Abstract
Objectives:
Diabetes mellitus is associated with a greater likelihood of developing certain oral mucosal disorders. This study was aimed at assessing the prevalence of oral mucosal lesions (OMLs) in patients with type 2 diabetes (DM2) and to investigate the association of such lesions with metabolic control of the disease.
Methods:
This cross-sectional study involved 391 patients with DM2 and 391 non-diabetic control subjects. Demographic information and data on the duration and type of diabetes, glycosylated hemoglobin (HbA1c) values, medical history, and current use of medication were obtained from medical records. Detailed oral examination was performed in accordance with international criteria.
Results:
The prevalence of OMLs was significantly higher among diabetic patients (45.5%) than among control subjects (38.4%) (P = 0.042). Patients with diabetes had a higher prevalence of geographic tongue (GT) (P = 0.017), denture stomatitis (P = 0.018), and angular cheilitis (P = 0.006) than controls. Overall, diabetic patients with poor metabolic control had a significantly higher prevalence of OMLs and xerostomia than patients with moderately and well-controlled disease (P < 0.05).
Conclusion:
The prevalence of OMLs was significantly higher in diabetic patients than in control subjects. Higher occurrence of OMLs was significantly associated with poor metabolic control.
Keywords: diabetes mellitus type 2, prevalence, mouth mucosa, oral pathology
Introduction
Diabetes mellitus (DM) is a group of metabolic diseases characterised by hyperglycemia resulting from defects in insulin secretion, insulin action, or both (1). The World Health Organization (WHO) recognises 2 major clinical forms: insulin-dependent diabetes mellitus (IDDM), or type 1 diabetes, and non-insulin-dependent diabetes mellitus (NIDDM), or type 2 diabetes (DM2).
Diabetes mellitus currently affects 246 million people worldwide, and it is expected to affect a staggering 380 million people by 2025 (2). An estimated 3-fold rise in the prevalence of the disease is expected in Asia—especially in China and India. Similarly, other rapidly developing Asian countries including Malaysia, Singapore, and Thailand will also see a dramatic increase in the number of DM cases (3).
Diabetic complications account for most of the socio-economic burden of the disease (4). DM is considered the leading cause of blindness, renal failure, lower-limb amputation, and deaths due to cardiovascular disease (5). Chronic hyperglycemia induces structural changes in tissues (6) and is associated with impaired wound healing, higher susceptibility to infections (7), and microvascular and macrovascular dysfunctions (8).
Similarly, a number of oral health complications are frequently associated with DM (9). These include various inflammatory diseases, reduced saliva secretion, and oral mucosal pathologies. Further, inflammatory diseases such as gingivitis, periodontitis, candidiasis, stomatitis, benign migratory glossitis or geographic tongue (GT), median rhomboid glossitis, and angular cheilitis have been reported frequently in various studies (10–13). DM predisposes an individual to bacterial and fungal infections as well, including those caused by Candida species (14).
DM is believed to promote periodontitis through an exaggerated inflammatory response to the periodontal microflora and hyperglycemiainduced vascular changes (15). Oral soft tissue abnormalities that are associated with DM include fissured tongue, irritation fibroma, traumatic ulcers, and parotid gland enlargement (16,17).
Certain studies have reported a possible association between DM and potentially malignant disorders such as leukoplakia (18,19), erythroplakia (19,20), and lichen planus (16,18,21,22). However, other studies neither demonstrated this association nor found any influence of DM on the duration, distribution, or type of lesion (23,24). These conflicting results stem from several variations in the sample populations with regard to age, type of diabetes, time of diabetes onset, level of metabolic control, and daily consumption of drugs. Additionally, comparing the sample population with an appropriate control group is fundamental when investigating the prevalence of oral mucosal alterations in patients with DM.
Hence, the purpose of this investigation was to study the prevalence of oral mucosal lesions (OMLs) in DM2 and non-diabetic control subjects in the Malay population and to determine the association between OMLs and metabolic control of the disease.
Materials and Methods
Research design
The present study was approved by the Human Ethics Research Committee of the School of Dentistry, Universiti Sains Malaysia (USM), Kelantan, Malaysia. The study was conducted in full accordance with the ethical principles of the World Medical Association Declaration of Helsinki (2002). All volunteers were informed of the aims and methods of this study, and written consent was obtained.
Malaysia is a multiracial country with a predominant Malay ethnic group in the state of Kelantan. This cross-sectional study involved 391 Malay patients with DM2 and 391 Malay nondiabetics as control subjects. The sample size of the study was calculated using a single formula, which was based on the proportion of oral lesions in diabetic patients from a previous study (16). The precision was set at 0.05 with a 95% confidence interval and a Z score of 1.96. Diabetic patients were recruited from the endocrinology clinic of the University Hospital, which is situated in the same complex that houses the medical and dental schools. Non-diabetic control subjects, identified by their normal fasting blood glucose levels, were recruited from the outpatient department of the dental clinic. Both patients and control subjects with immunosuppressive disease, or oral habits such as smoking, alcohol consumption, or tobacco or betel nut chewing, were excluded from the study.
Data collection sheets were used to gather demographic data, education level, medical and dental history, subjective xerostomia, and past and current use of medications. Data on the duration of disease, type of diabetes, glycosylated hemoglobin (HbA1c) values, any major complications, and type of diabetes therapy were retrieved from medical records. The patients were categorised into 3 groups according to their mean HbA1c values recorded in the past year (25). These were:
Well-controlled HbA1c < 7.5%
Moderately controlled HbA1c = 7.6% to 8.9%
Poorly controlled HbA1c > 9%
Oral examination
Visual examination of the mouth was carried out by a single examiner who was supervised and assessed by an oral medicine specialist. Extraoral and intraoral examination was performed under electrical overhead lights using a mouth mirror, tweezers, gauze, and a wooden tongue depressor. Diagnostic criteria for abnormalities of the oral mucosa were in accordance with World Health Organization (WHO) guidelines (26). Incision biopsy and histopathological examination were performed when necessary. The number of natural teeth and presence of dentures, either partial or complete, were also recorded. After the oral examination, patients who presented with diabetes-associated lesions were referred for appropriate treatment.
Statistical analysis
Statistical Package for the Social Sciences (SPSS), version 20, was used for data entry and analysis. Differences in categorical variables between diabetic patients and control subjects were compared by chi-square tests, while differences in continuous variables were compared by independent t tests. A Chi-square test was also used to determine the association between the frequency of oral lesions and level of metabolic control among diabetic patients. A P value of < 0.05 was considered significant.
Results
A total of 391 DM2 patients and 391 nondiabetic control subjects participated in this study. There were more women than men among both DM2 patients (56.5% women) and control subjects (61.1% women). The mean (SD) age of the DM2 patients was 54.71 years (8.48) and that of the control subjects was 53.04 years (12.06). The demographic characteristics are presented in Table 1.
Table 1.
Demographic data and characteristics of the study groups
| Variables | Diabetics (n = 391) | Controls (n = 391) | ||
|---|---|---|---|---|
| n (%) | Mean (SD) | n (%) | Mean (SD) | |
| Gender | ||||
| Male | 170 (43.5) | 152 (38.9) | ||
| Female | 221 (56.5) | 239 (61.1) | ||
| Age (years) | 54.71 (8.48) | 53.04 (12.06) | ||
| Education | ||||
| No schooling | 40 (10.2) | 48 (12.3) | ||
| Primary | 161 (41.2) | 157 (40.2) | ||
| Secondary | 190 (48.6) | 186 (47.6) | ||
| Medications∗ | ||||
| None | 261 (66.8) | 327 (83.6) | ||
| Cardiovascular agents | 91 (23.3) | 42 (10.7) | ||
| Antibiotics | 10 (2.6) | 4 (1.0) | ||
| NSAID | 14 (3.6) | 6 (1.5) | ||
| Antiasthmatic | 6 (1.5) | 7 (1.8) | ||
| Others | 9 (2.3) | 5 (1.3) | ||
∗Medication other than anti-diabetic drugs.
More DM2 patients (33.2%) than control subjects (16.4%) were on medications for indications other than diabetes. A small percentage of subjects reported taking medications such as sedatives and corticosteroids, which were categorised as “Others”.
Diabetes-related variables among DM2 patients are presented in Table 2. The mean (SD) duration of DM was 8.26 years (6.11) from the time of diagnosis, with 41.9% of subjects having DM for less than five years. The mean (SD) value of HbAc1%, indicative of metabolic control, was 8.39 (SD 2.23) with 65% of the subjects having moderately or well-controlled disease. Most patients (70%) were prescribed oral hypoglycemic drugs, while 23.3% were prescribed a combination of insulin and oral drugs, and 6.6% of patients were prescribed insulin alone. Diabetic complications including retinopathy, nephropathy, neuropathy, cardiovascular diseases, and amputations of the lower limbs were observed in 14.6% of diabetic patients.
Table 2.
Description of diabetes variables among diabetic patients
| Variables | n (%) | Mean (SD) |
|---|---|---|
| Duration of diabetes (years) | ||
| Duration categories | 8.26 (6.11) | |
| < 5 years | 164 (41.9) | |
| 6–10 years | 128 (32.7) | |
| > 10 years | 99 (25.3) | |
| Treatment of DM | ||
| Oral agents | 274 (70.1) | |
| Insulin | 26 (6.6) | |
| Insulin + Oral agents | 91 (23.3) | |
| Metabolic control (%) | 8.39 (2.23) | |
| Well | 170 (43.5) | |
| Moderate | 84 (21.5) | |
| Poor | 137 (35.0) | |
| Diabetes complications | ||
| Yes | 57 (14.6) | |
| No | 334 (85.4) | |
Approximately one-third of subjects in both groups used either complete or partial dentures. DM2 patients had an average of 14.2 (SD 10.11) remaining teeth, which was significantly less than the average of 18.7 (SD 10.14) remaining teeth in control subjects (P < 0.001). The dentition status for both groups is presented in Table 3.
Table 3.
Comparison of remaining teeth and denture wearing in diabetics and controls
| Variables | Diabetics (n = 391) | Controls (n = 391) | χ² Statistics (df) | P value | ||
|---|---|---|---|---|---|---|
| n (%) | Mean (SD) | n (%) | Mean (SD) | |||
| Remaining teeth | 14.2 (10.11) | 18.7 (10.14) | 0.001∗ | |||
| Dentures wearers | 157 (40.2) | 139 (35.5) | 1.76 (1) | 0.184∗∗ | ||
| CD | 112 (28.6) | 89 (22.8) | ||||
| PD | 37 (9.6) | 48 (12.2) | ||||
| PD + CD | 8 (2.0) | 2 (0.5) | ||||
∗independent t test.
∗∗Chi Square test.
Abbreviations: CD = complete dentures, PD = partial dentures, PD + CD = partial + complete dentures.
The OMLs observed in DM2 patients and control subjects are shown in Table 4. Twelve types of OMLs observed in DM2 patients were categorised into six main groups: tongue lesions, denture-related lesions, white lesions, ulcerative lesions, benign tumors, and precancerous lesions. The most common lesions in DM2 patients were fissured tongue (26.9%), denture stomatitis (11.5%), and GT (3.6%). OMLs were present in a significantly higher percentage of DM2 patients (45.5%) than control subjects (38.4%) (P = 0.042). Specific oral lesions found to occur with significantly higher frequency in DM2 patients than in control subjects included GT (P = 0.017), denture stomatitis (P = 0.018), and angular cheilitis (P = 0.006). The prevalence of traumatic ulcers was higher in DM2 patients than in control subjects, but this difference was not statistically significant (P = 0.056).
Table 4.
Comparison of the prevalence of oral mucosal lesions in diabetics and controls
| Variables | Diabetics n = 391 | Control n = 391 | χ² (df) | P value |
|---|---|---|---|---|
| n (%) | n (%) | |||
| Subjects with 1 or more lesions | 178 (45.5) | 150 (38.4) | 4.12 (1) | 0.042 |
| Fissured tongue | 105 (26.9) | 106 (27.1) | 0.006 (1) | 0.936 |
| Geographic tongue | 14 (3.6) | 4 (1.0) | 5.69 (1) | 0.017 |
| RMG | 4 (1.0) | 5 (1.3) | 1.000∗ | |
| Denture stomatitis | 45 (11.5) | 26 (6.6) | 5.6 (1) | 0.018 |
| Angular chelitis | 10 (2.6) | 1 (0.3) | 7.5 (1) | 0.006 |
| Denture granuloma | 2 (0.5) | 1 (0.3) | 0.500∗ | |
| Frictional keratosis | 8 (2.0) | 14 (3.6) | 1.68 (1) | 0.194 |
| Cheek biting | 4 (1.0) | 4 (1.0) | 0.0 (1) | 0.637 |
| Aphthous stomatitis | 3 (0.8) | 3 (0.8) | 1.000∗ | |
| Fibroma | 5 (1.3) | 5 (1.3) | 1.000∗ | |
| Lichen planus | 2 (0.5) | 0.0 (0.0) | 0.499∗ | |
| Traumatic ulcers | 8 (2.0) | 2 (0.5) | 3.67 (1) | 0.056 |
| Xerostomia | 119 (30.4) | 58 (14.8) | 27.17 (1) | 0.001 |
∗Chi-square test.
∗Fisher Exact test.
The distribution of OMLs in DM2 patients according to the level of metabolic control of disease is shown in Table 5. Higher prevalences of OMLs and xerostomia were significantly associated with poor metabolic control of disease (P < 0.05).
Table 5.
Distribution of oral mucosal lesions and xerostomia among diabetic patients according to the level of metabolic control
| Lesions | Metabolic Control (n = 391) | Total (%) | χ² (df) | P value | ||
|---|---|---|---|---|---|---|
| Well n = 170 | Fair n = 84 | Poor n = 137 | ||||
| One or more lesion | ||||||
| Yes | 63 (37.1) | 44 (52.4) | 71 (51.8) | 178 (45.5) | 8.7 (2) | 0.013 |
| No | 107 (62.9) | 40 (47.6) | 66 (48.2) | 213 (54.5) | ||
| Denture Stomatitis | ||||||
| Yes | 16 (9.4) | 5 (6.0) | 24 (17.5) | 45 (11.5) | 8.14 (2) | 0.02 |
| No | 154 (90.6) | 79 (94) | 113 (82.5) | 346 (88.5) | ||
| Geographic Tongue | ||||||
| Yes | 2 (1.2) | 4 (4.8) | 8 (5.8) | 14 (3.6) | 5.21 (2) | 0.07 |
| No | 168 (98.8) | 80 (95.2) | 129 (94.2) | 377 (96.4) | ||
| Traumatic Ulcers | ||||||
| Yes | 2 (1.2) | 1 (1.2) | 5 (3.6) | 8 (2.0) | 2.71 (2) | 0.26 |
| No | 168 (98.8) | 83 (98.8) | 132 (96.4) | 383 (98) | ||
| Angular Chelitis | ||||||
| Yes | 2 (1.2) | 4 (4.8) | 4 (2.9) | 10 (2.6) | 3.01 (2) | 0.22 |
| No | 168 (98.8) | 80 (95.2) | 133 (97.1) | 381 (97.4) | ||
| Xerostomia | ||||||
| Yes | 42 (24.7) | 23 (27.4) | 54 (39.4) | 119 (30.4) | 8.22 (2) | 0.016 |
| No | 128 (75.3) | 61 (72.6) | 83 (60.6) | 272 (69.6) | ||
Chi-square and Fisher exact test.
Discussion
Diabetes mellitus is a complex and pernicious syndrome characterised by abnormalities in carbohydrate, lipid, and protein metabolism resulting from either a profound or an absolute deficiency of insulin. Type 1 diabetes represents less than 5% of primary diabetes cases, and DM2 represents the remainder (25).
A number of specific oral mucosa alterations have been associated with DM (22). In the present study, the prevalence of OMLs was significantly higher in DM2 patients (45.5%) than in nondiabetic control subjects (38.4%) (P = 0.042). A similar study of 146 patients with DM2 and 111 non-diabetic control subjects showed that nearly twice the number of diabetic patients (88%) had one or more oral soft tissue lesions as compared to non-diabetic control subjects (45.0%), and the difference was statistically significant (P < 0.001) (27). Similarly, Guggenheimer et al., investigated the prevalence of OMLs in 405 patients with type 1 diabetes and 268 control subjects and found that 44% of diabetic patients had one or more oral soft tissue lesions as compared to 25% of control subjects; again, the difference was significant (16). Collin et al., investigated the occurrence of diabetic neuropathy in elderly patients with DM2 and examined the mucosal diseases, tooth loss, and temporomandibular joint dysfunction in 45 long-term DM patients and 77 control subjects (28). They showed that 42% of patients with DM had two or more mucosal lesions, as compared to 20% of control subjects (P = 0.008) (28). This higher point prevalence rate of mucosal lesions observed in diabetic patients may be due to slower healing rates observed in these patients, leading to a longer duration of a given lesion, and not be due to an increase in the incidence. In other words, if a lesion takes two months to heal in a diabetic patient and one month to heal in healthy control subject, the prevalence will be higher in patients with DM at a given point of time.
Specific lesions that occurred with significantly greater frequency in the present study included GT, denture stomatitis, and angular cheilitis. An association between GT and DM was suggested initially by Wysocki et al., by linking an increased prevalence of tissue type HLA-B15 with GT and in patients with IDDM. This study of 87 diabetic patients and 105 non-diabetic control subjects showed a 4-fold increase in the prevalence of GT in the diabetic group (12). Another study by Bastos et al., found a higher prevalence of GT in DM2 patients (5.4%) than in control subjects (0.9%), and this difference was statistically significant (P = 0.001) (27). Guggenheimer et al., also found a higher frequency of GT in diabetic patients (5.4%) than in control subjects (3.9%); however, this difference was not statistically significant (16). The cause of increased prevalence of GT in diabetic patients, although still unknown, may be associated with slower repair and delayed healing mechanisms caused by microangiopathy of the oral vasculature and hypoxia in diabetic patients.
The prevalence of denture stomatitis was found to be significantly higher in diabetic patients than in control subjects (P = 0.018). As the percentages of denture wearers in both groups were not significantly different, the prevalence of denture stomatitis was not adjusted for in terms of the differences in denture use between the groups. A literature search revealed conflicting reports about the association of denture stomatitis with DM (29,30). Similarly, the prevalence of angular cheilitis in the present study was found to be significantly higher in diabetic patients than in control subjects (P < 0.05). It is generally acknowledged that diabetic patients are more susceptible to fungal infections, particularly to Candida albicans infections, than non-diabetic subjects (31). Hyperglycemia due to poor metabolic control is one possible predisposing factor of oral candidiasis in diabetic patients. This can lead to the growth of Candida albicans and enhanced adhesiveness to the oral epithelium (32) in association with other local factors such as the presence of dental prostheses, salivary pH, salivary flow rate, and oral habits (33).
The relationship between lichen planus and DM has been extensively studied, with controversial results (34). This is due to a wide range of prevalence, from 1.6% (24) to 85% (21), of lichen planus in the study populations, and while some studies have verified this association (21,18,35), other studies could not (23,24). In the present study, no association between lichen planus and DM was found. Only 2 cases (0.5%) of lichen planus were found in DM2 patients, and none were found in control subjects. However, Bastos et al., reported a significantly higher prevalence of lichen planus in DM2 patients (6.1%) than in control subjects (27). Van Dis and Park (24) observed lichen planus in 4% of patients with diabetes.
Our results also demonstrated a significant association between metabolic control of disease and the occurrence of one or more oral lesions, denture stomatitis, GT, and angular cheilitis in DM2 patients (P < 0.05). As the level of metabolic control decreased, the possibility of having OMLs increased. Collin et al. (28), reported that patients with fewer than 2 OMLs had a mean HbA1c of 8.3%, while those with 2 or more lesions had a mean HbA1c of 9.5% (P = 0.08) (28). Poor metabolic control has been associated with various diabetic complications (36), including severe periodontitis (37). Uncontrolled DM may lead to many pathological changes such as increased glucose levels in saliva, decreased saliva secretion, vascular changes, delayed healing, inhibition of phagocytosis, and cellular immune responses, which can increase the susceptibility of oral tissues to infection and local irritants (38).
Conclusion
In this study, DM2 patients had a higher prevalence of oral mucosal alterations than control subjects. Higher occurrence of OMLs was significantly associated with poor metabolic control of DM. These findings highlight the necessity of regular clinical examinations to ensure early diagnosis and prompt management of OMLs in DM patients.
Acknowledgments
The authors would like to acknowledge all the patients who participated in this study.
Footnotes
Conflict of interest
None.
Funds
This study was funded by Universiti Sains Malaysia (short term grant 304/PPSG/6131595).
Authors’ contributions
Conception and design, provision of study materials or patient, obtaining of funding: ARI
Analysis and interpretation of the data, critical revision of the article for the important intellectual content: NMI, ARI
Drafting of the article, administrative, technical or logistic support: AAG
Statistical expertise, collection and assembly of data: SAAM
Final approval of the article: NMI
References
- 1.American Diabetes Association Standards of medical care in diabetes-2009. Diabetes Care. 2009;32(Suppl 1):S13–S61. doi: 10.2337/dc09-S013. doi: 10.2337/dc09-S013 . [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.International Diabetes Federation . 3th ed. Brussels (BE): International Diabetes Federation; 2006. The Diabetes Atlas. [Google Scholar]
- 3.Zaini A. Where is Malaysia in the midst of the Asian epidemic of diabetes mellitus? Diabetes Res Clin Pract. 2000;50(Suppl 2):S23–S28. doi: 10.1016/s0168-8227(00)00175-3. doi: 10.1016/S0168-8227(00)00175-3 . [DOI] [PubMed] [Google Scholar]
- 4.American Diabetes Association Economic consequences of diabetes mellitus in the U.S. in 1997. Diabetes Care. 1998;21(2):296–309. doi: 10.2337/diacare.21.2.296. doi: 10.2337/diacare.21.2.296 . [DOI] [PubMed] [Google Scholar]
- 5.Leung GM, Lam KS. Diabetic complications and their implications on health care in Asia. Hong Kong Med J. 2000;6(1):61–68. [PubMed] [Google Scholar]
- 6.Lacopino AM. Diabetic periodontitis: possible lipidinduced defect in tissue repair through alteration of macrophage phenotype and function. Oral Dis. 1995;1:214–229. doi: 10.1111/j.1601-0825.1995.tb00187.x. [DOI] [PubMed] [Google Scholar]
- 7.Hirsch T, Spielmann M, Zuhaili B, Koehler T, Fossum M, Steinau HU, et al. Enhanced susceptibility to infections in a diabetic wound healing model. BMC Surg. 2008;8:5. doi: 10.1186/1471-2482-8-5. doi: 10.1186/1471-2482-8-5 . [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Ahmed N. Advanced glycation endproducts-role in pathology of diabetic complications. Diabetes Res Clin Pract. 2005;67(1):3–21. doi: 10.1016/j.diabres.2004.09.004. doi: 10.1016/j.diabres.2004.09.004 . [DOI] [PubMed] [Google Scholar]
- 9.Lamster IB, Lalla E, Borgnakke WS, Taylor GW. The relationship between oral health and diabetes mellitus. J Am Dent Assoc. 2008;139(Suppl 1):19S–24S. doi: 10.14219/jada.archive.2008.0363. [DOI] [PubMed] [Google Scholar]
- 10.Kaur G, Holtfreter B, Rathmann WG, Schwahn C, Wallaschofski H, Schipf S, et al. Association between type 1 and type 2 diabetes with periodontal disease and tooth loss. J Clin Periodontol. 2009;36(9):765–774. doi: 10.1111/j.1600-051X.2009.01445.x. doi: 10.1111/j.1600-051X.2009.01445.x . [DOI] [PubMed] [Google Scholar]
- 11.Zegarelli DJ. Fungal infections of the oral cavity, Otolaryngol. Clin North Am. 1993;26(6):1069–1089. [PubMed] [Google Scholar]
- 12.Wysocki GP, Daley TD. Benign migratory glossitis in patients with juvenile diabetes. Oral Surg Oral Med Oral Pathol. 1987;63(1):68–70. doi: 10.1016/0030-4220(87)90342-2. doi: 10.1016/0030-4220(87)90342-2 . [DOI] [PubMed] [Google Scholar]
- 13.Guggenheimer J, Moore PA, Rossie K, Myers D, Mongelluzzo MB, Block HM, et al. Insulin-dependent diabetes mellitus and oral soft tissue pathologies. II. Prevalence and characteristics of Candida and candidal lesions. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2000;89(5):570–576. doi: 10.1067/moe.2000.104477. doi: 10.1067/moe.2000.104477 . [DOI] [PubMed] [Google Scholar]
- 14.Dorko E, Baranova Z, Jenca A, Kizek P, Pilipcinec E, Tkacikova L. Diabetes mellitus and candidiases. Folia Microbiol (Praha) 2005;50(3):255–261. doi: 10.1007/BF02931574. doi: 10.1007/BF02931574 . [DOI] [PubMed] [Google Scholar]
- 15.Cairo F, Rotundo R, Frazzingaro G, Muzzi L, Pini Prato GP. Diabetes mellitus as a risk factor for periodontitis. Minerva Stomatol. 2001;50(9–10):321–330. [PubMed] [Google Scholar]
- 16.Guggenheimer J, Moore PA, Rossie K, Myers D, Mongelluzzo MB, Block HM, et al. Insulin-dependent diabetes mellitus and oral soft tissue pathologies. I. Prevalence and characteristics of non-candidal lesions. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2000;89:563–569. doi: 10.1067/moe.2000.104476. doi: 10.1067/moe.2000 . [DOI] [PubMed] [Google Scholar]
- 17.Quirino MR, Birman EG, Paula CR. Oral manifestations of diabetes mellitus in controlled and uncontrolled patients. Braz. Dent J. 1995;6(2):131–136. [PubMed] [Google Scholar]
- 18.Albrecht M, Ba´no´czy J, Dinya E, Tama´ s Jr G. Occurrence of oral leukoplakia and lichen planus in diabetes mellitus. Oral Pathol Med. 1992;21(8):364–366. doi: 10.1111/j.1600-0714.1992.tb01366.x. [DOI] [PubMed] [Google Scholar]
- 19.Dikshit RP, Ramadas K, Hashibe M, Thomas G, Somanathan T, Sankaranarayanan R. Association between diabetes mellitus and pre-malignant oral diseases: across sectional study in Kerala, India. Int J Cancer. 2006;118(2):453–457. doi: 10.1002/ijc.21345. doi: 10.1002/ijc.21345 . [DOI] [PubMed] [Google Scholar]
- 20.Ujpa´l M, Matos O, Bı’dok G, Somogyi A, Szabo´ G, Suba Z. Diabetes and oral tumors in Hungary. Diabetes Care. 2004;27(3):770–774. doi: 10.2337/diacare.27.3.770. [DOI] [PubMed] [Google Scholar]
- 21.Seyhan M, O¨ zcan H, Sahin I, Bayram N, Karincaoglu Y. High prevalence of glucose metabolism disturbance in patients with lichen planus. Diabetes Res Clin Pract. 2007;77(2):198–202. doi: 10.1016/j.diabres.2006.12.016. doi: 10.1016/j.diabres.2006.12.016 . [DOI] [PubMed] [Google Scholar]
- 22.Skamagas M, Breen TL, Leroith D. Update on diabetes mellitus: prevention, treatment, and association with oral diseases. Oral Dis. 2008;14(2):105–114. doi: 10.1111/j.1601-0825.2007.01425.x. doi: 10.1111/j.1601-0825.2007.01425.x . [DOI] [PubMed] [Google Scholar]
- 23.Christensen E, Holmstrup P, Jo¨rgensen FW, Jensen BN, Pindborg JJ. Glucose tolerance in patients with oral lichen planus. J Oral Pathol. 1977;6(3):143–151. doi: 10.1111/j.1600-0714.1977.tb01875.x. doi: 10.1111/j.1600-0714.1977.tb01874.x . [DOI] [PubMed] [Google Scholar]
- 24.Van Dis ML, Parks ET. Prevalence of oral lichen planus in patients with diabetes mellitus. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1995;79(6):696–700. doi: 10.1016/s1079-2104(05)80302-6. doi: 10.1016/S1079-2104(05)80302-6 . [DOI] [PubMed] [Google Scholar]
- 25.Little JW, Falace DA, Miller CS, Rhodus NL. 8th ed. St Loius (MO): Mosby; 2012. Dental Management of the Medically Compromised Patient. [Google Scholar]
- 26.Kramer IR, Pindborg JJ, Bezroukov V, Infirri JS. Guide to epidemiology and diagnosis of oral mucosal diseases and conditions. World Health Organization. Community Dent Oral Epidemiol. 1980;8(1):1–26. doi: 10.1111/j.1600-0528.1980.tb01249.x. doi: 10.1111/j.1600-0528.1980.tb01249.x . [DOI] [PubMed] [Google Scholar]
- 27.Bastos AS, Leite AR, Spin-Neto R, Nassar PO, Massucato EM, Orrico SR. Diabetes mellitus and oral mucosa alterations: Prevalence and risk factors. Diabetes Res Clin Pract. 2011;92(1):100–105. doi: 10.1016/j.diabres.2011.01.011. doi: 10.1016/j.diabres.2011.01.011 . [DOI] [PubMed] [Google Scholar]
- 28.Collin HL, Niskanen L, Uusitupa M, Toyry J, Collin P, Koivisto AM, et al. Oral symptoms and signs in elderly patients with type 2 diabetes mellitus. A focus on diabetic neuropathy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2000;90(3):299–305. doi: 10.1067/moe.2000.107536. doi: 10.1067/moe.2000.107536 . [DOI] [PubMed] [Google Scholar]
- 29.Dorocka-Bobkowska B, Budtz-Jorgensen E, Wloch S. Noninsulin dependent diabetes mellitus as a risk factor for denture stomatitis. J Oral Pathol Med. 1996;25(8):411–415. doi: 10.1111/j.1600-0714.1996.tb00288.x. doi: 10.1111/j.1600-0714.1996.tb00288.x . [DOI] [PubMed] [Google Scholar]
- 30.Phelan JA, Levin SM. A prevalenc study of denture stomatitis in subjects with diabetes mellitus or elevated plasma glucose levels. Oral Surg Oral Med Oral Pathol. 1986;62(3):303–305. doi: 10.1016/0030-4220(86)90012-5. doi: 10.1016/0030-4220(86)90012-5 . [DOI] [PubMed] [Google Scholar]
- 31.Vazquez JA, Sobel JD. Fungal infections in diabetes. Infect Dis Clin North Am. 1995;9(1):97–116. [PubMed] [Google Scholar]
- 32.Darwazeh AM, Lamey PJ, Samaranayake LP, MacFarlane TW, Fisher BM, Macrury SM, et al. The relationship between colonisation, secretor status and in-vitro adhesion of Candida albicans to buccal epithelial cells from diabetics. J Med icrobiol. 1990;33(1):43–49. doi: 10.1099/00222615-33-1-43. doi: 10.1099/00222615-33-1-43 . [DOI] [PubMed] [Google Scholar]
- 33.Manfredi M, McCullough MJ, Polonelli L, Conti S, Al-Karaawi ZM, Vescovi P, et al. In vitro antifungal susceptibility to six antifungal agents of 229 Candida isolates from patients with diabetes mellitus. Oral Microbiol Immunol. 2006;21(3):177–182. doi: 10.1111/j.1399-302X.2006.00274.x. doi: 10.1111/j.1399-302X.2006.00274.x . [DOI] [PubMed] [Google Scholar]
- 34.Manfredi M, McCullough MJ, Vescovi P, Al-Kaarawi ZM, Porter SR. Update on diabetes mellitus and related oral diseases. Oral Dis. 2004;10(4):187–200. doi: 10.1111/j.1601-0825.2004.01019.x. doi: 10.1111/j.1601-0825.2004.01019.x . [DOI] [PubMed] [Google Scholar]
- 35.Romero MA, Seoane J, Varela-Centelles P, Diz-Dios P, Garcia-Pola MJ. Prevalence of diabetes mellitus amongst oral lichen planus patients. Clinical and pathological characteristics. Med Oral. 2002;7(2):121–129. [PubMed] [Google Scholar]
- 36.Bytzer P, Talley NJ, Hammer J, Young LJ, Jones MP, Horowitz M. GI symptoms in diabetes mellitus are associated with both poor glycemic control and diabetic complications. Am J Gastroenterol. 2002;97(3):604–611. doi: 10.1111/j.1572-0241.2002.05537.x. doi: org/10.1111/j.1572-0241.2002.05537 . [DOI] [PubMed] [Google Scholar]
- 37.Taylor GW, Burt BA, Becker MP, Genco RJ, Shlossman M, Knowler WC, et al. Severe periodontitis and risk for poor glycemic control in patients with noninsulin dependent diabetes mellitus. J Periodontol. 1996;67(10 Suppl):1085–1093. doi: 10.1902/jop.1996.67.10s.1085. doi: org/10.1902/jop.1996.67.10s.1085 . [DOI] [PubMed] [Google Scholar]
- 38.Sykes LM, Sukha A. Potential risk of serious oral infections in the diabetic patient: a clinical report. J Prosthet Dent. 2001;86(6):569–573. doi: 10.1067/mpr.2001.120200. doi: org/10.1067/mpr.2001.120200 . [DOI] [PubMed] [Google Scholar]