Diabetes belongs to a collection of disorders that have in common glucose intolerance. It is a multifaceted condition characterized by hyperglycemia. Historically, the first written account describing diabetes was recorded by the Egyptians in 1500 B.C. Currently, in the United States alone, approximately 2% to 4% of people are affected by diabetes mellitus. Twenty-five percent of all new cases presenting with end-stage renal failure and 50% of all lower extremity amputations are the result of diabetes complications. It is the leading cause of blindness. Additionally, diabetic patients requiring acute care account for 10% of patient days in hospitals.1
Normally, insulin is secreted into the bloodstream by the beta cells of the pancreatic islets of Langerhans. When a high-carbohydrate meal is consumed, the resulting elevation in blood glucose triggers insulin secretion. Once secreted, insulin's most important function is to cause glucose uptake, storage, and utilization by nearly every tissue in the body, especially the liver. The ideal insulin level ensures a balance between anabolic and catabolic processes.
Depending on the type of diabetes, the beta cells may be destroyed by autoantibodies (insulin--dependent diabetes mellitus), or they may degenerate or be suppressed (non-insulin-dependent diabetes mellitus or maturity-onset diabetes of youth). The resulting metabolic imbalance occurs in all forms of diabetes and differs only by degree. In diabetes mellitus, due to a lack of available insulin, catabolism is greater than anabolism and the net result is an abnormal accumulation of glucose in the blood. When the concentration of plasma glucose exceeds the renal threshold for glucose reabsorption, glucose is not resorbed from the urinary filtrate and appears in the urine (glucosuria). Glucose in the urine creates an osmotic imbalance. This results in a large amount of water excretion‹osmotic diuresis (polyuria). Consequently, dehydration ensures leading to excessive thirst (polydipsia).
Diabetics have a strong disposition to develop both acute and chronic complications as a result of abnormal fat, protein, and lipid metabolism.1, 2 Acute complications include diabetic ketoacidosis and nonketotic hyperosmolar syndrome. Among the chronic complications are atherosclerosis, arteriosclerosis, severe coronary heart disease, microangiopathy, retinopathy, and nephropathy. Additionally, diabetics are highly susceptible to bacterial infections and exhibit delayed healing.1
Key words: phenytoin overgrowth, diabetes, gingiva immune response
Diabetes mellitus is a genetically heterogenous condition. IDDM is an organ-specific autoimmune disease, and there exists evidence for autoimmune diseases to be associated with a particular HLA specificity. The highly polymorphic HLA Class II genes that determine immune responsiveness have been mapped to a specific region of chromosome 6. At residue 57 of the HLA-DQ beta chain, autoimmune response against insulin-producing islet cells is specified. It is here that an inherited predisposition to diabetes mellitus is determined.3 Heterozygotes for the haplotype DR3 and DR4 have demonstrated an increased risk of developing IDDM.
Clinically there are at least three subtypes: juvenile-onset, insulin-dependent diabetes mellitus (IDDM, Type 1); maturity-onset, non-insulin-dependent diabetes mellitus (NIDDM, Type 2); and maturity-onset diabetes of youth (MODY).4 It follows that testing for the development of autoantibodies to the islet cells of the pancreas may have a predictive value.5
Regarding periodontal disease and diabetes, some investigators have evaluated the relationship between impaired glucose tolerance and a family history of diabetes mellitus with bleeding and plaque scores and found no relationship.6 It should be noted that, in this study, isolated blood glucose values were used.
Transmission of NIDDM within families occurs by autosomal dominant inheritance. Onset is triggered by environmental factors superimposed on genetic predisposition. A strong association between obesity and hyperinsulinemia has been demonstrated. In one study, 60% to 90% of individuals suffering from NIDDM were obese, and their obesity was associated with hyperinsulinemia.7 Investigators reported decreased binding of insulin to adipocytes of obese hyperglycemic mice compared to littermates of normal weight.8 In NIDDM individuals, the HLA haplotypes DR3 and DR4 and autoantibodies to pancreatic islet cells have not been detected.
Diabetes, when poorly controlled, is known to be associated with an increased susceptibility to infection, more extensive established infections, and delayed wound healing. An increase in the severity and prevalence of periodontal disease in diabetic patients has been suggested.9, 10 Belting and coworkers examined 157 male veterans, approximately half with diabetes and half without, and reported that the severity of periodontal disease was significantly greater among those in the diabetic group.11 When age and diabetic status were taken into consideration, no relationship between diabetes and periodontal disease was found.12, 13
Increased periodontal breakdown has been reported in children with diabetes mellitus and in diabetics older than 30.7, 8, 14, 15 Some investigators have found significantly more 4-5 mm probing pocket depths in controlled diabetics younger than 45 than in nondiabetic controls.16 These and other findings have stimulated research to evaluate the degree of diabetic control as it relates to periodontal health status.
Fifty diabetics were grouped according to the degree of control and compared with 53 healthy controls. Well-controlled diabetics had better periodontal health than the controls. A comparison of the diabetic subgroups demonstrated a decline in the incidence of periodontal pockets which correlated with improved control of diabetes.17 These findings point to a positive correlation between diabetic control and periodontal disease. Yet, others have reported no association between the degree of diabetic control and periodontal disease.16, 18
Notwithstanding the aforementioned, on long-duration diabetics there were more tooth surfaces with probing pocket depths greater than or equal to 6 mm as well as radiographic evidence of more extensive bone loss.19 In these individuals with a long diabetic history, even when controlled, there was exhibited a greater loss of attachment and bone.
Galea and coworkers studied diabetics whose age of onset was before the age of 25 and none of whom were older than 29 years of age. The severity of periodontitis was closely related to metabolic instability, duration of diabetic disease experience, and complications of diabetes. In one diabetic group studied, compared to its control group, a fourfold increase in susceptibility to develop progressive periodontal disease was reported.20
In the Pima Indian tribe of Arizona, diabetic status was significantly related to both severity and prevalence of periodontal disease. These investigators reported that diabetes in this group of individuals increases the risk of developing aggressive periodontal disease threefold. 21, 22 Although the rate of occurrence of gingivitis and periodontitis appears to be the same for controlled diabetics and nondiabetics, uncontrolled diabetics demonstrate more rapid periodontal breakdown than their controlled counterparts. Furthermore, when a diabetic has periodontal disease, it is usually more aggressive than in nondiabetic controls.23
The relationship between oral health status and diabetes mellitus is well represented in the dental literature. Finnish adolescents with IDDM had higher GI scores and more surface bleeding after probing than their paired age- and sex-matched healthy controls.24 A group of Brazilian patients, ages 5 to 18 years and suffering from IDDM, were evaluated in terms of plaque and gingival indices, probing pocket depth, and alveolar bone loss. Compared to their sex- and age-matched controls, the mean plaque and gingival indices for the diabetic group were significantly higher. In the upper and lower anterior regions of the diabetic group, alveolar bone loss reached statistical significance. Probing pocket depth did not differ significantly between groups. When pocket depth was correlated with age, a positive correlation was observed in the diabetic group, and this correlation was not significant in the control group.25 Cohen and coworkers conducted a three-year longitudinal investigation comparing female diabetics and nondiabetics. Yearly periodontal and medical examinations were performed. The diabetic group consistently scored higher with respect to the gingival index and attachment loss, yet its plaque scores were consistently lower.26
Conversely, Hove and Stallard compared gingival biopsies from 28 diabetic and 16 control patients matched for age and socioeconomic status. They reported similar inflammatory responses for both groups. Control and duration of diabetes had very little effect on the inflammatory response. In fact, the researchers found that inflammatory response was dependent upon local etiologic agents rather than the severity or duration of diabetes. Yet, histologically, 71% of diabetics demonstrated vascular change compared with 19% of nondiabetics.12
According to leading medical authorities, there is a large body of evidence demonstrating that some of the most commonly occurring signs and symptoms of diabetes mellitus occur in the oral cavity.27 Depending on the age of the patient, duration of the disease, and control or management of the disease, the oral manifestations can range from relatively normal to severe. In the uncontrolled diabetic, xerostomia is a common complaint. The oral mucosa may have a red, edematous, and even ulcerated appearance. Without adequate oral hygiene, gingival reactivity is accentuated and patients may present with enlarged, erythematous bleeding papillae. Periodontal pockets may be accompanied by purulent exudate, multiple periodontal lateral abscesses, and pronounced destruction of supporting alveolar bone.28
Anatomical and histological changes associated with periodontal disease in diabetics include thickening of the vascular basement membrane and vascular degeneration of the gingiva. Electron microscopic examination was performed on gingival biopsies from seven nondiabetics with periodontal disease, eight without, and eight diabetics with periodontal disease. Significant thickening of the vascular basement membrane was noted in the diabetic group alone.29 The gingival angiopathies seen in these diabetic patients are consistent with those seen elsewhere in the bodies of diabetics. These angiopathies may contribute to compromised delivery of nutrients to the surrounding tissues and poor elimination of metabolic waste.30 In addition, collagen metabolism is defective in diabetics. Gingival collagen is removed excessively due to increased collagenase activity, and then it is incompletely replaced with highly polymerized but poorly cross-linked collagen.31 Additionally, in the periodontal pocket, bacterial collagenases magnify this diabetes-related collagen breakdown.32 This may provide one explanation for the aggressive removal of periodontal connective tissue seen in diabetics.
Associations between diabetic nephropathies, retinopathies, angiopathies, and ketoacidosis have been evaluated clinically. In 1968,102 men, 51 of whom were diabetics, were evaluated for associations between periodontal condition and diabetes duration, retinal changes, and insulin dosage. These investigators found that individuals who had suffered from diabetes for 10 years or more, especially those in the 30-to-40 age group, and those who exhibited retinopathy had significantly greater loss of attachment. There was a trend, which did not reach statistical significance, for both long-term (> 10 years) and short-term (< 10 years) diabetics with retinopathy to show a greater loss of interproximal bone height.33 Studies focusing on younger IDDM diabetics, age 11 to 25 years of age, reported that those individuals who had suffered from complications such as retinopathy, nephropathy, and ketoacidosis had significantly more gingival inflammation than those without complications.34, 35
Older IDDM and NIDDM patients were assessed for severity of periodontal disease. No differences in periodontal disease experience were found for insulin-dependent and non-insulin-dependent diabetics. There was no significant difference in the periodontal status concerning duration, control, or type of diabetes. Yet, diabetics with advanced retinopathy demonstrated more sextants with deep pockets.15
Diabetes mellitus is a complex metabolic disorder whose complications affect the healing of wounds. It is recognized as a risk factor for impaired wound healing and increased susceptibility to bacterial infection. This also may apply to infectious periodontal diseases. Wound healing, including healing of oral tissues, in diabetics is markedly delayed owing to lowered tissue resistance.36 Researchers have attempted to explain the mechanism for this lowered tissue resistance.
Silicone wound chambers with perforations were implanted in streptozotocin-induced diabetic mice and normal mice. The infiltration by leukocytes and the appearance of tumor necrosis factor alpha (TNF-alpha) and IL-6 were examined in wound fluid aspirated from the chambers on days 1, 3, and 7. The number of inflammatory cells in the wound fluid as well as levels of IL-6 on days 1 and 3 was comparable in both groups. On day 7 there were significantly fewer inflammatory cells and significantly more IL-6 in the wound fluid from diabetic mice. A histologic evaluation was performed on day 8. There was decreased new vascularization and less organization of granulation tissue in the diabetic animals. In these diabetic mice, delayed wound healing was associated with decreased leukocyte infiltration and increased IL-6 levels during the late inflammatory phase of healing.37
In uncontrolled or poorly controlled diabetics, hyperglycemia frequently occurs. Observed impairments in wound healing may be due, in part, to underlying factors associated with hyperglycemia. In diabetic rats hyperglycemia has been shown to increase collagenous activity in the gingiva.38 In induced-diabetic rats hyperglycemia correlated strongly with a 48% increase in newly synthesized collagen glycosylation that was not observed in nondiabetic rats. In the diabetic rats there was an increase in protease and collagenase activity. Additionally, both increased protease activity and collagenase activity correlated strongly with wound collagen glycosylation.39
In another investigation, 80 induced-diabetic rats and their controls received e ither topically applied epidermal growth factor (EGF) or insulin, or both. These medicaments were evaluated for their ability to improve wound repair. The combination of EGF and insulin resulted in a 202% increase in collagen synthesis compared with controls. Diabetic rats treated with either EGF or insulin alone had significantly less collagen than controls. All groups that received insulin had lower collagenase activity.40
On the basis of these results, and without consideration for other variables, it might be reasonable to expect normal healing in diabetics receiving insulin therapy or with normal blood glucose levels. Consider first that this is an animal study. Furthermore, it should be noted that the aspects of duration of disease and consistent diabetic control are not considered in this study. Therefore, more investigation of this type is indicated before the use of growth factors or hormones could be successfully implemented into routine clinical treatment.
The repair of vessels is crucial to uneventful healing following surgery. Re-endothelialization across a microvascular anastomosis in diabetic and nondiabetic rats was examined using scanning electron microscopy. At 10 days, mean re-endothelialization of a 200-micron area on either side of a microarterial anastomosis was 65% in nondiabetic controls, 16.5% in the untreated diabetic group, and 10% in the insulin-treated diabetic group. Repair was significantly less than in the controls in both diabetic groups.41
Although diabetes is not involved in the pathogenesis of periodontal disease, vascular and cellular changes associated with diabetes provide a susceptible environment for attachment loss and compromised cellular immunity. Findings from studies of immunologic response in diabetics point to a possible etiology for the severity of periodontal disease observed in these people. They propose that the increased sensitivity of diabetics to periodontal disease may be due to abnormalities in polymorphonuclear neutrophil (PMN) function. Along with changes in neutrophil activation and adherence, there appears to be a defect in neutrophil chemotaxis. This defect allows invading organisms to continue their ingress into host tissues unimpeded.
The relationship between the severity of periodontal disease and PMN chemotaxis in diabetics was evaluated. Diabetics with severe periodontitis had impaired neutrophil chemotaxis. Nondiabetics and diabetics with mild periodontitis did not.42 Therefore, diabetic patients are abnormally susceptible to infection and frequently present with severe periodontal disease.43
A recent case study evaluated the PMN function of a poorly controlled, adult IDDM patient with severe periodontitis. PMN function of this patient was evaluated and compared with a healthy control. These functions included killing of Porphyromonas gingivalis, phagocytosis, superoxide production, and chemotaxis. The migration of the IDDM PMNs along an FMLP (N-formyl-methionyl- leucyl-phenylalanine) gradient was depressed. Superoxide production was elevated, and phagocytosis and killing of two strains of P. gingivalis was significantly impaired.44
In another study, neutrophil function was evaluated in controlled IDDM patients. In this diabetic group, although chemotaxis toward bacterial chemotactic factors was normal, significantly reduced chemotaxis toward complement-derived chemoattractants was observed. Evaluation of basal activity level showed an elevated superoxide production and more efficient oxidation-reduction reactivity. Additionally, the diabetic neutrophils demonstrated a reduced surface charge and reduced amounts of intracellular Iysozyme. From these results it would appear that neutrophils of controlled IDDM patients show signs of being in an activated state.
The mechanism of pathogenesis and susceptibility to infection may be due, in part, to a defect in neutrophil adherence. Labeled neutrophils from 26 diabetic patients and from their age- and sex-matched controls were studied. Their neutrophils were evaluated for changes in adhesion to bovine aortic endothelial cells. After incubation with PMA, but not FMLP, adherence was significantly decreased in 62% of patients. When plasma from diabetic patients was added to both diabetic and control neutrophils in the basal state, a significant increase in adherence was observed. These adhesive effects were mediated through alterations in the endothelium. Enhanced adherence of neutrophils to endothelium was the result of two main factors. These factors included an intrinsic dysfunction of the diabetic neutrophils in conjunction with a diabetic protein plasma factor or factors. The outcome may be prevention of neutrophil emigration into tissues.45
Neutrophil production of toxic oxygen metabolites is damaging to other tissues and cells. Damage to endothelial tissue may occur in this fashion. PMN respiratory burst was studied in 24 IDDM children and 24 age-matched controls. Resting PMN chemiluminescence was compared to PMA (phorbol myristate acetate) -stimulated activity. The resting activity value for diabetic children was significantly higher than that for normal controls. The ratio of PMN resting chemiluminescence versus stimulated activity was much smaller for diabetic neutrophils compared with controls. There was an overall elevated release of toxic oxygen metabolites from neutrophils in diabetic children.46
In another study, normal neutrophils were incubated in either diabetic or normal rat serum. Then quantitative assessment of their chemotactic responses to FMLP, LPS-activated serum, and leukotriene B4 was performed using the micropore filter system. Those cells incubated in diabetic donor serum demonstrated reduced migratory responses to LPS-activated serum. Even when high concentrations of FMLP and leukotriene B4 were added to stimulate migration, the PMNs did not respond; yet in a previous trial, cells suspended in normal serum responded normally to synthetic chemoattractants. From the early stages of diabetes, PMN emigration (in vivo) into an inflamed area was inhibited. These investigations suggest that the chemotactic inhibitory factor may be a plasma protein that competes with complement- derived chemoattractants for neutrophil receptors. This competitive inhibition effectively abolishes neutrophil chemotactic responses.47
An association between diabetes and neutrophil activation has been suggested. Neutrophil elastase levels were measured by radioimmunoassay in 100 diabetic patients and 35 age-matched nondiabetic patients. Plasma neutrophil elastase and total neutrophil elastase were increased in the diabetic group.48
Heredity also may play a role in the increased sensitivity of diabetics to periodontal disease. The existence of functional aberrations in the neutrophil line is one explanation for this sensitivity. In fact, the relationship of a positive family history of diabetes and impaired neutrophil chemotaxis has been demonstrated.49
It seems clear that diabetes does not cause periodontitis, yet periodontitis is thought to be a complication of diabetes.9 Tissue alterations caused by diabetes result in a periodontium whose resistance is altered and thereby less able to repel invading microorganisms.17 Among other immunological responses to periodontitis, cell-mediated immunity plays a fundamental role in the pathogenesis of periodontitis.50 This role may manifest itself as either safeguarding or aggressive. Insoluble circulating immune complexes are believed to mediate many pathological manifestations of periodontal disease51 as well as in the pathogenesis of microvascular aberrations associated with diabetes. There is also an increased rate of occurrence of circulating immune complexes in diabetics.52
In one study, 50 NIDDM patients and an equal number of nondiabetics with periodontitis were evaluated for levels of circulating immune complexes (CIC). None of the diabetics had been diagnosed for longer than five years or fewer than three; all were considered well controlled. They were compared with 50 age- and sex- matched controls. CIC levels in both groups were elevated compared with controls.53 Elevated CIC levels in periodontitis patients, with or without diabetes, have been reported by other investigators.54, 55 There also were significantly higher levels of circulating immune complexes in the sera of the diabetic group compared with the nondiabetic group.53
Many of the same investigators orchestrated another study in which cell-mediated and humoral immune responses were examined. Again, the same type and number of patient pool and controls were employed. In this case, cell-mediated immunity was determined by the number of lymphocytes forming rosettes in the presence of sheep red blood cells. Both high-affinity and total rosette-forming cells were assessed. A computation of serum immunoglobulins G, A, M, D, and E by single radial immunodiffusion was performed to determine humoral immune response. There was very little variation from the control group with regard to cell-mediated immunity. As for humoral immune response, all immunoglobulins except IgD were significantly elevated in both diabetic and nondiabetic patients with periodontitis compared with controls. There were no significant differences between diabetics and nondiabetics,56 yet as this group of researchers began to examine specific aspects of immune response in diabetics, differences began to appear.
The complement system plays an essential role in inflammatory diseases, including periodontitis. Its primary function in the normal immune response is lysis of bacteria and viruses.5 In some hypersensitive responses, the complement cascade may contribute to tissue damage.5
A recent study, initiated by the same group mentioned above, was undertaken to determine total hemolytic activity as well as its fractions C3 and C4 in type II diabetic and nondiabetic patients with periodontitis. Again there were 50 patients in each group and 50 age- and sex-matched healthy controls. AI1 diabetic patients were diagnosed as having diabetes from three to five years and were controlled. Elevated hemolytic activity was observed in both diabetics and nondiabetics compared with controls. Significantly, there was higher complement activity in the diabetic group with periodontitis compared with the nondiabetics with periodontitis. Similarly, C3 and C4 fractions were elevated in both groups compared with controls. This rise was more pronounced in the diabetic group.57
The C3 component of the complement cascade is involved in increased susceptibility to infection by diabetics. This effect occurs in concert with hyperglycemia, which has been shown to impair several mechanisms of humoral host defense. Of special interest is the impairment of neutrophil functions such as chemotaxis, adhesion, and phagocytosis. The C3 component is inhibited from binding to a microbial surface. This occurs by the binding of glucose to its biochemically active site. Several pathogens are equipped with unique mechanisms of virulence and consequently thrive in a hyperglycemic environment. For example, Candida albicans expresses a glucose-inducible protein that is identical to a complement receptor on human phagocytes. This protein promotes adhesion by the yeast and prevents phagocytosis by the host. It is well documented that diabetics are particularly susceptible to yeast infections.58
Microbial plaque is the primary etiologic agent in most types of inflammatory periodontal disease. Many systemic diseases affect the local response to microbial components as well as the systemic host response. Since the appearance of the "specific plaque hypothesis,"59 many researchers have attempted to distinguish the microbial flora affiliated with the different types of periodontal disease. 60
For example, juvenile periodontitis possesses a characteristic flora consisting of gram-negative saccharolytic anaerobes, Actinobacillus actinomycetemcomitans, Capnocytophaga species, Eikenella corrodens, and Bacteroides intermedius.61, 62 The composition of the subgingival microflora of IDDM patients was determined to consist mainly of Capnocytophaga, Fusobacterium, Campylobacter, and occasionally Haemophilus actinomycetemcomitans.63 There have been other investigations that have attempted to identify any changes in the characteristic microflora of diabetics with periodontitis.These changes were compared with nondiabetics with inflammatory periodontal disease.
A morphotypic characterization of the subgingival microflora of Finnish IDDM adolescents was conducted. Eighty-five IDDM patients ranging in age from 12 to 18 years of age were examined using gram- and Rhodes-stained smears. Smears from age- and sex-matched healthy controls were used for comparison. There were differences in distribution of bacterial morphotypes between the two groups. Specifically, there were more gram-negative rods and total gram-negative bacteria in the diabetic patients. Clinically, in spite of similar plaque index scores, the diabetics demonstrated more gingivitis than the controls.24
The influence of diabetic control on the subgingival microflora of IDDM patients was examined. One group consisted of controlled diabetics with periodontitis and the other group was an uncontrolled version. There were 22 patients in total. Subgingival sites were examined for A. actinomycetemcomitans, black-pigmented Bacteroides species, and Capnocytophaga species. There were no significant differences in the subgingival microflora between the two groups. The authors concluded that metabolic control appeared to have no effect on the subgingival microflora.16, 18
Subgingival microflora and serum antibody response were determined in another, more extensive investigation. Subjects in this study were exclusively members of the Pima Indian tribe. Fifty-five adults with moderate to severe periodontitis were selected for microbial examination. They ranged in age from 17 to 64 years. In eight NIDDM patients subgingival plaque samples were taken from the deepest pockets in each of two quadrants. The predominant cultivable bacteria were determined, and direct immunofluorescence for P. intermedius, P. gingivalis and H. actinomycetemcomitans was performed. Indirect immunofluorescence was also performed on 47 additional subjects with moderate to severe periodontitis. Twenty-five of these individuals had NIDDM, six had impaired glucose tolerance (IGT), and 16 had normal glucose tolerance (NGT). A glucose tolerance test lasting two hours was used to determine diabetic status. Serum antibody to 13 oral microorganisms was evaluated in 377 subjects. Eighty-four of these were healthy, normal subjects, 112 were normal subjects with periodontitis, 19 were periodontally healthy with IGT, 15 were periodontally healthy with NIDDM, and 82 had NIDDM and periodontitis.
In the NIDDM patients with periodontitis, the resulting predominant cultivable bacteria were black-pigmented Bacteroides species. The predominant bacterial isolate was B. intermedius. Two serologically distinct strains of P. gingivalis were each isolated from either periodontitis patients with diabetes or those without.
Indirect immunofluorescence of the plaque samples from NGT, IGT, and IDDM patients with periodontitis suggested that the proportion of P. gingivalis, but not B. intermedius, increased in the NIDDM subjects. These NIDDM patients also had mean P. gingivalis counts that were double those seen in either of the other two groups. All three groups exhibited elevated serum IgG levels to both strains of P. gingivalis. The IGT patients demonstrated elevated titers to one of the strains of B. intermedius. The NGT patients exhibited elevated titers to the other strain.
In summary, the data from this study indicated that impaired host immune response was not reflected in the subgingival microflora. Also, the subgingival microflora of these NIDDM patients with severe periodontitis was similar to that of nondiabetics with severe periodontitis.64 Finally, there appears to be a composition of subgingival microflora in NIDDM patients that is distinctly different from that of IDDM patients.63
A reasonable interpretation of the present evidence indicates that diabetes, when a complication of periodontitis, acts as a modifying and aggravating factor in the severity of periodontal infection. Diabetics with periodontitis who were young and poorly controlled, those who were long-duration diabetics, especially those over 30 years old, demonstrated more attachment loss, bone loss, and deeper probing pocket depths than their nondiabetic controls.7, 8, 14, 15, 16, 20 It seems that the earlier the onset of diabetes and the longer the duration, especially without consistent control, the more susceptible the individual will be to periodontal disease.20, 21, 22 Consequently, once a diabetic contracts periodontal disease, it is usually more destructive.23
Although plaque scores of diabetics maybe comparable to or even less than those of nondiabetics, diabetics often exhibit higher gingival index scores.12, 24, 25, 26 The elevation of this particular clinical parameter is indicative of the microangiopathy associated with diabetes. Diabetic microangiopathy contributes to compromised delivery of nutrients to surrounding tissues and poor elimination of metabolic waste products.30, 41 The complications associated with diabetes such as macroangiopathy, microangiopathy (i.e., retinopathy), ketoacidosis, and hyperglycemia result in impaired wound healing, immunosuppression, and susceptibility to bacterial infection.36, 42, 43 Individuals ages 30 to 40 suffering from diabetic retinopathy had significantly more gingival inflammation than controls or diabetics without complications.34, 35
Collagen metabolism is defective in diabetics and is one component underlying delayed wound healing.31, 32 Animal studies have been instrumental in elucidating the details of delayed wound healing. Hyperglycemia was associated with increased collagenase and protease activity in the gingiva of rats.38, 39 Vascular wound healing in rats, particularly new re-endothelialization across vascular anastomoses, was significantly impaired.41
Diabetic abnormalities in immune response include impaired netrophil chemotaxis, phagocytosis, and adhesion.42, 44, 45 Decreased neutrophilic chemotactic response seems to be attributable to protein factors in diabetic serum that competitively bind neutrophil receptors, thereby preventing complement-mediated phagocytosis.58 Because diabetics are not able to eliminate circulating immune complexes (CIC) effectively, serum CIC levels are elevated.53
There are microbiological differences in the characteristic flora of NIDDM patients and IDDM patients with periodontitis.63 These differences are not associated with diabetic impaired immune response.16, 18, 24, 63, 64
Ultimately, bacterial plaque is the primary etiology of periodontal diseases. Evidently, the host's response to bacterial plaque and ability to heal following surgery is altered by diabetic disease. Therefore, a thorough history regarding onset of diabetes, duration, and diabetic control would prove useful in the clinical management of diabetics presenting for treatment of periodontal disease.