Effects of Diabetes Mellitus on Root Canal Treatments

Research Topic:Effects of Diabetes Mellitus (DM) on Root Canal Treatments (RCT) conducted in the Griffith University Dental Clinics: A Clinical Audit. 

1) Abstract:  Amy 

Introduction: Diabetes Mellitus (DM) is a chronic endocrine disease, that is multifactorial and affects immune function. Various literature has investigated whether DM can affect the treatment outcome of Root Canal Treatment (RCT) however discrepancy in the results of these studies exist. Further investigation is required to enhance the understanding on this topic. The following study aims to investigate the effect that diabetes mellitus has on endodontic treatment outcome by means of a clinical audit.
Methods: A case-control, retrospective study design was conducted through reviewing patient charts, medical history and clinical records at Griffith University Dental Clinic (GUDC). The endodontic treatment outcome (successful or unsuccessful) for 100 diabetic and 100 matched non-diabetic patients were recorded as part of data collection. Data and statistical analysis was conducted using SPSS to investigate for an association between diabetic and non-diabetic patients in healing outcomes post-endodontic treatment.
Results: Data and statistical analysis found similar rates of success for both diabetic and non-diabetic groups. No significant differences were seen between the success rates of the diabetic and non-diabetic groups (p>0.05).
Conclusion: There is no clinically significant difference in the endodontic treatment outcome of diabetic and non-diabetic patients treated at Griffith University Dental Clinic.

2) Background: (Amy)

2a) Introduction and literature review:

Non-surgical root canal treatment (RCT) is a procedure indicated for the treatment of necrotic or irreversibly inflamed dental pulp caused from either trauma or bacterial infection of the dental pulp (Arya et al., 2017). Apical periodontitis is a condition that presents as a chronic or acute inflammatory lesion present around the root apex of a tooth and is caused by polymicrobial irritants originating from the infected root canal system (Segura-Egea et al., 2012). The primary objectives of RCT involve preventing and treating peri-radicular lesions through facilitating the healing of the periapical tissues (Fouad & Burleson, 2003). This is attained through the removal of dental pulp, disinfection of the root canal system and sealing of the root canal system via obturation (Fouad & Burleson, 2003).

Evaluation of root canal treatment outcome is conducted through monitoring the tooth for cessation of signs and symptoms of both pulpal and periapical pathosis (Fouad & Burleson, 2003). For accuracy of determining endodontic treatment outcome, the RCT should be assessed for a minimum of two years post-operatively to monitor the resolution of pre-existing periapical lesions and to ensure no development of new periapical lesions (Fouad & Burleson, 2003). Root canal treated teeth that upon post-operative assessment present signs and symptoms of endodontic treatment failure will be required to either undergo endodontic re-treatment, extraction or periapical surgery (Olcay, Ataoglu, & Belli, 2018). Endodontic treatment outcome may depend on various other factors including the periodontal disease status of the tooth, restorability of the tooth, presence of decay and the occurrence of tooth fracture (Olcay et al., 2018) Furthermore, healing and resolution of periapical lesions subsequent to RCT can be dependent on systemic factors including that of the individual’s immune defences (Holland, Gomes Filho, Cintra, Queiroz, & Estrela, 2017). Numerous studies have investigated various systemic diseases suspected of affecting RCT outcome. Included in these systemic diseases is that of Diabetes Mellitus.

In Australia, currently over 1.2 million adults (6% of the population), suffer from Diabetes Mellitus (ABS, 2018). Diabetes Mellitus (DM) is a chronic endocrine disease, that is multifactorial and affects immune function (Arya et al., 2017; Mohiuddin, 2018). DM has a high morbidity rate among affected individuals, with potential for mortality as well (Fouad & Burleson, 2003). The main feature of DM is hyperglycemia, which is due to the impaired chemotaxis of neutrophils, and the affected metabolism of carbohydrates, proteins and lipids (Arya et al., 2017; Leandro et al., 2003). Overall, hyperglycemia causes a state of inflammation, which impairs the cellular proliferations of the host (Arya et al., 2017). Type I diabetics experience complete loss of insulin secretion, due to autoimmune and cellular-mediated destruction of beta cells in the pancreas (Segura-Egea et al., 2012). Type II diabetes results from resistance to insulin, in combination with failure producing an adequate amount of insulin for compensating this resistance (Segura-Egea et al., 2012). Poorly controlled diabetes results in delayed healing, tissue breakdown and reduced capacity of tissues to repair (Leandro et al., 2003; Rudranaik, Nayak & Babshet, 2016). Oral complications such as periodontal disease and apical periodontitis, are associated with DM (Arya et al., 2017), with a disproportionately large percentage of severe periodontal and pulpal infections reported in diabetics (Segura-Egea et al., 2012). DM has been shown to cause varying alterations in periapical tissues and pulp, through augmented bone resorption and impaired collateral circulation (Segura-Egea et al., 2012). More specifically, the periapical tissues in diabetic patients, is associated with a heightened risk for ill-response to odontogenic pathogens; meaning, residual infection is not eliminated effectively by the host after root canal treatment (Leandro et al., 2003).

DM is known to impair the body’s healing and immune response, thereby making the body more susceptible to systemic infection (Arya et al., 2017). Healing is affected by DM through advanced breakdown of tissues and via a decrease in the capacity of the tissues ability to repair (Arya et al., 2017; Segura-Egea et al., 2012). Numerous studies have found an association between the presence of DM and the outcome of endodontic treatment. One of these studies reported that DM may increase the individual’s susceptibility to severe endodontic infections (Fouad & Burleson, 2003). This may be due to the presence of different endodontic microbial flora in diabetic patients when compared to non-diabetic patients (Fouad & Burleson, 2003). This difference in microbial flora may increase the susceptibility of patients with DM to peri-radicular disease (Fouad & Burleson, 2003). This is supported by a study by Fouad et al., that reported the presence of an increased pathogenic microbial profile within the necrotic dental pulps of teeth in patients with DM when compared with non-diabetic patients (2002). This difference in pathogenic microbial profile may account for the greater incidence of painful apical periodontitis and flare-ups during endodontic treatment amongst diabetic patient’s when compared to non-diabetic patients (Fouad et al., 2002). Furthermore, a study by Bender, Seltzer and Freedland (1963) explored the effects of controlled and uncontrolled diabetes on endodontic treatment, reporting that endodontic lesions will only heal if diabetes is controlled and that endodontic lesions may even increase in size despite endodontic treatment if diabetes is not controlled (Fouad & Burleson, 2003).

Gaps in current research

Currently, the prevalence of apical periodontitis and periapical radiolucencies in DM patients has been widely explored, however the association of Diabetes Mellitus with endodontic success remain as a gap in knowledge (Arya et al., 2017; Moazami, 2011). Only a few studies have explored the effect of increased inflammatory response in diabetes, on the ability of apical tissues to overcome infections (Moazami, 2011; Olcay et al., 2018). The current animal and clinical studies available, suggest a compromised peri-radicular immune response, which may result in increased root canal treatment failure (Lopez at al., 2011); however, very limited long-term prospective data on humans is available (Olcay et al., 2018).

In comparison to the association between diabetes and periodontitis, the association between DM and pulpally-originating dental infections has been scarcely investigated (Lopez et al., 2011). It has been established that apical periodontitis shares similar gram-negative microbiota as periodontitis, which in turn increases the levels of systemic inflammatory mediators (Holland et al., 2017). However, the effect of these inflammatory reactions on the success of root canal treatment, have not been explored (Holland et al., 2017). It is currently hypothesised that liposaccharides in gram-negative bacteria cause an inflammatory response in the innate immune system (Moazami, 2011). When this innate immune system is weakened, there may be a heightened risk for compromised peri-radicular immune response (Marending, Peters & Zehnder, 2005).

Although it has been established that controlling diabetes is beneficial for the outcome of endodontic treatment, methods for improving NSRCT in DM patients has not been explored (Olcay et al., 2018). In addition, the overall immune system of each individual with diabetes is variant, and will contribute to their likelihood for positive response to root canal therapy (Marending, Peters & Zehnder, 2005; Moazami, 2011; Oginni, 2010).

Limitations of current research

         Amongst the current literature available exploring the effects of DM on endodontic treatment outcome, a variety of limitations were identified.

The study by Wang et al., focusing on investigating the impact of DM on extraction of non-surgical root canal treated teeth entailed the limitation of not being a case-controlled study (2011). The results of this study found that DM was a significant risk factor for tooth extraction after non-surgical RCT after univariate analyses (Wang et al., 2011). However, additional clinical studies focusing on case-control need to be carried out in order to further support the hypothesis that DM results in a significantly increased risk of tooth extraction subsequent to non-surgical RCT compared to patients without DM (Wang et al., 2011).

Furthermore, an alternate study investigating the prevalence of peri-radicular radiolucencies in root canal treated teeth in patients with DM presented with multiple limitations (Britto, Katz, Guelmann, & Heft, 2003). Although this study focuses on investigating the effect of DM on endodontic treatment outcome, one limitation involves the inability to completely exclude clinical cases where endodontic treatment failure was due to poor treatment rather than the effects of DM (Britto et al., 2003). A second limitation of this study was instigated through the assessment of radiographs to determine endodontic treatment outcome. Britto et al., reported that it is impossible to accurately ascertain through radiographic assessment alone whether peri-radicular radiolucency’s seen on x-rays subsequent to RCT are a residual healing lesion or an endodontic treatment failure (2003).

In addition, a limitation was identified in the paper by Segura-Egea et al., which examines DM, periapical inflammation and endodontic treatment outcome (2012). This research follows the assumption that the link between periodontitis and DM is similar to the link between apical periodontitis and DM (Segura-Egea et al., 2012). It is well known in research that diabetes has a significant effect on periodontal disease. However, limited studies have been conducted to explore its effect on endodontic treatment outcome.

A significant limitation was highlighted in the 2003 study by Fouad and Burleson that focused on investigating the effect of DM on endodontic treatment outcome via identifying diabetic and non-diabetic patients who received RCT and assessing the data through an electronic record system. A limitation of this study was the limited number of cases that provided follow-up data for a minimum of two years subsequent to RCT (Fouad & Burleson, 2003). Out of 5494 cases of RCT only 540 of these had adequate follow-up data (Fouad & Burleson, 2003).

In conclusion, an association between Diabetes Mellitus and endodontic treatment outcome for non-surgical RCT has been investigated in recent research. These studies are suggestive that DM has a negative association with NSRCT outcome, however a consensus regarding this correlation has not been established in current research. This is mostly attributed to the limitations in current research on this topic, including limited follow-up data over a short period of time, lack of case-control studies, and minimal human studies. A significant limitation in the current human studies has been small sample sizes, thus presenting difficulty extrapolating the data found. Further exploration is required to determine the effect of increased inflammatory response in DM, on the ability of apical tissues to overcome infections.

2b) Aims and Objectives:

–          Aims: The aim of the study is to investigate the effect that diabetes mellitus has on endodontic treatment outcome. To determine if a clinically significant difference exists between the failure rates of endodontic treatment in diabetic and non-diabetic patients. To determine the distribution of anterior/posterior teeth and hand file/rotary RCT amongst the successful and unsuccessful RCT from our sample population.

–          Objectives:

o   Randomised sampling will be used to select a sample population of diabetic and non-diabetic patients from the patient management system ‘Titanium’ used at Griffith University Gold Coast Dental Clinic.

o   Data on endodontic treatment outcome will be collected from the diabetic patient sample

o   Data on endodontic treatment outcome will be collected from the non-diabetic patient sample (control group)

o   The data collected will be synthesised to determine the effect that the medical condition diabetes mellitus has on endodontic treatment outcome.

3) Materials and Methods: (Rochella)

A case-control, retrospective study design was conducted through reviewing patient charts, medical history and clinical records at the School of Dentistry and Oral Health Clinic, at Griffith University. This study has been approved by Griffith University Ethics Committee (HREC GU Ref No: 2019/119). 100 diabetic patients (study group) were matched with 100 non-diabetic controls, based on age, gender, tooth number, and time of endodontic treatment. These matched patient factors, were chosen to control non-diabetes related treatment variables. This comparative study design, is in-line with the study aims of assessing the difference in endodontic treatment success in diabetic versus non-diabetic patients. The selection criteria for patients to be included in the study consisted of those with: patient consent signed, non-surgical RCT started in the undergraduate dental clinic at Griffith University (with student dentists), patient completed their root canal treatment (obturation finished), and root canal completed over 6 months ago. For the diabetic patient selection, patients with gestational diabetes or family history of diabetes were excluded from the study. A successful root canal treatment was defined as one where: the patient did not have any continuing pain, the tooth did not receive nor require further endodontic retreatment and was not extracted due to endodontic causes.

(a) Patient data: 

To retrieve patient data, the dental software system ‘Titanium’ at Griffith University was used. Firstly, appropriate diabetic patients were found, using the following searched terms on Titanium: “diabetes mellitus”, “DM” , “diabetes”, “type I DM” and “type II DM”. To ensure root canal treatments were completed, the ADA item code 419 (extirpation), 415 or 416 (chemo-mechanical preparation) , 417 or 418 (root canal obturation) were searched for each tooth. In order to reach the largest sample size possible, all patient data entries found on Titanium that fit the inclusion criteria, were included in the data collection. The initial search returned with 202 diabetic patients. Once this data was retrieved, patients who did not give consent for research and duplicate entries were deleted. Additionally, specialty medical tabs and patient medical history forms were read for each patient, to ensure they had diabetes mellitus. Once these diabetes participants were finalised, a matched non-diabetic patient was found for each on Titanium, and non-consented and duplicated patients were again deleted. The total sample size achieved was 200 participants: 100 diabetic, and 100 non-diabetic.

(b) Statistical analysis: 

Each root canal treated tooth was categorised as: successful or unsuccessful. The RCT was also sub-categorised into anterior or posterior cases, and hand-file or rotary. All incomplete RCT teeth were deleted (extirpation or CMP only). The retreatment codes that were assessed for each of the unsuccessful RCT’s included: extraction (311, 314, 322, 323 and 324), re-extirpation (419, 419R), re-treatment (451, 451R, 452, 452R). Additionally, all patient files following the RCT were read, to include any required re-treatment that had not yet been completed (and thus not entered as an item code). All RCT treatment outcomes were coded, ready for SPSS analysis. Data cleaning and data analysis was done. The Chi-squared test and Wilcoxon test were carried out for statistical analysis.

The statistical analysis was compared to current literature. An electronic search was conducted on PubMed, ClinicalKey, Google Scholar, ScienceDirect and ProQuest with the key terms of “Diabetes Mellitus”, “Endodontic treatment outcomes”, “Apical Periodontitis” and “Non-surgical Root Canal Treatment”. The search was limited to English articles written in the past 16 years. In addition to the electronic search, references of journal articles were manually searched to discover other relevant journal articles.

3) Results: Maddy and Eileen

Table 1. Descriptive statistics table.

Table 2. Chi square test.

Table 2 shows the results of chi square test. As the p > 0.05 (p = 0.579), the null hypothesis needs to be accepted that there is no significant differences in RCT outcome between diabetic and non-diabetic patients.

Table 3. Wilcoxon test results.

Table 3 shows the results of Wilcoxon test, which was used to compare RCT outcomes of matched diabetic and non-diabetic pairs. Again, as the p > 0.05 (p = 0.593), it can be concluded that there is no significant differences between the two groups.

Table 4. Comparison of endodontic outcome between diabetic and non-diabetic patients.

Table 4 shows that the number of successful or unsuccessful endodontic outcomes are very similar for both diabetic and non-diabetic groups, the results of which can also be supported by both Chi-square and Wilcoxon tests.

4) Discussion: Rochella + Amy (Sunday) 

1. Similarity to current research: there was discrepancy. Difference: majority of studies showed some link, even if small/weak (LIT REVIEW STUFF)….

Our study found that there was no clinically significant difference in the treatment outcome of endodontic treatment in patients with diabetes mellitus when compared against non-diabetic patients. A clear discrepancy exists in the results of current literature concerning the effect of DM on endodontic treatment outcome. The majority of current research suggests that DM has a clinically significant effect on endodontic treatment outcome. The contradicting results in this research field may be linked to the variation and difficulty in isolating variables amongst the different research methods.

Current research that contradicts the results of our study have demonstrated that the prognosis of root canal treated teeth in patients with DM, is poorer than in non-diabetic patients (Chandra, 2009; Segura-Egeal et al., 2012). This has been attributed to the fact that patients with DM patients have delayed peri-apical repair (Moazami, 2011). Overall prevalence of periapical lesions was shown to be highest in Type I DM patients (Khalighinejad et al., 2016). More specifically, females experiencing diabetes for long durations, had more root canal treated teeth with periapical lesions, than those with short duration diabetes and non-DM patients (Khalighinejad et al., 2016). Wang et al., (2017) investigated the long-term prognosis of non-surgically root canal treated teeth (NSCRT) in patients with DM. Results revealed that DM is an important risk factor to consider, for extraction of teeth after NSCRT (Wang et al., 2017). In particular, men with type 2 diabetes who had NSCRT, were significantly more likely to obtain non-healing residual lesions or persistent chronic apical periodontitis, that resulted in extraction (Wang et al., 2017). In cases where a preoperative periapical radiolucency was present, the success of NSRCT in diabetic patients was considerably decreased (Wang et al., 2017). In a 10 year, retrospective study by Minideola et al. (2011), it was found that the success rate of NSRCT was 89.7% for DM patients, compared to 96.1% for patients without DM; thus, endodontically treated teeth were not retained as consistently in diabetes patients. This study was only performed on an American-Indian population, and thus its extrapolation to other populations, may not be accurate (Minideola et al., 2011). The results of these research reports suggest that DM affects the healing outcome of endodontic treatment. Our study contradicts these findings.

Alternatively, the previous study by Arya et al., supports the results of our study by concluding that root canal treatment is effective even when diabetes is poorly controlled (2017). In addition, Segura-Egea et al., indicates that if DM is therapeutically controlled, periapical lesions associated with RCT heal at the same rate as non-diabetic patients (2012), thus creating some disparity in current research understanding (Fouad & Burleson, 2003).

Our research results support the findings in this field of study that there is a discrepancy in results/conclusion on whether diabetes Mellitus had a clinically significant effect on the treatment outcome of endodontic treatment. This suggests that further studies need to be undertaken with a focus on controlling specific variables.

2.               Importance of research + stating clinical implications of findings

The results of our study have contributed towards this field of study by adding to the pool of research available on this topic. Our research provided results established from a case-control study design. This allowed a direct comparison between failure rates of endodontic treatment from both our non-diabetic control group and diabetic patient sample.

The clinical implications of establishing whether DM has an affect on endodontic treatment outcome would include allowing patients who have DM to be informed of their greater risk of RCT failure and in addition guiding the direction of future research to be carried out on this topic.

Tooth loss due to dental extraction following RCT is often attributed to a variety of non-edontontic causes such as recurrent caries, periodontal disease or root fractures (Chiara, Stefano, Lucio & Carlo, 2015). A 20 year prospective study found that more RCT teeth were extracted owing to non-endodontic related causes than that of endodontic causes (Cite- A 20‐year historical prospective cohort study of root canal treatments. A Multilevel analysis). Previous studies have considered all RCT teeth that were extracted as endodontic failures (Wu et al. UNKNOWN YEAR). Our study has contributed to the research field by including in our study only those teeth extracted due to endodontic failure. RCT teeth extracted due to recurrent caries, periodontal disease or root fracture were not recorded in our study as RCT failure.

Through the process of designing, executing and synthesizing the results of our study several factors have been identified that may play an important role in the results and outcomes of the study.  During data collection RCT was deemed successful if there was no record of continuing pain, extraction or retreatment. However some patients from our sample population may not have had regular review appointments or indeed any follow-up appointment after their root canal treatment was completed at GUDC. This highlights the importance of regular review appointments to establish with certainty whether a root canal treated tooth was successful in the long-term. Furthermore, incomplete medical history records regarding the level of diabetic control of the patient rendered our study unable to investigate what affect the degree of diabetic control may have on endodontic treatment outcome. These factors may contribute to the presence of discrepancies between the results of our study and the results for the majority of current research available on this topic.

3.                Control of diabetes – and if it’s controlled, its effect is limited (new research):

Current literature indicates that diabetes patients with effective glycaemic control (fasting blood sugars less than 140 mg/dL), have a very low rate of systemic complications (Lorenzi et al., 2008; Mourão, Garcia, Passos, Lorena, & Canabarro, 2016; Raghavan & Matlock, 2017; Ross, Tildesley & Ashkenas, 2011). This finding may provide a possible explanation for the lack of association between DM and endodontic healing outcome in our study. As the patients in our study were not evaluated for how well-controlled their diabetes was, they may have been undertaking regular medication treatment, diet control, and general practitioner visits for monitoring of glycaemic control. A study by Bender, Seltzer and Freedland (1963) explored the effects of controlled and uncontrolled diabetes on endodontic treatment, reporting that endodontic lesions will only heal if diabetes is controlled (Fouad & Burleson, 2003). Similarly, a more recent study by Segura-Egea et al., (2012) claimed that if DM is therapeutically controlled, periapical lesions heal at the same rate as non-diabetics.

On the other hand, current literature also indicates that therapeutic treatment for diabetes is imperfect, and that ideal management of DM still remains ‘elusive’, despite numerous effective DM medications (Raghavan & Matlock, 2017). Although better glycemic control significantly reduces health complications, intensive glycemic control has also been consistently linked with increased risk of hypoglycemia (Raghavan & Matlock, 2017). This complex nature of glycaemic control, means that the patient compliance and knowledge, physician input and treatment factors significantly influence the effectiveness of DM management for each patient (Ross et al., 2011).

Several studies on DM and periodontitis, have shown that both type 1 and type 2 diabetes negatively affects periodontal status, even when well controlled (Mourão et al, 2016; Wang et al., 2017; Sunandhakumari et al., 2018). A case-control study by Mourão et al., (2016) compared well-controlled DM2 patients, with fasting blood glucose levels less than 130mg/dL, to non-diabetic patients. This study found that these DM2 patients still present with a strong association to worsened chronic periodontitis, that negatively affected their quality of life (Mourão et al, 2016). Further similar studies are required, to evaluate the effect of well-controlled diabetes on endodontic treatment outcomes.

4.                Follow-up: link between follow-up of patients and endodontic treatment success.

After RCT is completed, long term patient follow-up is pertinent to establishing treatment success (Lee, Cheung & Wong, 2012). Research indicates that, to determine treatment outcome accurately, annual or semi-annual follow-up examinations should be conducted for at least two to 4 years (Fouad et al., 2003). This allows the examination of post-RCT signs and symptoms, the monitoring of pre-existing periapical lesions (if were present), and the presence of any new periapical lesions (Fouad et al., 2003). As there were no consistent follow-up procedures in place for our study participants, the lack of correlation between DM and endodontic treatment success, may have been attributed to the fact that there were minimal (or no) follow-up notes following the root canal completions. A study by Prati et al., (2018) found that RCT teeth with residual periapical radiolucencies caused patients no clinical symptoms, and thus can be considered functional teeth. In our study, patients may have not reported back to the Griffith University clinic if they were in no pain; thus making it difficult to evaluate if the periapical lesion resolved or if it healed at a slower rate than non-diabetic patients. If a periapical lesion has not resolved in 4-years, the RCT is categorised as unfavourable (Lee, Cheung & Wong, 2012). As all the root canal treatments were in our study were completed less than 5 years ago, it was difficult to establish this long-term prognosis.

Despite this important in long-term follow-up, several studies have also shown that the endodontic outcome in the first 6-9 months, is considered as the most important time indicator in the final outcome of root canal treatment over the next 10 years (Lee, Cheung & Wong, 2012; Fouad et al., 2003). For those patients found to have uncertain healing at the 6-9 month mark, the radiographic quality of the RCT was the most important factor in determining long-term prognosis (Lee, Cheung & Wong, 2012). This study similarly showed that for periapical healing and tooth survival after RCT, a non-linear pattern was evident; there was a steep decrease in tooth survival until approximately 40 months after RCT, which subsequently slowed down over a longer duration of observation (Lee, Cheung & Wong, 2012).

5) Conclusion: (Rochella)

In conclusion, there was no clinically significant difference found in the endodontic treatment outcome between diabetic and non-diabetic patients. Thus, suggesting that diabetic mellitus does not influence endodontic treatment success. The key limitations of the study included: a small sample size, loss of patient follow-up, and limited information on how well managed the diabetes was for each patient. As the patients were not tracked beyond the Griffith University clinic, it is unknown whether further treatment such as endodontic re-treatment or extraction was completed externally, which would in-turn affect the endodontic treatment success. Further research is required to evaluate the long-term prognosis of root canal treatment, after a 5-year period. Similarly, the current body of literature on RCT success in diabetic patients would benefit from a cohort study, where the patients symptoms and any additional treatment required can be consistently monitored. This type of study, would assist in overcoming current limitations, as regular radiographic and intra-oral examinations can be conducted, to assess changes to diabetic patients root canal treatment outcomes over time.

References:

New links (yet to be referenced):

• https://search-proquest-com.libraryproxy.griffith.edu.au/docview/70172893?pq-origsite=summon 
• https://www-ncbi-nlm-nih-gov.libraryproxy.griffith.edu.au/pmc/articles/PMC5713086/?tool=pmcentrez&report=abstract 
• https://oce-ovid-com.libraryproxy.griffith.edu.au/article/01337496-201704000-00002/HTML 
• https://www-tandfonline-com.libraryproxy.griffith.edu.au/doi/full/10.1185/03007995.2011.621416 
• https://doaj.org/article/19994493260a4c62bae7374034710ad3
• https://doaj.org/article/8e684e8c962e4fac8e07de839098fd52 
• https://search-proquest-com.libraryproxy.griffith.edu.au/docview/1691226932?pq-origsite=summon 
• https://search-proquest-com.libraryproxy.griffith.edu.au/docview/1178665841?pq-origsite=summon