2014 Periodontal Treatment Guidelines for Patients with Diabetes (Revised Version 2)
CQ
NumberCQ

1

CQ1 Is periodontal treatment effective for improvement of HbA1c?

2

CQ2 Is periodontal disease improved by glycemic control?

3

CQ3 Is education to encourage patients with diabetes to establish a habit of mouthcleaning effective for maintenance of favorable glycemic control?

4

CQ4 As periodontal treatment for patients with diabetes, is concomitant use of local
or oral antimicrobial therapy more effective, compared to a single procedure ofscaling root planing (SRP)?

5CQ5 Is treatment for bacteremia necessary in basic periodontal treatment forpatients with diabetes?

6

CQ6 What level of glycemic control should be achieved in invasive procedures suchas periodontal surgery in patients with diabetes?

7

CQ7 Should warfarin be suspended when patients with diabetes undergo dental
extraction, basic periodontal treatment, or periodontal surgery?

8

CQ8 Should more thorough administration of antimicrobial drugs be used in surgery
for patients with diabetes?

9

CQ9 Can patients with diabetes obtain therapeutic effects of periodontal guided
tissue regeneration equivalent to those in non-diabetes patients?

10

CQ10 Can patients with diabetes obtain therapeutic effects of implant treatment
equivalent to those in non-diabetes patients?

11

CQ11 Does periodontal disease easily redevelop in the period of supportive
periodontal therapy (SPT) in patients with diabetes?

12

CQ12 Should the interval of SPT be shorter for patients with diabetes, compared toother patients with periodontal disease?

13

CQ13 What level of glycemic control should be provided to patients with diabetes in
the SPT period?

CQ/Contents

CQ1 Is periodontal treatment effective for
improvement of HbA1c?
A systematic review and meta-analysis of arandomized comparative study suggested
significant improvement of HbA1c by 0.36％

Recommendation/response1

Level of recommendation
Level of evidence

after periodontal treatment, but some reports arenegative. However, there is counterevidence forthe negative reports, and several meta-analyses
support the effects of periodontal treatment for
improvement of glycemic control. Therefore,
periodontal treatment is likely to be effective forpatients with diabetes, and is recommended forthese patients.
Grade B: Recommended to perform.
Evidence level: 1note)Note) Randomized control trials (RCTs) other than high-quality randomized
comparative studies, and related meta-analyses or systematic reviews
Background/objectives:
The relationship between periodontal disease and diabetes has long been
discussed in the literature. A recent Japanese large-scale epidemiological study
confirmed an interaction of these diseases. The effects of periodontal treatment
for patients with diabetes were first reported by Grossi et al. in 1997. However,
the results of many subsequent studies have been inconsistent. A meta-analysis
from 5 years ago showed no significant effects. Since many new studies havebeen performed since this analysis, we performed a new search.

Explanation

Explanation:
A meta-analysis by Simpson et al. in 2010 showed that scaling root planing(SRP) and oral hygiene instruction (with or without antimicrobial therapy)
significantly decreased HbA1c by 0.4% (p＝0.04) in 3-4 months after treatment.
A meta-analysis by Teeuw et al. in the same year showed similar results. A
meta-analysis in 2013 suggested improvement of HbA1c by 0.36％ (P<0.0001).
Simpson et al. reviewed 7 studies and included 3 in the meta-analysis. Fivestudies were examined in Teeuw et al., but 3 of these were the studies includedin Simpson et al. In the 2013 meta-analysis, 9 studies were selected from thosepublished since October 2009, using the same method as that of Simpson et al.
Among these 9 studies, 3 included data for more than 100 subjects, and theperiodontal disease conditions at the start of the studies varied from gingivitis tosevere periodontitis. Treatment of periodontal disease for the test group included
oral hygiene instruction and subgingival SRP, as well as general (4 subjects) andlocal (1 subject) administration of antimicrobial drugs as adjunctive treatment.
In a randomized clinical trial in 475 subjects performed in 2013, Engebretson etal. found that clinical conditions of periodontal disease were significantly
improved with no improvement of HbA1c in patients treated with oral hygiene
instruction, SRP, and gargling of chlorhexidine, compared to untreated controls.
In a clinical study in Japan in 278 subjects, there was significant improvement of
HbA1c 3 months after SRP and local administration of minocycline in patientswith a hs-CRP ≥500 ng/mL (type 2 diabetes + moderate to severe periodontitis).
Differences between these studies included race, age, and body mass index(BMI). The age of the Japanese subjects was higher (57 vs. 66 years old), and
BMI was significantly higher in the US study (34-35 vs. 22-25 kg/m2). hs-CRP
increased by severe periodontitis might have been compensated for by
inflammation caused by obesity in subjects with high BMI in the US study, andthus inflammation caused by obesity might have affected the results. A
counterargument to Engebretson et al. suggested that the disputed validity may
be due to ① an average HbA1c level of 7.8％ at baseline close to the target for
improvement, ② improvement of periodontal disease after treatment that wasless than standard values in other reports, and ③ improvement of inflammation
by periodontal treatment masked by severe obesity. In addition, the average
probing pocket depth (PPD) in the treatment group was 3.3 mm, which is close to
the normal range, which raises doubts about the severity of periodontal disease.
In an interventional study in China in subjects with BMI relatively close to that ofJapanese patients with diabetes, Chen et al. found that HbA1c tended to
improve in follow-up observation for 6 months after SRP under local anesthesia,
but without a significant effect. In contrast, in comprehensive periodontal
treatment, including pre- and postoperative use of antimicrobial drugs, SRP,
extraction of unsustainable teeth, and flap surgery, Sun et al. found a significant
improvement of HbA1c (0.5％) 3 months after treatment. The difference between
these studies include the severity of periodontal disease, HbA1c, and hs-CRP
level at baseline. In Chen et al. vs. Sun et al., average PPD, attachment level,
HbA1c, and hs-CRP were 2.5 vs. 4.5 mm, 3.3 vs. 4.9 mm, 7.3％ vs. 8.7％, and 3
vs. 5.8 mg/L, respectively. In addition, Sun et al. performed comprehensive
periodontal treatment, including flap surgery and antimicrobial drugs, andachieved improvement of periodontal disease and a decrease of hs-CRP, while
Chen et al. used only SRP, which resulted in a lower level of improvement of
periodontal disease. This suggests that improvement of HbA1c might be affectedby the severity of periodontal disease at baseline, diabetes status, level ofsystemic inflammation and improvement after treatment, and differences inperiodontal treatment methods and attendant therapeutic effects.
As mentioned above, improvement of HbA1c was found in a meta-analysis, butthere were several problems, including the small number of reports used in theanalysis, insufficient number of cases, difficulty with comparison due to various
conditions of periodontal disease and diabetes treatment in each study, andunclear improvement of periodontal disease. In addition, effects on inflammation
at sites other than the oral cavity should be taken into consideration whenantimicrobial drugs are concomitantly used. However, based on the systematic
review and interventional studies in Japanese and Chinese subjects, there arepatients in whom diabetes may be improved by periodontal treatment. In the
future, it will be important to examine which periodontal treatment is effective forwhat type of patient with diabetes more precisely by performing interventional

studies with division of subjects based on status of diabetes, including
complications, systemic inflammation, severity of periodontal disease atbaseline, and periodontal treatment methods. In particular, it will be desirable toperform interventional studies with a uniform protocol.

CQ/Contents

CQ2 Is periodontal disease improved byglycemic control?

Recommendation/response

Since patients with uncontrolled diabetes havehigh risks of increased severity of periodontal
disease and loss of teeth, glycemic control isimportant. It is ethically difficult to perform arandomized comparative study with a control
group with no glycemic control to examine theeffects of glycemic control on periodontal
disease. In addition, no randomized comparative
study has examined these effects in intensified
and normal treatment. In a before-and-after
controlled trial, gum inflammation improved withimproved glycemic control in diabetes treatment,
but with no improvement in periodontal pockets
and attachment level. More studies of
periodontal tissues after diabetes treatment are
required. However, the effects of this treatment
on these tissues are limited, and improvement of
periodontal disease with diabetes treatment isunlikely without periodontal treatment for dental
plaque bacteria, the cause of the disease. Since
poorly controlled diabetes may be a risk factor
for periodontal disease, tight control of diabetes
is needed for successful periodontal treatment.

Level of recommendation

Grade B: Recommended to perform.

2

Level of evidence

Evidence level: 3note)Note) Non-randomized comparative study, controlled before-and-after trial,
retrospective cohort study, case control study, related meta-analysis or
systematic review, and a sub-analysis of a predetermined RCT
Background/objectives:
Periodontal disease and diabetes are thought to affect each other, and theprevalence and severity of periodontal disease are higher in patients withdiabetes, compared to healthy persons. However, the effects of glycemic control
on periodontal disease have only been examined in a few studies.
Explanation
Explanation:
In a cross-sectional comparative study in patients with diabetes with favorable
and poor glycemic control, the severity of periodontal disease was significantly
higher in uncontrolled patients. In a longitudinal study of the effects of glycemic
control level on progress of periodontal disease in patients with type 1 and 2
diabetes, periodontal disease was significantly aggravated and the risk of tooth
loss was higher in patients with poorly controlled type 1 and 2 diabetes,
compared to healthy persons. One of the few reports on the effects of diabetes
treatment on periodontal disease suggested that gum inflammation is improved

by improved glycemic control in diabetes treatment, but there was no significant
improvement in periodontal pockets and attachment level.

CQ/Contents

CQ3 Is education to encourage patients withdiabetes to establish a habit of mouth cleaning
effective for maintenance of favorable glycemic
control?

Recommendation/response

A favorable mouth cleaning habit may increase
self-efficacy of patients with diabetes andprevent development or aggravation of diabetes.

Level of recommendation

Grade B: Recommended to perform.

3

Level of evidence

Evidence level: 4note)Note) Cross-sectional study and case accumulation
Background/objectives:
Risk factors for periodontal disease, such as diabetes, and decreased supportive
periodontal therapy (SPT) may promote tooth loss, and tighter oral care withprofessional mechanical tooth cleaning (PMTC) and mouth cleaning should be
performed for patients with poor glycemic control in whom periodontal treatment
is insufficient. SPT may also improve awareness of patients for oral care (mainly
tooth brushing). Other common risk factors for periodontal disease andmetabolic syndrome include nutritional balance, insufficient exercise, stress,smoking, alcohol, and insufficient mouth cleaning. Oral cavity management ofpatients with diabetes is also essential for diabetes management. However, therole of daily mouth cleaning in glycemic control in patients with diabetes has notbeen clarified. For prevention of development and aggravation of diabetes,interventional studies are required to evaluate oral health multidirectionally inmanagement of diabetes and its complications.

Explanation

Explanation:
Development and aggravation of periodontal disease and diabetes are related toinsufficient mouth cleaning and lifestyle habits (diet, exercise, sleep, stress,smoking, and alcohol). In this CQ, we conducted literature searches on therelationship between mouth cleaning habit (mainly frequency of tooth brushing)and development/aggravation of diabetes; effects of risk markers of metabolic
syndrome, diabetes, and its complications; and methods to improve awarenessof patients. The incidence and prevalence of metabolic syndrome, level ofneutral fat, and hs-CRP level were all found to be significantly higher in subjects
who performed tooth brushing once daily or less, compared to those whobrushed twice daily or more, suggesting that increased tooth brushing frequency
might contribute to prevention of metabolic syndrome.
A study of the self-efficacy of tooth brushing in management of diabetes showedthat patients with higher self-efficacy understood their condition of glycemic
control, and were healthier and less obese. Close correlations were foundbetween self-efficacy and plaque index, HbA1c level, and tooth brushing habit.
Furthermore, cognition of self-efficacy was suggested as a common behavioral
factor in oral health action and self-management of diabetes. Based on this, it
was suggested that a focus should be placed on diabetes-related behavioral
factors (diet, exercise, and blood glucose monitoring) and on oral health factors

for systemic health promotion in patients with type 2 diabetes. The risk ofcardiovascular events was increased (hazard ratio: 1.7) and hs-CRP and
fibrinogen levels were higher in subjects with low daily frequency or no habit of
tooth brushing. A significant correlation was also found between self-reported
mouth cleaning (brushing, flossing, professional care, and condition of the oralcavity) and risk factors for cardiovascular disease (total cholesterol and bloodpressure) and systemic inflammation markers (adiponectin, hs-CRP, fibrinogen,and sICAM-1). This suggests that regular tooth brushing is likely to be effective
for maintenance of favorable glycemic control and prevention of complications ofdiabetes, in addition to improvement of high blood pressure, discontinuation ofsmoking, and decrease of body weight, and that regular mouth cleaning is an
essential factor in systemic health management.
Based on these findings, a mouth cleaning habit (tooth brushing) may increase
self-efficacy of patients with metabolic syndrome, diabetes, or its complications,and be effective for prevention of development and aggravation of diabetes.
Longitudinal interventional studies are required to clarify the causal correlationand medical economic effects.

CQ/Contents

CQ4 As periodontal treatment for patients withdiabetes, is concomitant use of local or oral
antimicrobial therapy more effective, compared
to a single procedure of scaling root planing(SRP)?

Recommendation/response

Concomitant antimicrobial therapy should beconsidered in basic periodontal treatment forpatients with diabetes who develop periodontitis.
Such therapy is particularly recommended incases with diffuse chronic periodontitis thatdevelops with diabetes, severe diabetes-related
periodontitis, or severe periodontitis that isdifficult to reach using SRP.

Level of recommendation

Grade B: Recommended to perform.

4

Level of evidence

Evidence level: 1note)Note) RCT other than high-quality randomized comparative study, and related
meta-analysis or systematic review

Explanation

Background/objectives:
In summarizing reports on antimicrobial therapy for patients with periodontal
disease, a consensus emerged that a supplemental effect of concomitant
antimicrobial therapy was unlikely in systematically healthy patients with chronic
periodontitis who had a favorable response to normal mechanical plaque control.
In contrast, concomitant antimicrobial therapy is thought to be effective forpatients with refractory periodontitis or diffuse severe periodontitis who have apoor response to normal treatment. Furthermore, for compromised patients withperiodontitis with decreased host biophylactic function due to diabetes with poor
glycemic control, and those with periodontitis who have vascular endothelial
dysfunction due to arteriosclerotic disease, concomitant antimicrobial therapy isrecommended to increase the response to periodontal treatment and decrease
adverse effects on the whole body and other organs. Therefore, we examinedthe effects of concomitant antimicrobial therapy in periodontal treatment forpatients with diabetes from a standpoint of improvement of clinical parameters.
Explanation:
We conducted literature searches on improvement of clinical parameters of
periodontal tissues (probing pocket depth [PPD], attachment level [clinicalattachment loss, CAL], and bleeding on probing [BOP]) due to antimicrobial
therapy (local and systemic) concomitantly performed with basic periodontal
treatment for patients with diabetes. In two studies of concomitant use of SRP
and an oral antimicrobial drug, doxycycline (100 mg/day for 14 days) in patientswith type 2 diabetes, there was no significant difference in clinical parameters inevaluation for 3 to 6 months. In a study of concomitant doxycycline (100 mg/day
for 15 days) in patients with type 1 diabetes, deep PPD (≥6 mm) and BOP weresignificantly improved after 3 months, compared to patients treated with SRP
alone. In long-term administration of low-dose doxycycline (40 mg/day for 3

months) to inhibit collagenase activity, in which antimicrobial effects were
expected, a significant improvement of clinical parameters was found in a periodof 3-6 months, compared to SRP alone. However, oral administration ofamoxicillin concomitantly with one-stage full-mouth SRP (FMSRP), in which SRP
is performed for the full mouth within 24 h in patients with type 2 diabetes, did not
significantly improve clinical parameters in 3 months, compared to FMSRP
alone. Similar improvement of periodontal local inflammation (BOP) was found 9months after basic periodontal treatment in patients with metabolic syndrome
concomitant with SRP and a combination of metronidazole and amoxicillin
compared to supragingival scaling alone. In contrast, SRP with an oral
combination of metronidazole and amoxicillin in patients who developed diffuse
chronic periodontitis with type 2 diabetes showed a significant improvement ofclinical parameters, compared to SRP alone.
In studies of local administration of antimicrobial drugs, there was no significant
improvement of clinical parameters after use of FMSRP and chlorhexidine gel inpatients who developed diffuse periodontitis and type 2 diabetes with poor
glycemic control. There was also no significant improvement of clinicalparameters with use of SRP and minocycline gel, compared to SRP alone, inpatients who developed periodontitis and type 2 diabetes with poor glycemic
control. In contrast, significant improvement in clinical parameters was foundusing SRP with clarithromycin gel in patients with chronic periodontitis and type 2
diabetes with favorable glycemic control, compared to SRP alone. Similarly, SRP
and doxycycline gel produced a significant improvement of clinical parameters inpatients with type 1 diabetes, compared to SRP alone.
Based on this evidence, concomitant oral administration of antimicrobial drugs
and local administration of tetracyclines or macrolides may be more effective for
diffuse periodontitis, but the effects of oral and local antimicrobial drugs may beless effective in patients with periodontitis and diabetes. Therefore, concomitant
antimicrobial therapy may be effective in compromised patients with diabetes,
and thus the recommendation level was determined to be B (level 1). In the
future, comparative studies with a sufficient sample size, the same protocol, anda uniform antimicrobial drug that take into account the severity and expansion of
periodontitis as inclusion criteria, glycemic control and BMI (which are important,especially in a study with inflammation markers, rather than clinical parameters,
as the endpoint, as explained in CQ1), local and systemic inflammation, and thelevel of insulin resistance. A study in Japanese subjects suggested thatconcomitant antimicrobial drugs are effective even if improved glycemic control
is used as an outcome, and thus further studies are warranted to establish aneffective antimicrobial therapy.

CQ/Contents

CQ5 Is treatment for bacteremia necessary inbasic periodontal treatment for patients withdiabetes?

Recommendation/response

Bacteremia may be caused by scaling root
planing (SRP) in basic periodontal treatment, bya periodontal tissue test with a probe, and bymechanical plaque control such as brushing.
However, since bacteremia develops for a shortperiod of time with an extremely low level ofinvasion, the possibility of diabetes aggravatingby this disease is low. Since no reports havesuggested that the incidence and severity ofbacteremia are higher in patients with diabetes
than in healthy persons, and the advantages ofdecreased inflammation in periodontal tissues
are high, no particular countermeasures forbacteremia are necessary.

Level of recommendation

Grade C: Reasons not clear to recommend.

5

Level of evidence

Evidence level: 3note)Note) Non-randomized comparative study, controlled before-and-after trial,
retrospective cohort study, case control study, related meta-analysis or
systematic review, and sub-analysis of prescribed RCT

Explanation

Background/objectives:
Basic periodontal treatment is performed to remove causes of bacteremia fromthe oral cavity, and its outcome may affect subsequent periodontal treatment.
However, SRP may damage tissues and cause bacterial invasion in the body,as seen in tooth extraction. Such bacterial invasion might also be caused by aperiodontal tissue test such as probing and by daily tooth brushing, andbacteremia could develop temporarily. Bacteremia derived from the oral cavity
including periodontal tissues is a concern in compromised patients, as thecause of focal infection. For immune-compromised patients with diabetes withlocal protracted wound healing and prolonged bleeding time, there areconcerns about aggravation and development of complications.
Explanation:
Bacterial invasion of periodontal tissues in SRP and supragingival scaling
during periodontal treatment or in a periodontal tissue test with a probe causes
the blood endotoxin level to increase, inducing development of bacteremia(level 4). Daily activities including mechanical oral cleaning with brushing andinterdental brushing and mastication might also cause bacteremia (level 4).
There are no clinical differences in the incidence, severity, and duration
between bacteremia caused by dental treatment and those caused by daily
activities such as brushing and mastication. In bacteremia caused by dental
treatment, the bacteria level is ≤104 colony forming units (CFU) per 1 mL ofblood and rapidly decreases in 10-30 min after development, and thus this isconsidered to be a biologically less-invasive and temporal disease. However,
the incidence of bacteremia caused by scaling is significantly higher in patientswith periodontitis than in those with gingivitis and in healthy persons, and thebacteria level is positively correlated with gingival index, plaque index, and thenumber of positive bleeding sites upon probing. Thus, advanced periodontitis
may increase the risk of bacteremia (level 4). Therefore, basic periodontal
treatment to improve gum inflammation and maintain oral cleanliness is likely
to contribute to prevention of oral cavity-derived bacteremia.
Diabetes tends to be associated with increased susceptibility to infection andprotracted wound healing. The migratory capability of leukocytes and thecapacity to generate active oxygen may be decreased in host immune
function, and careful attention should be paid to development of complications
such as bacterial endocarditis because the incidence of bacteremia isincreased when the blood glucose level is high. However, the risk of oralcavity-derived bacteremia in patients with diabetes is no higher than that inhealthy persons. In a cross-sectional study in patients with type 2 diabetes,
there were no significant differences in risks for bacteremia, other than urinary
tract infection, in comparison to non-diabetes patients, and no difference intherapeutic results.
Temporal bacteremia may develop after basic periodontal treatment in healthy
persons, but there is no high-level evidence for its severity and adverse effects.
Patients with diabetes with poor control should obtain opinions from aphysician, but the advantages of improvement of periodontal tissue
inflammation are greater than the risk of development of bacteremia, even inpatients with diabetes, and thus basic periodontal treatment is recommended.
However, it is important to maintain favorable glycemic control to avoid
unnecessary development of bacteremia. For cases in which invasive surgicaltreatment may be required due to severe inflammatory symptoms caused bypoor control, refer to section CQ8.

CQ/Contents

CQ6 What level of glycemic control should beachieved in invasive procedures such as
periodontal surgery in patients with diabetes?
There is no standard for glycemic control in open
procedures such as dental surgery in patientswith diabetes. However, in a study in Japanesepatients with diabetes who underwent
percutaneous coronary revascularization, theRecommendation/response

outcomes of patients with HbA1c <6.9％ were
better than those with HbA1c ≥6.9％. Therefore,

6

in periodontal surgery with relatively low
invasiveness, HbA1c around 6.9％ can be usedas the reference level.
Level of recommendation
Level of evidence

Grade B: Recommended to perform.
Evidence level: 3note)Note) Non-randomized comparative study, controlled before-and-after trial,
retrospective cohort study, case control study, related meta-analysis or
systematic review, and sub-analysis of prescribed RCT
Background/objectives:
Postoperative complications are common in patients with diabetes in surgery for
cardiac disease. Incidences of postoperative death and complications are
particularly high in patients receiving insulin treatment. Patients with diabetes
tend to develop infection, and those with poor glycemic control have wider andseverer infection. Such patients also tend to develop infection with an increase inblood glucose, which may decrease resistance to the infection, and thus it isimportant to prevent postoperative complications. For this, there is a need toclarify the level of glycemic control required for periodontal surgery.
Explanation

Explanation:
There have been no randomized comparative studies on complications(infections) after periodontal surgery in patients with diabetes. In a retrospective
cohort study in Japanese subjects, the incidence of infection after coronary
artery bypass surgery was significantly higher in patients with diabetes (average
HbA1c: 7.1％ [NGSP]), compared to non-diabetes patients (average HbA1c:5.7％). In addition, in the above-mentioned study of outcomes of percutaneous
coronary intervention, the incidence of major cardiovascular events in patientswith preoperative HbA1c ≥6.9％ was significantly higher than that in those with
HbA1c <6.9％. However, multivariate analyses in both studies suggested nosignificant relationship between preoperative HbA1c and development of major
cardiovascular events. This may be because patients with diabetes have various

complications and a difference in disease background might be due topreoperative glycemic control. In a prospective cohort study in Canada, there
were no differences in incidences of major complications and infection in
non-diabetes patients and patients with diabetes with HbA1c <6.5％, but theseincidences were significantly higher in patients with diabetes with HbA1c ≥6.5％.
In a report on postoperative outcomes of percutaneous coronary arteryintervention, insulin therapy showed a positive correlation with postoperative
cardiovascular events, but a negative correlation with biguanide drugs.
In the Training Guidebook for Board Certified Diabetologists edited by the Japan
Diabetes Society, a fasting blood glucose level of 100-140 mg/dL andpostprandial blood glucose level of 160-200 mg/dL are proposed as targets
during surgery or preoperative control in the ICU. In intraoperative managementof small-scale surgery, a level of 150-250 mg/dL is the target. Preoperative,
intraoperative and postoperative glycemic control are all important to prevent
postoperative complications and obtain favorable therapeutic results.
If the standard level of glycemic control in periodontal surgery for patients withdiabetes is based on these reports, preoperative HbA1c should be <6.9％, or
fasting and postprandial blood glucose levels should be 100-140 mg/dL and
160-200 mg/dL, respectively, according to the Training Guidebook for Board
Certified Diabetologists. However, since periodontal surgery is less invasive
compared to coronary artery surgery, the results above should be considered
only as a guide (safety threshold). The targets should not be used in a case inwhich the merits of a surgical procedure, such as tooth extraction, are expected
to be larger than the disadvantages of tooth conservation. In such a case,however, it is important to increase intraoperative blood concentrations of
antimicrobial drugs sufficiently by implementing more thorough measures for
antimicrobial therapy, as discussed in CQ8.
At present, in Japan, the target HbA1c to prevent complications is <7.0％(NGSP) and the desired HbA1c for favorable long-term therapeutic outcomes is<7.0％. In addition, in the Evidence-based Practice Guidelines for Treatment of
Diabetes in Japan 2013 of the Japan Diabetes Society, it is suggested that
diabetes specialists should cooperate with other physicians and dentists intreatment of patients who require surgery or treatment for dental caries orinfection. Thus, it is desirable to establish a good cooperative relationship withdiabetes specialists for periodontal surgery and commencement of periodontal
treatment.

CQ/Contents

CQ7 Should warfarin be suspended when
patients with diabetes undergo dental extraction,
basic periodontal treatment, or periodontal
surgery?

Recommendation/response

The risk of events that may be caused bycessation of warfarin is likely to be larger than
the risk of bleeding in invasive treatment forpatients with continuous administration of the
drug. Therefore, it is recommended not todiscontinue warfarin for tooth extraction, basic
periodontal treatment, and periodontal surgery.

Level of recommendation

Grade D: Recommended not to perform.

7

Level of evidence

Evidence level: 1note)Note) RCT other than a high-level randomized comparative study, and related
meta-analysis or systematic review

Explanation

Background/objectives:
Since patients with diabetes have a high risk of circulatory disease, they require
stricter management of blood pressure and often receive administration of
anticoagulant and antiplatelet drugs to prevent embolization. Warfarin (warfarin
potassium) is the most frequently used anticoagulant in Japan, and bleeding
may be extended after invasive procedures in patients taking this drug. In 1957,
Ziffer et al. recommended suspension of anticoagulants for tooth extraction inpatients receiving these drugs because postoperative bleeding developed after
tooth extraction in a case with continuous administration of anticoagulant. Sincemany bleeding events occur during endoscopic treatment or from the digestive
tract in patients taking warfarin, suspension or a decrease in the anticoagulant
dose has been considered as an option for invasive treatment.
In 1963, Marshall et al. reported a case in which cardiac infarction developed
after discontinuation of an anticoagulant before tooth extraction, andemphasized the risk of infarction upon drug discontinuation. It was reported that
warfarin might show a rebound phenomenon to facilitate clot formation after
discontinuation and recommencement, and that thrombosis often developed
during suspension of anticoagulants and that serious disease was induced.
These cases illustrate the various conflicting opinions on continuous use of
anticoagulants for prevention of thrombosis or a decrease or suspension of
anticoagulants to avoid postoperative bleeding events in minor oral surgery.
Thus, there is a need to establish clear guidelines for tooth extraction or
periodontal surgery for patients under treatment with anticoagulants.
Explanation:
There is no large difference in bleeding after invasive dental procedures with andwithout continuous administration of warfarin. Since postoperative bleeding can
be arrested in most cases by appropriate local procedures, even in patientstaking warfarin, it is not recommended to discontinue the drug for scaling, tooth
extraction, or periodontal surgical treatment. There is evidence (level 2) for thisconclusion from several randomized comparative studies.
In a literature search, we found two randomized comparative studies on
accidents such as postoperative bleeding after continuous administration or
discontinuation of warfarin for minor oral surgery. In one study in 214 patients
receiving anticoagulants who were scheduled to undergo tooth extraction at adental department of a hospital in Saudi Arabia, the subjects were randomized
into four groups: no suture + discontinuation, no suture + continuation, suture +discontinuation, and suture continuation. There was no difference inpostoperative bleeding and wound healing with discontinuation and continuation,although postoperative bleeding was more common in patients with suture (level1). The second study was a randomized comparative (prospective open-label)
study in the dental department of a hospital in Italy in 131 patients under
anticoagulant treatment who were scheduled to undergo tooth extraction. The
subjects were randomized into groups with decreased or continuous
anticoagulants. Mild postoperative bleeding occurred in 15.1％ and 9.2％ ofcases in the respective groups, suggesting that there is no need to decrease theanticoagulant dose for normal tooth extraction (level 1). Furthermore, the resultsof a meta-analysis of a randomized comparative study including level 1 evidence
also suggested that continuous administration of anticoagulants in dental
surgery including tooth extraction does not increase the risk of postoperative
bleeding, compared to decreased or suspended administration (level 1).
Since these studies were not performed in Japanese subjects, there is a concern
about the applicability of the results to Japanese people, who have a relatively
low incidence of infarction. Regarding this possible ethnic difference, 5 hospitalcohort studies (with controls) have been performed in Japanese subjects
receiving anticoagulant therapy to compare continuous use and discontinuationof warfarin. All of these studies suggested no differences between continuousand suspended administration of warfarin for tooth extraction (level 3), and thus
similar procedures to those used overseas can be used in Japan. The 2010
guidelines announced by the Japanese Society of Dentistry for MedicallyCompromised Patients, the Japanese Society of Oral and Maxillofacial
Surgeons, and the Japanese Society of Gerodontology suggested that noserious bleeding complications occur after tooth extraction with continuous
administration of warfarin, if the patient has stable underlying disease, and that
the International Normalized Ratio (INR) or PT (prothrombin time)-INR (target
international normalized ratio of blood coagulation time calculated based onprothrombin time) had a standard level of 1.0. An increase in this ratio showsincreased difficulty in blood clotting, but the ratio was within the therapeutic
range (level 1). In addition, a study of periodontal surgery suggested nodifference in postoperative bleeding in patients with INR ≤3.0, and thus it isrecommended that warfarin should be continued for tooth extraction andperiodontal surgery (level 4).
As mentioned above, tooth extraction and periodontal treatment can be
performed with continuous administration of warfarin for patients with periodontal
disease if INR is ≤3.0, but evidence is not sufficient for periodontal disease.
However, since it is often difficult to arrest bleeding after surgery in patients
under anticoagulant therapy, compared to healthy persons, careful attention
should be paid to minimize invasion as much as possible in surgery, perform
appropriately local arrest of bleeding, and remove inflammatory tissues. In
addition, it is important to obtain the latest INR level when possible and use
sufficient anti-inflammatory procedures before surgical treatment.

CQ/Contents

CQ8 Should more thorough administration of
antimicrobial drugs be used in surgery forpatients with diabetes?

Recommendation/response

Since the risk of surgical site infection (SSI) after
periodontal surgery for patients with diabetes
with favorable glycemic control is equivalent tothat in healthy persons, there is no need forthorough use of antimicrobial drugs. However,patients with diabetes with poor glycemic control
have a risk of infection in surgery, and it isdesirable to use preventive administration of
antimicrobial drugs before and after surgery.

Level of recommendation

Grade B: Recommended to perform.

8

Level of evidence

Evidence level: 3note)Note) Non-randomized comparative study, controlled before-and-after trial,
retrospective cohort study, case control study, related meta-analysis or
systematic review, and sub-analysis of prescribed RCT

Explanation

Background/objectives:
Increased susceptibility to infection and protracted wound healing are clinicalcharacteristics of patients with diabetes. Long-term continuous hyperglycemia
due to abnormal glycometabolism is known to cause microvascular damage,abnormal collagen metabolism, and mild immunodeficiency, and is generally
considered to increase the risk of SSI in surgical procedures.
One patient with diabetes (blood glucose: 305 mg/dL) was reported to havedeveloped clostridium deep neck infection after tooth extraction. A second
patient with poor glycemic control developed serious Mucormycosis after tooth
extraction. As seen in these cases, patients with diabetes have a higher risk ofinfection after invasive procedures such as tooth extraction, compared to healthy
persons, but there are cases in which such procedures are required. Thus, there
is a need to clarify whether thorough chemotherapy is required.
Explanation:
Patients with diabetes with poor glycemic control tend to be infected by bacteria,
tubercle bacilli, and fungi, and these infections can easily become serious.
However, there are no randomized comparative studies that suggest the needfor thorough chemotherapy after surgery for patients with diabetes. In a
retrospective observational study, the incidence of infection was significantly
decreased after surgery for patients with preoperative HbA1c <7％ (NGSP)(level 3), and no special considerations were required for supportive periodontal
therapy (SPT) and surgical periodontal treatment if HbA1c is controlled at ≤7.0％(NGSP). In contrast, in total knee arthroplasty for patients with HbA1c ≥6.8％(NGSP), leucocyte count and CRP level in postoperative week (POW) 1 andwhite blood cell count in POW 2 were significantly elevated, even with preventive

administration of antimicrobial drugs, suggesting the importance of glycemic
control in the perioperative and antimicrobial therapy periods. In a study of SSI
risk factors after colectomy in patients with diabetes, postoperative thoroughglycemic control and administration of antimicrobial drugs within 24 h after
surgery were found to be more important for prevention of postoperative
infection, compared to preoperative procedures (level 2). A study of preventive
administration of antimicrobial drugs for wound infection after spinal surgery
showed that 1-day administration of these drugs could prevent postoperative
infection for patients with no complication of diabetes, while antimicrobial drugs
were required for 3 days, including the day of surgery, for patients with acomplication of diabetes (level 2). Furthermore, in patients with diabetes who
underwent spinal instrumentation surgery, the rate of SSI in those withproteinuria (qualitative examination) was 6.28-fold higher than in those with noproteinuria. There was no significant difference in glycemic control (mean HbA1c
7.2％ (NGSP)) between these groups, and therefore it was suggested that
proteinuria may be a useful index of SSI risk.
These findings suggest the need to examine glycemic control status (HbA1c<7% as a guide) and complications (inadequate blood flow caused by
microangiopathy and macroangiopathy) to determine whether thorough use of
antimicrobial drugs should be selected for prevention of SSI in patients withdiabetes. Indiscriminant excessive administration of antimicrobial drugs forprevention of postoperative infection should be avoided. Since microcirculatory
disturbance and poor wound healing are likely when diabetic complications
develop due to poor glycemic control, or complications that may be caused bydiabetes, such as proteinuria, develop, thorough preventive administration of
antimicrobial drugs should be performed immediately before and during surgery.
If microcirculatory disturbance due to long-term hyperglycemia is suspected or ina case in which no treatment has been performed for diabetes, cooperation withor introduction to a diabetes specialist is required before surgery.

CQ/Contents

CQ9 Can patients with diabetes obtaintherapeutic effects of periodontal guided tissue
regeneration equivalent to those in non-diabetes
patients?

Recommendation/response

There is insufficient evidence for long-term
therapeutic results of periodontal regeneration inpatients with diabetes. It is not recommended forpatients with diabetes with poor glycemic control
to receive periodontal regeneration.

Level of recommendation

Grade D: Recommended not to perform.

9

Level of evidence

Evidence level: 4note)Note) Cross-sectional study, and case accumulation

Explanation

Background/objectives:
Periodontal guided tissue regeneration to regenerate tissues destroyed byperiodontal disease includes bone transplantation, guided tissue regeneration(GTR), and regeneration with enamel matrix protein (Emdogain). In regenerative
therapy, treatment with a scaffold and cytokines is performed in clinical practiceand is developing into cell treatment. These regeneration methods are likely to
be used for patients with diabetes, but such patients have high risks of protracted
wound healing and postoperative infection caused by functional deterioration ofleucocytes, decreased collagen metabolic capacity, deteriorated function offibroblast cells to repair tissues, and poor circulation caused by microcirculatory
disturbance. Since patients with diabetes have a high risk of infection, it isimportant to provide tight plaque control and glycemic control in periodontal
treatment. However, there are few comparative reports on responses toperiodontal treatment in patients with and without diabetes. Many reportssuggest that the response to periodontal treatment is similar in patients withdiabetes with favorable glycemic control and non-diabetes patients in short-term
observation. In addition, a comparison performed 5 years after basic periodontal
treatment showed favorable results at surgical and non-surgical treatment sites
in both groups. The subjects in this report continued to visit on a quarterly basis
and maintained extremely favorable plaque control, which suggests that patientswith diabetes can receive periodontal treatment, including surgical procedures, if
they have good maintenance for a long period. However, the response toperiodontal regeneration, which requires higher level techniques and active
regeneration capacity, is unclear in patients with diabetes. In the current era of
growing expectation for regeneration therapy, guidelines for the efficacy of
periodontal regeneration for patients with diabetes are necessary.
Explanation:
In a literature search, we found only two case reports of GTR performed in thecontext of diabetes. Furthermore, these two reports were on the same patient.
The first described GTR performed for left mandibular nos. 5 and 7 (sites withsevere periodontal disease) in a 57-year-old female with type 2 diabetes thatwas well controlled with a conventional method. Favorable results were obtainedfor regeneration of alveolar bone on X-ray examination 12 months after surgery.
The second report described the clinical course of the same patient at 10 years
after the first report (11 years after GTR). She had lowered compliance, norevisits, and redevelopment of periodontal disease caused by poor control ofdiabetes due to a transition to insulin dependence, aggravated conditions
compared to those before GTR, and loss of the two teeth. Based on thesefindings, it was concluded that GTR is contraindicated in patients with diabetes
with poor control.
An animal study on GTR performed as preparative treatment for implantationsuggested no difference in neonatal bone between diabetes animals with poor
control and non-diabetes control animals, but in a retrospective clinical study on
autogenous bone graft for formation of an alveolar ridge in humans, high failure
rates were found in patients with diabetes.
Based on these findings, the evidence level of the derived report is low (level 6),
and no clear suggestion cannot be made. A speculative recommendation is that
periodontal regeneration is contraindicated in patients with diabetes with poor
control or with compliance that is likely to decrease.

CQ/Contents

CQ10 Can patients with diabetes obtaintherapeutic effects of implant treatment
equivalent to those in non-diabetes patients?

Recommendation/response

Patients with diabetes with favorable control
may obtain therapeutic effects equivalent tothose for non-diabetes patients because
success and survival rates are high after
implantation, but there are some negative
reports. Standards of control are unclear inmany cases, and thus the treatment cannot be
actively recommended.

Level of recommendation

Grade C: Reasons not clear to recommend.

10

Level of evidence

Evidence level: 3note)Note) Non-randomized comparative study, controlled before-and-after trial,
retrospective cohort study, case control study, related meta-analysis or
systematic review, and sub-analysis of prescribed RCT

Explanation

Background/objectives:
Many reports have discussed the indication and prediction of implant treatment
in systemically healthy patients. Patients who request implants for tooth loss
caused mainly by periodontal disease include many in late middle age or older
who may develop diseases of the elderly. Patients with diabetes generally haveconsiderable tooth loss, and thus require many implants and have a highexpectation of treatment. Thus, dentists have increasing opportunities for use of
implants in patients with systemic disease. It is reasonable to expect protracted
wound healing based on results in animal diabetes models, but osseointegration
has been achieved in diabetes and non-diabetes animals. Successful use of
implants in patients with other systemic diseases has been reported, but there
has been no detailed analysis of implant treatment in patients with diabetes.
Therefore, guidelines based on evidence are needed regarding the efficacy andprediction of implant treatment in patients with diabetes.
Explanation:
In a literature search, six reports were found, including 1 clinical review, 3
retrospective cohort studies, 1 case control study, and 1 report on caseaccumulation. Three systematic reviews were also found. Recent systematic
reviews suggest that patients with type 1 and 2 diabetes with favorable glycemic
control achieved a high implant survival rate, as seen in non-diabetes patients, ina randomized comparative study, retrospective cohort study, and prospective
cohort study. This suggests that implant treatment is not contraindicated inpatients with diabetes if glycemic control is favorable. However, since few reports
included blood glucose levels and HbA1c, the required level of glycemic control
is unclear. The results of each study were evaluated as sufficiently successful orsomewhat unsuccessful. This evaluation is satisfactory, but there are reportssuggesting that the survival rate of implants in patients with diabetes withfavorable control is lower than that in non-diabetes patients, that significantlyhigher rates of unsuccessful implant use occurred in patients with type 2
diabetes compared to non-diabetes patients, that patients with diabetes tended
to develop peri-implantitis (odds ratio of 1.9 compared to non-diabetes patientsin logistic analysis), and that the disease duration of diabetes and length of theimplant body are significant predictive factors for unsuccessful implant treatment.
Therefore, further studies are needed on use of implants in patients withdiabetes, and there is a need to establish clear guidelines based on studies with
objective standards for disease type of diabetes, age of onset, disease duration,therapeutic method, and long-term control (HbA1c).

CQ/Contents

CQ11 Does periodontal disease easily redevelop
in the period of supportive periodontal therapy(SPT) in patients with diabetes?

Recommendation/response

Even during SPT, diabetes is a risk factor forperiodontal disease redevelopment, and the risk
is especially high in patients with diabetes withpoor glycemic control. Thus, it is recommended
that patients with diabetes receive sufficient
glycemic control and tighter SPT.

Level of recommendation

Grade B: Recommended to perform.

11

Level of evidence

Evidence level: 2note)Note) Prospective cohort study, related meta-analysis or systematic review, andsub-analysis of prescribed RCT
Background/objectives:
Patients with diabetes have reduced function of polymorphonuclear leukocytes,
increased collagenase activity, and lower capacity to produce collagen. Thosewith poor glycemic control more frequently develop alveolar bone resorption andattachment loss due to periodontal disease, compared to those with favorable
control. Periodontal disease in patients with diabetes tends to be more severe,and patients may redevelop periodontal disease during SPT after active
treatment.

Explanation

Explanation:
Studies on the relationship between periodontal disease and diabetes clearlysuggest that diabetes is a risk factor for periodontal disease. We examined theeffects of diabetes on redevelopment of periodontal disease in the SPT period
after active periodontal treatment.
Costa et al. investigated redevelopment of periodontitis and tooth loss in a 5-year
SPT period after treatment of periodontitis, and found that redevelopment of
periodontal disease occurred more frequently in patients with diabetes with poor
glycemic control, compared to those with favorable control and non-diabetes
patients.
Investigations of risk factors for periodontal disease redevelopment in the SPT
period have resulted in an unclear relationship with diabetes, but several reports
have suggested that smoking and diabetes are risk factors based on the resultsof multivariate analysis. In these reports, the odds ratio of diabetes forredevelopment of periodontal disease was 1.9-4.2.
These findings suggest that patients with diabetes with poor control can easily
redevelop periodontal disease, even in the SPT period. Therefore, it is importantto perform sufficient glycemic control and stricter SPT in these patients.

CQ/Contents

CQ12 Should the interval of SPT be shorter forpatients with diabetes, compared to other
patients with periodontal disease?

Recommendation/response

Since patients with diabetes have a high risk forperiodontal disease, even in the SPT period, it isrecommended to shorten the interval of SPT to
3-4 times per year or shorter.

Level of recommendation

Grade B: Recommended to perform.

12

Level of evidence

Evidence level: 2note)Note) Prospective cohort study, related meta-analysis or systematic review, andsub-analysis of prescribed RCT
Background/objectives:
Patients with diabetes are at high risk for periodontitis. Thus, thorough control isrequired, even in the SPT period, after periodontal treatment. Guidelines areneeded to determine whether the SPT interval should be shortened to prevent
redevelopment of periodontal disease, compared to that for non-diabetes
patients.

Explanation

Explanation:
No randomized comparative study on this issue was found, but there was aforward-looking case control study. By selecting pairs with various matchedfactors in the cohort, patients were divided into two groups, in which only the
SPT interval differed. Investigation of the SPT period over 3 years showed that
redevelopment of periodontal disease and tooth loss were lower in patients withan average SPT interval of 3.3 months, compared to those with an interval of 8.1
months.
No other studies on SPT interval in patients with diabetes were found, but risk
factors including smoking and diabetes may be involved in redevelopment of
periodontal disease in the SPT period. Multivariate analysis gave an odds ratio of
diabetes for redevelopment of periodontal disease in the SPT period of 1.9-4.2.
Based on this, periodontal disease redevelopment can be predicted using risk
factors in the SPT period and the SPT interval can be adjusted.
A retrospective study compared therapeutic effects in a high susceptibility group(HSG) of subjects who did not have diabetes, but were diagnosed with advanced
periodontitis and received normal non-surgical periodontal treatment, and anormal group (NG) with normal sensitivity. When SPT mainly with oral cleaning
instruction was performed 3-4 times per year and debridement was performed,
no aggravation of periodontal disease occurred in the NG group, but significant
alveolar bone resorption and attachment loss were observed in the HSG group.
This suggests that periodontitis can easily redevelop in patients with highdisease sensitivity, even if normal SPT is performed.
Based on these findings, the sensitivity of a patient for onset of periodontal
disease can be predicted based on various risk factors, including diabetes. If therisk is high, it is recommended to perform SPT with an interval shorter than thenormal interval of 3-4 times per year (interval of 3 or 4 months).

CQ/Contents

Recommendation/response

CQ13 What level of glycemic control should be
provided to patients with diabetes in the SPT
period?
To prevent redevelopment of periodontitis in the
SPT period, glucose should be controlled at as
close to the normal level as possible. Even if
control is difficult, the risk of periodontitis
redevelopment is comparatively low if HbA1c(NGSP) is <7.0％. It is recommended to confirm

13

the glycemic control level and perform thoroughSPT depending on the control level.
Level of recommendation
Level of evidence

Grade B: Recommended to perform.
Evidence level: 2note)Note) Prospective cohort study, related meta-analysis or systematic review, andsub-analysis of prescribed RCT
Background/objectives:
Alveolar bone resorption and attachment loss easily develop due to periodontal
disease in patients with diabetes with poor glycemic control, compared to thosewith favorable control. Thus, to prevent progression of periodontal disease inpatients with diabetes, it is important to maintain favorable glycemic control. A
target glycemic control level required to prevent redevelopment or progression of
periodontal disease should be set in patients with diabetes in the SPT period.

Explanation

Explanation:
No randomized comparative study of this issue was found. In an epidemiologicalstudy, progression of periodontal disease and increased tooth loss were morecommon in patients with diabetes with poor glycemic control in the SPT period,
compared to those with favorable control. In the study, appropriate glycemic
control was defined as HbA1c (NGSP) of 6.5％. It is unclear whether there is adose-response relationship between the HbA1c level and the rate of progressionof periodontal disease.
A prospective cohort study in Germany suggested that attachment loss was highin patients with poor glycemic control (HbA1c >7.0％) in type 1 and 2 diabetes.
However, there was no significant difference in attachment loss between healthy
persons and patients with diabetes with favorable glycemic control.
Based on these findings, favorable glycemic control should be maintained toprevent redevelopment of periodontal disease. The target level of glycemic
control has not been closely examined, but HbA1c (NGSP) <7.0％ may have ahigh risk of redevelopment.
Generally, the goals of diabetes treatment are prevention of progression anddevelopment of complications. For this, glucose should be controlled at as close
to the normal level as possible, but the level should be determined individuallybased on age and risk of hypoglycemia in actual treatment. The Japan Diabetes
Society defined the target of glycemic control as HbA1c (NGSP) <7.0％ from astandpoint of complication prevention. This was based on a report suggestingthat development or progression of microangiopathy was almost inhibited when
HbA1c (NGSP) was <6.9％, and on targets defined in several other countries.
However, the risk of development or progression of macroangiopathy is high inthe stage of abnormal glucose tolerance, in which only the postprandial blood
glucose level is high. This means that all complications cannot be prevented witha target HbA1c (NGSP) <7.0％.
Based on these findings, it is desirable for the glucose level to be controlled at as
close to the normal level as possible to prevent redevelopment of periodontal
disease in the SPT period in patients with diabetes. Even if such glycemic control
is difficult in individual patients, the risk of periodontal disease redevelopment isrelatively low if HbA1c (NGSP) is <7.0％. It is important to confirm the level ofglycemic control and estimate the risk of periodontal disease redevelopment at
hospital visits. It is recommended to adjust the details and interval of SPT basedon data for individual patients.