The Relationship Between Glycated Hemoglobin Level and The Stage of Periodontitis in Individuals Without Diabetes

doi:10.21203/rs.3.rs-1453545/v1

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The Relationship Between Glycated Hemoglobin Level and The Stage of Periodontitis in Individuals Without Diabetes

https://doi.org/10.21203/rs.3.rs-1453545/v1

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Background:

Glycemic control appeared to have a significant impact on the relationship between periodontitis and diabetes. Since the classification of periodontitis was updated, the current study aims to investigate the association between the stage of periodontitis and HbA1c level in patients considered to be normoglycemic

Methods:

135 patients with no history of diabetes were included in the study. All patients received full mouth periodontal exam. Periodontal diagnosis was determined according to the 2017 World Workshop on the classification of periodontal disease. The glycemic state of patients was assessed using a chair-side HbA1c analyzer.

Results:

90 patients in the study were diagnosed with periodontitis. Higher average HbA1c were associated with the different stages of periodontitis (p <0.01). Most of the non-periodontitis patients were in the non-diabetes group (67%), while most of the periodontitis patients were in the undiagnosed pre-diabetes group (47% of the stages I and II group, and 44% of the stages III and IV group (p <0.001).

Conclusion:

Periodontitis patients are more likely to have undiagnosed dysglycemia. The elevation in HbA1c level was more evident in patients with stage III and Iv periodontitis. The result of this study suggests that patients with advanced periodontitis might be targeted for diabetes screening.

Periodontal diseases

hyperglycemic

dysglycemia

Diabetes mellitus

Prediabetes

Diabetes is a metabolic disease characterized by sustained hyperglycemia due to a defect in insulin secretion or insulin uptake. Global reports on diabetes trends show an alarming rise in the number of people affected by diabetes worldwide.¹ According to the International Diabetes Federation, diabetes prevalence has increased by 62% between 2009 and 2019.² It has also been estimated that half of the people with diabetes remain undiagnosed, during which micro and macrovascular complications may be already developed.²

Periodontitis is a highly prevalent inflammatory condition that results in the destruction of the connective tissue attachment and the alveolar bone supporting the teeth. Periodontal disease and diabetes are closely associated chronic conditions. Periodontitis is well established as a comorbidity of diabetes.³ Epidemiological studies found that people with diabetes are approximately 3–4 times more likely to experience a severe and progressive form of periodontitis. ^{4, 5} A recent meta-analysis comparing periodontal health of diabetic patients and healthy individuals concluded that the prevalence of periodontitis is 1.7 times greater in those with diabetes.⁶ The state of hyperglycemia elicits an exaggerated immune-inflammatory response to periodontal pathogens in the subgingival environment leading to a severe form of periodontal destruction.⁷ Many authors have found this relation to be independently bidirectional. ^{8, 9} Previous research has explored the pathophysiology by which periodontal disease affects diabetes and vice versa. ^{8, 10} Persistent periodontal infection may negatively impact the metabolic state of diabetic patients. Periodontitis, by its nature, is an inflammatory disease, and inflammation plays a major role in diabetes. Polak et al.¹¹ summarized the possible mechanism by which periodontitis affects glycemic control. They suggested that the persistence of local inflammation in cases of untreated periodontitis will lead to ample production of inflammatory mediators such as tumor necrosis factor (TNF-α), Interlukin-6 (IL-6), C-reactive protein (CRP) and oxygen radicals. These inflammatory mediators, together with the bacterial antigens sourced from the plaque microbial biofilm, will enter the blood stream and enhance the upregulation of systemic inflammatory state. Consequently, insulin signaling will be negatively affected and insulin resistance will be increased.¹¹

To date, the exact biologic mechanisms associating diabetes and periodontitis are not entirely understood. However, the level of glycemic control appears to be a fundamental factor that links both diseases together in a dose-dependent manner. The severity of periodontitis in patients with diabetes is greatly influenced by the metabolic state of the patient.^{12, 13} In a prospective clinical study, Costa et al.¹⁴ found that elevated HbA1c level is significantly associated with the progression of periodontitis and tooth loss. Similarly, Demmer et al.¹⁵ detected up to 3 fold increase in the probability of tooth loss in patients with severe hyperglycemia. In contrast, few studies explored the relationship between periodontitis and glycosylated hemoglobin in patients not diagnosed with diabetes. A pilot study by Wolff et al.¹⁶ reported a higher mean HbA1c level in periodontitis cases than non-periodontitis controls after adjusting for several variables. Although the difference in HbA1c level between the two groups was small (0.12%), it was statistically significant. A large population-based study also found that the presence of chronic periodontal infection at the baseline exam was correlated positively with the change in HbA1c level over time .¹⁷ The evidence presented thus far suggest that HbA1c test might be utilized as an objective measure to predict diabetes risk in periodontitis patients or to predict the severity and progression of periodontitis in people with diabetes.

Periodontitis classification was updated in 2017 to align with the current scientific evidence on periodontal disease pathophysiology and risk factors. A grade part that addresses individuals' variability to disease progression was added. Additionally, well-established risk factors of periodontitis such as glycemic control and smoking were used as grade modifiers¹⁸. Like previous periodontal disease classification systems, diabetes-associated periodontitis is not considered a separate disease entity due to the lack of evidence supporting unique pathophysiology linking diabetes and periodontitis¹⁹. Since the classification was recently changed, previously explored association themes between the severity of periodontitis and its effect on diabetes should be revisited and reshaped. The goals of this study are: (1) to investigate whether the level of dysglycemia increase with increasing severity of periodontitis (assessed as 2018 EFP/AAP periodontitis stages) and (2) to investigate whether the severity of periodontitis (assessed as 2018 EFP/AAP periodontitis stages) increase with increasing dysglycemia level.

This cross-sectional study was performed between 2017 and 2019 and was approved by the research ethical committee at King Abdulaziz University, faculty of dentistry. The study was conducted in accordance with the Helsinki Declaration of 1975, as revised in 2013. The study population included adult not diagnosed with diabetes or prediabetes. who attended the undergraduate dental clinic, graduate periodontal clinic, and the periodontics specialty clinic at the school of dentistry King Abdulaziz University.Other exclusion criteria were: 1) use of hypoglycemic medications, 2) current long-term use of corticosteroids, 3) renal insufficiency, 4) pregnant women, 5) patients with HIV infection, and 6) antibiotic use within the last 6 months or need for prophylactic antibiotic before any dental procedures.

Study groups and sampling:

Following a comprehensive periodontal exam, eligible patients were divided based on their periodontal diagnosis into three categories: 1) no periodontitis, 2) periodontitis stage I & II, 3) periodontitis stage III & IV. An equal number of participants was randomly selected from each category.

Sample size calculation:

Sample size was calculated using G*Power version 3.1.9.4, to detect an effect size f = 0.36 with a degree of freedom df = 2, representing 0.2 differential in HbA1c between the three equally sized periodontitis groups (5.5%, 5.7% and 5.9%), by assuming an overall mean (SD) HbA1c = 5.7% (0.45) in a group of 38 among non-diabetic Saudi individuals. ²⁰ The statistical power was set to 0.9 and type 1 error to 0.05, the total sample size was N = 102, i.e. 34 participants in each periodontitis group. The sample size was increased to 45 by group for higher statistical power.

Periodontal assessment:

Patients received full-mouth periodontal examination performed by two periodontists. The exam included measurements of the probing depth and the gingival margin position taken at six sites per tooth for all teeth in the mouth except third molars. Clinical attachment level was calculated by adding the probing depth reading to the gingival margin level when recession was present, and by subtracting the gingival margin level from the probing depth reading when the gingival margin was coronal to the CEJ. Alveolar bone loss was determined in the molar and premolar teeth on horizontal bitewings radiographs and in the anterior teeth on periapical radiographs. All radiographs were taken and assessed before the periodontal examination.

The stage of Periodontitis was established according to the 2018 EFP/AAP periodontitis classification for periodontal diseases and condition.²¹ Patients were recognized as having periodontitis when there were at least two non-adjacent interproximal sites with clinical attachment loss > 2mm. The site with greatest loss in clinical attachment was used to establish the periodontitis stage. When other complexity factors were present, the stage was shifted to a higher degree. The stage of periodontitis was categorized as follow:

Stage 1: CAL is 1-2 mm, bone loss is less than 15%, and not tooth loss due to periodontitis.
Stage 2: CAL is 3-4 mm, bone loss is less than 15-20%, and not tooth loss due to periodontitis.
Stage 3: CAL is ≥ 5mm, bone loss is beyond the middle of the root, and no more than 4 teeth lost due to periodontitis.
Stage 3: CAL is ≥ 5mm, bone loss is beyond the middle of the root, more than 4 teeth lost due to periodontitis, and grade 2/3 mobility.

Assessment of HbA1C:

The glycemic state of subjects was determined using the chair-side HbA1C and it was defined according the American Diabetes Association criteria.²² * The analyzer is certified according to the International Federation of Clinical Chemistry & Laboratory Medicine (IFCC) and the National Glycohemoglobin Standardization Program (NGSP). First, the test cartridge was placed in the analyzer, and a 4 mL finger-prick capillary blood sample was obtained. The blood sample was collected in the sampling area of the reagent pack, which was then inserted in the cartridge test in the analyzer. The percentage of HbA1c level for each patient was available in 5 minutes. Single-use check-up cartridges were used for quality control every month before samples were tested or on suspicion of an inaccurate result.

Despite that none of the patients has been previously diagnosed with diabetes, patients were recognized in the diabetes category if the HbA1c percentage was 6.5% or higher, in prediabetes category if the HbA1c was between 5.7% and 6.4%, and non-diabetes if the HbA1c was less than 5.7%.

BMI assessment:

The BMI was calculated using the height and weight measurements and patients were categorized as underweight for BMI <18.5 kg/m2; 2) healthy weight for BMI 18.5 to 24.9 kg/m2; 3) overweight for BMI 25 to 30 kg/m2; or 4) obese for BMI >30 kg/m2.

Other patient’s data:

All participants completed a questionnaire that comprised questions about: the patient’s age, sex, level of education, family history of diabetes, sign and symptoms of diabetes, history of gestational diabetes for women, smoking status, history of hypertension, and dyslipidemia.

Statistical analysis:

The mean HbA1c and standard deviation (SD) were calculated by characteristics of the study population. Descriptive statistics were also calculated for the study participants by categories of diabetes diagnoses i.e. non-diabetes, pre-diabetes, and diabetes. Chi square tests were used to compare categorical variables, and t-test and ANOVA to compare continuous variables. Linear regression models were used to estimate the mean change in HbA1c comparing the periodontitis stages I/II group and the periodontitis stage III/IV group to the non-periodontitis group (reference). The model was adjusted for the confounding variables including age, sex, BMI, smoking, level of education and family history of diabetes. The power of the analysis, a=0.5, was calculated and it was 0.95. Analysis was done using SAS statistical software (version 9.4; SAS Institute, Cary, NC).

The study included 135 adults between the age of 21 and 73 years old. Demographic data by periodontal diagnosis are presented in Table 1. The total number of subjects diagnosed with periodontitis was 90 (50% stages I/II and 50% stages III/IV). Comparison between periodontally healthy patients and patients with any stage of periodontitis revealed no significant difference in gender distribution between the groups. Periodontitis patients showed a significantly higher mean age compared to patients without periodontitis (p < 0.001). As regards to educational level; periodontitis patients were more likely to present with low educational attainment (p < 0.001). Smoking history was not significantly different between periodontitis and non-periodontitis groups. Conversely, BMI was higher in periodontitis patients, and periodontitis patients were more likely to have a family history of diabetes. Finally, Table 1 shows the significantly greater prevalence of diabetes in those with periodontitis.

Table 1

Characteristics of the study population by periodontitis diagnosis
Characteristic	Total (N = 135)	No Periodontitis (N = 45)	Periodontitis Stage I & II (N = 45)	Periodontitis Stage III & IV (N = 45)	P-value
Sex					0.48
Female	100 (74%)	33 (33%)	31 (31%)	36 (36%)
Male	35 (26%)	12 (34%)	14 (40%)	9 (26%)
BMI^*					< 0.001
≤ 24.9	47 (36%)	25 (53%)	13 (28%)	9 (19%)
25-29.9	43 (33%)	14 (33%)	16 (37%)	13 (30%)
≥ 30	40 (32%)	4 (10%)	16 (40%)	20 (50%)
Smoking					0.25
Former	11 (8%)	3 (27%)	4 (36%)	4 (36%)
Current	20 (15%)	7 (35%)	9 (45%)	4 (20%)
Education^*					< 0.001
None	9 (7%)	2 (22%)	3 (33%)	4 (44%)
Elementary	16 (12%)	2 (13%)	6 (38%)	8 (50%)
Intermediate	13 (9%)	0 (0%)	4 (31%)	9 (69%)
Secondary	37 (27%)	10 (27%)	17 (46%)	10 (27%)
College or higher	50 (38%)	29 (58%)	15 (30%)	6 (12%)
Family history of diabetes					0.3
No	59 (44%)	27 (46%)	16 (27%)	16 (27%)
Yes	76 (56%)	18 (24%)	29 (38%)	29 (38%)
Age					< 0.001
Mean (SD)	38.4 (11.1)	29.7 (6.2)	40.8 (10.4)	44.7 (10.0)
Diabetes Dx					< 0.001
No diabetes	58 (43%)	30 (52%)	16 (28%)	12 (21%)
Pre-diabetes	55 (41%)	14 (25%)	21 (38%)	20 (36%)
Diabetes	22 (16%)	1 (5%)	8 (36%)	13 (59%)
^*N do not add up to 135 due to missing data.

The mean HbA1c values for the study population by their main exposure and covariate categories are presented in Table 2. Higher average HbA1c values were associated with the different stages of periodontitis (p < 0.01). Compared to the healthy-weight group, overweight and obese individuals had higher HbA1c (p = 0.04). Most of the non-periodontitis individuals were in the non-diabetes group (67%), while most of the periodontitis individuals were in the previously undiagnosed pre-diabetes group (47% of the stages I and II group, and 44% of the stages III and IV group (p < 0.001) (Table 3). Periodontitis stage III and IV group had the highest proportion of previously undiagnosed diabetes (29%). Those with pre-diabetes and diabetes tended to be older (p < 0.001) (Table 3). The Distribution of HbA1c level in periodontally healthy patients and patients with periodontitis is presented in Fig. 1. More patients with HbA1c level greater than 6.4% were found in patients with stage III/IV periodontitis (p value < 0.01).

Table 2

Mean glycated hemoglobin (HbA1c) and standard deviation (SD) by periodontal diagnosis and study covariates.
Characteristic	N	Mean HbA1c (SD)	P-value
Periodontal diagnosis			< 0.01
Periodontal health	45	5.52 (0.49)
Periodontitis Stage I & II	45	6.17 (1.41)
Periodontitis Stage III & IV	45	6.52 (1.71)
Sex			0.94
Female	100	6.07 (1.35)
Male	35	6.08 (1.43)
BMI^*			0.04
≤ 24.9	47	5.67 (0.69)
25-29.9	43	6.16 (1.38)
≥ 30	40	6.49 (1.84)
Smoking			0.22
Former	11	6.01 (0.96)
Current	20	5.79 (0.59)
Education^*			0.07
None	9	6.08 (0.40)
Elementary	16	6.86 (2.28)
Intermediate	13	6.38 (1.22)
Secondary	37	6.04 (1.50)
College or higher	50	5.70 (0.69)
Family history of diabetes			0.79
Yes	76	6.04 (1.35)
No	59	6.10 (1.39)
^*N do not add up to 135 due to missing data

Table 3

Characteristics of the study population by diabetes diagnosis
Characteristic	No diabetes (N = 58)	Pre-diabetes (N = 55)	Diabetes (N = 22)	P-value
Periodontal diagnosis				< 0.001
Periodontal health	30 (67%)	14 (31%)	1 (2%)
Periodontitis Stage I & II	16 (36%)	21 (47%)	8 (18%)
Periodontitis Stage III & IV	12 (27%)	20 (44%)	13 (29%)
Sex				0.65
Female	41 (41%)	43 (43%)	16 (16%)
Male	17 (49%)	12 (34%)	6 (17%)
BMI^*				0.09
≤ 24.9	25 (53%)	18 (38%)	4 (8%)
25-29.9	15 (35%)	21 (49%)	7 (16%)
≥ 30	16 (40%)	13 (33%)	11 (28%)
Smoking				0.26
Former	5 (45%)	4 (36%)	2 (18%)
Current	10 (50%)	9 (45%)	1 (5%)
Education^*				0.06
None	2 (22%)	6 (67%)	1 (11%)
Elementary	4 (25%)	5 (31%)	7 (44%)
Intermediate	4 (31%)	6 (46%)	3 (23%)
Secondary	17 (46%)	15 (41%)	5 (14%)
College or higher	28 (56%)	18 (36%)	4 (8%)
Family history of diabetes				0.93
Yes	32 (42%)	32 (42%)	12 (16%)
No	26 (44%)	23 (39%)	10 (17%)
Age				< 0.001
Mean (SD)	34.2 (9.6)	40.2 (11.0)	45.0 (10.6)
HbA1c				< 0.001
Mean (SD)	5.30 (2.9)	6.04 (0.23)	8.18 (2.28)
^*N do not add up to 135 due to missing data.

Table 4 presents results of the linear regression models. In the crude model, those with periodontitis stage I or II had HbA1c that was on average 0.65% (absolute value) higher than those without periodontitis (95% confidence interval (CI): 0.11–1.20, p = 0.02), while periodontitis stage III and IV individuals had HbA1c that was on average 1.00% (absolute value) higher than those without periodontitis (95% CI: 0.46–1.55, p < 0.001). After adjusting for age, the association was attenuated but remained statistically significant among the periodontitis stage III/IV group but lost its significance among the periodontitis stage I/II group. In the fully adjusted model, those with periodontitis stage III /IV had HbA1c that was 0.85 on average higher than those without periodontitis (95% CI: 0.14–1.56, p = 0.02), while periodontitis stage II/III individuals had HbA1c that was on average 0.56 higher than those without periodontitis (95% CI: -0.09-1.2, p = 0.09).

Table 4

Mean increase in HbA1c by periodontal diagnosis (linear regression)
	Mean increase in HbA1c (95% CI)	P-Value
Model 1
No Periodontitis (Reference)
Periodontitis I & II	0.65 (0.11–1.20)	0.02^*
Periodontitis III & IV	1.00 (0.46–1.55)	< 0.001^*
Model 2
No Periodontitis (Reference)
Periodontitis I & II	0.57 (-0.05-1.19)	0.07
Periodontitis III & IV	0.90 (0.23–1.56)	< 0.01
Model 3
No Periodontitis (Reference)
Periodontitis I & II	0.56 (-0.09-1.20)	0.09
Periodontitis III & IV	0.85 (0.14–1.56)	0.02^*
Model 1: Unadjusted
Model 2: Adjusted for age, and sex.
Model 3: Adjusted for age, sex, BMI, smoking, education and family history of diabetes.
^*Statistically significant

The relationship between periodontitis and diabetes has been an area of extensive research for decades. The present study supports the literature that periodontitis has a negative impact on glycemic control. The result of the present study indicates that patients diagnosed with periodontitis are more prone to have higher mean HbA1c levels compared to periodontally healthy. In addition, patients with periodontitis were more likely to have undiagnosed prediabetes or diabetes than those without periodontitis. This analysis of 135 patients (90 with periodontitis and 45 without periodontitis) revealed that 23.3% (21/90) of the periodontitis group had an HbA1c level consistent with the diagnosis of diabetes compared to only 2% in the non-periodontitis group. Furthermore, 45.5% (41/90) of periodontitis patients had previously undiagnosed pre-diabetes compared to 31.1% (14/45) of patients without periodontitis. The influence of periodontitis on mean HbA1c level was more evident on patients diagnosed with stage III/IV periodontitis.

In the current study, the definition of periodontitis cases and data categorization for periodontitis stages is based on the consensus of the 2017 world workshop on the classification of periodontal diseases and peri-implant conditions.²¹ Unlike the previous classification schemes, the 2018 classification addressed the effect of glycemic control on periodontitis by adopting a two-dimensional approach for periodontitis diagnosis. The stage part describes the severity and the complexity of management of periodontitis while the grade part assesses individuals' susceptibility to disease progression based on well-established risk factors.¹⁸ Similar to previous periodontal disease classification systems, diabetes-associated periodontitis is not considered as a separate disease entity due to the lack of evidence to support a unique pathophysiology for patients having diabetes and periodontitis.¹⁹ Nevertheless, diabetes, with HbA1c level as a reference range, is set as a grade modifier and a risk assessor. ²¹ To the authors’ knowledge, the present research explores, for the first time, the association between the stages of periodontitis and HbA1c levels. Since the classification of periodontitis was recently updated, previously explored association themes between the severity of periodontitis and its effect on diabetes should be revisited and reshaped.

In 2011, the World Health Organization approved the HbA1c as a test for diabetes diagnosis.²³ In the current study, HbA1c level was measured using a commercially available point of care system*. The device is convenient to use and provides the HbA1c result within few minutes allowing instant feedback. The analytical performance of the device used in this study was evaluated in a primary care setting. They study reported 6% bias and a total coefficient of variation of less than 2% for more than 96% of the results meeting the NGSP requirements.²⁴

Consistent with findings of the current study, Saito et al.²⁵ demonstrated that in patients with no diabetes, more severe forms of periodontitis are associated with impaired glucose tolerance. In this study, the change in HbA1c level was evaluated 10 years retrospectively. It was observed that for each millimeter increase in probing depth measurements, the HbA1c level increased by 0.13%.²⁵ Moreover, Demmer et al.²⁶ reported that patients with intermediate level of periodontal diseases exhibited a twofold increased risk of diabetes. In another longitudinal study by Demmer et. al. following a non-diabetic population over 5 years, showed that severe forms of periodontitis are influential on HbA1c levels and they can be used as a predictor for worsening of HbA1c levels.¹⁷A recent systematic review by Graziani et al.²⁷ revealed evidence that in non-diabetic periodontitis patients, the glycemic control is compromised. This was demonstrated by higher levels of HbA1c, oral glucose tolerance test and fasting blood glucose.²⁷ In contrast to most findings reported in the literature, one longitudinal study by Kebede et al.²⁸ failed to find any association between periodontitis and diabetes incidence over 11 years follow up period. Their analysis demonstrated no potential correlation between changes in HbA1c and the baseline periodontal status. The authors discussed two explanations of this rather contradictory result. First was survivor bias as most of the periodontitis subjects with a high susceptibility to diabetes were less likely to complete the study. The second was the lack of inflammatory progression since participants with incident diabetes/prediabetes were more likely to present with central obesity at baseline.²⁸

Results of the current study indicate that many of the patients previously thought to have normal glucose dynamics and diagnosed with periodontitis were in the prediabetes category based on their HbA1c levels. In line with this finding, a recent cross-sectional study by Isola et al.²⁹ found that almost one third of their periodontitis group had HbA1c levels that are within the range of prediabetes value. It has been previously reported that individuals with prediabetes are more likely to develop diabetes, retinopathy, and cardiovascular diseases.^{30, 31} One longitudinal study in American Indian population established the utility of HbA1c to predict the incidence of diabetes. The analysis revealed that the incidence rate of diabetes is higher in children with prediabetes compared to those without.³²

This study is based on a sample obtained from a single university dental hospital and cannot be extrapolated to populations with different sociodemographic, or environmental backgrounds. Also, since the data was collected cross sectionally, it is not possible to determine if the incidence and progression of periodontal disease preceded the elevation in HbA1c level. Further longitudinal studies are needed to reveal and specify the causality between different stages of periodontitis and HbA1c levels. Additionally, prospective monitoring of a population with respect to the effect of the stage of periodontitis on HbA1c level would give an insight on the temporal relationship between periodontitis stages and the HbA1c level.

The observations in the current study suggest that periodontitis patients, particularly those with advanced stages of periodontal disease, might be targeted for opportunistic screening for diabetes. Our suggestion is supported by findings from a previous case control study in a Danish cohort by Holm et al.,³³ where chairside HbA1c test was used to screen chronic periodontitis patients for undiagnosed diabetes.Their investigations revealed that the proportion of patients with undiagnosed dysglycemia is higher in the periodontitis group (32.7%) compared to the control group (17.4%). The reported odd ratio of having undiagnosed diabetes in the study was 2.3 in periodontitis patients compared to the periodontally healthy patients.³³

Diabetes complications impose a substantial financial burden worldwide. The cost of diabetes was estimated to increase significantly by 2030.³⁷ Dental offices have been studied as potential places for opportunistic screening for diabetes.³⁴ It has been reported that approximately 70% of adults in the U.S visit their dentists at least once a year. Many of them do not see their physician regularly³⁵. Involving dentists in the screening of common medical conditions may improve medical diagnosis and reduce the healthcare cost. Studies evaluating dentists willingness to perform medical screening revealed that dentists believe in their vital role to screen for medical conditions in their offices.^{36, 37} A survey assessing dentists attitudes toward chairside medical screening reported that dentists are willing to use tests that generate immediate results to be discussed with the patient during the dental visit.³⁷ Further large-scale studies would be needed to determine the cost-effectiveness of this patient-centered approach.

Patients with periodontitis are more likely to present with undiagnosed dysglycemia compared to periodontally healthy patients. Periodontitis was found to be significantly associated with the elevation in glycated hemoglobin level in patients not previously diagnosed with diabetes. The association between the mean HbA1c level and periodontal disease was more evident on patients diagnosed with stage III/IV periodontitis.

Ethical approval: the study was approved by the research ethical committee at King Abdulaziz University, faculty of dentistry. Informed consent was obtained from all subjects before participating in the study.

Consent for publication: not applicable (the study does not include images or videos)

Availability of data and materials: Data that support the study result will be available upon request. To request data, please contact dr. Arwa Banjar ([email protected])

Competing interest: The authors declare that they have no competing interests.

Funding statement: The current study received no financial support.

Authors' contributions: All authors have made substantial contributions to the conception and design of the results, interpretation of data, drafted and revised the work, and approved the submitted version.

Acknowledgements: The authors express their gratitude to Khalid Kerra for Statistical Consulting and his support with statistical calculations.

Footnotes:

* HemoCue HbA1c 501 analyzer, Angelholm, Sweden

Roglic G. WHO Global report on diabetes: A summary. International Journal of Noncommunicable Diseases 2016;1(1):3.
Saeedi P, Petersohn I, Salpea P, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas. Diabetes research and clinical practice 2019;157:107843.
Löe H. Periodontal disease: the sixth complication of diabetes mellitus. Diabetes care 1993;16(1):329 − 34.
Emrich LJ, Shlossman M, Genco RJ. Periodontal disease in non-insulin‐dependent diabetes mellitus. Journal of periodontology 1991;62(2):123 − 31.
Taylor GW, Burt BA, Becker MP, et al. Non-insulin dependent diabetes mellitus and alveolar bone loss progression over 2 years. Journal of periodontology 1998;69(1):76–83.
Khader YS, Dauod AS, El-Qaderi SS, Alkafajei A, Batayha WQ. Periodontal status of diabetics compared with nondiabetics: a meta-analysis. Journal of diabetes and its complications 2006;20(1):59–68.
Mealey BL, Ocampo GL. Diabetes mellitus and periodontal disease. Periodontology 2000 2007;44(1):127 − 53.
Grossi SG, Genco RJ. Periodontal disease and diabetes mellitus: a two-way relationship. Annals of periodontology 1998;3(1):51–61.
Lamster IB, Lalla E, Borgnakke WS, Taylor GW. The relationship between oral health and diabetes mellitus. The Journal of the American Dental Association 2008;139:19S-24S.
Preshaw PM, Foster N, Taylor JJ. Cross-susceptibility between periodontal disease and type 2 diabetes mellitus: an immunobiological perspective. Periodontology 2000 2007;45(1):138 − 57.
Polak D, Shapira L. An update on the evidence for pathogenic mechanisms that may link periodontitis and diabetes. Journal of Clinical Periodontology 2018;45(2):150 − 66.
Taylor GW, Burt BA, Becker MP, Genco RJ, Shlossman M. Glycemic control and alveolar bone loss progression in type 2 diabetes. Annals of Periodontology 1998;3(1):30–39.
Tervonen T, Knuuttila M. Relation of diabetes control to periodontal pocketing and alveolar bone level. Oral Surgery, Oral Medicine, Oral Pathology 1986;61(4):346 − 49.
Costa FO, Miranda Cota LO, Pereira Lages EJ, et al. Progression of periodontitis and tooth loss associated with glycemic control in individuals undergoing periodontal maintenance therapy: A 5-year follow‐up study. Journal of periodontology 2013;84(5):595–605.
Demmer RT, Holtfreter B, Desvarieux M, et al. The influence of type 1 and type 2 diabetes on periodontal disease progression: prospective results from the Study of Health in Pomerania (SHIP). Diabetes care 2012;35(10):2036-42.
Wolff RE, Wolff LF, Michalowicz BS. A pilot study of glycosylated hemoglobin levels in periodontitis cases and healthy controls. Journal of periodontology 2009;80(7):1057-61.
Demmer RT, Desvarieux M, Holtfreter B, et al. Periodontal status and A1C change: longitudinal results from the study of health in Pomerania (SHIP). Diabetes care 2010;33(5):1037-43.
Tonetti MS, Greenwell H, Kornman KS. Staging and grading of periodontitis: Framework and proposal of a new classification and case definition. Journal of periodontology 2018;89:S159-S72.
Sanz M, Ceriello A, Buysschaert M, et al. Scientific evidence on the links between periodontal diseases and diabetes: Consensus report and guidelines of the joint workshop on periodontal diseases and diabetes by the International Diabetes Federation and the European Federation of Periodontology. Journal of clinical periodontology 2018;45(2):138 − 49.
Ewid M, Sherif H, Billah SMB, et al. Glycated hemoglobin predicts coronary artery disease in non-diabetic adults. BMC cardiovascular disorders 2019;19(1):1–7.
Caton JG, Armitage G, Berglundh T, et al. A new classification scheme for periodontal and peri-implant diseases and conditions–Introduction and key changes from the 1999 classification. Journal of periodontology 2018;89:S1-S8.
Association AD. 2. Classification and diagnosis of diabetes. Diabetes care 2017;40(Supplement 1):S11-S24.
Alwan A. Global status report on noncommunicable diseases 2010: World Health Organization; 2011.
Andersson A, Lindh J, Eriksson A. Evaluation of the HemoCue HbA1c 501 system in primary care settings. Point of Care 2017;16(3):128 − 30.
Saito T, Shimazaki Y, Kiyohara Y, et al. The severity of periodontal disease is associated with the development of glucose intolerance in non-diabetics: the Hisayama study. Journal of Dental Research 2004;83(6):485 − 90.
Demmer RT, Jacobs DR, Desvarieux M. Periodontal disease and incident type 2 diabetes: results from the First National Health and Nutrition Examination Survey and its epidemiologic follow-up study. Diabetes care 2008;31(7):1373-79.
Graziani F, Gennai S, Solini A, Petrini M. A systematic review and meta-analysis of epidemiologic observational evidence on the effect of periodontitis on diabetes An update of the EFP‐AAP review. Journal of Clinical Periodontology 2018;45(2):167 − 87.
Kebede T, Pink C, Rathmann W, et al. Does periodontitis affect diabetes incidence and haemoglobin A1c change? An 11-year follow-up study. Diabetes & metabolism 2018;44(3):243 − 49.
Isola G, Matarese G, Ramaglia L, et al. Association between periodontitis and glycosylated haemoglobin before diabetes onset: A cross-sectional study. Clinical oral investigations 2019:1–10.
Cheng YJ, Gregg EW, Geiss LS, et al. Association of A1C and fasting plasma glucose levels with diabetic retinopathy prevalence in the US population: implications for diabetes diagnostic thresholds. Diabetes care 2009;32(11):2027-32.
Welsh C, Welsh P, Celis-Morales CA, et al. Glycated hemoglobin, prediabetes, and the links to cardiovascular disease: data from UK Biobank. Diabetes care 2020;43(2):440 − 45.
Vijayakumar P, Nelson RG, Hanson RL, Knowler WC, Sinha M. HbA1c and the prediction of type 2 diabetes in children and adults. Diabetes Care 2017;40(1):16–21.
Holm NCR, Belstrøm D, Østergaard JA, et al. Identification of individuals with undiagnosed diabetes and pre-diabetes in a Danish cohort attending dental treatment. Journal of periodontology 2016;87(4):395–402.
Yonel Z, Cerullo E, Kröger A, Gray L. Use of dental practices for the identification of adults with undiagnosed type 2 diabetes mellitus or non-diabetic hyperglycaemia: a systematic review. Diabetic Medicine.
Herman WH, Taylor GW, Jacobson JJ, Burke R, Brown MB. Screening for prediabetes and type 2 diabetes in dental offices. Journal of public health dentistry 2015;75(3):175 − 82.
Greenberg BL, Glick M, Frantsve-Hawley J, Kantor ML. Dentists' attitudes toward chairside screening for medical conditions. The Journal of the American Dental Association 2010;141(1):52–62.
Laurence B. Dentists consider medical screening important and are willing to incorporate screening procedures into dental practice. The journal of evidence-based dental practice 2012;12(3 Suppl):32–33.

No competing interests reported.

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The Relationship Between Glycated Hemoglobin Level and The Stage of Periodontitis in Individuals Without Diabetes

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