Periodontology 2000, Vol. 23, 2000, 63–72 Copyright C Munksgaard 2000Printed in Denmark ¡ All rights reserved

PERIODONTOLOGY 2000ISSN 0906-6713

Periodontal management ofthe patient with diabetes mellitusTERRY D. REES

The interrelationship between diabetes mellitus andperiodontitis has been studied for many years. Atpresent there is strong evidence to suggest that theincidence and severity of periodontitis is influencedby the presence or absence of diabetes mellitus, aswell as the degree to which the disease is controlledby patients (9, 19, 42, 62–64, 66, 76, 86, 96). Otherreports indicate that the existence of severe general-ized periodontitis may adversely influence the con-trol of underlying systemic disease (29–31, 52, 80, 93,105, 106). Further, several oral effects of undetectedor poorly controlled diabetes mellitus have beenidentified and must be taken into consideration dur-ing treatment of diabetic patients with periodontaldisease (71). The clinician must be prepared to pro-vide periodontal therapy for patients who have ex-perienced renal disease, retinopathy, neuropathy orcardiovascular disease as an adverse effect of theirdiabetic state, as well as to manage medical emerg-encies related to these adverse effects or to hypo- orhyperglycemia (5, 49).

Epidemiological data indicate that a growingnumber of individuals in the United States sufferfrom diabetes mellitus (58, 59, 102). Some popula-tion groups may be at particular risk for this disease,including African-Americans, Hispanics, AmericanIndians and native Hawaiians (46, 58, 59, 90). Thegrowing elderly population in this country has a farhigher incidence of type 2 diabetes mellitus than doyounger age groups (28, 49, 58, 102). In general, anestimated 10 to 15 million individuals (7%) in theUnited States are affected. The incidence of diabetesmellitus may be increasing by up to 6% per annum,with more than 500,000 new cases diagnosed annu-ally. An estimated 8 million type 2 diabetics are un-diagnosed (49, 54). The epidemiological data regard-ing diabetes mellitus coupled with the possibleinterrelationship between diabetes mellitus andperiodontal disease suggests that all dentists will en-counter patients with diabetes mellitus and that cli-

63

nicians who perform periodontal therapy must beespecially aware and knowledgeable regarding thisdisease (49, 71).

The recently redefined diagnostic criteria of dia-betes mellitus proposed by the Expert Committee ofthe American Diabetes Association has helped toclarify the nature and severity of the condition. Dia-betes mellitus is considered to be present whensequential fasting plasma glucose levels are at or be-low 126 mg/dl or 2-hour post-glucose loadingplasma levels are at or above 200 mg/dl. Patientswith diabetes mellitus symptoms and casual plasmaglucose levels at or above 200 mg/dl should be re-tested on a subsequent day using fasting plasma glu-cose or 2-hour post-glucose loading plasma levels(5). Type 1 diabetics experience b cell destruction ofthe islets of Langerhans of the pancreas, which maylead to an absolute insulin deficiency. Those individ-uals are dependent on insulin for metabolic controlof their disease (5, 6) and may suffer from a moresevere form of the disease, which features abrupt on-set, increased frequency and severity of ketoacidosis,wider fluctuations in plasma glucose levels andpossibly more severe systemic complications (54, 88,102). Type 2 diabetes mellitus patients experience in-sulin resistance, with or without insulin deficiency.These individuals may experience a more gradualonset of signs and symptoms and may be less likelyto develop ketoacidosis (2, 5, 8). Individuals with im-paired fasting glucose demonstrate fasting plasmalevels of 110–126 mg/dl, while those with impairedglucose tolerance display 2-hour post-glucose load-ing plasma levels between 140 mg/dl and 200 mg/dl. Impaired fasting glucose and impaired glucosetolerance represent intermediate stages betweennormal glucose homeostasis and diabetes mellitus.Impaired fasting glucose and impaired glucose toler-ance are risk factors for future development of dia-betes mellitus and cardiovascular diseases, but theirrelationship with periodontal disease or other oral

Rees

features of diabetes mellitus has not been studied(5). Glucose intolerant individuals or those with ges-tational diabetes mellitus may experience either typeof diabetes mellitus at a later date. Other types ofdiabetes mellitus exist but are beyond the scope ofthis report. Untreated type 1 diabetic patients aremore likely to manifest the classic signs and symp-toms of diabetes mellitus, which include the triad ofpolyuria, polydypsia and polyphasia, as well as prur-itis, weakness and fatigue. Weight loss may occur inassociation with this type, while obesity is a com-mon feature in individuals with type 2 disease (53,58). Severely hyperglycemic individuals with ketoac-idosis may experience nausea, vomiting, dehy-dration, restlessness, irritability, apathy, coma andeven death (102).

Long-term systemic complications of diabetesmellitus may include diabetic retinopathy, poten-tially leading to loss of vision, atherosclerotic cere-brovascular, cardiovascular and peripheral vasculardiseases, peripheral neuropathy, which may lead toloss of limbs and dyesthesias (burning), progressiverenal dysfunction, delayed wound healing and in-creased susceptibility to periodontal disease (47, 53,60, 61, 97).

Oral manifestations

Oral manifestations of diabetes mellitus were firstdescribed more than 100 years ago (3) and may bemore severe in individuals with uncontrolled type 1diabetes mellitus compared to those with uncon-trolled type 2 diabetes mellitus (8, 103). Severalstudies suggest, however, that patient age at onset ofdiabetes mellitus, duration of diabetes mellitus anddegree of metabolic control may exert a greater in-fluence on oral and systemic complications than thetype of diabetes mellitus present (5, 6, 9, 26, 30, 31,38, 66, 92, 93, 101), although recent evidence indi-cates that diabetic complications such as retinopa-thy, cardiovascular disease and neuropathy may be-gin several years before the diagnosis of type 2 dia-betes mellitus is established (102). This evidencesuggests that all individuals should be tested period-ically for diabetes mellitus.

Diminished salivary flow is a common oral featureof diabetes mellitus and may or may not includesymptoms of burning mouth or tongue and con-comitant enlargement of the parotid salivary glands(4, 55, 56, 71, 85, 99). Some reports indicate that thebasement membrane of salivary gland ducts may bealtered and other histopathological changes may oc-

64

cur within the salivary glands (55, 56, 85, 99). Thepresence or absence of these histological alterationsmay help explain why parotid enlargement may bereduced when diabetes mellitus is diagnosed andmetabolic control achieved. Others have reportedthat salivary flow rates may remain slightly dimin-ished and that increased levels of salivary glucosemay persist despite effective diabetes mellitus con-trol (4, 14, 99). These factors have not been ad-equately studied, however, since increasing empha-sis on strict metabolic control of diabetes mellitushas become the accepted therapy (18, 65, 101). Inpoorly controlled or uncontrolled diabetes mellituswhole saliva and gingival crevicular fluid may con-tain increased quantities of glucose (21, 40), whichmay in part alter plaque microflora with a resultantinfluence on the development of dental caries andpossibly periodontal disease (33, 49, 102).

The dessication of oral mucosa induced by dia-betes mellitus–associated xerostomia may cause oraltissues to be more easily damaged by trauma andmore susceptible to opportunistic infections such ascandidiasis. Xerostomia may also lead to increasedaccumulation of bacterial plaque and food debriswith an associated increased susceptibility to dentalcaries and periodontitis. Two recent studies haveidentified a correlation between xerostomia inducedby Sjogren’s syndrome and increased incidence andseverity of periodontitis, so it would be reasonableto assume that diabetes mellitus-induced xero-stomia could have the same effect (15, 57). Xero-stomia may be further exacerbated by medicationsprescribed for individuals suffering from compli-cations of diabetes mellitus such as nephropathy,neuropathy or cardiovascular diseases (3, 27, 33).

Burning mouth or tongue and altered taste sen-sation have been reported in diabetes mellitus pa-tients, probably as a result of xerostomia and/or sec-ondary candidiasis. It has also been suggested, butnot clearly established, that burning tongue may oc-cur in patients with severe diabetes mellitus as a re-sult of diabetic neuropathy (71, 72). Altered tastesensation may occur as a result of xerostomia andcandidiasis; as a direct result of diabetic neuropathy;or by medications that may induce alterations in glu-cose receptors within taste buds. Decreased tastesensation may be more pronounced for sucrose thanother taste test components, suggesting a direct ef-fect of diabetes mellitus (34, 43).

An increased incidence of dental caries has beenreported among uncontrolled or poorly controlleddiabetes mellitus in both animal and human studies(11, 20, 24, 26, 74, 94). Conversely, well-maintained

Periodontal management of the patient with diabetes mellitus

diabetes mellitus patients tend to also be compliantwith oral health measures and may experience anormal or reduced incidence of dental caries due todietary restrictions, effective metabolic control ofserum glucose levels and compliance with oral hy-giene procedures and dental recall appointmentschedules (2, 27, 36, 45, 74, 81, 96, 98).

An association between oral lichen planus anddiabetes mellitus has been suggested but not con-firmed (78). Although some reports indicate an in-creased frequency of oral lichen planus among dia-betes mellitus patients, it appears likely that this mayrepresent a lichenoid drug reaction to medicationsused in treatment of diabetes mellitus or its associ-ated complications (10, 44). In the StomatologyCenter at Baylor College of Dentistry, the incidenceof diabetes mellitus among 248 patients with histo-logically diagnosed oral lichen planus was comparedto the incidence of diabetes mellitus among 248 age-and sex-matched controls. Although a slightly largernumber of individuals with oral lichen planus werefound to also have diabetes mellitus, the differencewas not statistically significant.

The rapidly accumulating data regarding the ef-fect of diabetes mellitus on the oral cavity suggestthat oral tissues are adversely affected by uncon-trolled diabetes mellitus similarly to other bodysystems (84). Increased susceptibility to oral infec-tion, including gingivitis, periodontitis and delayedwound healing, has been described (1, 4, 7, 12, 13,25, 71, 100, 104). Pronounced gingival enlargementmay be an early sign of diabetes mellitus onset,and some case reports describe marked improve-ment in periodontal and/or oral health when pre-viously undiagnosed diabetes mellitus was recog-nized and metabolic control established (1, 7, 12,13, 84, 104). The mechanism by which this occurshas been discussed in a previous section of thischapter. The periodontist should be especially alertto the possibility that an individual has undiag-nosed or poorly controlled diabetes mellitus in thepresence of multiple or recurrent periodontal ab-scesses, unexplained edematous gingival enlarge-ment, rapid destruction of alveolar bone or delay-ed healing following periodontal or oral surgicalprocedures (71, 79, 104). Conversely, there is in-creasing evidence in controlled studies to indicatethat severe oral infections of any type, includinggeneralized periodontitis, may increase insulin re-sistance and possibly interfere with metabolic con-trol of diabetes mellitus (17, 29–31, 49, 52, 82, 95,105). On occasion, oral infections have been life-threatening to diabetic patients (12, 35, 75).

65

Patient evaluation

As previously discussed, the dental practitioner is ex-tremely likely to encounter periodontal patients whosuffer from undiagnosed or poorly controlled dia-betes mellitus or others who are diagnosed and wellmaintained. More stringent medical standards havenarrowed the criteria for good metabolic control,with the result that an increased number of peri-odontal patients may now fall into the inadequatelycontrolled category. To properly evaluate peri-odontal patients, the dental clinician must be awareof the general and oral signs and symptoms of dia-betes mellitus. Appropriate dental practice requiresa thorough oral examination and an appropriatemedical history. The medical history format must in-clude questions that elicit information regarding thepatient’s family history of diabetes mellitus and anygeneral symptoms that may raise the practitioner’slevel of suspicion regarding this disease. The oral ex-amination should identify oral features suggestive ofdiabetes mellitus, and the presence of any such fea-tures may indicate a need for medical consultation.In that event, the consultation request should pro-vide information regarding any general or oral fea-tures that have raised the dental practitioner’s levelof suspicion. On some occasions it may be prefer-able for the dentist to perform screening blood glu-cose tests prior to referring the patient for medicalevaluation. Often dental patients are reluctant toseek medical evaluation and occasionally even re-sentful that the dentist would require medical con-sultation as a condition for receiving dental treat-ment. In these circumstances several screening testsare available for determining blood glucose levels(28, 33, 53, 73). Long, laborious and costly tests suchas the 4- to 6-hour glucose tolerance test should beavoided. Such tests must be performed under exact-ing circumstances and carefully interpreted by thepatient’s physician. Therefore the glucose tolerancetest has little place in dental practice. Traditionally,urine glucose levels have been used as a screeningmechanism. For the test to be positive, however,high blood glucose levels must be present and lesssevere blood glucose abnormalities may go un-detected.

The National Diabetes Data Group and the ExpertCommittee on the Diagnosis and Classification ofDiabetes Mellitus have published specific recom-mendations for diabetic screening, including meas-urement of fasting plasma glucose, glucose tolerancetests and glycated hemoglobin (5, 59, 61). The firsttwo tests require rigid compliance with the appropri-

Rees

ate pre-test protocol and careful interpretation of re-sults. If the test is positive, medical referral is essen-tial to establish the diagnosis. The dentist shouldavoid telling a patient that he or she has diabetes,since plasma glucose levels may fluctuate widelyeven in healthy individuals due to factors such asstress and exercise. Other illnesses can also affectplasma glucose levels (49).

A simple screening test for dental patient evalu-ation is to obtain a fasting plasma glucose level (8 ormore hours of fasting) alone or in combination witha 2-hour post-glucose loading plasma test to evalu-ate glucose utilization. Under ideal circumstances,the 2-hour post-glucose loading plasma test shouldinclude ingestion of a measured quantity of glucose.The disadvantage to the fasting plasma glucose and2-hour post-glucose loading plasma is that the testsare costly and they require patient compliance withpre-test fasting and a controlled pre-test diet for the2-hour post-glucose loading plasma evaluation. Inaddition, the tests may require two visits to themedical laboratory for completion.

Although not advocated by many diabetologists(5, 6), in the periodontist’s office the glycated hemo-globin test (hemoglobin A1c) has been proposed asoffering several advantages as a screening test fordentists (69). The test is based on the fact that glu-cose binds to blood hemoglobin within the circu-lating erythrocytes and remains attached for the lifecycle of the red blood cell. It is often the preferredtest for medical evaluation of diabetic control be-cause it measures blood glucose levels over a periodof 8 to 12 weeks. The test is accurate and relativelyinexpensive; it requires only one medical laboratorytest and patient compliance is not required as it isfor a fasting and 2-hour post-glucose loading plasmatest (41, 68). There are variations in the reported re-sults from one laboratory to another, however, andthe practitioner must be aware of the standard ob-served by the laboratory to which the patient hasbeen referred. In general, normal levels for glycatedhemoglobin are 5.0–7.5% (5, 6, 61, 69, 77). Any pa-tient with a higher result should be referred formedical evaluation.

Home monitoring devices (glucometers) arecommonly used by diabetes mellitus patients forfrequent or daily monitoring of their blood glucoselevels. It is not uncommon for patients under strictmetabolic control to test their blood glucose levelsfour to six times daily. To perform the test, a one-or two-drop blood sample is obtained by fingerstick, placed on a reagent strip and inserted intothe reflector monitor, which determines the glu-

66

cose level and displays the results. In the past thistechnique has been used in dental offices as ascreening test for suspected diabetic individuals.The test is simple, inexpensive and reasonably ac-curate; however, current United States federal stan-dards regarding regulation and inspection of medi-cal laboratories preclude its use as a screening testfor suspected diabetes mellitus patients unless thedental office has been approved as a medical lab-oratory. It should be noted, however, that knowndiabetic patients can perform the reagent stripprocedure in the dental office using their own glu-cometer as a means of monitoring their diabetesmellitus status prior to an extensive periodontal ororal surgical treatment procedure or prior to treat-ment likely to disrupt the patient’s normal dietaryroutine (49, 53, 73).

Management of knowndiabetic patients

When the practitioner is called upon to provide peri-odontal therapy for a previously diagnosed diabetesmellitus patient, a certain amount of detailed infor-mation should be gathered. The patient should bequestioned regarding the type of diabetes, the age atonset and duration of the disease; any current medi-cations and their method of administration. The pa-tient’s degree of compliance and monitoring tech-nique should be discussed. The practitioner shouldreview any previous history of diabetic compli-cations, determine the most recent laboratory resultsand record the name and address of the patient’sphysician(s). By gathering this information the clini-cian can best relate the patient’s oral condition to hisor her systemic status and determine whether or notmedical consultation is required. Under most cir-cumstances it would be prudent to obtain medicalclearance prior to performing any extensive peri-odontal therapy, especially if surgery is indicated (33,73).

In most instances the well-controlled type 1 ortype 2 patient can be managed in a manner consist-ent with a healthy non-diabetic individual (33, 48,49, 72, 73, 83, 89). Periodontal surgical procedurescan be performed, although it must be assured thatthe patient can maintain a normal diet post-surgic-ally. In the event that the treatment procedure modi-fies the patient’s dietary habits, dietary supplementsshould be recommended. Supportive periodontaltherapy should be provided at relatively close inter-

Periodontal management of the patient with diabetes mellitus

vals (2 to 3 months) since some studies indicate aslight but persistent tendency to progressive peri-odontal destruction despite effective metabolic dia-betes mellitus control.

In many instances, the type 2 patient is not wellcontrolled by rigid standards, yet the patient’sphysician will provide medical clearance to per-form periodontal therapy because the patient islikely to tolerate the procedure without undue dif-ficulty. In this circumstance the periodontistshould proceed with caution since the treatmentoutcome may be compromised. It should be re-membered that inadequate diabetes mellitus con-trol can adversely affect the severity of the peri-odontal disease response, the patient’s wound-healing capacity and the ability of the patient towithstand both emotional and physical stress. Theclinician should insist that the patient achieve andsustain a highly effective level of oral physio-therapy, and in most instances a nonsurgical ap-proach to periodontal therapy is preferred, with orwithout the use of appropriate antibiotic therapy.In the event that antibiotic therapy is anticipated,microbiological testing to identify putative peri-odontal pathogens is suggested.

Management of uncontrolled orpoorly controlled diabetic patients

The uncontrolled or poorly controlled diabetic pa-tient or the diabetes mellitus patient who does notknow his or her control status should not receiveelective dental treatment until the condition is sta-bilized or medical clearance obtained. Prophylacticantibiotic therapy should be used for performanceof emergency oral or periodontal surgical proceduresto minimize the potential for postoperative infec-tions and delayed wound healing (4).

Periodontal therapy other than emergency treat-ment may be contraindicated in the poorly con-trolled diabetes mellitus patient until appropriatemetabolic controlled is achieved. In many in-stances this may require short- or long-term pre-scription of insulin or oral medications by thephysician. The physician should be made aware ofrecent controlled studies that indicate that peri-odontal therapy may facilitate metabolic control ofdiabetes mellitus and, when possible, a coordi-nated medical-dental plan of action should be im-plemented to achieve optimum patient health (18,29–31, 52, 65, 86, 101, 105).

67

Oral medicationsfor diabetic control

For many years, type 2 diabetes mellitus has beentreated by diet control and various hypoglycemicagents, usually a first- or second-generationsulfonylurea (acetohexamide, chlorpropamide, tola-zamide, tolbutamide, glimepiride, glipizide or glybu-ride). Sulfonylureas promote insulin secretion, andimportantly, they are all capable of inducing hypo-glycemia (32, 102).

Non-sulfonyluria drugs may be used as monother-apy or in combination with other oral hygoglycemicagents or insulin. Troglitazone is a thiazolidinedioneagent which improves insulin sensitivity and de-creases insulin resistance. When used as monother-apy it does not induce hypoglycemia. It is active onlyin the presence of insulin. Repaglinide is a new anti-diabetic agent that potentiates glucose-stimulatedinsulin secretion. It can produce hypoglycemia, andserious cardiovascular events have been reported.The biguanide, metformin, is often used as a mono-therapy. When combined with sulfonyluria or insu-lin, however, it may also induce hypoglycemia. Thealpha-glucosidase inhibitors, acarbose and meglitoldo not cause hypoglycemia unless given in combi-nation with sulfonylurias (32, 50, 102).

Insulin

Insulins are classified as rapid-, short-, intermediate-or long-acting. Each category induces variable onsetof peak activity and duration. Insulin injections aretimed so that peak plasma levels coincide with peakpostprandial glucose levels. It is important for thepractitioner to know the medication regimen beingused by the patient, and periodontal therapy shouldbe timed to avoid peak insulin activity and possiblehypoglycemic crisis (49).

Periodontal therapy

The well-controlled diabetes mellitus patient withperiodontal disease is often an acceptable candi-date for complete periodontal therapy, includingsurgical procedures when indicated. As discussedpreviously, however, the presence of medical com-plications associated with diabetes mellitus shouldbe carefully evaluated and considered in any peri-odontal therapeutic decision. In most instancesperiodontal surgical therapy should be carefully

Rees

planned and coordinated with the patient’s physi-cian to insure minimal disruption of metabolicdiabetes mellitus control. Most authorities rec-ommend that periodontal surgery be scheduled inthe morning after breakfast and medication ad-ministration. Treatment procedures should beshort (2 hours or less), as atraumatic as possibleand should not significantly interfere with the pa-tient’s normal dietary intake. Patient anxietyshould be managed to minimize endogenousepinephrine release, because epinephrine may in-crease insulin utilization and deplete insulin levelsmore quickly. In most instances preoperative oralsedation is suitable for this purpose. In the eventthat general anesthesia or intravenous conscioussedation techniques are necessary or if extensivesurgical procedures are likely to alter the patient’sdietary intake, then changes in the type 1 patient’sinsulin intake may be necessary under the guid-ance of the patient’s physician. Decisions regardingthe prophylactic use of antibiotics in conjunctionwith periodontal surgery are best made on a case-by-case basis since there is no evidence-based in-formation to indicate that antibiotic premedicationis necessary (73).

The poorly controlled type 1 patient is not a goodcandidate for periodontal therapy other than necess-ary emergency services. Medical coordination isprobably indicated for any type of periodontal ther-apy and hospitalization may be required for emer-gency care. If time permits, microbiological testing isdesirable to identify putative periodontal pathogensprior to antibiotic therapy. If stable metabolic con-trol is achieved, routine periodontal therapy may beconsidered with close medical monitoring (16, 48,49).

In general, all diabetes mellitus patients should beencouraged to maintain meticulous oral hygiene andto receive supportive periodontal therapy at intervalsnecessary to sustain a high level of periodontalhealth. Patients should be carefully monitored fordental caries and home and office use of fluoridecaries preventive agents is recommended. Diabetesmellitus–related xerostomia should be managed ona case-by-case basis, but in general patients shouldbe encouraged to adhere to strict diabetes mellitusmetabolic control and to avoid smoking or the useof alcohol (including mouthrinses with high alcoholcontent) and caffeine-containing beverages. Arti-ficial saliva substitutes and frequent ingestion ofwater may be of benefit. A pilocarpine-containingdrug (SalagenA) has recently been approved by theFood and Drug Administration for management of

68

xerostomia resulting from therapeutic radiation ex-posure and Sjogren’s syndrome (23, 50). The benefitsof this drug in managing diabetes mellitus or drug-induced xerostomia have not yet been studied, andit should only be prescribed with the consent of thepatient’s diabetologist. There is some evidence tosuggest that oral hygiene products containing thedetergent sodium lauryl sulfate may be irritating tothe mucous membranes of xerostomic patients, andthis agent should be avoided if xerostomia is a prob-lem for the diabetes mellitus patient. Patients shouldbe encouraged to stimulate salivary flow by the useof sugarless gum or natural salivary stimulants suchas chewing raw carrots and celery (37).

Frequent monitoring for the overgrowth of oralfungal organisms such as Candidia albicans is in-dicated, and on occasion the prophylactic use oftopical antifungal agents may be necessary. Mosttopical oral antifungal products contain sucroseand may be contraindicated for caries-susceptiblediabetes mellitus patients. The topical agent, nys-tatin, however, can be obtained in a powder formwhich is sucrose-free, but it must be mixed withwater for each use. More recently, an oral anti-fungal rinse containing itraconazole has becomeavailable that uses saccharin in place of sucrose(50). Improvement in burning mouth and alteredtaste sensation may occur when diabetes mellitusmetabolic control is established or when xero-stomia and associated candidiasis are controlled.Some patients respond more effectively, however,to the prescription of low-dose amitryptyline-con-taining antidepressant drugs, probably due to theireffect on neural inflammation. Again, use of suchagents should be coordinated with the consultingphysician and some diabetes mellitus compli-cations or medications may contradict its use (22,102).

Implants

Placement of implants in diabetic patients is a mat-ter of great interest to periodontists. Successful im-plantation has been described in well-controlled in-dividuals with diabetes mellitus (25), but two recentstudies of uncontrolled diabetes mellitus in animalshave suggested an altered pattern of bone formationin relation to implants (39, 91). In view of thesestudies, plus clinical evidence of delayed healing indiabetic patients, it is doubtful that the uncontrolledor poorly controlled diabetes mellitus patient is asuitable candidate for implant placement.

Periodontal management of the patient with diabetes mellitus

Management ofdiabetic emergencies

Dental practitioners must remain alert for possiblecomplications and/or emergencies associated withdiabetes mellitus. Hyperglycemia may lead to shock(diabetic coma), although the condition developsrelatively slowly and abrupt onset is unlikely. Thehyperglycemic patient may become disoriented,breathing may become rapid and deep (Kussmaul’srespiration), the skin may be hot and dry and ‘‘ace-tone’’ breath may be evident. Severe hypotensionand coma may follow. Coma is usually associatedwith plasma glucose levels of between 300 and 600mg/dl. Patients experiencing this condition willusually remain conscious but should be transferredimmediately to a hospital emergency room forevaluation. If the patient becomes unconscious,basic life support procedures should be initiated(open airway, administration of 100% oxygen) andthe emergency medical alert system activated. If cir-cumstances allow, non-glucose-containing intra-venous fluids should be administered to prevent vas-cular collapse. Patient recovery from diabetic comamay be slower than from hypoglycemic shock (49,53, 70, 73).

In contrast, hypoglycemic shock is associated withrelatively sudden onset when plasma glucose levelsdrop below 40 mg/dl. It may be precipitated by exer-cise, diabetes mellitus drug overdose, stress or failureby the patient to properly control his or her dietaryintake. In many instances hyperglycemic or hypogly-cemic shock may be difficult to differentiate basedon signs and symptoms. In both circumstances thepatient may experience mood changes, mental con-fusion, lethargy and increasingly bizarre behavior.Although careful analysis may indicate the true na-ture of the patient’s condition, it is usually more pru-dent to treat unknown reactions by diabetes mellituspatients in the dental office as though they were ex-periencing hypoglycemia. Treatment should be in-itiated as quickly as possible since hypoglycemiamay lead to tachycardia, hypotension, hypothermia,loss of consciousness, seizures and even death. Earlytreatment includes the administration of oral carbo-hydrates such as orange juice, soft drinks, candy orglucola. Such agents administered during hypergly-cemic states will have little additional detrimentaleffects, while they may reverse hypoglycemic status.Dextrose can be administered intravenously to theconscious or unconscious patient, while glucogonmay be administered subcutaneously, intramuscul-arly, or intravenously (1 mg), followed by epine-

69

phrine (0.5 mg of 1 : 1000 concentration). Glucagonmay be less useful in type 2 diabetes mellitus, sinceits function is to stimulate insulin secretion ratherthan decrease resistance. If the patient remains un-responsive, the emergency alert system should beactivated and the patient transferred to a hospitalemergency room. In most instances, patients will be-come alert in response to therapy within five to tenminutes. In this event careful observation is necess-ary until the patient is fully stabilized. If possible thepatient’s own glucometer should be used to evaluatehis or her status. In any event the patient’s physicianshould be notified ((28, 53, 70, 73).

Ongoing multi-center studies of diabetic patientsindicate that strict control of blood glucose levels inboth type 1 and type 2 patients close to the range ofnormal for non-diabetic individuals results in fewermedical complications (18, 65, 101). Consequently,increased emphasis is being placed on home moni-toring and rigorous efforts by patients to maintainstrict blood sugar control. Although, on balancethese efforts may greatly benefit the diabetes mel-litus patient, there is also strong evidence to suggestthat maintenance of blood glucose levels close to therange of normal can lead to an increased incidenceof hypoglycemia. Elderly diabetes mellitus patientsare prone to develop insidious hypoglycemia andany diabetes mellitus patient may develop hypogly-cemia without displaying or sensing the commonsigns and symptoms. The dental practitioner mustremain constantly alert for evidence of the conditionduring therapy and take steps to prevent its occur-rence in relation to periodontal therapy (48, 102).

Summary

Diabetes mellitus is a common medical disorder thatwill be encountered by every practicing dentist.Knowledge by the dentist of the general and oralsigns and symptoms of undiagnosed or poorly con-trolled diabetes mellitus are essential, and patientsdisplaying these signs or symptoms should receivemedical referral. Patients suspected, or known tosuffer from undiagnosed or uncontrolled diabetesmellitus should receive only emergency care untiltheir health status has been properly evaluated. Inthe event the degree of control of a known diabeticis unknown or the patient is poorly controlled, anti-biotic therapy should be administered in conjunc-tion with any necessary surgical procedure or in thepresence of oral infection. The practitioner must beprepared to manage diabetic emergencies should

Rees

they occur in the dental office, and hypoglycemic in-cidents are most likely. The developing therapiesnow available for medical management of diabetesmellitus suggest that this condition will be more ef-fectively controlled in the future, but medical con-sultation is important to proper periodontal patientmanagement. New evidence suggests that advancedperiodontal disease may interfere with diabetes mel-litus control and the physician should be madeaware of the patient’s periodontal status. Under mostcircumstances, the well-controlled diabetes mellituspatient can receive safe and effective periodontaltherapy with some modification of office protocol,and there is little reason to anticipate that the con-trolled diabetes mellitus patient cannot look forwardto a lifetime of periodontal health if proper andtimely periodontal therapy is rendered and the pa-tient maintains effective oral hygiene measures ac-companied by appropriate supportive periodontalrecall therapy.

References

1. Akintewe TA, Kulasekara B, Adetuyibi A. Periodontitis dia-betica: a case report from Nigeria. Trop Geogr Med 1984:36: 85–86.

2. Albrecht M, Banoczy J, Baranyi E, Tamas G Jr, Sozabay J,Eqyed I, Simon G, Ember G. Studies of dental and oralchanges of pregnant diabetic women. Acta Diabetol Lat1987: 24: 1–7.

3. Albrecht M, Banoczy J, Tamas G Jr. Dental and oral symp-toms of diabetes mellitus. Community Dent Oral Epider-miol 1988: 16: 378–380.

4. American Dental Association. Council of Access, Preven-tion and Interpersonal Relations. Patients with diabetes.Chicago: American Dental Association, 1994: 1–17.

5. American Diabetes Association. Expert Committee on theDiagnosis and Classification of Diabetes Mellitus. Com-mittee report. Diabetes Care 1997: 20: 1183–1197.

6. American Diabetes Association. Position statement. Im-plications of the diabetes control and complications trial.Diabetes Care 1997: 20(suppl 20): S62–S64.

7. Archer CB, Rosenberg WMC, Scott GW, MacDonald DM.Progressive bacterial synergistic gangrene in a patientwith diabetes mellitus. J R Soc Med 1984: 77(suppl 4): 1–3.

8. Atkinson MA, Maclaren MK. What causes diabetes? SciAm 1990: 263: 62–71.

9. Bacic M, Plancak D, Granic M. CIPTN assessment of peri-odontal status in diabetics. J Periodontol 1988: 59: 816–822.

10. Bagan-Sebastian JV, Milian-Masanet M, Penarrocha-Di-ago M, Jimenex Y. A clinical study of 205 patients withoral lichen planus. J Oral Maxillofac Surg 1992: 50: 116–118.

11. Bahru Y, Abdu SS. A study of dental problems in diabeticpatients. Ethiopian Med J 1992: 30: 95–103.

70

12. Baranda L. Facial erythema and edema in a diabetic man.Arch Dermatol 1986: 122: 329–334.

13. Bartolucci EG, Parks RB. Accelerated periodontal break-down in uncontrolled diabetes. Pathogenesis and treat-ment. Oral Surg Oral Med Oral Pathol Oral Radiol Endod1981: 52: 387–390.

14. Campbell MJA. Glucose in the saliva of the non-diabeticand the diabetic patient. Arch Oral Biol 1965: 10: 197–205.

15. Celenligil H, Eratalay K, Kansu E, Ebersole J. Periodontalstatus and serum antibody responses to oral microorgan-isms in Sjogren’s syndrome. J Periodontol 1998: 69: 571–577.

16. Christgau M, Palitzsch K-D, Schmalz G, Kreiner U, FrenzelS. Healing response to non-surgical periodontal therapyin patients with diabetes mellitus: clinical, microbiologi-cal and immunologic results. J Clin Periodontol 1998: 25:112–124.

17. Cianciola LJ, Park BH, Bruck E, Mosovich L, Genco RJ.Prevalence of periodontal disease in insulin dependentdiabetes mellitus (juvenile diabetes). J Am Dent Assoc1982: 104: 653–660.

18. Diabetes Control and Complications Trial ResearchGroup. The effect of intensive treatment of diabetes onthe development and progression of long-term compli-cations in insulin-dependent diabetes mellitus. N Engl JMed 1993: 329: 977–986.

19. Emrich IJ, Shlossman M, Genco RJ. Periodontal disease innon-insulin dependent adolescents. J Periodontol 1991:62: 123–130.

20. Falk H, Hugoson A, Thorstensson H. Number of teeth,prevalence of caries and periapical lesions in insulin-de-pendent diabetics. Scand J Dent Res 1989: 97: 198–206.

21. Ficara AJ, Levin MP, Grower MF, Kramer GD. A compari-son of the glucose and protein content of gingival fluidfrom diabetics and non-diabetics. J Periodontal Res 1975:10: 171–175.

22. Gage TW, Pickett FA, ed. Dental drug reference. 4th edn.St. Louis: Mosby Publishing, 1998: 47–49.

23. Gage TW, Pickett FA, ed. Dental drug reference. 4th edn.St. Louis: Mosby Publishing, 1998: 534–535.

24. Galea H, Aganovic I, Agnaovic M. The dental caries andperiodontal disease experience of patients with early on-set insulin-dependent diabetes. Int Dent J 1986: 36: 219–224.

25. Gian-Grasso JE, Nagelberg SB. The relationship betweendiabetes and periodontal disease. Pract Diabetol 1997:Sep: 8–10.

26. Glavind L, Lund B, Loe H. The relationship between peri-odontal state, diabetes duration, insulin dosage and reti-nal changes. J Periodontol 1968: 39: 341–347.

27. Goteiner D, Vogel R, Deasy M, Goteiner C. Periodontaland caries experience in children with insulin-dependentdiabetes mellitus. J Am Dent Assoc 1986: 113: 277–279.

28. Gottsegen R. Diabetes mellitus, cardiovascular diseasesand alcoholism. In: Schluger S, Yuodelis R, Page RC, John-son RH, ed. Periodontal diseases. 2nd edn. Philadelphia:Lea and Febiger, 1990: 273–279.

29. Grossi SG, Genco RJ. Periodontal disease and diabetesmellitus: a two-way relationship. Ann Periodontol 1998: 3:51–61.

30. Grossi SG, Skrepcinski FB, DeCaro T, Robertson DC, HoAW, Dunford RG, Genco RJ. Treatment of periodontal dis-ease reduces glycated hemoglobin. J Periodontol 1997: 68:713–719.

Periodontal management of the patient with diabetes mellitus

31. Grossi SG, Skrepcinski FB, DeCaro T, Zambon JJ, Cum-mins D, Genco RJ. Response to periodontal therapy indiabetics and smokers. J Periodontol 1996: 67: 1094–1102.

32. Hall R. Oral medications for diabetes. Periodontal Insights1998: 5: 12–13.

33. Hallmon WW, Mealey BL. Implications of diabetes mel-litus and periodontal disease. Diabetes Educ 1992: 18:310–315.

34. Hardy SL, Brennard CP, Wyse BW. Taste thresholds of indi-viduals with diabetes mellitus and control subjects. J AmDietetic Assoc 1981: 79: 286–289.

35. Harrison GA, Schultz TA, Schaberg SJ. Deep neck infec-tion complicated by diabetes mellitus. Report of a case.Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1983:55: 133–137.

36. Harrison R, Bowen WH. Periodontal health, dental cariesand metabolic control in insulin-dependent children andadolescents. Pediatr Dent 1987: 9: 283–286.

37. Haverman CW, Redding SW. Dental management andtreatment of xerostomic patients. Tex Dent J 1998: June:43–56.

38. Hugoson A, Thorstensson H, Falk H, Kuylenstierna J. Peri-odontal conditions in insulin-dependent diabetics. J ClinPeriodontol 1989: 16: 215–223.

39. Iyama S, Takeshita F, Ayukawa Y, Kido MA, Suetsugu T,Tanaka T. A study of the regional distribution of boneformed around hydroxyapatite implants in the tibiae ofstreptozotocin-induced diabetic rats using multiple flu-orescent labeling and confocal laser scanning microscopy.J Periodontol 1997: 68: 1169–1175.

40. Kjellman O. The presence of glucose in gingival exudateand resting saliva of subjects with insulin treated diabetesmellitus. Swed Dent J 1970: 63: 11–19.

41. Knowler WC. Screening for NIDDM: opportunities for de-tection, treatment and prevention. Diabetes Care 1994:17: 445–450.

42. Lalla E, Lamster IB, Schmidt AM. Enhanced interaction ofadvanced glycation end products with their cellular re-ceptor RAGE: implications for the pathogenesis of accel-erated periodontal disease in diabetics. Ann Periodontol1998: 3: 13–19.

43. Lamey P-J. Salivary gland and chemosensory disorders.In: Millard HP, Mason D, ed. Second World Workshop inOral Medicine. Ann Arbor: University of Michigan, 1995:273–344.

44. Lamey P-J, McCartan BE, MacDonald DG, MacKie RM.Basal cell cytoplasmic autoantibodies in oral lichenoid re-actions. Oral Surg Oral Med Oral Pathol Oral Radiol En-dod 1995: 79: 44–49.

45. Leeper SH, Kalkwarf KL, Strom EA. Oral status of ‘‘con-trolled’’ adolescent type I diabetics. J Oral Med 1985: 40:127–133.

46. Lichton IJ, Bullard LR, Sherrell BU. A conspectus of re-search on nutritional status in Hawaii and western Samoa,1960–1980, with references to diseases in which diet hasbeen implicated. World Rev Nutr Diet 1983: 41: 40–75.

47. Loe H. Periodontal disease. The sixth complication of dia-betes mellitus. Diabetic Care 1993: 16(suppl 1): 329–344.

48. Mealey BL. Periodontal implications: medically compro-mised patients. Ann Periodontol 1996: 1: 256–326.

49. Mealey BL. Impact of advances in diabetes care on dentaltreatment of the diabetic patient. Compendium ContinEduc Dent 1998: 19: 41–58.

71

50. The Medical Letter. Treatment of xerostomia. Med Lett1988: 30: 74–76.

51. The Medical Letter. Oral drugs of type 2 diabetes. MedLett 1998: 40: 55–56.

52. Miller LS, Manwell MA, Newbold D, Reding ME, RasheedA, Blodgett J, Kornman K. The relationship between re-duction in periodontal inflammation and diabetes con-trol: A report of 9 cases. J Periodontol 1992: 63: 843–848.

53. Montgomery MT, Rees TD, Moncrief JW. The diagnosisand management of the diabetic patient: implications fordentistry. Austin, TX: Department of Health, 1992.

54. Murrah VA. Diabetes mellitus and associated oral mani-festations: a review. J Oral Pathol 1985: 4: 272–281.

55. Murrah VA, Crosson JT, Sank JJ. Parotid gland basementmembrane variation in diabetes mellitus. J Oral Pathol1985: 4: 236–246.

56. Muscumeci V, Cherubini P, Zuppi C, Zappacostan B, Gher-banda G, Di Salvo S. Aminotransferases and lactate de-hydrogenase in saliva of diabetic patients. J Oral PatholMed 1993: 22: 73–76.

57. Najera MP, Al-Hashimi I, Plemons JM, Rivera-Hidalgo F,Rees TD, Haghighat N, Wright JM. Prevalence of peri-odontal disease in patients with Sjogren’s syndrome. OralSurg Oral Med Oral Pathol Oral Radiol Endod 1997: 83:453–457.

58. Nathan DM, Dale DC, Federman DD, ed. Diabetes mel-litus. Sci Am Med 1996: 6: 1–24.

59. National Diabetes Data Group. Diabetes in America. NIHPublication No. 95-1468. Washington, DC: NIH, 1995: 11–13, 37.

60. National Diabetes Data Group. Diabetes in America. NIHPublication No. 95-1468. Washington, DC: NIH, 1995:283–506.

61. National Diabetes Data Group. Diabetes in America. NIHPublication No. 95-1468. Washington, DC: NIH, 1995: 15–35.

62. Nelson RG, Shlossman M, Budding LM, Pettitt DJ, SaadMF, Genco RJ, Knowler WC. Periodontal disease andNIDDM in Pima Indians. Diabetes Care 1990: 13: 836–840.

63. Nishimura F, Takashashi K, Kurihara M, Takashiba S, Mu-rayama Y. Periodontal disease as a complication of dia-betes mellitus. Ann Periodontol 1998: 3: 20–29.

64. Novaes AB Jr, Gutierrez FG, Novaes AB. Periodontal dis-ease progression in type II non-insulin-dependent dia-betes mellitus patients (NIDDM). 1. Probing pocket depthand clinical attachment. Braz Dent J 1996: 7: 65–73.

65. Ohkubo Y, Kishikaua H, Araki E, Miyata T, Isami S, Mo-toyoshi S, Kojima Y, Furugoshi N, Shichiri M. Intensiveinsulin therapy prevents the progression of diabeticmicrovascular complications in Japanese patients withnon-insulin dependent diabetes mellitus: a randomizedprospective 6 year study. Diabetes Res Clin Proc 1995: 28:103–117.

66. Oliver RC, Tervonen T. Periodontitis and tooth loss. Com-paring diabetics with the general population. J Am DentAssoc 1993: 124: 71–76.

67. Oliver RC, Tervonen T, Flynn DG, Keenan KM. Enzymeactivation in crevicular fluid in relation to metabolic con-trol of diabetes and other risk factors. J Periodontol 1993:64: 358–362.

68. Peters AL, Davidson MB, Schriger DL, Hasselblad V. TheMeta-analysis Research Group on the diagnosis of dia-betes using glycated hemoglobin levels 1996. A clinical

Rees

approach for the diagnosis of diabetes mellitus; an analy-sis using glycated hemoglobin levels. JAMA 1996: 276:1246–1252.

69. Piche JE, Swan RH, Hallmon WW. The glycosylated hemo-globin assay for diabetes: its value to the periodontist.Two case reports. J Periodontol 1989: 60: 640–642.

70. Redding SW, Montgomery M. Dentistry in systemic dis-ease. Portland: JBK Publishing, 1990: 140–153.

71. Rees TD. The diabetic dental patient. Dent Clin North Am1994: 38: 447–463.

72. Rees TD, Hallmon WW. Endocrine disorders. In: WilsonTG Jr, Kornman KS, ed. Fundamentals of periodontics.Chicago: Quintessence Publishing, 1996: 251–256.

73. Rees TD, Otomo-Corgel J. The diabetic patient. In: WilsonTG, Kornman KS, Newman MG, ed. Advances in peri-odontics. Chicago: Quintessence Publishing, 1992: 278–295.

74. Reuterving CO, Hagg E, Gustafson GT. Root surface cariesand periodontal disease in long-term alloxan diabeticrats. J Dent Res 1986: 65: 689–694.

75. Reyna J, Richardson JM, Mattox DE, Banowsky LH, Nicas-tro-Lutton JJ. Head and neck infection after renal trans-plantation. JAMA 1982: 247: 3337–3339.

76. Ringelberg ML, Dixon DO, Francis AO, Plummer RW.Comparison of gingival health and gingival crevicularfluid flow in children with and without diabetes. J DentRes 1977: 56: 108–111.

77. Rosenthal IM, Abrams H, Kopczyk A. The relationship ofinflammatory periodontal disease to diabetic status in in-sulin-dependent diabetes mellitus patients. J Clin Peri-odontol 1988: 15: 425–429.

78. Salley K, Kovesi G, Dori F. Circulating immune complexstudies on patients with oral lichen planus. Oral Surg OralMed Oral Pathol Oral Radiol Endod 1989: 68: 567–570.

79. Salvi GE, Beck JD, Offenbacher S. PGE2, IL-1b and TNF-aresponses in diabetics and modifiers of periodontal dis-ease expression. Ann Periodontol 1998: 3: 40–50.

80. Sammalkorpi K. Glucose intolerance in acute infections.J Int Med 1989: 225: 15–19.

81. Sarnat H, Eliaz R, Geiman G, Flexer Z, Karp M, Laron Z.Carbohydrate consumption and oral status of diabeticand nondiabetic young adolescents. Clin Prev Dent 1985:7: 20–23.

82. Sastrowijoto SH, van der Velden U, van Steenberen TJM,Hillemans P, Hart AAM, de Graaff J, Abraham-Inpijn L.Improved metabolic control, clinical periodontal statusand subgingival microbiology in insulin-dependent dia-betes mellitus. A prospective study. J Clin Periodontol1990: 17: 233–242.

83. Sbordone L, Ramaglia L, Barone A, Ciaglia RN, Iacono VJ.Periodontal status and subgingival microbiota of insulin-dependent juvenile diabetics: a 3-year longitudinal study.J Periodontol 1998: 69: 120–128.

84. Seppala B, Sorsa T, Ainamo J. Morphometric analysis ofcellular and vascular changes in gingival connectivetissue in long-term insulin-dependent diabetes. J Peri-odontol 1997: 68: 1237–1245.

85. Sharon A, Ben-Aryeh H, Itzhak B, Yoram K, Szargel R, Gut-man D. Salivary composition in diabetic patients. J OralMed 1985: 40: 23–26.

86. Shlossman M, Knowler WC, Pettitt DJ, Genco RJ. Type 2diabetes mellitus and periodontal disease. J Am Dent As-soc 1990: 121: 532–536.

72

87. Smith GT, Greenbaum CJ, Johnson BD, Persson GR. Short-term responses to periodontal therapy in insulin-depend-ent diabetic patients. J Periodontol 1996: 67: 794–802.

88. Smith U. Insulin action-biochemical and clinical aspectsActa Med Scand 1987: 222: 7–13.

89. Soskolne WA. Epidemiological and clinical aspects ofperiodontal diseases in America. Ann Periodontol 1998: 3:3–12.

90. Sugarman JR. Prevalence of diagnosed hypertensionamong diabetic Navajo Indians. Arch Intern Med 1990:150: 359–362.

91. Takeshita F, Murai K, Kyama S, Ayukawa, Y, Suetsugu T.Uncontrolled diabetes hinders bone formation around ti-tanium implants in rat tibiae. A light and fluorescencemicroscopy, and image processing study. J Periodontol1998: 69: 314–320.

92. Taylor GW, Burt BA, Becker MP, Genco RJ, Shlossman M.Glycemic control and alveolar bone loss progression intype 2 diabetics. Ann Periodontol 1998: 3: 30–39.

93. Taylor GW, Burt BA, Becker MP, Genco RJ, Shlossman M,Kinder WC, Pettitt DJ. Non-insulin dependent diabetesmellitus and alveolar bone loss progression over twoyears. J Periodontol 1998: 69: 76–83.

94. Tenovuo J, Alanen P, Larjava H, Viikari J, Lehtonen O-P.Oral health of patients with insulin-dependent diabetesmellitus. Scand J Dent Res 1986: 94: 338–346.

95. Tervonen T, Knuuttila M, Pohjamo L, Nurkkala H. Im-mediate response to non-surgical periodontal treatmentin subjects with diabetes mellitus. J Periodontol 1991: 61:431–435.

96. Ternoven T, Oliver R. Long-term control of diabetes mel-litus and periodontitis. J Clin Periodontol 1993: 20: 431–435.

97. Teuscher A, Egger M, Herman J. Diabetes and hyperten-sion. Arch Intern Med 1989: 149: 1942–1945.

98. Thorstensson H, Falk H, Hugoson A, Kuylenstiero J. Den-tal care habits and knowledge of oral health in insulin-dependent diabetics. Scand J Dent Res 1989: 97: 207–214.

99. Thorstensson H, Falk H, Hugoson A, Olsson J. Some sali-vary factors in insulin-dependent diabetics. Acta OdontolScand 1989: 47: 175–183.

100. Ueta E, Osaki T, Yoneda K, Yamamoto T. The prevalenceof diabetes mellitus in odontogenic infections andoralcandidiasis: an analysis of neutrophil suppression. J OralPathol Med 1993: 22: 168–175.

101. UK prospective diabetes study (UKPDS) group. Effect ofintensive blood-glucose control with metformin on com-plications in overweight patients with type 2 diabetes.Lancet 1998: 352: 854–865.

102. United States Pharmacopeia Drug Information. Type 2diabetes. USPDI, 18th edn. 1998: Vol I,II: 822–1028.

103. Ureles SD. Case report: a patient with severe periodontitisin conjunction with adult-onset diabetes. CompendiumContin Educ Dent 1983: 4: 522–528.

104. Van Dis ML, Allen CM, Neville BW. Erythematous gingivalenlargement in diabetic patients: a report of four cases. JOral Maxillofac Surg 1988: 46: 794–798.

105. Williams RC Jr, Mahan CJ. Periodontal disease and dia-betes in young adults. JAMA 1960: 172: 776–778.

106. Yki-Jarvien H, Sammalkorpi K, Koivisto VA, Nikkila EA. Se-verity, duration and mechanisms of insulin resistanceduring acute infections. J Clin Endocrinol Metab 1989: 69:317–323.