The Two-Way Relationship between Diabetes Mellitus and Periodontal Disease: A New Insight

*Leela Subhashini C. Alluri, Kristen Puckett, Chethan Sampath, David A. Mott, Kaitlyn Logan, Jazmyne Walker, Gerald Davis, Cherae Farmer-Dixon and Pandu R. Gangula*

## **Abstract**

Periodontal Disease and Diabetes Mellitus are two chronic systemic diseases that are intimately connected. A bidirectional relationship exists between the two; to study this unique relationship, they must be studied separately as independent malfunctions and in tandem. Patients that experience these conditions exhibit similar innate immune responses, which lead to aggravated dysfunction of specific body systems. In patients where both conditions exist simultaneously, Diabetes and Periodontal Disease can act in a synchronistic manner, worsening symptoms. In this chapter, the epidemiology of the diabetes mellitus and periodontal disease, presence of biomarkers have been reviewed, and the metabolic syndrome, clinical relevance and treatment modalities, complications of diabetes mellitus, and guidelines for the general dentists, primary care physician, periodontist have been discussed.

**Keywords:** diabetes mellitus, biomarkers, periodontitis, periodontal disease, type one diabetes mellitus, type two diabetes mellitus

## **1. Introduction**

The epidemiologic relationship between Diabetes Mellitus Type I and II (TIDM and TIIDM, respectively) and Periodontitis is well documented and multifaceted. Diabetes is a widespread disease estimated to affect 415 million adults, 20–79 years of age, with many remaining undiagnosed with approximately 193 million. Further, half a million children aged 14 and under live with Type 1 Diabetes Mellitus (TIDM). Additionally, 318 million adults are believed to have some form of glucose intolerance, placing them into the "pre-diabetic" category and increasing their risk of eventually developing the disease. TIDM and TIIDM caused 5 million deaths in 2015, accumulating a financial burden of between USD 673 billion and USD 1197 billion in healthcare spending. If this rise is not slowed, it is estimated that by the year 2040, there will be 642 million people living with diabetes [1]. There exists a large pool of evidence for the association between periodontitis and TIIDM, and the bidirectional nature of

the relationship is well established [2]. In turn, people with TIIDM exhibit decreased glycemic control. Further studies must examine the association between periodontitis and TIDM. In TIDM, an immune cascade results in the beta cells of the pancreas being attacked, decreasing insulin secretion. TIDM only accounts for approximately 10% of all diabetic patients [3]. In a small percentage of these patients, there is no β cell destruction, making the pathogenesis idiopathic [4]. TIIDM is a systemic metabolic disease in which there is insulin resistance or defective in insulin secretion or a combination of both. The number of people living with Diabetes Mellitus has nearly quadrupled in the last four decades [5].

Periodontal disease (PD) affects 47.2% of adults aged 30 years and older, and the incidence of developing some form of periodontal disease increases with age, with 70.1% of adults aged 65 and older having periodontal disease [6]. Periodontal disease affects men more than women, with the incidence rates being 56.4% and 38.4%, respectively. Socioeconomic factors also play a role, with 65.4% of individuals affected living below the poverty line and 66.9% of those without a high school education [6]. In addition, smoking plays a factor, with 64.2% of current smokers developing periodontal disease [6]. The pathogenesis of periodontal disease is well studied and understood. The interaction between periodontal pathogenic microorganisms and the host immune system leads to the secretion of proinflammatory cytokines, which leads to the destruction of the periodontium compromising the affected tooth prognosis [7].

## **2. Detection of the presence of type 2 diabetes mellitus and periodontitis using biological markers**

Periodontitis has been intricately linked to TIDM and TIIDM in various documented studies, showing that uncontrolled diabetes can initiate and promote the progression of periodontal disease. In return, periodontitis can decrease in insulin secretion leading to hyperglycemic state and the risk for further complications [5]. Therefore, early detection of both these diseases is of the utmost importance. Clinically, diagnosing periodontitis via clinical attachment level, periodontal probing depth, bleeding on probing, and radiographic evidence of bone loss are implemented and true methods; however, early detection using biological markers such as salivary proteins can be beneficial to earlier management of periodontitis. Levels of inflammatory chemokines such as interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α) increase in the case of PD; thus, these are used in studies as biological markers along with IL-1β, interleukin-6 (IL-6), and several macrophage molecules such as macrophage inflammatory protein (MIP)-1α and matrix metalloproteinase-8 (MMP-8) [8]. The primary functions of these cytokines in the body are an increased immune response and systemic inflammation, which further causes decrease in insulin secretion or insulin resistance in diabetic patients [8]. In addition, lipopolysaccharide (LPS) from the surface membrane of Gram-negative bacteria in the oral cavity can trigger the production of proinflammatory cytokines. Thus, increasing the number of pathogenic Gram-negative bacteria in the oral cavity can further exacerbate local and systemic inflammation.

One advantage of using biomolecules for detecting periodontitis in diabetic patients is the non-invasive nature of detection and earlier intervention. Salivary concentrations of IL-1β, IL-6, and macrophage inflammatory protein (MIP)-1α can be easily sampled from gingival crevicular fluid, and quantitative analysis is performed

### *The Two-Way Relationship between Diabetes Mellitus and Periodontal Disease: A New Insight DOI: http://dx.doi.org/10.5772/intechopen.108948*

via fluorescent immunoassay. A study published by Miller et al. in 2020 demonstrated that several biomarkers could yield greater specificity for the detection of periodontitis [8]. This provides promising results for early detection and diagnosis. The study also concluded that MMP-8 and IL-1β present in the gingival crevicular fluid (GCF) could discriminate periodontitis in patients with TIIDM [8]. MMP-8 has been studied extensively as a biomarker for periodontal disease, and meta-analysis studies have shown it to be both practical and a promising biomolecule for more accurate early diagnosis in the near future [9].

Another useful biological marker that can be utilized for the detection of both periodontal disease and TIIDM is the hormone somatostatin. The autoregulation of somatostatin receptor 2 in periodontal cells has been studied under several conditions, including inflammatory and specific obesity-related conditions. Immunocytochemistry, a study method in which antibodies are used as markers to test for antigens, is utilized in these studies, such as these and polymerase chain reactions to replicate and better view DNA fragments. There is significant upregulation in somatostatin receptor 2 in periodontal ligament cells, including osteoblasts, osteoclasts, odontoblasts, cementoblasts, fibroblasts, and undifferentiated mesenchymal cells when exposed to proinflammatory molecules [8]. In addition, Leptin and visfatin are adipokines that have been studied, and both exist at heightened levels in obese patients [8]. These adipokines are marked and studied in patients with periodontitis and can be quantitatively measured in the gingival crevicular fluid [10]. In the presence of periodontal disease, leptin and visfatin exist at heightened levels, suggesting an increase in local and systemic production.

## **2.1 Interleukin-1 biomarker**

IL-1β is a key mediator of the host inflammatory response, and it increases damage at the cellular and tissue level during times of chronic disease, which is of particular interest in patients with existing periodontal disease. IL-1β is the most studied IL-1 family, and no signal sequence is required for IL-1β secretion; instead, it employs several non-conventional pathways rather than conventional protein secretion [11]. This is favorable for study and why IL-1β is such an effective biomarker for periodontitis analysis. The IL-1 family of cytokines contributes to leukocyte migration and relocation, stimulating osteoblasts and resulting in bone resorption, which is vital for longitudinal periodontitis study. A study conducted by Kornman et al. found that non-smoking, healthy patients with altered IL-1β alleles indicative of a positive genotype showed a risk of developing chronic periodontitis up to seven times compared to the baseline [12]. This cornerstone study opened other studies focusing on the IL-1 family and utilizing cytokines as biological markers for periodontal disease and other proinflammatory diseases such as TIIDM and metabolic disorders.

Interleukin-1 genotypes were explored more thoroughly in a study by Brodzikowska et al., in which the presence of two specific polymorphisms of IL-1 was observed in vivo to determine whether severe periodontitis has a genetic factor [13]. IL-1β is released into the oral environment and displays agonistic action upon receptor binding [13]. IL-1α and IL-1β are located on the "q" arm of chromosome 2 – the human chromosome that provides instructions for making proteins. Differences in the amount of IL-1 secretion in response to microbial infection may contribute to differences in risk for periodontitis and the severity of the disease [13]. This distinction is in allele 2 on chromosome 2, the substitution of nucleotide thymine for cytosine [13]. Like the study cited above, this study also concludes that in individuals with this allele substitution, periodontitis is

seven times more likely to develop [13]. Without simultaneous substitution of alleles, patients instead developed moderate periodontitis compared to severe when both alleles are present, demonstrating that genetic factors play a role in not only the development of the disease but the severity as well [13].

### **2.2 C-reactive protein (CRP)**

C-reactive protein (CRP) is a biological marker that is highly sensitive and nonspecific, making it an ideal biomarker. It is produced in the liver in response to systemic and local injury or trauma. Certain conditions have been shown to increase levels of CRP, including but not limited to pregnancy, smoking, and obesity [14]. CRP also exists at heightened levels in the body after the production of interleukins, such as IL-1α and IL-1β, as mentioned previously in this chapter. CRP is considered a risk factor for developing TIIDM and cardiovascular disease [14]. CRP has also been studied regarding periodontitis, though sparingly. In one study, Esteves-Lima et al. showed that a heightened level of CRP contributes to higher rates of periodontitis, and this further demonstrates the systemic impact that periodontitis has on the body [14].

Interestingly, the presence of *Porphyromonas gingivalis,* a Gram-negative pathogenic bacterium, increases CRP levels in 20% of patients [14]. Whether the levels of CRP can be quantified and extrapolated to the severity of the periodontal disease is slightly debated. One study by Torrungruang et al. shows promising results that increased levels of CRP are directly correlated to the severity of periodontal disease; for every 1 mm increase in periodontal probing depth or clinical attachment loss, the odds of having sST2, a serum cardiac biomarker like CRP, in increased by 70% and 30%, respectively [15]. Biomarkers help in detection, earlier intervention, and managing periodontal disease and diabetes mellitus.

## **3. The bidirectional relationship between type 2 diabetes mellitus, periodontal disease, and obesity: a metabolic syndrome**

### **3.1 Periodontal disease and obesity**

Periodontal disease is defined as chronic, progressive destruction of the periodontium. Obesity is a chronic metabolic disease, which increases the risk of developing various other medical conditions, such as atherosclerosis, hypertension, TIIDM, and cardiovascular disease. In addition, obesity is a risk factor for periodontitis [16]. Statistically significant changes in histology of periodontium have been observed in cases of hereditary obesity [14]. The link between obesity and periodontal disease has been studied as well, with alveolar bone resorption rate being higher in obese rats as compared to non-obese animals [14]. Excess body fat accumulation causes metabolic syndromes and diseases, the most notable being insulin resistance, high triglycerides, low levels of HDL (High-Density Lipoprotein), nonalcoholic fatty liver disease (NAFLD), β cell dysfunction in the pancreas, and TIIDM. Research has shown that periodontitis is correlated with insulin resistance and increased systemic inflammation. Periodontitis, obesity, and TIIDM all have similar pathogenic pathways. Body fat distribution has been demonstrated to play a role in the development of TIIDM and periodontitis. Visceral adipose tissue is metabolically more active than subcutaneous adipose tissue, in addition to secreting higher levels of adipocytokines than subcutaneous adipose tissue [17]. Because adipose tissue secretes proinflammatory cytokines

## *The Two-Way Relationship between Diabetes Mellitus and Periodontal Disease: A New Insight DOI: http://dx.doi.org/10.5772/intechopen.108948*

such as adipocytokines, there is a higher chance of insulin resistance developing, which further causes infiltration of proinflammatory macrophages and an increase in plasma free fatty acids (FFAs) [18]. Huang et al. demonstrated that periodontal pathogen-derived virulence factors such as lipopolysaccharide (LPS) and palmitate (major saturated fatty acid) upregulated periodontal expression of free fatty acid receptors (GPR40 and CD36) in obese and TIIDM patients [17]. Systematic reviews strongly suggest a physiologic association between periodontitis, obesity, and type 2 diabetes mellitus. In addition, there is an association between obesity and periodontal disease regarding health behaviors such as inactivity. Obesity can contribute to a chronic systemic inflammatory state, producing malignant microflora in the oral cavity that promotes inflammatory pathways [18]. Studies have also shown that increased gingival index and periodontal pocket depths are associated with increased triglyceride levels and low HDL [19].

## **3.2 Periodontal disease and diabetes mellitus**

Diabetes is a multifaceted chronic, systemic disease involving decreased insulin secretion, peripheral tissues resistant to insulin, or a combination of both. The effects of periodontal disease on glycemic control demonstrate that diabetes mellitus and periodontal disease have a bidirectional relationship [20] (**Figure 1**).

Individuals with existing diabetes increase the risk of developing periodontal diseases, and patients with comorbidities such as diabetes and periodontal diseases develop poor glycemic control and rapid progression of the periodontal disease. To understand the effects of periodontal disease, the advanced glycated end products (AGE)-receptors of AGE (RAGE) pathway must be explained [4]. The AGE-RAGE signaling pathway is a cascade feed-forward loop, AGE interacts with RAGE present on the immune, endothelial, and epithelial cells, this phenomenon results in increased

### **Figure 1.**

*The bidirectional and pathophysiological mechanisms involved in periodontal and TIIDM. The figure is created with BioRender©.*

oxidative stress, increased RAGE expression (due to the forward-feedback loop), and pro-inflammatory cytokines lead to cell and tissue damage.

There exists a bidirectional relationship between diabetes and periodontal disease, with one influencing another and sometimes exhibiting overlapping physiological patterns and symptoms. In one 2-year longitudinal study, patients with diabetes (TIDM and TTDM) and severe periodontitis were at a sixfold higher risk of poor glycemic control [4]. Effective treatment in the periodontally diseased patient can significantly improve the metabolic function of TIDM and TIIDM patients. After the periodontal intervention, such as scaling and root planning, glycosylated hemoglobin (HbA1c) levels in people with diabetes decreased. In a meta-analysis, periodontal therapy, and appropriate maintenance intervals (3 and 6 months) caused a statistically significant reduction in HbA1c [21]. Furthermore, periodontal treatment with a 1-year follow-up examination was administered to patients with periodontal disease, and diabetes results showed a statistically significant amount of decreased gingival crevicular fluid biomarkers from baseline to 12 months compared with untreated patients with periodontal disease [22]. Patients also had a 0.6% decrease in HbA1c score post-treatment [22]. This further shows the dynamic relationship between the two diseases and how systemic inflammation can be reduced through the treatment of periodontal disease, and that this should be a core component of diabetes care.

## **3.3 The bidirectional relationship between type 2 diabetes mellitus and periodontal disease: age and gender -related factors**

The bidirectional relationship between TIIDM and periodontitis is established. However, other factors such as BMI (Body Mass Index), age, and smoking status must also be considered. Age is one factor that significantly contributes to both TIIDM and periodontal disease. With advancing age comes higher susceptibility to microbial infections due to higher levels of Gram-negative bacteria in the oral cavity [19]. One in four adults in the United States over the age of 65 has been diagnosed with TIIDM, this number tripling since 2007 [23]. Their mortality risk is approximately 50% higher, and life expectancy is 5–7 years shorter among men and women, respectively [24]. However, it is essential to note the chronological and biological age difference significantly when correlating age with periodontitis and TIIDM. While chronologic age is determined by the time of birth, biological age is determined via cellular changes and is more intimately associated with morbidity, mortality, and the progression of the disease [24]. Biological age can be traced on the cellular level using several biological markers. In a study, markers such as creatinine, serum albumin, blood pressure and A1c levels were used, and the results showed that TIIDM is correlated with an increase in biological age on a statistically significant level [24]. To understand whether the increased biological age was the cause or result of the development of TIIDM, a study of the population of pre-diabetic patients was observed and showed an approximate 2.7-year increase in biological age compared with the control group. However, the highest increase in biological age observed in these patients occurred after diagnosis of TIIDM, thus providing evidence for the fact that accelerated biological age is not a cause, but a result of TIIDM [24]. Further studies on this subject would be beneficial to understanding the relationship between accelerated cellular aging and diabetes as it relates to oral and systemic health and disease.

There is something to be said about gender -related factors when it comes to both periodontal disease and obesity. Female patients that go through pre- and post-menstrual phases have higher induction of proinflammatory cytokines in the

### *The Two-Way Relationship between Diabetes Mellitus and Periodontal Disease: A New Insight DOI: http://dx.doi.org/10.5772/intechopen.108948*

periodontium, which can cause an increased risk of periodontitis [25]. In one study by Estevez-Lima et al., the incidence of women developing TIIDM with a previous medical history of gestational diabetes was observed at approximately 18%, and the incidence of periodontitis was approximately 10% [14]. The way in which the body handles renal glucose also has a gender -related component, and since this plays a significant role in HbA1c levels, which in turn has implications for periodontal disease severity, it must be discussed. Studies also show that women are less likely to develop TIIDM and periodontitis, although they are more likely than men to develop diabetic comorbidities such as cardiovascular and end-stage renal disease [26].

## **3.4 The bidirectional relationship between type 2 diabetes mellitus and periodontal disease: lifestyle habits**

According to the latest National Institute of Health data (2021), adult obesity affects approximately 16 of the world's population. Behavioral patterns play a significant role in this. A cross-sectional study by Khan et al. in 2020 explored the relationship between behavioral change that reduces systemic inflammation and the reduction of periodontitis risk [16]. The results of this study suggested that the effect of TIIDM on periodontitis is higher than the effect of obesity on periodontitis [16]. This demonstrates that confounding variables exist when exploring the relationship between diabetes mellitus and periodontitis and that further studies demonstrating causality should be performed. Somatostatins, interleukins, and adipokines have been discussed previously in this chapter as biological markers for studying both diabetes and periodontal disease. In addition, several members of the IL-6 family exist at elevated levels in patients with periodontitis [17]. The prevalence of periodontitis was 97% in patients with obesity, and approximately 60% of these obese patients had mild to moderate periodontitis (CPI score 3.) An additional 38% of patients studied had a CPI score of 4, indicating severe periodontitis [25].

Interestingly, in this study, the prevalence of periodontitis was significantly higher in patients in the middle age range compared to younger obese adults. Aging and periodontal disease are closely related, as there is a cumulative periodontal tissue and alveolar bone breakdown with age [25]. This is compounded by aging, increasing body fat, and decreasing lean protein mass and bone mineral density.

## **4. Clinical relevance and treatment modalities**

Improving glucose control may be key to preventing complications of TIIDM and chronic periodontitis [27, 28]. Metformin, a second-generation biguanide, is a medication that assists in blood glucose level control. It decreases glucose absorption by the small intestine and increases the body's sensitivity to insulin. In one study, differing percentages of metformin gel were applied in the periodontal pockets of participants, as well as a placebo gel for control [29]. Local delivery of Metformin gel stimulates a significant increase in probing depth reduction [29]. Local treatment of metformin in the periodontal pocket can be enhanced with biological aids such as the drug delivery carrier polylactic-co-glycolic acid (PLGA) [30]. In-vitro bioavailability is significantly improved with PLGA, and when drug efficacy is increased, treatment is enhanced, and prognosis improves. PLGA simultaneously increases the concentration of Metformin at the action site and decreases the concentration at non-target sites [30]. When the clinical efficacy of Metformin was studied, a significant reduction in pocket depth and increase in clinical attachment level were observed, and results still showed an improvement in

periodontal health [31]. This evidence suggests the importance of using biological aids such as Metformin as an adjunct therapy to traditional treatments such as SRP (Scaling and Root Planing) [31]. The use of local drug delivery into the periodontal pockets is traditional; systemic antimicrobials such as minocycline, doxycycline, chlorhexidine, and tetracycline have been used in patients with periodontal disease [31]. Recently, adjuvant antibiotic therapy has been studied on periodontal patients with diabetes.

TIDM and TIIDM are considered risk factors for periodontitis due to the increased risk of systemic infection, collagen synthesis impairment, and impairment of glycosaminoglycan by gingival fibroblasts [32]. In addition, collagen breakdown and the gingival crevicular fluid are increased. Adjunctive therapy may improve the efficacy of SRP in reducing probing depth in patients with diabetes. Local drug delivery directly into the periodontal pockets is an example of adjunct therapy on the rise due to its promising clinical results. SRP with ozone gas therapy as an adjunct constituent can reduce Hb1Ac levels in diabetic patients [33]. Poor response to traditional periodontal treatment, such as scaling and root planning, is associated with an increased risk (37%) of developing TIIDM in the future [29]. Regardless of treatment modality, the treatment of periodontal disease, in general, improves the overall metabolic health of those patients with TIDM and TIIDM. Non-surgical periodontal therapy, such as SRP, improves general health for patients with TIIDM [34].

Periodontal treatment in a diabetic patient can help improve glycemic control. At least seven randomized clinical trials and four systemic meta-analyses have demonstrated that there is a clinically significant reduction in glycosylated hemoglobin levels in TIIDM diabetes patients [35, 36]. The results from these studies showed a decrease between 0.27 and 0.48% 3–4 months post-periodontal therapy. More research must be conducted to demonstrate that this positive result is consistent after 6 months or more post-treatment. Improvements in glycosylated hemoglobin levels are consistent with the magnitude of increase in HbA1c levels experienced by diabetic patients with periodontitis, an average of 0.29% [36]. Therefore, there is a remarkably similar inverse relationship between the rise in HbA1C attributed to periodontitis in the diabetic patient and the fall in HbA1C levels after the periodontal intervention. Periodontal therapy and appropriate maintenance intervals can help diabetic patients with short-term glycemic control. In the other direction, examining the periodontitis patient regarding diabetes, severe periodontal disease is strongly associated with elevated Hb1AC levels. In patients diagnosed with diabetes, hyperglycemia was observed, and in patients without diabetes, there was still an increase in Hb1AC, the difference being a lower serum level [37]. There is also a direct correlation between the severity of periodontal disease and the severity of cardiovascular and nephrotic complications [38]. Elevated lipid levels and elevated oxidative stress markers exist in the serum of TIIDM patients [39]. New evidence also demonstrates that people with severe periodontitis have an increased risk of developing TIIDM [40–42]. Metaanalyses provide abundant evidence for improved glycemic control in the TIIDM patient after periodontal treatment for up to 3 months. One systematic review showed a mean reduction of 0.36% 3 months after periodontal treatment [35].

There is a continuous global research effort on the bidirectional relationship between periodontitis and diabetes. This abundance of evidence-based information allows the medical team, including physicians, to follow specific guidelines to better manage diabetic/periodontal patients and their overall health. A workshop conducted by the European Federation of Periodontology (EFP) and the International Diabetes Federation (IDF) in 2012 provided guidelines for the treatment and management of

## *The Two-Way Relationship between Diabetes Mellitus and Periodontal Disease: A New Insight DOI: http://dx.doi.org/10.5772/intechopen.108948*

these patients, resulting in consensus statements and intervention treatments to be followed by oral healthcare workers and the medical team [43]. Among people who have not been diagnosed with diabetes, periodontitis is still associated with increased blood glucose levels. Patients with periodontitis alone have higher fasting glucose levels when compared to periodontally healthy patients [44]. Because of this, periodontal patients exhibit a higher chance of developing pre-diabetes or diabetes [44]. In diabetic patients, cytokines and other biomarkers play a role in the pathogenesis of periodontitis. Elevated levels of pro-inflammatory mediators such as TNF- α, IL-1, and IL-6 exist in the periodontal pocket in uncontrolled or poorly controlled diabetes patients. Cell cultures exposed to high glucose levels display the destruction of hard and soft tissues; therefore, high glucose levels in the oral cavity in people with diabetes play a significant role in destroying the periodontium [45]. Short-term (3–6 months) periodontal intervention reduces HbA1C levels, similarly, to adding another antidiabetic medication to the patient's regimen. If this can be extrapolated past 6 months of periodontal treatment with further studies, it would have positive implications for reducing diabetes-associated morbidity and mortality rates.

## **5. Complications of diabetes**

The complications of diabetes include cardiovascular diseases, end-stage renal disease, retinopathy, nephropathy, neuropathy, and neuropathic foot ulcers. Periodontitis is the sixth most complication in diabetic patients. These comorbidities

have been studied extensively among 34,149 study subjects through meta-analysis and have been adjusted for confounding variables. In patients with comorbid periodontitis and diabetes, retinopathy is significantly increased, and severity is directly proportional to the severity of the periodontal disease. Further, evidence from three studies demonstrates more renal complications in patients with either TIDM or TIIDM and periodontitis. In one study, chronic kidney disease was found to be strongly associated with cardiovascular disease when both diabetes and periodontal disease were present in the patient, compared with patients with only one of the comorbidities [46]. Periodontal patients exhibiting severe periodontitis (in conjunction with diabetes) have an increased incidence of foot ulcerations. There is a demonstratable association between patients with TIIDM and periodontitis and several cardiovascular conditions, including cardiovascular mortality, coronary heart disease, cerebrovascular accidents, and heart disease. Overall, mortality is significantly increased in patients with both TIIDM and periodontitis and is well documented in the literature. **Figure 2** explains the macrovascular and microvascular complications in uncontrolled diabetic patients.

## **6. Guidelines for the medical team**

The dental team and other medical professionals must know the signs of periodontal disease and its link to poor glycemic control. Pre-diabetes and undiagnosed diabetes can be managed better through early intervention by the entire medical team. Guidelines should be followed to minimize the negative impacts of chronic, systemic pathogenesis associated with periodontal disease and diabetes. Since there is an increased risk of developing periodontitis in the diabetic patient and, in turn, negative complications associated with periodontitis and glycemic control, the following guidelines are recommendations for physicians and dentists alike [1]:

## **7. Recommendations for the general dentist and periodontist**


symptoms are not worsening, the disease can still progress. Because of this, regular dental visits and adherence to a maintenance schedule must occur.


## **8. Recommendations for the primary care provider**


## **9. Conclusions**

Dentists often focus on treating the periodontium and dentition rather than overall health of the patient. This chapter highlights the fallacy in this approach and reminds dental specialists that systemic diseases such as Type 2 Diabetes Mellitus and Periodontal Disease are often comorbid and should be treated as such. Several therapies discussed are improving, and several loom on the horizon, promising to improve both periodontal health and the overall health of the patient. Therapies such as traditional, non-surgical intervention and local delivery of Metformin provide promising results for both periodontal and systemic health.

## **Conflict of interest**

The authors declare no conflict of interest.

*The Two-Way Relationship between Diabetes Mellitus and Periodontal Disease: A New Insight DOI: http://dx.doi.org/10.5772/intechopen.108948*

## **Author details**

Leela Subhashini C. Alluri1 \*, Kristen Puckett<sup>2</sup> , Chethan Sampath3 , David A. Mott1 , Kaitlyn Logan4 , Jazmyne Walker4 , Gerald Davis2 , Cherae Farmer-Dixon<sup>5</sup> and Pandu R. Gangula<sup>3</sup>

1 Department of Periodontics, Meharry Medical College, Nashville, TN, USA

2 Department of Restorative, Meharry Medical College, Nashville, TN, USA

3 Department of ODS and Research, Meharry Medical College, Nashville, TN, USA

4 Meharry Medical College, Nashville, TN, USA

5 Department of Dental Public Health, Meharry Medical College, Nashville, TN, USA

\*Address all correspondence to: lalluri@mmc.edu

© 2023 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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## **Chapter 5**
