Diabetes and Oral Disease

Agenda

*Presentation times are subject to change.

Abstracts

SESSION I: CURRENT CONCEPTS IN DIABETES

Diabetes Epidemic and Need for Collaborative Healthcare Delivery

William C. Knowler, MD, DrPH, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health

Diabetes is a serious and common chronic disease, the frequency of which is dramatically increasing in most parts of the world. Morbidity and mortality due to each major type of diabetes (type 1 and type 2) are primarily due to the long-term complications that have long been recognized to affect the eyes, kidneys, heart, blood vessels, and nerves. More recently, periodontitis has been recognized as a complication of both types of diabetes. Type 1 diabetes is due to autoimmune or idiopathic destruction of the pancreatic beta cells. Prevention research has focused on immune modulation, but so far has not met with reproducible success. By contrast, prevention research in type 2 diabetes has focused on its major causes including a combination of insulin resistance and impaired insulin secretion. Prevention or delayed onset of type 2 diabetes has been successful to varying degrees in a number of studies using either lifestyle modification aimed at weight loss or drugs affecting insulin resistance or secretion. Because of its complex set of causes, diabetes prevention research requires a multidisciplinary scientific approach, and because diabetes affects many organ systems, preventing and treating diabetes complications requires collaboration among many health care professionals.

Current Concepts in the Pathogenesis and Treatment of Diabetes

Rudolph L. Leibel, MD, Columbia University College of Physicians and Surgeons

Diabetes is ultimately a failure to produce sufficient insulin to meet metabolic need. The molecular bases for such failure differs among clinical types of diabetes (autoimmune destruction, metabolic intoxication, beta cell autonomous genetic defects, etc). Also of importance are developmental processes that affect the mass of beta cells an organism develops in early life, and the ability of the constituent beta cells to respond by hypertrophy and/or hyperplasia to metabolic stresses. The advent of stem cell biological techniques applied to human cells, promises to enable elucidation of these processes in humans, and, ultimately, to provide the bases for cellular replacement strategies.

SESSION II: THE DIABETES - ORAL DISEASE CONNECTION

The Bidirectional Relationship between Diabetes and Periodontal Disease

George W. Taylor, DMD, DrPH, University of Michigan School of Dentistry (CRSE) and School of Public Health (Epid)

Diabetes mellitus and periodontal disease are two common chronic diseases that have long been considered to be biologically linked. Diabetes is an important chronic disease globally and considered an epidemic by the World Health Organization (WHO). This presentation will review the evidence regarding the adverse effects of diabetes on periodontal health, the role of periodontal infection in adversely affecting glycemic control, and the relationship of periodontal infection to the risk for developing diabetes complications and possibly diabetes itself.

The focus will be evidence derived from both epidemiological observational studies and investigations of non-surgical periodontal therapy. Longitudinal observational studies provide evidence to support both the adverse effects of diabetes on periodontal health and severe periodontitis on increased risk for poorer glycemic control and diabetes complications. The treatment studies are a heterogeneous set of reports that include randomized clinical trials (RCTs) and studies that are not RCTs. Of the RCTs reported in the literature, several report a beneficial effect for periodontal therapy although some RCTs do not. Recent meta-analyses of the intervention studies provide supporting evidence that non-surgical periodontal therapy improves glycemic control. Additionally, emerging evidence from a limited number of observational studies suggests periodontal disease is associated with increased risk for diabetes complications, including cardiovascular disease, cardio-renal mortality, and renal disease. There is also evidence that periodontal infection may be a risk factor for the development of diabetes.

Conclusion: The evidence supports the bidirectional, adverse relationship between periodontal infection and diabetes. Further rigorously conducted randomized clinical trials are necessary to unequivocally establish that treating periodontal infections can contribute to glycemic control and to the reduction of the burden of diabetes complications. However, given the current evidence, it is prudent to consider treating periodontal infection in people with diabetes as an important component of their overall management plan for diabetes care.

Diabetes and Oral Health in Children and the Elderly

Ira B. Lamster, DDS, MMSc, Columbia University College of Dental Medicine

Recent research has examined oral manifestations of diabetes mellitus in children and adolescents. For these individuals, it appears that periodontal destruction starts earlier in life than previously recognized. Evaluation of periodontal complications in cases and controls (6 to 18 years of age) revealed that patients with diabetes were at increased risk for periodontal destruction with odd ratios ranging from 1.8 to 3.7. A further analysis examining the association of diabetes variables (BMI for age, duration of diabetes, mean HbA1c) and increased risk for periodontal complications revealed an association with mean HbA1c. This is in keeping with the recognized association of HbA1c with other diabetes complications.

Periodontal complications of diabetes mellitus in elderly patients (≤ 65 years of age) have not been extensively studied. Early published data identified duration of diabetes mellitus as a risk factor for more severe periodontitis. For older adults with diabetes mellitus, the severity of periodontitis is correlated with HbA1c. Further, older adults with diabetes have been shown to have poor oral hygiene relative to controls, and have reduced utilization of dental services. The cumulative nature of periodontal disease, and the loss of teeth as individual’s age, are important complicating factors when studying periodontal manifestations of diabetes in the elderly.

Gestational Diabetes Mellitus, Periodontitis and Negative Maternal/Fetal Outcomes:  Is There a Link?

Karen F. Novak, DDS, PhD¹, George W. Taylor, DMD, DrPH², James E. Ferguson, MD³, M. John Novak, BDS, LDS, PhD⁴,¹American Dental Education Association, Washington, DC, ²University of Michigan School of Dentistry, Ann Arbor, Michigan, ³University of Virginia School of Medicine, Charlottesville, Virginia,  ⁴University of Kentucky College of Dentistry, Lexington, Kentucky

Gestational Diabetes Mellitus (GDM) complicates approximately 5% of pregnancies. Substantial evidence documents the association between GDM and adverse pregnancy outcomes but limited data are available on the effects of periodontitis on pregnancy outcomes in women with GDM. Objective:  To test the hypothesis that a combination of GDM and periodontitis is more likely to result in adverse pregnancy outcomes than GDM alone or periodontitis alone. Methods:  This prospective study consisted of 320 pregnant women, ages 17-46, classified into four groups based on the presence or absence of GDM and the presence or absence of periodontitis. Women with GDM were matched with non-GDM controls for race, age, and gestational age; women with type 1 or type 2 diabetes were excluded.  Prior to delivery, participants received a comprehensive periodontal evaluation documenting plaque index, probing pocket depths (PD), clinical attachment loss (LOA), bleeding on probing (BOP) and calculus.  Periodontitis was defined as participants having at least 4 teeth with PD >4mm, LOA >2mm, and BOP.  The adverse maternal outcome was a composite measure that included having at least one of the following: pre-eclampsia, premature labor, premature rupture of membranes, urinary tract infections, chorioamnionitis/funisitis, induction of labor, operative vaginal deliveries or unplanned cesarean delivery.  Multivariable logistic regression, accounting for the matching variables and controlling for calculus index, and cigarette smoking, was used for analysis. Results:  Women with GDM and periodontitis were 2.3 times more likely to have an adverse pregnancy outcome than women without GDM and without periodontitis (OR=2.3; 95% CI=1.06, 4.84).  Women with periodontitis only or GDM only had no greater risk for adverse maternal outcomes than women with neither of these diseases. Conclusion:  GDM and periodontitis combined, significantly contribute to increased risk for adverse pregnancy outcomes.  Supported by:  NIH/NCRR Center of Biomedical Research Excellence P20 RR020145 and UK CR-DOC.

Diabetes and Dental Implant Therapy

Thomas W. Oates, DMD, PhD, University of Texas Health Science Center at San Antonio, Texas

Diabetes mellitus is one of the most commonly encountered contraindications to dental implant therapy. As a result, well-controlled diabetes patients may be considered appropriate for implant therapy, while diabetes patients lacking good glycemic control may be denied the benefits of implant therapy. With increasing prevalences of type 2 diabetes, periodontal disease and tooth loss with age, the need to understanding the appropriate use of dental implant therapy for patients with diabetes becomes critical, especially so for individuals critically dependent on dietary management for their condition.

This review will highlight our current understanding of the relationship between diabetes and dental implant therapy as we look to optimize the benefits of dental implant therapy in meeting the needs of our patients with diabetes.

SESSION III: UNRAVELING THE MECHANISTIC LINKS BETWEEN PERIODONTITIS AND DIABETES

The RAGE/Inflammation Story in Diabetic and Periodontal Complications

Evanthia Lalla, DDS, MS¹, and Ann Marie Schmidt, MD², ¹Columbia University College of Dental Medicine, New York, New York and ² New York University School of Medicine, New York, New York

The Receptor for Advanced Glycation Endproducts was discovered as a cell surface receptor for the advanced glycation endproducts (AGEs), the products of nonenzymatic glycation and oxidation of proteins and lipids that accumulate in diabetes (driven by high glucose), oxidative stress, renal failure and inflammation. The discovery that RAGE was a multi-ligand receptor capable of interacting with non-AGEs such as S100/calgranulins and high mobility group box1 (HMGB1), which were upregulated in inflammation settings, led to the discovery that RAGE played key roles in autoimmune/inflammatory disorders. RAGE is expressed on T cells, B cells, dendritic cells, monocytes and macrophages and in T cells plays key roles in T cell priming; in monocytes/macrophages RAGE mediates upregulation of inflammatory cytokines and promotes cellular migration. In human diabetic periodontal disease tissue, RAGE expression was increased and in parallel, expression of AGEs was higher vs. non-diabetic tissues, and compared to uninfected periodontal tissue. To test the potential relevance of RAGE in the pathogenesis of diabetes-accelerated periodontal disease and alveolar bone loss in diabetes, C57BL/6 mice were rendered diabetic with streptozotocin. In these animals, oral/anal exposure of diabetic mice to Porphyromonas gingivalis resulted in increased alveolar bone loss vs. that observed in non-diabetic mice. Consistent with roles for RAGE ligand-RAGE interaction in the pathogenesis of diabetes accelerated periodontal disease, in animals treated with the RAGE ligand decoy soluble RAGE, bone loss and alveolar inflammation were attenuated in a dose-dependent manner. Recent studies have identified that the cytoplasmic domain of RAGE interacts with the formin mDia1 (diaphanous1), and that mDia1 is essential for RAGE-mediated signaling and cellular migration in transformed cells and macrophages. Future studies will dissect the potential roles of mDia1 in diabetes and periodontal complications. Our findings reveal that RAGE may be an effective target in diabetes and periodontal disease for the reduction in alveolar bone loss and inflammation that accompanies chronic hyperglycemia.

Impact of Diabetes on Cell Death and Bone in Periodontal Disease

Dana T. Graves, DDS, MSc*, Jun Kang⁺, Oelisoa Andriankaja*, *University of Pennsylvania School of Dental Medicine and ⁺Peking University

We investigated the response of normal and diabetic mice to bacteria-induced tissue destruction by inoculating the scalp of control or diabetic mice, with the pathogen P.gingivalis. The diabetic group had significantly impaired ability to produce new connective tissue and bone, which was linked to her fibroblast and bone-lining cell apoptosis. When apoptosis was blocked with a caspase inhibitor the repair of tissue was significantly improved. Diabetes-enhanced apoptosis was shown to be due to greater levels of inflammation. Similar events occur in experimental periodontitis in the rat where diabetic animals had an increased inflammatory infiltrate, greater osteoclast activity and a decreased capacity to form new bone following bone resorption. These deficits were reversed when the higher degree of inflammation was blocked in the diabetic group.

SESSION IV: INTER-PROFESSIONAL RELATIONSHIPS IN PATIENT CARE

Considerations for the Management of the Diabetic Patient: The Role of Dental and Medical Professionals

Evie Lalla, DDS, MS, Columbia University College of Dental Medicine

Patients with diabetes mellitus present a challenge when treated for oral/periodontal conditions in dental care settings. Key components of their proper management by the dental team will be presented. Moreover, patients with type 2 diabetes or pre-diabetes often remain undiagnosed for years. The role of dental professionals in the early identification and referral for formal diagnosis and medical care of those affected will be discussed. Finally, similarly to diabetes, periodontal infections often go undiagnosed and remain untreated and this is especially relevant to diabetic individuals. The role of medical professionals in increasing awareness about the oral complications of diabetes among their diabetic patients and in providing guidance about prevention and treatment strategies for periodontal infections will be discussed.

Dentists' Attitudes and Orientations in the Management of the Patient with Diabetes

Carol Kunzel, PhD, MA, Columbia University College of Dental Medicine

Given the linkages that have been identified between oral infection and systemic diseases, the dental office is an appropriate place to screen for and evaluate certain systemic disorders. Diabetes is an established risk factor for periodontitis, and periodontitis has been called the “sixth complication of diabetes.” The role of the dentist in the management of patients at risk for diabetes or pre-diabetes can be categorized into three phases of involvement: assessment, discussion, and active management. Information published about the practices and attitudes of general dentist and periodontists with respect to diabetes management found that few dentists are engaged in proactive management behaviors. A majority of surveyed dentist did not agree with the notion that patients and colleagues expect them to perform such activities. This presentation will consider these findings from a comparative and international perspective, assessing dentists’ perceived barriers in managing these patients, perceived expectations on the part of patients and colleagues, and self-assessed knowledge and competence in these areas. It will further consider dentists’ attitudes and orientations within the context of an expansion of primary health care activities in the dental office to include screening to identify undiagnosed diabetes, with the ultimate goal of improving health care outcomes for patients in the dental office.

Working Across Medical-Dental Boundaries in the Management of Diabetes and its Complications

Pamela Allweiss, MD, MPH, Division of Diabetes Translation, Centers for Disease Control and Prevention, Atlanta, GA

Oral health care professionals are vital components of the health care team that provides comprehensive care for the person with diabetes. Integrated care among many health professionals (including but not limited to: oral health professionals, primary care providers, podiatrists, pharmacists, eye care professionals etc) can help to improve the delivery of evidence based interventions to improve outcomes in people with diabetes. The National Diabetes Education Program, a joint CDC/NIH, program has developed materials for providers and has established partnerships to promote the collaboration of health care professionals. These tools are in the public domain and will be presented.

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