Association of Candida Infection with Glycemic and Lifestyle Factors

Table 5: Association of Candida Infection with Clinical and Disease-Related Variables

Table 6: Clinical Manifestations of Oral Lesions in Candida-Positive Patients (n = 248)

The current study reported high prevalence of oral Candida infection (62%) in diabetic patients with oral lesions, with Candida albicans as the most commonly isolated followed by non-albicans Candida, which includes C. glabrata, C. tropicalis and C. krusei. These results are in line with various global studies, which have invariably reported diabetes mellitus as an effective predisposing factor to oral Candida colonization. The prevalence of C. albicans in our research is consistent with that of a meta-analysis that indicated Candida detection rates of 47.3% in diabetic groups, and much higher odds of colonization than in non-diabetics (OR=3.16).[13] This substantiates the idea that hyperglycemia and compromised immunity in diabetes provide a good environment where fungi thrive.

Poor glycemic control in the present study was strongly associated with Candida positivity, which suggests uncontrolled diabetes is a major risk factor that predisposes people to oral fungal infection. The same findings were observed in a cross-sectional study in which patients with more elevated HbA1c levels were found to have much more Candida colonization and worse oral lesions[14]This supports the contribution of unrelenting hyperglycemia in augmenting salivary glucose levels, inhibiting neutrophil action, and encouraging fungus settlement and growth in the mouth.

In the current research, denture use, inadequate oral hygiene, and smoking were also noted to be significantly linked with the increase in Candida prevalence. This is consistent with a cross-sectional study that found dental prosthesis use and low salivary PH to be the main causes of Candida colonization among type 2 diabetic patients in 2025.[15] In the same way, another study also cited that in diabetic patients, poor oral hygiene and xerostomia were major contributors to fungal load and recurrence of oral candidiasis infection.[16] These repeated results indicate that local oral environmental influences are important in the development of the disease in association with systemic metabolic impairment.

In terms of species distribution, the C. albicans dominance in this study is similar to a number of recent reports. In a study carried on diabetic patients, C. albicans was found to be the most common organism (68.6%), then C. glabrata and C. tropicalis.[15] Equally, a different study indicated that C. albicans was the most frequently identified isolate (49.5%), with the emergence of more non-albicans species becoming increasingly prevalent in diabetic populations.[17] This change has clinical implications as non-albicans species can be less susceptible to commonly used antifungal agents, thereby complicating the management.

The present research also proved that more years with diabetes were closely related to the increased rates of Candida infections. This observation is echoed by the previous studies that imply chronic exposure to hyperglycemia causes gradual immune malfunction and greater fungal colonization in the long-term. The same pattern was observed in diabetic periodontitis patients, where Candida prevalence rose significantly in long-term disease cases in comparison with newly-diagnosed cases of periodontitis. This indicates that cumulative dysregulation of the metabolism is important in the pathogenesis of oral fungi.

In general, the results of this research are in agreement with more recent literature that diabetes mellitus is a strong cause of oral Candida infections due to the interaction of systemic immunosuppression and local changes in the oral environment. The high level of consistency among various studies makes the current findings more valuable and emphasizes the clinical significance of early oral screening among diabetic patients to diagnose and manage candidal infections on time.

Limitations:

In interpreting the results, this study had some limitations that ought to be taken into consideration. It was a single-center and cross-sectional study, which could only prove association and not causation between oral Candida infection and diabetes. Non-probability consecutive sampling can result in selection bias, and this can restrict the external validity of the results to the general population of diabetics. Moreover, no antifungal susceptibility testing was conducted, and this limited the evaluation of resistance patterns across the various Candida species. Long-term follow-up was not available to assess the outcomes of treatment or infection recurrence. Also, not all possible confounding variables, like the dietary habits, specific medication history, and flow rate of saliva, were investigated completely.

Oral Candida infection was extremely common in diabetic patients with oral lesions and that Candida albicans was the most prevalent species, with the emergence of non-albicans species. The increased Candida colonization was greatly correlated with poor glycemic control, prolonged duration of diabetes, poor oral health, smoking, and denture use. These results point to the fact that there are not only local but also systemic contributing factors to oral fungal infections in diabetic patients. Prevention and effective management of candidal infections in this high-risk population should be done by early oral screening, strict glycemic control, and enhanced oral hygiene practices.

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