Periodontal status at two years of follow-up in patients with Newly Diagnosis of type 2 Diabetes Mellitus

Background: Diabetes increases the risk of periodontal disease. Integrating periodontal care with the treatment of type 2 diabetes (T2DM) may facilitate the management of both diseases.

Aim of the study: To evaluate the periodontal status at two years in patients with T2DM and assess glycated hemoglobin (HbA1c) according to the severity and extension of periodontitis.

Methods: This is a descriptive cohort study. Full-mouth periodontal evaluation was performed and blood samples were obtained to analyze HbA1c at baseline, 3, 12 and 24 months. Clinical attachment level, probing depth, bleeding on probing and oral hygiene were measured. We analyzed mean HbA1c according to severity and extension of periodontitis.

Results: We included 160 patients with T2DM. Basal HbA1c was 7.7 ± 2.2%. Periodontal health increased 27.5 % at 24 months. At baseline, moderate and severe periodontitis was present in 29.9% and 13.4% patients, respectively. At two years, 22.5% and 11.8% had moderate and severe periodontitis, respectively.

Bleeding on probing decreased from 15.7% to 6.4% at 24 months. HbA1c was higher in subjects with severe and generalized periodontitis.

Conclusions: The periodontal status in patients with newly diagnosis of T2DM who received a comprehensive diabetes care improved at 3 months. This improvement was maintained at 24 months of follow-up.

Introduction

It has been shown that people with diabetes have a higher risk for development of periodontal disease and that periodontitis is more severe in patients with diabetes compared to those who do not have diabetes [1]. However, very few studies have evaluated the relationship of diabetes and periodontal health in Latin America [2].

Severe periodontitis is considered the sixth complication of diabetes. It implies a three times greater risk for developing periodontal disease in patients with diabetes, especially in those with poor glycemic control [3]. On the other hand, people with periodontitis have higher risk for hyperglycemia and insulin resistance. Also, periodontitis is associated with an increased risk of incident type 2 diabetes mellitus (T2DM) [4,5].

Additionally, some studies have demonstrated that periodontal treatment can lead to improvement in diabetes control [1,6].

Some studies demonstrated that patients with diabetes have insufficient oral health awareness [7]. Patients do not receive information about their increased risk for periodontitis and the importance of its management to optimize general health [8]. In Mexico, only 8.4% of people with diabetes attend dental check-ups as a preventive measure to avoid or delay the oral complications of diabetes [9].

Integrating periodontal health status into standard comprehensive evaluations for all adults with T2DM can be effectively undertaken by either dentists or dental hygienists. This approach facilitates the multidisciplinary management of comorbid chronic diseases [10,11].

The aim of this study is to evaluate the periodontal status in a comprehensive program and at two years of follow up in patients with recently diagnosed T2DM. Additionally, we assessed HbA1c levels according to the severity and extension of periodontitis.

Materials and Methods

This is a descriptive cohort study in patients who attended the “Center of Comprehensive Care for the Patient with Diabetes” (CAIPaDi, an acronym for its name in Spanish) [12], located in the National Institute of Medical Sciences and Nutrition Salvador Zubirán (INCMNSZ), in Mexico City, between January 2014 and September 2017. We included patients with less than 5 years of diagnosis of diabetes, between 18 and 70 years, non-smokers, and without disabling chronic complications. The CAIPaDi program consists of four monthly visits, followed by annual evaluations. In every visit, the patients received professional care by endocrinologists, nutritionists, psychologists, psychiatrists, exercise physiologists, nurses, ophthalmologists, periodontists and diabetes educators. Standardized procedures for specialty care are followed in each intervention. For pharmacological treatment, specialists follow a prescription algorithm for glucose, lipids, blood pressure, antidepressants or anxiolytic drugs. Metabolic control goals (based on glycated hemoglobin, LDL cholesterol, and triglycerides) and blood pressure are established. In the other interventions, validated tools are used to assess mental health status, skills for self-care activities, retinal evaluation, renal function and strategies to avoid diabetic foot [12].

The research conducted in CAIPaDi was approved by the Research and Ethics Board of the INCMNSZ (Ref 1198) and registered in ClinicalTrials.gov (NCT02836808). All patients signed an informed consent form.

Periodontal examination

The periodontal status was determined in visit 1 (baseline), visit 4, 5 and 6 (3, 12 and 24 months of follow-up, respectively). A full-mouth periodontal evaluation was performed by two periodontists certified by Mexican Council of Periodontics. We used the periodontal probe Hu Friedy PUNC 15. Clinical attachment level (CA), probing depth (PD), and bleeding on probing (BoP) were measured in six sites of all present teeth, excluding third molars. We used the Simplified Oral Hygiene Index (IHOS) to evaluate oral hygiene, and examined six representative teeth of the entire mouth. Oral hygiene was classified according to the score obtained: 0, 0.1-1.2, 1.3-3 and 3.1-6 for excellent, good, regular and poor oral hygiene, respectively.

The clinical diagnosis of periodontal disease was established according to the 1999 Classification of Periodontal Diseases and Conditions of the American Academy of Periodontology [13,14]. Then, it was categorized into: periodontal health (PD < 3 mm, no clinical attachment loss (CAL) and absence of BoP), gingivitis (PD < 3 mm, no CAL, and presence of BoP), and periodontitis (PD > 4 mm and CAL). Likewise, chronic periodontitis was classified as mild (CAL 1-2 mm), moderate (CAL 3-4 mm) and severe (CAL > 5 mm). Regarding the extension, chronic periodontitis was classified as localized (<30% of affected sites) and generalized (>30% of affected sites). In addition to the periodontal evaluation, patients received oral hygiene instructions (OHI) in a 30-minute group session. In visit 2 we reinforced OHI and removed plaque and supra gingival calculus with ultrasound (Dentsply Cavitron Bobcat Pro). Visit 3 included OHI and non-surgical periodontal treatment (scaling and root planning) of localized sites with PD > 4 mm. The subgingival instrumentation was carried out with manual curettes (Hu Friedy, Gracey curettes) and ultrasound (Dentsply Cavitron Bobcat Pro).

The patients who needed additional sessions of non-surgical periodontal treatment, or surgical periodontal treatment (e.g. moderate and severe periodontitis) were referred to the dentist or periodontist to complete the therapy. Patients who needed dental extractions (poor periodontal prognosis), cavities removal, and replacement of poor dental restorations or dental prothesis for a proper mastication were also referred for specialized treatment. In the annual evaluations (visits 5 and 6) we asked patients if they attended the dentist in the last year for routine dental revision or to complete the treatment for which they were referred.

Glycated hemoglobin (HbA1c)

Blood samples were obtained from each patient after a fasting period of 8 to 12 hours. The HbA1c levels were estimated using high performance liquid chromatography (Bio-Rad, Variant II Turbo) in the Endocrinology and Metabolism Department (certified by the American College of Pathologists) in the INCMNSZ. Glycemic control was classified according to HbA1c levels as <7% for good control and >7% for bad control [10].

Statistical analyses

The distribution of the variables was examined with the Kolmogorov-Smirnov normality test. Categorical variables were analyzed with frequencies and percentages. Means and standard deviations (SD) were used for parametric variables. We used Wilcoxon test to compare BoP values between visits. To compare changes in periodontal status and IHOS throughout the visits we used Friedman test, and one-way ANOVA to compare mean HbA1c level according to severity of periodontitis. T-test for independent samples compared mean HbA1c levels regarding the extension of periodontitis. A value of p <0.05 was considered statistically significant. The analyses were performed in SPSS 25.

Results

We included 160 patients with T2DM, mean age was 54.3 ± 8.8 years, 84 (52.5%) were women, time of diagnosis of diabetes was 1 year [1-5], and basal mean HbA1c 7.7 ± 2.2%. We analyzed the periodontal status and severity of periodontitis at two years of follow-up. We observed that the proportion of patients with periodontal health increased from 2.5% in baseline to 30% in the two-year evaluation. The presence of gingivitis decreased from 13.8% to 6.3%. The progression of the disease stopped in 20% of the patients with periodontitis, and achieved clinical conditions compatible with periodontal health (p <0.001) (Table 1).

At baseline, mild, moderate and severe periodontitis was present in 56.7%, 29.9% and 13.4% respectively. At three months, moderate and severe periodontitis decrease to 15.1% and 11.8% respectively, and mild periodontitis increased to 73.1%. This improvement disappeared in visit 5, since severity of periodontitis was very similar than baseline (56.2%, 29.2% and 14.6% had mild, moderate and severe periodontitis). However, in the sixth visit, we observed that moderate and severe periodontitis decreased to 22.5% and 11.8%, respectively (Table 2).

BoP decreased from 15.7% (7.7-29.0) to 3.3 % (0.01-7.78) at 3 months (p<0.001). For the annual evaluations (visits 5 and 6), BoP was 9.3% (3.11-18.45) and 6.4% (1.66-16.66) respectively, and statistically significant lower compared to baseline (p<0.001). Similar findings regarding the presence of sites with PD 4-5 mm were observed. It decreased from 7.1% (1.8-14.3) to 2.0 % (0.0-6.3) at three months. At 1 and 2 years, we observed 2.4% (0.0-9.4) and 3.2% (0.0-10.2) of sites with PD 4-5 mm (p<0.001) (Table 3).

Oral hygiene improved from baseline to 3 months and was maintained throughout the study period (p< 0.001) (Table 4).

When we analyzed HbA1c values according to severity of periodontitis, we observed that patients with severe periodontitis had higher HbA1c compared to patients with moderate and mild periodontitis. However, only at three months the difference in HbA1c between the groups was statistically significant (p = 0.008) (Table 5). HbA1c was higher in patients with generalized periodontitis at baseline (HbA1c 9.9% ± 3.0), 12 months (HbA1c 7.7% ± 1.8) and 24 months (HbA1c 8.2% ± 2.3), compared to localized periodontitis (HbA1c 7.7% ± 2.2, 6.6% ± 1.0 and 7.1% ± 1.4 respectively). These differences were statistically significant at 12 and 24 months (Table 6).

In visit 6, 60.6% of the patients reported visiting the dentist at least once during the last year.

Discussion

In this study we observed a high prevalence of periodontal disease in patients with T2DM, since 97.6% had gingivitis or periodontitis and only 2.5 % had periodontal health at baseline. Advanced periodontitis (moderate and severe), was present in a high proportion of patients in the initial visit (43.3%), despite 56.3% having good and excellent oral hygiene. This may be due to the negative impact of glycemic control on the development and progression of periodontitis since 48.1% had HbA1c >7% at baseline (mean HbA1c was 7.7 ± 2.2%). In a recent cross-sectional study, Torrungruang et al. [15], found that 90% of patients with diabetes had moderate and severe periodontitis, and 10% had no or mild periodontitis. The differences in the results between that study and ours may be due to the categorization of degrees of periodontitis according to the case definitions for population-based surveillance of periodontitis. This is not intended nor approved for clinical use or biological research [16].

Although 60.6% of the patients in visit 6 reported attending the dentist during the last year, most of them received other dental treatment (mainly cavities removal and dental restorations) but not the periodontal therapy needed.

For this reason, we assume that the outcomes in periodontal parameters are attributable to the periodontal treatment given in CAIPaDi, even though in some of the patients we were not able to complete the therapy. We observed a statistically significant reduction in BoP at 3, 12 and 24 months of follow up compared to baseline. This is relevant because BoP is considered an important risk predictor for progression of periodontal disease (lower BoP values are compatible with periodontal health).

The percentage of sites with a PD of 4-5 mm reduced, and this improvement was maintained over the study period. These results showed that the intervention given is effective in preventing the progression of the disease at two years of follow up.

Regarding the association between periodontal status and HbA1c, we observed that patients with severe periodontitis had higher mean HbA1c compared to those with moderate and mild periodontitis in all the visits. The differences in HbA1c between the groups were statistically significant only at three months. Besides, patients with generalized periodontitis had higher HbA1c values, compared to those with localized periodontitis.

Similar results have been shown in three recent cross-sectional studies, showing that the greater the glycemic control, the greater the prevalence of periodontitis. Albuquerque et al. [17,] observed that moderate and severe periodontitis are associated with higher fasting glucose levels compared with milder forms of the disease. Teeuw et al. [18], found that patients with periodontitis had significantly higher HbA1c values compared to subjects with no periodontitis. Pumerantz et al. [8], showed that HbA1c was higher as the periodontal condition worsened.

A limitation of the study is that periodontal treatment was not carried out completely in some cases due to logistics of the program. Besides, periodontal support therapy was not performed, which is essential for the maintenance of periodontal health and prevent periodontitis progression. Another limitation is the population studied, since all are patients with recent diagnosis, without disabling complications, non-smokers, and with an age range of 18-70 years. These make that the results are not generalized to an open population.

One of the strengths of our study is that we evaluated the periodontal status of patients with diabetes who received a comprehensive care for the disease at baseline, 3 months and annually (12 and 24 months). Most of the studies that have evaluated the relationship between diabetes and periodontal disease are cross-sectional or short-term follow-up. Furthermore, most comprehensive care programs for patients with diabetes do not include an oral care service even though it has been demonstrated that periodontitis negatively affects glycemic control and oral health is imperative for a proper chewing and nutrition. Moreover, patients with diabetes are not often aware of the bidirectional relationship between periodontal disease and diabetes. Sixty two percent of patients do not know that periodontitis and diabetes may negatively influence each other10. In future studies it would be interesting to look for the impact of clinical and metabolic variables on periodontal disease, and vice versa. Another strength is that our intervention included education of patients about the importance of oral health, providing information about oral diseases and diabetes, as well as oral hygiene instructions. All of these are considered part of the treatment of periodontal disease [19].

The periodontal evaluation and treatment provided to the patients of CAIPaDi program are low-cost interventions consisting of 30-minute sessions once a month for 3 months and annual reevaluation visits. This strategy showed to be effective in stopping the progression of periodontitis, decreasing BoP and improving oral hygiene in patients with T2DM.

The inclusion of a periodontal intervention into a comprehensive care program for patients with diabetes helps to improve glycemic control through the prevention or resolution of periodontitis, or limiting the progression of periodontitis. Likewise, it could help avoid tooth loss that causes chewing impairment and decreases quality of life.

Conclusion

Improvement in periodontal status was obtained at three months and is maintained at 24 months. This intervention limited the progression of periodontal disease in patients with diabetes as a part of a comprehensive program.

Carlos Hernández, Valeria Hernández, Emmanuel Velázquez, Alberto Talavera, Daniel García, Alejandro Vázquez, Miguel Estrada, Gisela Medina, María Fernanda González, Areli Escamilla, Danika Ocampo.

Group of study CAIPaDi

Sofía Ríos-Villavicencio, Denise Arcila-Martínez, María Victoria Landa-Anell, Héctor Rafael Velázquez-Jurado, Marco Antonio Melgarejo-Hernández, Rodrigo Arizmendi-Rodríguez, Oswaldo Briseño-González, Humberto Del Valle-Ramírez, Arturo Flores-García, Eduardo González-Flores, Fernanda Garnica-Carrillo, Mariana Granados-Arcos, Héctor Infanzón-Talango, Claudia Lechuga-Fonseca, Angélica Palacios-Vargas, Liliana Pérez-Peralta, Alberto Ramírez-García, David Rivera de la Parra, Francis Rojas-Torres, Marcela Ruiz-Cervantes, Vanessa Ruiz-González, Sandra Sainos-Muñoz, Alejandra Sierra-Esquivel, Erendi Tinoco-Ventura, Luz Elena Urbina-Arronte, María Luisa Velasco-Pérez, Andrea Villegas-Narvaez, Verónica Zurita-Cortés.

Funding: The CAIPaDi program has received grants from Astra Zeneca, Fundación Conde de Valenciana, Novartis, Consejo Nacional de Ciencia y Tecnología (“Proyectos de Desarrollo Científico para Atender Problemas Nacionales 2013 project 214718), Nutrición Médica y Tecnología, NovoNordisk, Boehringer Ingelheim, Dirección General de Calidad y Educación en Salud, Eli Lilly, Merck Serono, MSD, Silanes, Chinoin and Carlos Slim Health Institute. There are no other potential conflicts of interest relevant to this article.

1. Polak D, Shapira L (2018) An update on the evidence for pathogenic mechanisms that may link periodontitis and diabetes. J Clin Periodontol 45:150-166. Link: https://goo.gl/8tPQ9o
2. Oppermann R, Haas A, 2. Kuchenbecker C (2015) Epidemiology of periodontal diseases in adults from Latin America. Periodontology 2000. 67:13-33. Link: https://goo.gl/6kN5P5
3. Loe H (1993) Periodontal disease. The sixth complication of diabetes mellitus. Diabetes Care 16: 329-334. Link: https://goo.gl/rozjM6  
4. Sanz M, Ceriello A, Buysschaer M, Chapple I, Demmer RT, et al. (2018) 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 45:138-149. Link: https://goo.gl/stVy4e  
5. Graziani F, GennaiS, Solini A, Petrini M (2017) A systematic review and meta-analysis of epidemiologic observational evidence on the effect of periodontitis on diabetes. An update of the EFP-AAP review. J Clin Periodontology 45: 167-187. Link: https://goo.gl/jHHLWh  
6. Mauri-Obradors E, Merlos A, Estrugo-Devesa A, Jané-Salas E, López-López J, et al. (2018) Benefits of non-surgical periodontal treatment in patients with type 2 diabetes mellitus and chronic periodontitis: A randomized controlled trial. J Clin Periodontology 45: 345-353. Link: https://goo.gl/py5Jbs
7. Weinspach K, Staufenbiel I, Memenga-Nicksch S, Ernst S, Geurstsen W, et al. (2013) Level of information about the relationship between diabetes mellitus and periodontitis - results from a nationwide diabetes information program. European Journal of Medical Research 18: 6. Link: https://goo.gl/w3PjSa
8. Pumerantz A, Bissett S, Dong F, Ochoa C, Wassall R, et al. (2017) Standardized screening for periodontitis as an integral part of multidisciplinary management of adults
with type 2 diabetes: an observational cross-sectional study of cohorts in the USA and UK. BMJ Open Diabetes Research & Care 5: e000413. Link: https://goo.gl/jkiqSq
9. Instituto Nacional de Salud Pública. Encuesta Nacional de Salud y Nutrición de Medio Camino 2016 Informe Final de Resultados. Link: https://goo.gl/56QhGE  
10. American Diabetes Association (2018) Standards of medical care in diabetes-2018. The Journal of Clinical and Applied Research and Education 41: 1. Link: https://goo.gl/cZhNvc  
11. Casanova L, Hughes, Preshaw P (2014) Diabetes and periodontal disease: a two-way relationship. British Dental Journal 217: 433-437. Link: https://goo.gl/jc1J2e  
12. Hernández-Jiménez S, Garcia-Ulloa AC, Mehta R, Aguillar-Salinas CA, Kershenobich D (2014) Innovative Models for the Empowerment of Patients with Type 2 Diabetes: The CAIPaDi Program. Recent Patents on Endocrine, Metabolic & Immune Drug Discovery 8: 202-209. Link: https://goo.gl/E2ovHn  
13. Armitage G (1999) Development of a classification system for periodontal diseases and conditions. Annals of Periodontology 4: 1-6. Link: https://goo.gl/wdWrRC
14. Holtfreter B, Albandar J, Dietrich T (2015) Standards for reporting chronic periodontitis prevalence and severity in epidemiologic studies – Proposed standards from the Joint EU/USA Periodontal Epidemiology Working Group. Journal of Clinical Periodontology 42: 407-412. Link: https://goo.gl/dQXar4  
15. Torrungruang K, Ongphiphadhanakul B, Jitpakdeebordin S (2018) Mediation analysis of systemic inflammation on the association between periodontitis and glycemic status. Journal of Clinical Periodontology 45: 548-556. Link: https://goo.gl/QWhvCv  
16. Eke P, Page R, Wei L (2012) Update of the case definitions for population-based surveillance of periodontitis. Journal of Periodontology 83: 1449-1454. Link: https://goo.gl/EuVTp1  
17. Albuquerque Z, Linhares K, Régia V, Furlaneto FA, Montenegro R, et al. (2018) Periodontitis, edentulism, and glycemic control in patients with type 2 diabetes: a cross-sectional study. BMJ Open Diabetes Research & Care 6: e000453. Link: https://goo.gl/kuqEzV  
18. Teeuw W, Kosho M, Poland D, Gerdes VE, Loos BG (2017) Periodontitis as a posible early sign of diabetes mellitus. BMJ Open Diabetes Research & Care 5. Link: https://goo.gl/FvuJ8Y  
19. Simpson T, Weldon J, Worthington H, Needleman I, Wild SH, et al. (2015) Treatment of periodontal disease for glycaemic control in people with diabetes mellitus. Cochrane Database of Systematic Reviews 11: CD004714. Link: https://goo.gl/Mmupd8