Abstract
Background
Type 2 diabetes mellitus (T2DM) is an important systemic disease, predisposing patients to inflammatory conditions including periodontitis and peri-implantitis and negatively affects dental implant success through various mechanisms. This study aimed to compare clinical and microbiological findings of individuals with dental implants with or without T2DM.
Methods
A total of 82 dental implants which were in function >3 years, were involved. The participants were divided into 2 groups; T2DM (n: 45 implants) and systemically healthy controls (n:37 implants). Periodontal indexes (Bleeding on probing (BOP), plaque index (PI), pocket depth (PD), and radiographic bone loss were recorded around implants in function >3 years. Subgingival microbiological samples were also collected from the peri-implant sites. Pathogens include Fusobacterium nucleatum, Camphylobacter rectus, Porphyromonas gingivalis, Tannerella forsythia, Actinobacillus actinomycetemcomitans, Treponema denticola, Prevotella intermedia, Peptostreptococcus micros, Eikinella corrodens, Prevotella nigrescens were evaluated.
Results
Peri-implant heatlh was determined in systemically healthy (54.1%) and type 2 diabetes patients (24.4%). Peri-implantitis was also evident in systemically healthy (8.1%) and T2DM (35.6%) groups. No differences was found in shallow peri-implant pockets in both groups in terms of the prevelance of all evaluated bacteria (p > 0.05). However, C. rectus, P. gingivalis, A. actinomycetemcomitans and T. forsythia were isolated more frequently in deep peri-implant pockets in systemically healthy patients compared to T2DM patients (p < 0.05).
Conclusions
Evaluted periodontal pathogens may not be affected by the presence of T2DM in implants. T2DM may not significantly alter the levels of specific periodontal pathogens in shallow and deep peri-implant pockets. C. rectus, P. gingivalis, A. actinomycetemcomitans and T. forsythia may be affected by T2DM in implants in deep pockets.
Keywords: Dental implant, Microflora, Diabetes mellitus, Peri-implant pocket
Graphical abstract
Several clinical studies conducted in various populations have long highlighted the negative effects of type 2 diabetes mellitus (T2DM) and on peri-implant tissues. As it is known, T2DM is a risk factor for peri-implant diseases. Many studies have compared the prevalence of subgingival pathogens between diabetic and nondiabetic patients in periodontal infections using various microbiological techniques. The results are still limited for peri-implant infections. To our knowledge, no study has evaluated the impact of T2DM on peri-implant microbiology in shallow and deep peri-implant pockets. The current study is a cross-sectional microbial analysis on this topic. This study revealed that T2DM did not complicate the bacterial flora in peri-implant sulcus more complex in the shallow and deep peri-implant pockets. It was also observed that although T2DM had long-term effects on implant peri-implant health and in the inflammatory process, it had no significant impact on peri-implant microbial flora.
1. Introduction
Dental implant treatment, which is an essential alternative in restoring missing teeth in partial and total edentulism, provides better outcomes in terms of aesthetics, function and, comfort than traditional prosthetic restorations.1 Pathological changes that occur in peri-implant tissues are defined as peri-implant diseases. Peri-implant diseases are also caused by microorganisms, as in periodontal diseases.2 Periodontal and peri-implant deep pockets are the most suitable environment for periodontal pathogens, the leading etiological causes of microbial diseases seen in periodontal and peri-implant tissues.2
Several clinical studies conducted in various populations have long highlighted the negative effects of type 2 diabetes mellitus (T2DM) and on peri-implant tissues. As it is known, T2DM is a risk factor for peri-implant diseases.3,4 Microvascular complications of hyperglycemia could severely affect soft tissues, reducing tissue vascularization, delaying recovery, and rendering the wound vulnerable to infection. Such conditions contribute to an increased implant failure in patients with diabetes mellitus.5, 6, 7
Given the abnormalities in clinical and immunoinflammatory features in patients with diabetes, T2DM may also cause alterations in the subgingival microbiota. This factor can affect in the subgingival microenvironment's redox potential, temperature, and concentration of nutrients in the subgingival microenvironment. Looking at the microbiological effects of this risk factor on periodontal disease, chronic periodontitis in diabetic individuals results from cellular and molecular changes caused by hyperglycemia and the host inflammatory response to Gram-negative infection.8,9
Many studies have compared the prevalence of subgingival pathogens between diabetic and nondiabetic patients in periodontal infections using various microbiological techniques.10, 11, 12, 13 In addition, although some studies have reported that pathogens isolated in the microbial flora of peri-implant infections are similar to those isolated in periodontitis regarding microbiological aspects, the results are still limited for peri-implant infections.14 Therefore, it is important to understand the microbial profile in shallow and deep peri-implant pockets in this risk group. Understanding the similarities and variations in the subgingival microbiota composition of patients with T2DM is critical for the development of treatments specific to this group at risk for peri-implant diseases. According to our knowledge, no study has evaluated the impact of T2DM on peri-implant microbiology in shallow and deep peri-implant pockets. This study aimed to determine the effects of T2DM on peri-implant sulcus microbial flora. According to our hypothesis, T2DM can selectively modulate bacterial growth.
2. Material and method
2.1. Study design and population
This study was approved by Clinical Research Ethics Committee of Health Sciences, Inonu University, Malatya, Turkey (2017/77). The study is designed cross-sectional. Participants were T2DM patients and healthy individuals who received implant treatment in Inonu University Faculty of Dentistry, Periodontology Department. Participants were divided into two groups: The T2DM group with T2DM participants (45 peri-implant site, n:14 patients) and the control group of healthy participants (37 peri-implant site, n: 12 patients). Written information regarding the study was given to the participants, and then a written consent was obtained. Detailed clinical and radiographic examinations of these individuals were performed. After collecting peri-implant microbial samples taken from the implants, microbiological analyzes were performed.
2.2. Patient selection
All patients were >30 years old, had at least one dental implant, and had implant functioning for at least three years. From the medical records, information about the duration of T2DM was obtained. For inclusion criteria in the study, diabetic participants had to have a current diagnosis of type 2 diabetes that had been confirmed by a physician for at least 5 years. Furthermore, all diabetic patients had to have a glycated HbA1c >6.5% according to American Diabetes Society diagnostic criteria.15 Patients without a history of chronic systemic disease or smoking were chosen as controls. Pregnant or lactating women, patients who had used local or systemic antibiotics, anti‐inflammatory medication, antiseptic therapy within the previous three months, the presence of any oral pathology and oral cancer, history of chronic systemic disease (other than T2DM) or with a history of smoking were excluded.
2.3. Clinical and radiographic evaluations
All clinical index measurements in the study were performed by a single researcher (A.S.). All periodontal parameters including the plaque index (PI) (Silness and Löe 1964), bleeding on probing (BOP) % and pocket depth (PD) were recorded using Williams periodontal probes (Hu-Friedy, Chicago, IL, USA). Prior to the study, the researcher performed repetitive measurements on five individuals meeting the study participation criteria to ensure adequate accuracy and reproducibility while recording clinical parameters and indices. These individuals used for calibration were not included in the study. Panoramic radiographs were taken for radiographic evaluation and the data were analyzed using the Planmace Romexis program (Planmeca Proline XC Panoramic X-Ray Unit, HELSINKI, FINLAND).
2.4. Evaluation of peri-implant status
Based on clinical and radiographic evaluations, the peri-implant status of each participant was classified according to the peri-implant disease diagnostic criteria described by Lang et al.16 Healthy implant was diagnosed with no bacterial plaque, BOP (−), PD < 4 mm, and no suppuration. Individuals with bleeding on probing, a maximum probing depth of 4 mm, suppuration, and no hard tissue loss on radiography diagnosed with peri-mucositis. Peri-implantitis diagnosed with bleeding on probing, implant mobility, probing depth exceeding 4 mm, peri-implant hard tissue loss on radiography, and suppuration. For data analysis, we selected pockets with PD < 4 mm as shallow pockets and pockets with PD ≥ 4 mm as deep pockets.
2.5. Collection of microbiological specimens
After clinical measurements, if there is bleeding in the sample area, it was waited for the bleeding to stop. If the bleeding did not stop, the participant was called the next day. Samples were collected from the deepest site of each peri-implant sulcus. The following procedures were used to obtain the peri-implant subgingival plaque samples: the sample area was isolated with cotton rolls. The supragingival plaque was removed. Then, the sample area was dried with a sterile cotton ball and 2 sterile paper points no. 40 (Paper Points, Dia Dent, Korea) were placed under the peri-implant sulcus for 20 s. The bacterial specimens were collected from the peri-implant site using sterile paper points, and then transferred these paper points into aseptic tubes containing 2 ml of distilled water and stored at −20 °C for nucleic acid isolation.
2.6. Microbiological analysis
Microbiological analyses of the specimens were carried out at Inonu University Turgut Ozal Medical Center Medical Microbiology Department. The Polymerase Chain Reaction (PCR) method was used to detect pathogens. The total DNA isolation of the sample was carried out using a QIA symphony DNA isolation device (QIAGEN, Germany). For DNA amplification, the Qiagen TopTaq Master Mix Kit (QIAGEN, Germany) was used. Specific primers were used for the identification of Fusobacterium nucleatum, Camphylobacter rectus, Porphyromonas gingivalis, Tannerella forsythia, Actinobacillus actinomycetemcomitans, Treponema denticola, Prevotella intermedia, Peptostreptococcus micros, Eikinella corrodens, Prevotella nigrescens (Table 1). The PCR procedure was carried out in a volume of 25 μl. Containing 12.5 μl 2X master mix, 2.5 μl 10X coral load, 1 μl forward primer, 1 μl reverse primer, 6 μl H2O and 2 μl total DNA.
Table 1.
Primer sequences for each bacterial species.
| Primer | Primer Sequence 5’→3′ | Primer size (bp) |
|---|---|---|
| Nucleatum-F | CTT AGG AAT GAG ACA GAG ATG | 120 |
| Nucleatum-R | TGA TGG TAA CAT ACG AAA GG | |
| C. rectus 1 | TTT CGG AGC GTA AAC TCC TTT TC | 598 |
| C. rectus 2 | TTT CTG CAA GCA GAC ACT CTT | |
| T. fors-F | GCG TAT GTA ACC TGC CCG CA | 641 |
| T. fors-R | TGC TTC AGT GTC AGT TAT ACC T | |
| Porp.ging-R | ACT GTT AGC AAC TAC CGA TGT | 404 |
| Porp.ging-F | AGG CAG CTT GCC ATA CTG CGG | |
| T. denticola-R | TCA AAG AAG CAT TCC CTC TTC TTC TTA | 316 |
| T. denticola-F | TAA TAC CGA ATG TGC TCA TTT ACA | |
| Provetella-F | TTT GTT GGG GAG TAA AGC GGG | 575 |
| Provetella-R | TCA ACA TCT CTG TAT CCT GCG T | |
| Peptost-R | TCC AGA GTT CCC ACC TCT | 1074 |
| Peptost-F | TCG AAC GTG ATT TTT GTG GA | |
| Prev. nigres-R | TTC CAT TGG ACA CAT CAG CAT T | 804 |
| Prev. nigres-F | CAG CCA AAC ACG TAC CTG TTG | |
| E. corro-R | CTA CTA AGC AAT CAA GTT GCC C | 688 |
| E. corro-F | CTA ATA CCG CAT ACG TCC TAA G | |
| A. actinom-R | ATG CCA ACT TGA CGT TAA AT | 557 |
| A. actinom-F | AAA CCC ATC TCT GAG TTC TTC TTC |
In order to observe the PCR product obtained after the amplification, a 1.5% agarose gel was prepared with 1X Tris-Boric acid-EDTA (TBE) buffer. After cooling the gel to a certain extent, 15 μl of ethidium bromide (5 μg/ml) was added and then poured into a gel mold and allowed to freeze. 5 μl of 100 bp DNA ladder was loaded into the first well, and 20 μl of PCR product was loaded into subsequent wells. A voltage of 100 V was run until the PCR product bands were separated from each other. The results were photographed on Kodak Molecular Imaging System Gel Logic 2200 (Kodak Company, NY, USA).
2.7. Statistical analysis
The statistical analyses of the research data were carried out using the IBM SPSS Statistics 22 software package. (SPSS IBM, Turkey). The normal distribution was determined by using a Kolmogorov–Smirnov test. Chi-square test, Fisher's Exact Chi-square test, Continuity (Yates) Correction and Fisher Freeman Halton test were used for comparison of qualitative data. P-values < 0.05 were considered statistically significant.
3. Results
The study included 26 subjects with and without T2DM who were age and sex matched. The average age of the participants was 50.83 ± 7.94. A total of 82 implants were evaluated, and the functional time of the implants varied between 36 months and 84 months, with a mean duration of 55.83 ± 16.4 months.
3.1. Clinical findings
Demographic descriptive data of the peri-implant status of the groups is presented in Table 2. The healthy rate of implants in the control group (54.1%) was significantly higher than T2DM group (24.4%). The incidence of peri-implantitis in the T2DM group (35.6%) was significantly higher than control group (8.1%). In the T2DM group, the prevalence of PD > 6 mm sites were significantly higher than the control group (Table 2).
Table 2.
Peri-implant health status of the groups.
| Control |
T2DM |
||
|---|---|---|---|
| n (%) | n (%) | ||
| Implant diagnosis | Healthy | 20 (54.1%) | 11 (24.4%) |
| Peri-mucositis | 14 (37.8%) | 18 (40%) | |
| Peri-implantitis | 3 (8.1%) | 16 (35.6%) | |
| PI | 0 | 11 (29.7%) | 12 (26.7%) |
| 1 | 20 (54.1%) | 19 (42.2%) | |
| 2 | 2 (5.4%) | 14 (31.1%) | |
| 3 | 4 (10.8%) | 0 (0%) | |
| BOP | BOP (−) | 18 (48.6%) | 10 (22.2%) |
| BOP (+) | 19 (51.4%) | 35 (77.8%) | |
| PD | 0–3 mm | 14 (37.8%) | 10 (22.2%) |
| 4–6 mm | 20 (54.1%) | 26 (57.8%) | |
| >6 mm | 3 (8.1%) | 9 (20%) |
BOP, bleeding on probing; DM, diabetes mellitus; PD, pocket depth; PI, plaque index.
3.2. Microbiological findings
The most common species detected in shallow and deep peri-implant pockets in both groups were F. nucleatum and T. forsythia, respectively. Especially F. nucleatum (100%), C. rectus (95.6%), P. gingivalis (73.9%), T. forsythia (100%), T. denticola (69.5%), E. corrodens (65.2%) and P. nigrescens (65.2%) species were highly isolated in control group in the deep peri-implant pockets while F. nucleatum (94.2%), C. rectus (60%), T. forsythia (71.4%), E. corrodens (62.8%) and P. nigrescens (60%) species were highly isolated in T2DM group in the deep peri-implant pockets (Table 3). However, there were no statistically significant differences in the numbers of all bacterial species in shallow pockets in both groups (P > 0.05). The numbers of T. forsythia, P. gingivalis, and C. rectus species were statistically significantly higher in the control group than the T2DM group in deep pockets (p:0.004, p:0.024, p:0.006) (Table 3).
Table 3.
Percentages of healthy and diseased sites colonized by periodontal pathogens of the groups.
| Shallow pockets |
Deep pockets |
|||||
|---|---|---|---|---|---|---|
| Control (n = 14) |
T2DM (n = 10) |
Control (n = 23) |
T2DM (n = 35) |
|||
| n (%) | n (%) | p | n (%) | n (%) | p | |
| Fusobacteriun nucleatum | 14 (100%) | 10 (100%) | a1.000 | 23 (100%) | 33 (94.2%) | a0.151 |
| Camphylobacter rectus | 9 (64.3%) | 4 (40%) | a0.238 | 22 (95.6%) | 21 (60%) | b0.006* |
| Porphyromonas gingivialis | 3 (21.4%) | 6 (60%) | a0.092 | 17 (73.9%) | 14 (40%) | b0.024* |
| Tannerella forsythia | 10 (71.4%) | 7 (70%) | a1.000 | 23 (100%) | 25 (71.4%) | a0.004* |
| A. actinomycetemcomitans | 1 (7.1%) | 0 (0%) | a1.000 | 7 (30.4%) | 0 (0%) | a0.001* |
| Treponema denticola | 5 (35.7%) | 7 (70%) | b0.214 | 16 (69.5%) | 16 (45.7%) | b0.129 |
| Prevotella intermedia | 0 (0%) | 2 (20%) | a0.163 | 6 (26%) | 3 (8.5%) | a0.135 |
| Peptostreptococcus micros | 7 (50%) | 2 (20%) | a0.210 | 13 (56.5%) | 13 (37.1%) | b0.237 |
| Eikinella corrodens | 11 (78.6%) | 6 (60%) | a0.393 | 15 (65.2%) | 22 (62.8%) | b1.000 |
| Prevotella nigrescens | 11 (78.6%) | 7 (70%) | a0.665 | 15 (65.2%) | 21 (60%) | b0.901 |
C.rectus, P. gingivalis, A. actinomycetemcomitans and T. forsythia were isolated more frequently in deep peri-implant pockets in systemically healthy patients compared to T2DM patients.
Fisher's Exact Test.
Continuity (yates)correction *p < 0.05.
In the control group, the detection rate of P. gingivalis was statistically significantly lower in areas with PD 0–3 mm than in areas with PD 4–6 mm and> 6 mm. The detection rate of T. forsythia and T. denticola in areas with PD 0–3 mm was significantly lower than in areas with PD 4–6 mm. In the T2DM group, the detection rate of E. corrodens was statistically significantly higher in areas with PD > 6 mm than in areas with PD 0–3 mm and PD 4–6 mm (p < 0.05) (Fig. 1A and B).
Fig. 1.
(A–B). The relationship between pocket depth (PD) and peri-implant microflora in the control and T2DM groups.
4. Discussion
This study compared peri-implant health status and the prevalence of target periodontal pathogens in patients with and without T2DM. Based on the findings of our study, we concluded that peri-implant status presented worse outcomes in patients with T2DM. The presence of target pathogens was found similar in both groups. The results indicated that chronic hyperglycemia might be a stronger mediator of inflammation whereas T2DM did not significantly affect the levels of target periodontal pathogens.
T2DM is known as a risk factor for peri-implant disease.17,18 Fiorellini et al. reported that the implant success rate in diabetic individuals who were followed for more than six years was 85.6%.19 In our study, the high incidence of peri-implantitis in the T2DM group was consistent with the results in the literature. The control group was detected to have better implant health, which was compatible with the previous research findings.
Since periodontal and peri-implant diseases are diseases caused by microorganisms, microbiological parameters have an important role in routine diagnosis and follow-ups. A. actinomycetecomitans, T. forsythia, and P. gingivalis are responsible for the development and progression of periodontal and peri-implant diseases. Also many pathogens, such as F. nucleatum, C. rectus, P. intermedia, P. micros, and E. nodatum play role in these diseases.20 Drawing on these findings, we performed microbiological analyses to identify periodontal pathogens commonly detected in peri-implant lesions, and to show the most effective bacteria species whose pathogenic capacity has been demonstrated by previous studies. Sigrun eick et al. evaluated the microbiota between the tooth and the implant, and it was reported that the dominant species in implants were F. nucleatum, C. rectus, T. forsythia, and P. micra, and the lowest prevalence of A. actinomycetemcomitans, P. intermedia, and Eubacterium nodatum were found.21 In our study, especially T. forsythia, F. nucleatum, and C. rectus species were highly isolated in peri-implant pockets in both groups, and A. actinomycetemcomitans, P. intermedia species were detected at low rates in peri-implant pockets in both groups.
T2DM is an environmental factor affecting subgingival flora. There are research in the literature indicating no difference between the subgingival microbial flora of systemically healthy individuals and patients with T2DM. Yuan K et al., in their study on patients with T2DM and systemically healthy controls, compared the presence of specific pathogens like A. actinomycetemcomitans, P. gingivalis, E. corrodens, T. denticola, and Candida albicans on the subgingival plaque through the PCR method. It was reported that except for A. actinomycetemcomitanes, the prevalence of periodontal microorganisms tested was significantly higher in disease sites compared to healthy sites in both groups.22 The subgingival microbiota of diabetics, smokers and diabetic smokers with chronic periodontitis were evaluated in a recent study. The results demonstrated that in patients with chronic periodontitis, the levels and prevalence of critical periodontal pathogens were unaffected by T2DM or smoking, both together and separately.10 In a single microbiological study performed on the implants of T2DM patients, Tatarakis et al. investigated clinical and microbiological profiles of implants at the beginning of treatment and in the first year after dental implant therapy. They found that subgingival pathogenic bacteria content was similar in T2DM patients and healthy controls.23 The current study reported that T2DM did not affect periodontal pathogen differentiation in shallow pockets. C. rectus, P. gingivalis, A. actinomycetemcomitans and T. forsythia were higher in the control group than the T2DM group in deep pockets. The adverse effects of T2DM on immunoinflammatory responses to pathogens in these patients may be critical in the progression of disease severity.
According to microbiological studies, it has been reported that peri-implant deep pockets provide living space for pathogenic bacteria, which is a sign of peri-implantitis.24,25 Therefore, this study also investigated the peri-implant microbiological profile with respect to pocket depth. In a study conducted by Sigrun Eick et al. implants that were functional for ten years were evaluated, and T. forsythia, T. denticola, C. rectus, and E. nodatum were found to be associated with PD in implants and teeth.21 In addition, as a result of the microbiological study in which Sato et al. included the implants classified according to the treatment needs, P. gingivalis and T. forsythia were detected for the first time around implants with pocket depths ≥4 mm.26 In our study, T. forsythia, T. denticola, and P. gingivalis were observed with a higher rate in deep pockets of the control group. Moreover, we observed an increase in deep pockets in the control group, especially in red complex types, compared to shallow pockets. In the T2DM group, E. corrodens was observed with a higher rate in pocket depth >6 mm than in shallower pockets. All in all, differences in tissue destruction rate may alter microbiologic results. Furthermore, it is critical to mention that these differences among the studies may also be caused by microbiological sampling procedures, techniques, glycemic variability, and clinical features.
5. Conclusion
This study revealed that T2DM did not complicate the bacterial flora in peri-implant sulcus more complex in the shallow and deep peri-implant pockets. It was also observed that although T2DM had long-term effects on implant success and in the inflammatory process, it had no significant impact on peri-implant microbial flora.
The strength of this study is to understand the microbial impact of T2DM, and the leading risk factor for peri-implant disease and to provide an insight into the microbiological aspects of peri-implant areas.
The limitations of this study; since other factors which affects biofilm formation and development such as prosthetic variables, implant surface roughness, implant properties were not evaluated, peri-implant microbiota could not be objectively examined. Furthermore, the number of samples analyzed is limited due to the cost and time constraints. That is why, more research is required to obtain more compact results. Even though these bacteria are among the most commonly found in oral infections, information on virulence factors of bacterial pathogens is limited, and further studies are needed. Additional studies can identify microbial or immune factors that might be useful to indicate the pinpoint of peri-implant disruption.
Funding
The authors did not receive support from any organization for the submitted work.
Informed consent
A written consent form was obtained from each participant prior to the initiation of research protocols.
Author contributions
A. Sabancı, A. Eltas Concept/Design, Data analysis/interpretation, Drafting article; A. Sabancı, collected the data; B. Celik, B. Otlu microbiological analyses of the specimens; A. Sabancı wrote the paper; A. Sabancı, A. Eltas critical revision of article.
Declaration of competing interest
There is no conflict of interest for this study.
Acknowledgements
The authors would like to thank the staff in the Department of Medical Microbiology, Turgut Ozal Medical Center for the microbiological data analyses, and the staff in Inonu University Faculty of Dentistry, Periodontology Department for valuable input.
Contributor Information
Arife Sabancı, Email: dtcicekarife@hotmail.com.
Abubekir Eltas, Email: aeltas@yahoo.com.
Betul Celik, Email: duzleme@udel.edu.
Barıs Otlu, Email: baris.otlu@inonu.edu.tr.
References
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