MOST COMMON DENTAL AND ORAL DISEASES IN DIABETIC PATIENTS
D. Muacevic-Katanec1, D. Katanec2, Z. Metelko1, H. Juric3
1Vuk Vrhovac Institute, University Clinic for Diabetes,
Endocrinology and Metabolic Diseases,
Dugi dol 4a, 10000 Zagreb, Croatia
2Department of Oral Surgery, and
3Department of Pedodontics, School of Dental Medicine,
Gunduliceva 5, 10000 Zagreb, Croatia
Received: March 8, 1998
Key words: diabetes mellitus, changes in oral mucosa, periodontal diseases
Diabetes mellitus is a systemic disease associated with a whole range of oral manifestations, among which periodontal disease is the most important one. The increased incidence of various gingival changes with consequential periodontium destruction is considered to be primarily the result of a reduced chemotactic and phagocytic capacity of peripheral blood polymorphonuclears in patients with diabetes mellitus. Many studies indicate several other pathogenic mechanisms responsible for a more intense development of periodontal disease in patients with diabetes mellitus. These are: disturbed collagen metabolism, reduced capillary lumen, and change in subgingival bacterial flora. Special attention should therefore be paid to the care and treatment of teeth and oral cavity in patients suffering from diabetes, along with mandatory education aimed at prevention.
In patients with diabetes mellitus, diseases of the oral cavity which would be characteristic of diabetes do not occur (1). In patients with controlled diabetes, tissue reactions are identical to those found in healthy individuals. However, patients with uncontrolled diabetes have been observed to be more prone to inflammation of highly vulnerable mucosa, due to a decreased systemic immunity and disturbed function of polymorphonuclear lymphoctes, which represent first-line defense of the oral cavity and the whole body against bacterial noxae (2). Numerous studies have shown that the chemotactic and phagocytic capacity of peripheral blood polymorphonuclears is impaired in patients with diabetes mellitus. Special attention should therefore be paid to education of such patients in the prevention of dental and oral diseases (2).
CHANGES IN ORAL MUCOSA
Patients with poor disease control, due to weaker immunity of oral mucosa and acidic reaction of the saliva, become more susceptible to multiplication of some fungi, Candida albicans in particular (3). Although some cases may be free from marked clinical symptoms, inflammation of the oral mucosa (cheilitis) can develop. The mucous membrane is edematous and red, occasionally even whitish, and ulcers may also develop. In case of an infection by Candida albicans, the tongue is usually involved (glossitis), being red and swollen, with atrophy of the papillae and increased susceptibility to bleeding. Patients report a sense of burning.
Dry mouth (xerostomia) is a frequent symptom of diabetes mellitus characteristic of patients with poor disease control. It is caused by decreased salivary secretion and occurs in about 40% of patients. Some reports have shown that salivary glands in diabetic patients produce only a third of the amount of saliva secreted in healthy controls, and discomforts are reduced by appropriate diabetes therapy (2). Some patients (10%-25%) who generally do not suffer from these discomforts, were observed to have symmetrically increased salivary glands (4).
The above mentioned symptoms and an increased proneness to infections require special attention to be paid to patients with mobile prosthetic substitutes (prostheses) who frequently suffer from decubital ulcerations. It is therefore of utmost importance, in addition to a well adjusted prosthesis, that the patients be educated in keeping regular hygiene of such substitutes and urged to visit their dentist regularly, especially in case of any disturbances.
Gingivitis is the most common periodontal disease, initially manifesting as inflammation of marginal gingiva which is painless but may bleed on brushing. The earliest clinical signs of gingivitis usually include changes in the color and texture, with slight tissue enlargement, and with partial loss of firmness and adaptation to the teeth. The disease may persist in this state or may progress to the loss of gingival attachment to the tooth and formation of periodontal pockets (5). A vast body of evidence indicates that the primary cause of both gingivitis and periodontitis is bacterial activity. Bacteria attach to the tooth surface at and slightly under the gingival margin. They colonize and form an organized mass that is referred to as bacterial plaque (6). This plaque, if allowed to remain in place, leads to inflammatory changes in the tissues. Subgingival plaque is formed by apical progression of bacteria from the supragingival plaque into the periodontal pocket. Experimental studies have proved that this process occurs as a continuous progression of all bacteria, but certain colonies may progress faster moving apically into the inflamed periodontal pocket by means of mobile bacteria chemotaxis. These subgingival microorganisms are well adapted to substances from the gingival liquid. They are also capable of inactivating the host's defense mechanisms like gingival liquid immunoglobulins or leukocyte phagocytosis (7). The plaque pathogenic potential may vary from one individual to another and from tooth to tooth in a single individual. The reaction of host tissues to this bacterial attack occurs through an inflammatory and immune defense mechanism (8).
Most studies have reported higher levels of gingival inflammation in diabetic children and adolescents than in healthy controls. Although not all gingivitis develops into periodontitis, the same mechanisms may lower host resistance toward plaque and increase the risk of gingivitis in children and poorly controlled adolescent diabetics (9).
Many studies confirm the relationship between glucose balance and gingival inflammation. Hyperglycemia in newly diagnosed diabetic children and adolescents was associated with severe gingival bleeding, which was reduced by glucose metabolism improvement after the introduction of insulin therapy. Poorly controlled long-term diabetic subjects (mean HbA1c, 15.0%) had more gingival bleeding than those with good or moderate diabetes control (10). An increase in gingival bleeding in association with hyperglycemia suggests that hyperglycemia-associated biologic alterations, which lower host's resistance toward plaque, have apparently taken place (11,12).
A number of studies have reported abnormal morphologic features of capillaries in the gingiva and labial mucosa in diabetic patients as compared with non-diabetic controls. Longstanding hyperglycemia causes thickening of vascular basement membranes, which reduces tissue nutrition and migration of leukocytes. Furthermore, diabetic individuals with both retinopathy and nephropathy had significantly more gingival inflammation than diabetic individuals without vascular complications (13). These observations as well as the findings of the present study might support a concept that morphologic and functional diabetic microvascular changes may be important in periodontal disease in patients with insulin dependent diabetes mellitus (IDDM) (14).
Polymorphonuclears play an important role in periodontal wound healing (15). These alterations of tissue structures and host's immune response might lead to an increased risk of infections and of wound healing impairment in diabetic patients (9,16,17).
Consequently, although not all gingivitis develops into destructive periodontal disease, prevention of plaque-induced gingival inflammation should be emphasized, particularly in children and adolescents with poorly controlled diabetes.
Periodontitis is defined as the loss of both periodontal ligament attachment and bony support of the tooth, which usually occurs with inflammation of the gingival tissues (18).
Periodontium or the supportive apparatus of the teeth is a functional unit which consists of the gingiva, cementum of the teeth, periodontal ligament connecting the teeth to the bone, and alveolar bone surrounding the teeth for their fixation. If the periodontium is healthy, the teeth are hard, and the gingiva is light-pink, adheres firmly to the teeth and completely fills the space between the teeth. Numerous clinical and epidemiologic studies have provided evidence that a major factor in the onset and progression of periodontal disease are soft deposits on the teeth, which include many microorganisms (bacterial plaque). It has also been proven that various systemic diseases can modify host's response to harmful factors of bacterial plaque, thus leading to a different development of periodontal disease in these patients. Diabetes mellitus is one of the diseases most commonly reported in association with periodontal disease.
The host's response in periodontal disease is produced by immune and non-immune inflammatory factors and activities involving many complex and interdependent cellular and biochemical reactions.
Many studies point to several pathogenic mechanisms responsible for a more intense development of periodontal disease in patients with diabetes mellitus. These mechanisms are: disturbed collagen metabolism (increased resorption, decreased synthesis), reduced capillary lumen (reduced oxygenation and aggravated elimination of harmful metabolic products), change in subgingival bacterial flora, and impaired polymorphonuclear function mentioned above, this time in the periodontal pocket.
Although the mechanisms by which diabetes mellitus increases the severity of periodontal disease are poorly understood, one may propose that increased susceptibility to periodontal infection, impaired host's response, and excessive collagenolytic activity all play a major role.
Results from the Diabetes Control and Complications Study have shown that intensive treatment aimed at achieving blood glucose levels as close as possible to the normal range significantly reduced diabetic complications, especially retinopathy (19). The biochemical basis whereby hyperglycemia may lead to the microvascular complications seen in diabetes is the accumulation of advanced glycosylation end products (AGEs) (20). The degree of AGE accumulation is directly related to the time-integrated extracellular glucose concentration (21). AGEs are also primarily responsible for collagen cross-links seen in diabetes, indicating that most of the macrovascular complications associated with diabetes mellitus, such as hardening of arteries and large vessels, are also glucose-mediated (22).
The interaction of macrophages with AGE-modified proteins, and secretion of TNF-? and IL-1 are increased (23). The interaction of endothelial cells with AGE-protein complexes leads to an increased production of endothelin-1, a potent vasoconstrictor, resulting in excessive vessel vasoconstriction and focal thrombosis (24,25).
The above mentioned cellular reactions may also be operative in the initiation of destruction seen in periodontal disease, thus accounting for the increased risk of severe attachment loss exhibited by diabetic patients compared to non-diabetics (26).
Tissues from the retina, kidney, and nerves have been shown to be freely permeable to glucose (27). The possibility exists that periodontal connective tissues exhibit similar permeability to glucose. Therefore, one may propose that the pathogenesis of periodontal disease, in a manner similar to other diabetic complications, is glucose-mediated (28).
Several specific bacteria, including Porphyromas gingivalis, Actinobacillus actinomycetemcomitans, Prevotella intermedia, Bacteriodes forsythus, and perhaps others such as Wolinella recta, Fusobacterium nucleatum, and spirochetes, are associated with severe forms of periodontal disease (29). In addition, a group of pathogens not normally found in the oral cavity have been related to periodontal disease, including Enterobacteracea, Pseudomonadacea and Acinetobacter (30). Periodontal disease is probably an infection, with severe forms of the disease associated with specific bacteria that have colonized the subgingival area in spite of the host's protective mechanisms.
Periodontal disease begins as an inflammation of the gingiva (gingivitis), manifesting as bleeding from the gums during dental hygiene. In case of prolonged disease, swelling and redness of the gingivae, accompanied by an unpleasant odor develop. In this stage, the disease can still be quickly and simply treated by removing dental tartar and soft deposits, along with thorough dental and oral cavity hygiene. In the advanced stage of the disease, beside the teeth becoming loose and pushed aside and the gums detached, periodontal pockets with possible pus are formed. The periodontal pocket surroundings is very specific and depends to a high degree on the level of oral hygiene, composition of gingival liquid, possibilitiy of oxygenation, and depth of the periodontal pocket itself. The probing depth and loss of attachment were found to be significantly greater in diabetic than in non-diabetic control subjects (30-33).
In many IDDM patients, alveolar bone resorption begins during in adolescence and advances with age. Collagen, the main protein of the periodontal tissues, makes between 30% and 40% of the dry weight of gingival tissue and about 90% of bone matrix. Patients with diabetes are considered to have an increased collagenase activity, which causes collagen disorganization and destruction. Impaired bone architecture, along with reduced immunity and small blood vessel lesions, enables development of harmful microorganisms, leading to accelerated development of periodontal disease. The onset and development of the disease are usually painless, which results in visiting a dentist only at an advanced stage of the disease. According to some clinical investigations, periodontal disease is more common in patients with diabetes duration of more than 10 years or with pronounced eye complications of diabetes (diabetic retinopathy).
TREATMENT OF PERIODONTAL DISEASE
A number of studies have shown that periodontal disease more frequently occurs in diabetic population than in healthy individuals, and that good glycemia control reduces the incidence and severity of periodontal disease (34). Dental procedures should be avoided or limited to reducing or removing pain by analgesics, antiobiotic therapy and, if necessary, surgical opening (incision) and drainage of pussy swellings (abscesses) in states of poor diabetes control. Removal of soft deposits and dental tartar are sometimes sufficient for the treatment of periodontal disease, whereas deeper periodontal pockets require more complicated surgical procedures. In case of some complicated procedures, antibiotics are recommended for two days before and five days after the procedure.
During surgical procedure, special attention should be paid to the administration of anesthetics. Most of the currently used anesthetics contain adrenaline, which stimulates neoglyconeogenesis and liver glycogenolysis, which may produce a hyperglycemic effect. Slow administration of the lowest effective dosage of anesthetics following negative aspiration is therefore recommended (2,35,36).
Impossible intake of the recommended diet during a certain period after some therapeutic procedures and of insulin dosage adjustment during that time, in agreement with a diabetologist, should be taken in consideration.
It should be stressed that periodontal disease does not spontaneously disappear and that, without medical intervention, the disease will slowly advance until the teeth fall out. In addition, no medical procedure, however well performed it may be, will prove successful unless the patient carries out regular and thorough daily oral hygiene. Before the procedure on the periodontium is carried out, the patient should take the drug recommended by his diabetologist. The best time for carrying out the procedure is 1.5-3 hours after the patient's usual morning therapy and breakfast, when the possibility of hypoglycemic complications is reduced to minimum. In case of the patient's blood glucose self-monitoring, most recent values should be considered. Blood glucose levels of 80-180 mg/dl are usually suggested as an optimal range. Lower levels are not considered strict contraindication for routine dental care, but the clinician must recognize an increased risk of hypoglycemic complications. A blood glucose value greater than 400 mg/dl requires consultation with the patient's physician (2,37). Diabetic dental patients with poor metabolic control require special vigilance in treating infection because of impaired leukocyte function caused by hyperglycemia. The dentist should initiate preoperative antibiotic therapy in the presence of infection or when postoperative infection is likely to develop (38). Also, the presence of acute odontogenic infection and the stress caused by dental treatment will sometimes increase blood glucose levels. This adverse effect on the metabolic control may require an increase in insulin dosage for type I diabetic patient or initiation of insulin therapy for type II diabetic patient (39).
PERIODONTAL DISEASE IN CHILDREN WITH INSULIN DEPENDENT DIABETES MELLITUS
Results of various studies of the periodontal status in children with type I diabetes mellitus have revealed a significantly increased incidence of different gingival alterations in these patients, which consequently leads to destruction of the periodontium and endangers the teeth when the conditions of oral hygiene remain unchanged (40). Periodontitis most frequently occurs at the age of 12, with a prevalence of 9.8% at the age of 13-18. After the age of 19, the prevalence increases to 39% (41). Therefore, such patients need special care during dental treatment, preceded by appropriate education aimed at prevention and efficient care of the stomatognathic system.
In these patients, education should begin with the choice of an appropriate way of tooth brushing. Before brushing, a tooth brush and tooth paste appropriate for the patient's age should be chosen. The patient should be instructed in the technique of massaging and stimulating the gingiva (methods according to Stillman, Bass, and Charters or their modifications). The frequency and duration of daily tooth brushing should be discussed with the patient. In addition, the patient should be informed on other methods of dental plaque reduction. The usage of dental silk (interdental space cleansing) should be explained to the patient (42). Water pick may be recommended for the same purpose. The patient can also perform topical fluoridation by a solution or gel once a week by himself. Sugar-free chewing gums, especially those with xylitol and fluorides, can be recommended as well. The use of interdental brushes, stimulators and devices for oral cavity rinsing can improve oral hygiene and help maintaining oral health. Further preventive procedures are the responsibility of professionals (43,44).
Noninvasive methods for the reduction of dental plaque and caries as well as of periodontal disease, carried out by a dentist, could be recommended in the following order:
- fissures in all newly grown premolars and molars without dental caries should be sealed as soon as possible;
- all hard and soft deposits should be removed by means of a rotating brush and some of protective tooth pastes (Proxyt, Protect) at regular 3-month visits;
- after the teeth have been cleansed and polished, some of the fluorine-containing polishes (Fluor Protector, Cervitec) should be applied;
- before and after initial dental therapy, it is recommended that assessment of the risk of caries be made by tests for Lactobacillus and Streptococcus mutans, amount of stimulated saliva, and buffer capacity; these tests should be carried out at least once a year (45,46); and
- all forms of topical fluoridation (by topical solution, gel or iontophoresis) can be performed as in healthy individuals.
In case a therapeutic procedure is required after initial therapy, appropriate conditions identical to those for adult patients should be provided (the patient should present in the morning, approximately two hours after breakfast and insulin administration). Further procedure is a standard one, with the equipment for antishock therapy and hemostasis at hand (2,47).
DENTAL CARIES AND DIABETES MELLITUS
Dental caries is a destructive disease of the hard tissues of the teeth due to infection with Streptococcus mutans and other bacteria. Formerly one of the commonest human diseases, caries has shown marked changes in recent years, due to artificial fluoridation of drinking water, with additional effects of fluoride-containing tooth pastes and topical fluoride application.
In case of carious lesion progression, infection of dental pulp may occur, causing acute pulpitis. The tooth may become sensitive to warm and cold, and then severe throbbing pain ensues. At this stage, pulp damage is irreversible and it is necessary to remove the contents of the pulp and root canals, followed by thorough cleansing, antiseptics, and filling with an inert material (root canal therapy). Alternatively, extraction of the tooth may be indicated.
If the pulpitis is not successfully treated, the infection may spread beyond the tooth apex into the periodontal ligament. If the infection causes acute inflammation, a periapical abscess may form.
Before the insulin era, clinical investigations pointed to a marked proneness of diabetics to dental caries. The possible causes of the higher frequency of dental caries include increased blood glucose concentration entailing increased salivary and sulcus liquid glucose concentrations, thus providing favorable conditions for cariogenic microorganisms, microvascular complications with compromised tooth vascularization, depression of the immune system, reduced salivary flow, increased number of daily meals containing low-molecule carbohydrates, brusing the teeth as frequently as healthy persons do, and unfavorable dietary relation between calcium and phosphorus (48,49).
After the introduction of insulin in diabetes treatment, the frequency of dental caries in diabetics has considerably decreased.
The patient should be warned that a tooth affected by caries cannot be regenerated. A dentist can very easily remove the damaged part of the tooth and substitute it with a filling. The sooner one visits the dentist, the easier and less painful the treatment will be. If the process extends to dental pulp, the treatment takes longer and is not always successful.
In patient education, attention should be drawn to dental caries prevention. This requires special accent on the importance of good diabetes control, need of more frequent tooth washing daily, and visiting a dentist for preventive fluoridation.
A number of factors contribute to the increased incidence of various diseases of oral mucosa because of its reduced immunity. Good glycemia control reduces the incidence and severity of periodontal disease, and after the advent of insulin therapy a reduction in dental caries in diabetic patients has been observed. Patient education on the measures of prevention of different changes of the gingiva with consequential periodontium destruction and of dental caries prevention is, beside good glycemia control, considered the most important measure of dental care in diabetic patients. In case that any of the above mentioned diseases of the oral mucosa or teeth occurs, the patient should be informed on the necessity of early dental treatment.
- Oliver RC, Tervonen T. Periodontitis and tooth loss: comparing diabetics with the general population. JADA 1993;124:71.
- Levin JA, Muzyka BC, Glick M. Dental management of patients with diabetes mellitus. Compendium 1996;1:82-90.
- Quirino MR, Birman EG, Paula CR. Oral manifestations of diabetes mellitus in controlled and uncontrolled patients. Braz Dent J 1995;2:131-136.
- Greenspan D. Xerostomia: diagnosis and management. Oncology 1996;10:7-11.
- Anonymous. Periodontal therapy: a summary status report 1987-1988. J Periodontol 1988;59:306-310.
- Hammond B. The microbiology of periodontal disease with emphasis on localized juvenile periodontitis. Alpha Omean 1983;76:27.
- Bacic M. Parametri alteriranog parodonta i periferne krvi bolesnika sa secernom bolesti. Doctoral dissertation, Zagreb, 1986.
- Nisengard RJ. The role of immunology in periodontal disease. J Periodontol 1977;48:505.
- Tervonen T, Oliver RC. Long-term control of diabetes mellitus and periodontitis. J Clin Periodontol 1993;20:431-435.
- Karjalainen KM, Knuuttila MLE. The onset of diabetes and poor metabolic control increase gingival bleeding in children and adolescents with insulin-dependent diabetes mellitus. J Clin Periodontol 1996;23:1060-1067.
- Morain WD, Colen LB. Wound healing in diabetes mellitus. Clin Plast Surg 1990;17:493-501.
- Mustard JF, Packham MA. Platelets and diabetes mellitus. N Engl J Med 1984;311:665-667.
- Sastrovijoto SH, Velden U, Steenbergen TJM, et al. Improved metabolic control, clinical periodontal status and subgingival microbiology in insulin-dependent diabetes mellitus. J Clin Periodontol 1990;17:233-242.
- Manouchehr-Pour M, Spagnuolo PJ, Rodman HM, Bissada NF. Comparison of neutrophil chemotactic response in diabetic patients with mild and severe periodontal disease. J Periodontol 1981;52:410-415.
- Rosenstock J, Challis P, Strowig S, Raskin Ph. Improved diabetes control reduces skeletal muscle capillary basement membrane width in insulin-dependent diabetes mellitus. Diab Res Clin Pract 1988;4:167-175.
- Christgau M, Palitzsch KD, Schmalz G, Kreiner U, Frenzel S. Healing response to non-surgical periodontal therapy in patients with diabetes mellitus: clinical, microbiological and immunologic results. J Clin Periodontol 1988;15:112-124.
- Thorstensson H, Kuylenstierna J, Hugoson A. Medical status and complications in relation to periodontal disease experience in insulin-dependent diabetics. J Clin Periodontol 1996;23:194-202.
- Genco RJ. Current view of risk factors for periodontal diseases. J Periodontol 1996;67:1041-1049.
- The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and prognosis of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329:977-986.
- Grossi SG, Skrepcinski FB, DeCaro T, Zambon JJ, Cummins D, Genco RJ. Response to periodontal therapy in diabetics and smokers. J Periodontol 1996;67:1094-1102.
- Brownlee M, Cerami A. The biochemistry of the complications of diabetes mellitus. Ann Rev Biochem 1981;50:385-432.
- Brownlee M. Glycation products and the pathogenesis of diabetic complications. Diabetes Care 1992;15:1835-1843.
- Brownlee M, Vlassara H, Kooney T, Ulrich P, Cerami A. Aminoguanidine prevents diabetes-induced arterial wall protein cross-linking. Science 1986;232:1629-1632.
- Schmidt AM, Hasu M, Popov D, et al. The receptor for advanced glycation endproducts (AGEs) has a central role in vessel wall interactions and gene activation in response to circulating AGE-proteins. PNAS 1994;91:8807-8811.
- Takahashi K, Takashiba S, Nagai A, et al. Assessment of IL-6 in the pathogenesis of periodontal disease. J Periodontol 1994;65:147-153.
- Vlassara H, Brownlee M, Monogue K, Dinarello CA, Pasagian A. Cachectin/TNF and IL-1 induced by glucose modified proteins: role in normal tissue remodeling. Science 1988;240:1546-1548.
- Grossi SG, Zambon JJ, Ho AW, et al. Assessment of risk for periodontal disease. I. Risk indicators for attachment loss. J Periodontol 1994;65:260-267.
- Nishimura F, Terranova V, Foo H, Kurihara M, Kurihara H, Murayama Y. Glucose-mediated alteration of cellular function in human periodontal ligament cells. J Dent Res 1996;75:1664-1671.
- Haffajee AD, Socransky SS. Microbial etiological agents of destructive periodontal diseases. Periodontol 2000 1994;5:78-111.
- Slots J, Feik D, Rams TE. Age and sex relationships of superinfecting microorganisms in periodontitis patients. Oral Microbiol Immunol 1990;5:305-308.
- Rylander H, Ramberg P, Blohme G, Lindhe H. Prevalence of periodontal disease in young diabetics. J Clin Periodontol 1986;13:38-43.
- Shlossman M, Knowler WC, Pettitt DJ, Genco RJ. Type 2 diabetes mellitus and periodontal disease. J Am Dent Assoc 1990;121:532-536.
- Emrich LJ, Shlossman M, Genco RJ. Periodontal disease in non-insulin-dependent diabetes mellitus. J Periodontol 1991;62:123-130.
- Thorstensson H, Hugoson A. Periodontal disease experience in adult long-duration insulin-dependent diabetics. J Clin Periodontol 1993;20:352-358.
- Katz PP, Wirthlin MR, Szpunar SM, Selby JV, Sepe SJ, Showstack JA. Epidemiology and prevention of periodontal disease in individuals with diabetes. Diabetes Care 1991;14:375-385.
- Jainkittivong A, Ye CK, Guest GF, Cottone JA. Evaluation of medical consultations in a predoctoral dental clinic. Oral Surg Oral Med Oral Pathol Oral Radiol Endodont 1995;4:409-413.
- Zinman B. Insulin regimens and strategies for IDDM. Diabetes Care 1993;16(Suppl 3):24-28.
- Lamey PJ, Darwazed AMG, Frier BM. Oral disorders associated with diabetes mellitus. Diabet Med 1992;9:410-416.
- Shamoon H. Pathophysiology of diabetes, a review of selected recent developments and their impact on treatment. Drugs 1992;44(Suppl 33):1-12.
- Radionov D, Lulic-Dukic O, Verzak Z, Juric H. Insulin-dependent diabetes mellitus and periodontal disease in children. Med Jad 1996;14:48-52.
- Cianciola LJ, Park BH, Bruck E, Mosovich L, Genco RJ. Prevalence of periodontal disease in insulin-dependent diabetes mellitus (juvenile diabetes). JADA 1982;104:653-660.
- Spangler JG, Konen JC. Oral health behaviors in medical patients with diabetes mellitus. J Dent Hyg 1994;6:287-293.
- Anonymous. Diabetes and periodontal diseases. J Periodontol 1996;2:166-176.
- Aldridge JP, Lester V, Watts TL, Collins A, Vibreti G, Wilson RF. Single-blind studies of the effects of improved periodontal health on metabolic control in type 1 diabetes mellitus. J Clin Periodontol 1995;22:271-275.
- Gusberti FA, Syed SA, Bacon G, Grossman N, Loesche WJ. Puberty gingivitis in insulin-dependent diabetic children. J Periodontol 1983;12:714-720.
- Mashimo PA, Yamamoto Y, Slots J, Park BH, Genco RJ. The periodontal microflora of juvenile diabetics. J Periodontol 1983;7:420-430.
- Bavitz JB. Emergency management of hypoglycemia and hyperglycemia. Dent Clin North Am 1995;3:587-594.
- Bernick SM, Cohen DW, Baker L, Laster L. Dental disease in children with diabetes mellitus. J Periodontol 1975;4:241-245.
- Twetman S, Nederfors T, Stahl B, Aronson S. Two-year longitudinal observations of salivary status and dental caries in children with insulin-dependent diabetes mellitus. Pediatr Dent 1992;3:184-188.