Diabetes Mellitus and Oral Diseases
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- Brian L. Mealey, DDS, MS
Strong evidence suggests that, unlike the conditions discussed above, diabetes is a risk factor for the prevalence and severity of gingivitis and periodontitis. Diabetes is associated with increased gingival inflammation in response to bacterial plaque, but the degree of glycemic control is an important variable in this relationship. In general, well-controlled diabetic individuals and nondiabetic people have similar degrees of gingivitis, with the same level of plaque. Conversely, poorly controlled diabetic subjects have significantly increased gingivitis, compared to either well-controlled diabetic or nondiabetic individuals.
In large epidemiologic studies, diabetes has been shown to significantly increase the risk of attachment loss and alveolar bone loss approximately threefold when compared to nondiabetic control subjects. These findings have been confirmed in meta-analyses of multiple studies in various diabetic populations. Diabetes increases not only the prevalence and severity of periodontitis but also the progression of bone loss and attachment loss over time.
Periodontitis is similar to the classic complications of diabetes in its variation among individuals. Just as retinopathy, nephropathy, and neuropathy are more likely to be seen in diabetic patients with poor glycemic control, progressive destructive periodontitis is also more common in those with poor control. However, some poorly controlled diabetic patients do not develop significant periodontal destruction, just as some do not develop the classic diabetic complications. Conversely, well-controlled diabetes places the person at a lower risk for periodontal disease, similar to the risk of nondiabetic individuals; yet, well-controlled diabetic patients may still develop periodontitis, just as nondiabetic individuals do. Other risk factors for periodontitis, such as poor oral hygiene and smoking, play a similar deleterious role in both diabetic and nondiabetic individuals.
The mechanisms by which diabetes influences the periodontium are similar in many respects to the pathophysiology of the classic diabetic complications. There are few differences between the subgingival microbiota of diabetic patients with periodontitis and nondiabetic patients with periodontitis. This lack of significant differences in the primary bacteriologic agents of periodontal disease suggests that differences in host response may play a role in the increased prevalence and severity of periodontal destruction seen in patients with diabetes.
Hyperglycemia results in increased gingival crevicular fluid glucose levels, which may significantly alter periodontal wound-healing events by changing the interaction between cells and their extracellular matrix within the periodontium. Vascular changes seen in the retina, glomerulus, and perineural areas also occur in the periodontium. The formation of AGEs results in collagen accumulation in the periodontal capillary basement membranes, causing membrane thickening. AGE-stimulated smooth-muscle proliferation increases the thickness of vessel walls. These changes decrease tissue perfusion and oxygenation. AGE-modified collagen in gingival blood vessel walls binds circulating LDL, which is frequently elevated in diabetes, resulting in atheroma formation and further narrowing of the vessel lumen. These changes in the periodontium may dramatically alter the tissue response to periodontal pathogens, resulting in increased tissue destruction and diminished repair potential.
Diabetes results in changes in the function of host defense cells such as polymorphonuclear leukocytes (PMNs), monocytes, and macrophages. PMN adherence, chemotaxis, and phagocytosis are impaired. Defects in this first line of defense against periodontopathic microorganisms may significantly increase periodontal destruction. Monocytes and macrophages in diabetic individuals are often hyper-responsive to bacterial antigens.65 This up-regulation results in a significantly increased production of proinflammatory cytokines and mediators. The net effect of these host defense alterations is an increase in periodontal inflammation, attachment loss, and bone loss.
Collagen is the primary structural protein in the periodontium. Changes in collagen metabolism in diabetic individuals contribute to wound-healing alterations and periodontal destruction. The production of matrix metalloproteinases (MMPs) such as collagenase is increased in many diabetic patients. Increased collagenase production readily degrades newly formed collagen. Conversely, AGE modification of existing collagen decreases its solubility. The result of these changes in collagen metabolism is a rapid dissolution of recently synthesized collagen by host collagenase and a preponderance of older AGE-modified collagen. Thus, diabetes induces a shift in the normal homeostatic mechanism by which collagen is formed, stabilized, and eventually turned over; this shift alters healing responses to physical or microbial wounding of the periodontium. Tetracycline antibiotics and chemically modified tetracycline agents reduce host collagenase production and collagen degradation through mechanisms that are independent of their antimicrobial activity. These drugs may have benefits in managing conditions such as periodontitis, arthritis, diabetes, osteoporosis, and others in which collagen metabolism is altered.
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