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Oral Inflammation and Diabetes
Advisory Panel
Maria Emanuel Ryan, DDS, PhD, Department of Oral Biology and Pathology Stony Brook University School of Dental Medicine Ray Williams, DMDChair, Department of Periodontology Diabetes mellitus is a chronic metabolic disorder contributing to bacterial proliferation and oral affecting carbohydrate, fat, and protein metabolism.
inflammation. Second, hyperglycemia increases the It is characterized by hyperglycemia (i.e., elevation formation of advanced glycation end-products of blood glucose concentration) caused by the (AGEs); the overexposure of proteins (such as defective secretion of insulin (type I), or impaired collagen) or lipids to aldose sugars induces non- insulin action due to tissue resistance (type II). While enzymatic glycation and oxidation.6 These there is no known cure for diabetes, appropriate glycosylated products can create complex molecular measures can be taken to control blood glucose levels arrangements, reducing collagen solubility and and prevent both acute and chronic complications.
increasing levels of pro-inflammatory mediators Poor glycemic control in diabetic patients has several responsible for the degradation of connective tissues repercussions, including some on oral health. Patients throughout the body of the diabetic, including the with diabetes are prone to develop oral complicationssuch as gingivitis and periodontal disease, fungal Factors Accentuating Periodontal
infections (oral candidiasis, lichen planus), dental Disease in Diabetic Patients
caries, tooth loss, enlarged parotid glands, xerostomia, taste dysfunction, and burning mouth syndrome.1,2 The most prominent oral symptom associated with diabetes is the increased prevalence and severity • Angiopathy (heart disease and stroke) of periodontitis; it is recognized as one of the major complications of diabetes.3-5 Persistent poor glycemic control has been associated with an increased incidence and more rapid progression of gingivitis and periodontitis with associated alveolar bone loss.2 The degree of metabolic control and the duration of (e.g., adolescence, pregnancy, menopause) diabetes are closely associated with the severity of The pathogenesis of periodontal disease involves two components: bacterial infection and the host response. Bacteria present in periodontal pockets initiate an oral inflammatory response that can lead oral cavity. Changes to collagen metabolism result in to the deterioration of the supporting periodontal accelerated degradation of both non-mineralized tissues. When the host response is comprised of an connective tissue and mineralized bone.6 Research excess of pro-inflammatory mediators known as has demonstrated the presence of elevated levels of cytokines, prostanoids, and enzymes, the destruction pro-inflammatory mediators in the gingival crevicular of periodontal tissues occurs. This results in increased fluid of periodontal pockets of poorly controlled pocket depths, loss of clinical attachment, and diabetics, compared to non-diabetics or well- radiographic evidence of bone loss.7 In patients with controlled diabetics, resulting in significant poorly controlled diabetes, periodontal destruction periodontal destruction with an equivalent bacterial challenge.3,6,8 For clinicians and diabetic patients, this means that the oral hygiene of the diabetic must be Hyperglycemia and Oral Health
optimized to prevent further stimulation of an already The effects of hyperglycemia on oral health are primed and heightened host response.
two-fold. First, it causes an increase in the The interaction of AGEs with target cells, such as This article was prepared with the assistance of concentration of glucose in the saliva and the gingival macrophages, via cell-surface polypeptide receptors BioMedCom Consultants, inc., Montreal, Canada.
crevicular fluid of the periodontal pocket, stimulates the production of cytokines and matrix Copyright 2005 Colgate-Palmolive Company. All rights reserved.
metalloproteinases, including collagenases and further stimulates periodontal disease. Poor first step is reduction and control of bacteria, both other connective tissue-degrading enzymes.3 This metabolic control of diabetes can also increase supragingival and subgingival, in the tooth exacerbation of the pro-inflammatory response the risk for other complications of diabetes, such pockets and spaces around teeth. Scaling and in diabetics can lead to delayed wound repair root planing helps remove bacterial plaque and and amplify damage to connective tissues.6 This neuropathy, and delayed wound healing.
associated toxins from the tooth and root surfaces, is important to consider when evaluating the Prevention and control of oral infection and response of poorly controlled diabetic patients inflammation, i.e., periodontal disease, is essential accumulation that is common on rough surfaces.
to periodontal therapy. The pro-inflammatory The second step is inhibition of the enzymes that response may be further heightened by the destroy periodontal tissue so that connective It is also thought that elevations of AGEs in monocytes which differentiate into the chronic gingival tissue increases vascular permeability.11 modulation therapy). Clinical trials have An inflamed periodontium is highly vascular demonstrated the efficacy of some tetracycline Degradation of newly synthesized collagen and may serve as a portal to the systemic analogs to inhibit a series of host-derived, tissue- in connective tissues and alterations in the circulation for bacterial products (bacteremias) mediators,5,8 thereby reducing the connective predisposition to periodontal disease and mediators.10 Other connections between a poor tissue damage associated with periodontitis.
periodontal status and systemic health sequelae Conclusion
metabolic control and the presence of other have been studied; adverse pregnancy outcomes Diabetes is a complex disease with a wide complications (e.g., retinopathy and and cardiovascular disease are both known range of potential complications, including effects nephropathy) can be predictive of the periodontal complications in diabetics. Recent research has on oral health. Integrated strategies for the status. Concurrent risk factors (plaque, smoking, prevention and treatment of periodontal disease periodontitis have a higher risk of giving birth involving the removal of periodontal pathogens to preterm low-birth-weight babies. Other studies and host modulation therapy greatly reduce the considered in the assessment of the periodontal have shown that the risk of major cardiovascular risk for severe periodontitis, and can help in the events, such as heart attack and stroke, is overall management of the diabetic patient. A The presence of AGEs has also been linked significantly higher in those with severe diabetic patient who maintains rigorous glycemic to thickening of the basement membrane and periodontal disease.9 It has become apparent that control and good oral health has the same risk altered vasculature. These changes may be prevention and treatment of periodontitis are of severe periodontitis as a non-diabetic patient, associated with enlargement of the parotid essential to optimal systemic health, particularly emphasizing the importance of diabetes and oral glands and decreased salivary flow seen in diabetics, which facilitates plaque accumulation Management of Diabetes and Oral Inflammation
and increases the risk for caries, gingivitis, References
Control of blood glucose is the fundamental periodontitis, and candidiasis. Degenerative 1. Ship JA. Diabetes and oral health: An overview. JADA 2003;134:4S-10S.
aspect of diabetes management to minimize 2. Vernillo AT. Dental considerations for the treatment of patients with vascular changes may interfere with nutrient and related complications. Adequate glycemic control diabetes mellitus. JADA 2003;134:24S-33S.
leukocyte migration to gingival tissue, decreasing 3. Ryan ME, Ramamurthy NS, Sorsa T, Golub LM. MMP-mediated events in will not only reduce glucose concentration in diabetes. Ann NY Acad Sci 1999;878:311-334.
oxygen diffusion and elimination of metabolic serum, gingival crevicular fluid, and saliva, but 4. Selwitz RH, Pihlstrom BL. How to lower risk of developing diabetes and waste, thereby increasing the severity of its complications: recommendations for the patient. JADA 2003;134:54S-58S.
5. Ryan ME. Host response in diabetes-associated periodontitis: Effects of periodontitis by decreasing dental healing inflammation.11 Prevention and control of tetracycline analogues. Dissertation Abstracts International 1999;59(8).
capacity.6 Collectively, diabetes creates specific 6. Ryan ME, Carnu O, Kamer A. The influence of diabetes on the periodontal periodontal disease must be considered an tissues. JADA 2003;134:34S-40S.
integral aspect of diabetes management, since 7. Ryan ME, Preshaw PM. Host modulation. In: Newman MG, Takei HH, inflammation associated with overproduction Carranza FA, Klokkevold PR, eds., Carranza’s Clinical Periodontology 10th ed. improved oral health can lead to improvements of inflammatory mediators and degradation in the overall health of diabetic patients.11 8. Ryan ME, Usman A, Ramamurthy NS, Golub LM, Greenwald RA. Excessive enzymes, all of which participate in worsening matrix metalloproteinase activity in diabetes: Inhibition by tetracycline Given the increased susceptibility of diabetic analogues with zinc reactivity. Curr Med Chem 2001;8(3):305-316.
patients for oral inflammation, emphasis should 9. Li X, Kolltveit KM, Tronstad L, Olsen I. Systemic diseases caused by oral infection. Clin Microbiol Rev 2000;13(4):547-558.
Oral-Systemic Interactions
be placed on reduction of bacterial infection and 10. Taylor GW. The effects of periodontal treatment on diabetes. JADA While a systemic condition like diabetes can gingivitis. An optimal prevention plan should 11. Matthews DC. The relationship between diabetes and periodontal disease. affect oral health, there is growing evidence that include twice-daily brushing and flossing to J Can Dent Assoc 2002;68(3):161-164.
remove bacterial plaque from teeth.12 Adentifrice 12. Ryan ME. Non-Surgical Approaches for the Treatment of Periodontal Diseases. In: Scannapieco FA, ed., The Dental Clinics of North America. repercussions.9 This bi-directional relationship containing triclosan/copolymer (Colgate Total® is especially important for the metabolic control Toothpaste) has been shown to be very effective 13. Gaffar A, Scherl D, Afflitto J, Coleman EJ. The effect of triclosan on mediators of gingival inflammation. J Clin Periodontol 1995;22(6):480-484.
of diabetes. Studies of active inflammatory in controlling bacterial infection, reducing connective tissue disease have shown that inflammation can trigger insulin resistance.10 slowing the progression of periodontitis.13 Cytokines, such as tumor necrosis factor (TNF)- Restriction of oral infection and inflammation as a, have been reported to interfere with lipid manifested in periodontitis contributes to the metabolism and to cause insulin resistance, while maintenance of normal blood glucose levels, interleukins (IL)-1b and IL-6 antagonize insulin which aids in the overall management of diabetic response can thus hinder glycemic control in For the treatment of periodontitis, a two-step diabetic patients, in turn creating a vicious cycle process aimed at the two components of the of events that compromises diabetes control and disease offers the most favorable outcome.12 The


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