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Received: 8 May 2018    Revised: 25 October 2018    Accepted: 28 November 2018

DOI: 10.1111/jcpe.13044

S Y S T E M AT I C R E V I E W

Impact of diabetes on clinical periodontal outcomes following

non-­surgical periodontal therapy

Yung-Ting Hsu1 | Maya Nair2 | Nikola Angelov3 | Evanthia Lalla4 | Chun-Teh Lee3

1
Division of Graduate
Periodontology, Department of Graduate Abstract
Studies, University of Detroit Mercy School Aim: This systematic review aimed to evaluate the impact of diabetes mellitus on
of Dentistry, Detroit, Michigan
2
clinical outcomes of non-­surgical periodontal therapy.
University of Texas at Austin, Austin, Texas
3 Materials and Methods: Searches were conducted in electronic databases to screen
Department of Periodontics and Dental
Hygiene, University of Texas Health Science studies published from January 1960 to August 2018. The included studies had at
Center at Houston, Houston, Texas
least two groups of patients: chronic periodontitis only (P) or both diabetes and
4
Division of Periodontics, Columbia
University College of Dental Medicine, New chronic periodontitis (DMP). Outcomes of interest included the difference between
York City, New York the two groups in probing depth (PD) reduction and clinical attachment level (CAL)

Correspondence gain following non-­surgical periodontal therapy. Meta-­regression was conducted to

Chun-Teh Lee, Department of Periodontics
and Dental Hygiene, University of Texas
Health Science Center at Houston, Houston,
TX.
Email: chun-teh.lee@uth.tmc.edu
evaluate the correlation between the outcomes of interest and contributing factors.
Results: A total of 12 studies with a follow-­up period up to 6 months were included.
There was no significant difference in PD reduction (p = 0.55) or CAL gain (p = 0.65)
between the two groups. A positive association between PD reduction and baseline
PD difference (p = 0.03), and a negative association between PD reduction and age
(p = 0.04) were found. The level of HbA1c at baseline did not significantly affect the
difference in PD reduction (p = 0.39) or CAL gain (p = 0.44) between two groups.
Conclusions: Recognizing the study’s limitations, we conclude that diabetes mellitus
(HbA1c ≤ 8.5%) does not appear to significantly affect short-­term clinical periodontal
outcomes of non-­surgical periodontal treatment.

KEYWORDS
blood glucose, diabetes, meta-analysis, periodontitis, root planing

1 | I NTRO D U C TI O N
The prevalence of diabetes mellitus (DM) among adults has in-
creased to 8.5% globally, resulting in 1.5 million deaths annually
(World Health Organization, 2016). The adverse effects of DM on
periodontal health have been widely discussed for many decades
(Finestone & Boorujy, 1967; Lalla & Papapanou, 2011). Previous lit-
erature suggests a significant link between the two diseases: DM is
associated with increased occurrence and severity of periodontitis.
Severe periodontitis may contribute to poorer glycaemic control, the
development of complications in people with DM, (Graziani, Gennai,
Solini, & Petrini, 2018; Sanz et al., 2018; Taylor, 2001) and DM onset
in previously normoglycaemic individuals (Chapple, Genco, Working
group 2 of the joint EFPAAPw, 2013). Some studies also reported
decreased HbA1C values after patients with periodontitis received
periodontal treatment (Kıran, Arpak, Ünsal, & Erdoğan, 2005;
Stewart, Wager, Friedlander, & Zadeh, 2001).
Glycaemic status is highly associated with periodontal inflamma-
tion. Alteration in host defence due to the microbial–host interaction
leads to numerous changes in cellular and molecular levels, including
increased release of pro-­inflammatory cytokines and mediators, al-
ternations of connective tissue metabolism and suppression of func-
tional activity of immune cells (Bissada, Manouchehr-­Pour, Haddow,
& Spagnuolo, 1982; Mowat & Baum, 1971). The accumulation of
advanced glycation end-­products (AGEs) in diabetic gingiva and the
interaction between AGEs and their receptor (Receptor for AGEs,

206  |  wileyonlinelibrary.com/journal/jcpe

© 2018 John Wiley & Sons A/S. J Clin Periodontol. 2019;46:206–217.
Published by John Wiley & Sons Ltd
HSU et al.
RAGE) induce a cascade of inflammatory events via oxidative stress-­
mediated pathways (Mealey & Oates, 2006; Schmidt et al., 1996).
ADM is a risk factor for periodontal disease; it has been shown to
have a positive correlation with clinical attachment loss (Grossi et al.,
1994), periodontal bone loss (Taylor et al., 1998), and formation of
pathological pockets (Campus, Salem, Uzzau, Baldoni, & Tonolo,
2005). Indeed, periodontal disease has been considered as a true
complication of DM (Lalla & Papapanou, 2011).
Impaired tissue response and healing following therapeutic inter-
ventions in patients with DM have been a concern for clinicians in the
treatment of periodontal diseases. Delayed osseous healing is expected
in patients with DM due to suppressed osteoblastic activity and deteri-
orated bone quality (Retzepi & Donos, 2010). In contrast, a pilot study
with short-­term follow-­up reported a similar reduction of pocket depth,
periopathogenic bacteria and oxidative burst response of polymorpho-
nuclear leucocytes between non-­DM patients and those with well-­
controlled DM (Christgau, Palitzsch, Schmalz, Kreiner, & Frenzel, 1998).
A similar recurrence rate was also shown between groups with and
without DM (Westfelt, Rylander, Biohmé, Jonasson, & Lindhe, 1996).
In recent years, there have been several systematic reviews
discussing the impact of periodontitis treatment on glycaemic
control, including the effects of adjunctive periodontal therapies
in periodontitis patients with DM (Engebretson & Kocher, 2013;
Grellmann, Sfreddo, Maier, Lenzi, & Zanatta, 2016). However, to our
knowledge, there is no comprehensive review assessing the impact
of DM on clinical periodontal outcomes in response to non-­surgical
periodontal treatment. Therefore, the purpose of this meta-­analysis
is to evaluate the impact of DM on non-­surgical periodontal treat-
ment outcomes in periodontitis patients.
2 | M ATE R I A L S A N D M E TH O DS
This systematic review was performed following the PRISMA
(Preferred Reporting Items for Systematic Reviews and Meta-­
Analyses) guidelines (Liberati et al., 2009; Moher et al., 2015) and
other published recommendations (Needleman, 2002; Needleman,
Moles, & Worthington, 2005).
2.1 | Focused question
Based on the PICOS principle—the Population: patients with peri-
odontitis and diabetes; the Intervention (or exposure): non-­surgical
periodontal therapy; the appropriate Control (or comparator): pa-
tients with periodontitis but without diabetes; the Outcomes of
interest and the Study design: probing depth reduction and clinical
attachment level gain after non-­surgical periodontal therapy in a
prospective study—the following focused question was proposed:
What are the clinical effects, such as probing depth
reduction or clinical attachment level gain, of non-­
surgical periodontal therapy in patients with chronic
periodontitis and DM compared to patients with
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Clinical relevance
Scientific rationale for the study: Diabetes is strongly associ-
ated with periodontal disease and may influence the re-
sponse to periodontal therapy. This systematic review
aimed to evaluate the impact of diabetes on clinical out-
comes following non-­surgical periodontal therapy.
Principal findings: The presence of diabetes did not signifi-
cantly affect short-­
term treatment outcomes following
non-­
surgical periodontal treatment. Instead, baseline
probing depth and age played a significant role in the
amount of probing depth reduction achieved.
Practical implications: Based on the current results, promis-
ing clinical outcomes may be expected in patients with dia-
betes receiving non-­surgical periodontal treatment.
chronic periodontitis alone during the first year of
follow-­up?
2.2 | Study selection criteria
1. Studies had to have at least two groups of patients, patients with
chronic periodontitis and DM and patients with chronic periodon-
titis only. These studies had to be prospective cohort studies and
have at least 10 subjects in each group.
2. Studies had to define periodontal status, such as periodontal di-
agnosis, and DM status, such as HbA1c level. Patients in these
studies should not have systemic diseases known to significantly
influence periodontal health (other than DM).
3. Patients in these studies should have received non-surgical peri-
odontal treatment. Treatment outcomes should include change in
probing depth and clinical attachment level. The outcomes up to
1 year after non-surgical treatments should be reported.
2.3 | Search strategy
A search was conducted for studies published from January 1960
to August 2018 in several electronic databases, including MEDLINE
(PubMed), EMBASE, Scopus and ClinicalTrials.gov., using specific key
terms. Details of the search method are described in the Supporting
Information Appendix S1. Moreover, a search was performed in the
following journals: Journal of Periodontology, Journal of Clinical
Periodontology, Journal of Periodontal Research, International
Journal of Periodontics and Restorative Dentistry, and Journal of
Dental Research. Finally, the reference lists of identified articles were
screened to find additional articles that might fit the selection criteria.
2.4 | Quality assessment
The Newcastle–Ottawa scale (NOS) was used to assess the meth-
odological quality of the selected cohort studies (Wells et al., 2001).
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208       HSU et al.

TA B L E   1   Overview of the selected studies

Perio No. of Gender Smokers/

Study Group DM Dx Dx patients (F/M) Age (years) FU (mon) Measurement Non-­Smokers Base HbA1c (%)

Navarro-­ DMP Type 2 DM Mod 10 2 F 57.4 6 FMPE (4 sites/ 8/2 7.2 ± 1.3
Sanchez GCP 8 M tooth)
et al. (2007)
P NA Mod 10 7 F 56.4 6 3/7 NA
GCP 3 M

da Cruz et al. DMP Type 2 DM GCP 10 NA 47.1 3 FMPE (4 sites/ 0/10 9.23 ± 2.6
(2008) tooth)
P NA GCP 10 NA 45.6 3 0/10 5.88 ± 0.16

Shen et al. DMP Type 2 DM CP 30 NA NA 3 PMPE (Ramfjord NA 7.22 ± 1.53

(2008) tooth)
P NA CP 30 NA NA 3 NA 4.71 ± 0.86

Dag et al. DMP Poorly CP 15 10 F 53.13 3 FMPE (6 sites/ 0/15 9.96 ± 1.45
(2009) Controlled 5 M tooth)
Type 2 DM

Well-­ CP 15 8 F 52.2 3 NA 6.26 ± 0.72

Controlled 7 M
Type 2 DM

P NA CP 15 7 F 49.5 3 0/15 5.26 ± 0.4

8 M

Kardesler DMP Poorly CP 12 5 F 50.25 3 FMPE (6 sites/ 4/8 9.64 ± 2.41

et al. (2010) Controlled 7 M tooth)
Type 2 DM

Well-­ CP 13 2 F 55.31 3 1/12 5.9 ± 0.61

Controlled 11 M
Type 2 DM

P NA CP 15 6 F 51.31 3 9/6 5.09 ± 0.48

9 M

Wei et al. DMP Type 2 DM CP 50 21 F 54.5 3 FMPE (6 sites/ NA 7.35 ± 1.73

(2011) 29 M tooth)

P NA CP 43 25 F 53.7 3 NA 5.64 ± 0.29

18 M

Cirano et al. DMP Type 2 DM CP 16 44% F 56.1 6 FMPE (6 sites/ 0/16 8.1 ± 1.2
(2012) 56% M tooth)

P NA CP 15 36% F 54.7 6 0/15 NA

64% M

Camargo et al. DMP Type 2 DM GCP 10 NA 52.0 3 FMPE (4 sites/ 0/10 Grapha
(2013) tooth)
P NA GCP 10 NA 41.6 3 0/10 Grapha

Mirnic et al. DMP Poorly CP 23 11 F 55.3 3 FMPE (4 sites/ 1/22 8.5 ± 1.53
(2013) Controlled 12 M tooth)
Type 2 DM

DMP Well-­ CP 18 12 F 57.67 3 4/14 6.19 ± 0.44

Controlled 6 M
Type 2 DM

P NA CP 21 14 F 55.1 3 2/19 NA

7 M

Silva-­ DMP Type 2 DM Mod CP 20 12 F 45.8 3 FMPE (4 sites/ 0/20 9.43 ± 1.8
Boghossian 8 M tooth)
et al. (2014)
P NA Mod CP 20 10 F 43.65 3 0/20 NA
10 M

Kara et al. DMP Type 2 DM CP 15 7 F 42.8 3 FMPE (6 sites/ 3/12 7.27 ± 0.62
(2015) 10 M tooth)

P NA CP 15 10 F 47.73 3 4/11 5.42 ± 0.28

5 M

Dogan et al. DMP Type 2 DM CP 15 9 F 47.53 6 weeks FMPE (6 sites/ 0/15 7.31 ± 0.46
(2016) 6 M tooth)

P NA CP 15 7 F 48.73 6 weeks 0/15 5.09 ± 0.65

8 M

Notes. Data are shown as mean ± standard deviation.

CAL: clinical attachment level; CP: chronic periodontitis; DM: diabetes mellitus; DM Dx: diabetes diagnosis; DMP: diabetes and periodontitis group;
FU: follow-­up; FMPE: full-­mouth periodontal examination; GCP: generalized chronic periodontitis; HbA1c: glycated haemoglobin A1c; Mod GCP:
moderate generalized chronic periodontitis; NA: not available; P: periodontitis group; PD: probing depth; Perio Dx: periodontitis diagnosis;
PI: plaque index; PMPE: partial-­mouth periodontal examination.
a
The values were presented in a graph format and, therefore, are not included here.
HSU et al. |
      209

Final HbA1c
(%) Baseline PD (mm) Final PD (mm) Baseline CAL (mm) Final CAL (mm) Baseline PI (%) Final PI (%)

5.9 ± 0.6 4.1 ± 0.3 3.0 ± 0.4 5.7 ± 1.9 5.2 ± 2.0 84.7 ± 25.8 11.1 ± 12.2

NA 3.7 ± 0.5 2.6 ± 0.2 4.9 ± 0.8 4.5 ± 0.8 83.9 ± 16.6 7.9 ± 9.7

9.4 ± 2.53 5.72 ± 1.13 5 ± 1.29 4.49 ± 0.7 3.28 ± 0.54 90.24 ± 16.41 7.21 ± 2.98

5.82 ± 2.6 4.79 ± 0.9 3.97 ± 0.82 4.03 ± 0.37 2.9 ± 0.26 91.33 ± 12.94 6.01 ± 2.66

6.79 ± 1.29 5.21 ± 0.62 4.39 ± 0.53 3.97 ± 1.12 3.91 ± 1.18 1.99 ± 0.78 1.14 ± 0.71

4.67 ± 0.77 4.38 ± 0.43 3.45 ± 0.42 3.34 ± 0.71 3.31 ± 0.94 2.12 ± 0.96 1.22 ± 0.87

9.77 ± 1.15 2.84 ± 0.65 2.37 ± 0.59 4.3 ± 0.97 3.04 ± 0.81 2.05 ± 0.68 0.3 ± 0.22

6.05 ± 0.77 2.67 ± 0.45 2.3 ± 0.43 4.25 ± 0.82 3.03 ± 0.79 1.82 ± 0.66 0.19 ± 0.05

5.24 ± 0.27 2.61 ± 0.38 2.36 ± 0.68 4.31 ± 0.59 2.91 ± 0.56 2.34 ± 0.52 0.19 ± 0.26

8.13 ± 1.88 4.1 ± 1 3.1 ± 0.6 4.3 ± 0.9 3.8 ± 1 99.7 ± 1.2 44.2 ± 6.3

5.88 ± 0.49 3.7 ± 0.4 2.8 ± 0.4 4.3 ± 0.9 3.9 ± 0.9 97.4 ± 5.4 35.6 ± 8.7

NA 3.9 ± 0.6 2.7 ± 0.3 4.3 ± 0.7 3.9 ± 0.7 95.5 ± 9.4 39.5 ± 13.5

6.8 ± 1.21 3.17 ± 0.53 1.96 ± 0.32 4.3 ± 1.02 3.58 ± 0.97 2.57 ± 0.23 1.3 ± 0.33

5.58 ± 0.23 2.9 ± 0.92 1.67 ± 0.35 4.22 ± 0.97 3.2 ± 0.95 2.6 ± 0.26 1.52 ± 0.19

NA 5.3 ± 0.3 3 ± 0.5 6.0 ± 0.7 3.9 ± 0.8 67.5 ± 16.4 17.6 ± 10.5

NA 5.9 ± 0.2 3.2 ± 0.5 6.7 ± 0.7 4.2 ± 0.9 65.5 ± 17.1 19.1 ± 11.4

Grapha 3.46 ± 0.55 2.81 ± 0.55 3.71 ± 0.62 2.85 ± 0.66 83.64 ± 14.09 52.85 ± 26.56

Grapha 2.62 ± 0.6 2.49 ± 0.48 3.3 ± 0.9 2.92 ± 0.48 29.39 ± 18.3 30.35 ± 13.95

NA 2.16 ± 0.54 2.04 ± 0.41 2.79 ± 1.47 2.52 ± 1.4 1.85 ± 0.35 1.32 ± 0.34

NA 2.18 ± 0.58 2.06 ± 0.59 2.89 ± 1.09 2.65 ± 1.1 1.71 ± 0.51 1.14 ± 0.53

NA 2.53 ± 0.63 2.14 ± 0.27 2.11 ± 1.12 1.67 ± 0.98 1.33 ± 0.47 0.49 ± 0.34

9.03 ± 1.94 4.2 ± 0.9 2.7 ± 0.4 4.9 ± 1.5 4.3 ± 1.3 NA NA

NA 3.6 ± 0.6 2.4 ± 0.3 4.3 ± 1.0 3.9 ± 0.8 NA NA

7.18 ± 0.97 4.13 ± 0.44 2.34 ± 0.26 4.78 ± 0.58 3.06 ± 0.73 1.65 ± 0.3 0.46 ± 0.19

5.48 ± 0.30 4.12 ± 0.43 2.31 ± 0.29 4.49 ± 0.41 2.75 ± 0.49 1.83 ± 0.03 0.32 ± 0.17

NA 4.06 ± 0.38 2.65 ± 0.33 4.75 ± 0.43 3.38 ± 0.4 2.26 ± 0.46 0.46 ± 0.32

NA 3.98 ± 0.32 2.59 ± 0.33 4.63 ± 0.4 3.26 ± 0.43 2.23 ± 0.41 0.46 ± 0.34

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210       HSU et al.
The total NOS score for each study ranged from 0 to 9. Furthermore,
the evidence level of each study was evaluated following the Oxford
Centre for Evidence-­
Based Medicine recommendation (Oxford
Centre for Evidence-­
Based Medicine: levels of evidence (March
2009)). The quality assessment was conducted by two authors (C.L
and Y.H) independently, and the agreement between the two au-
thors was evaluated using the kappa statistic.
2.5 | Grading the body of evidence
Quality-­of-­evidence (risk of bias in reported outcomes, inconsist-
ency of outcomes among studies, indirectness of reported out-
comes, imprecision of reported outcomes and potential publication
bias) assessment was based on the Grading of Recommendations
Assessment, Development and Evaluation (GRADE) system (Guyatt,
Oxman, Schunemann, Tugwell, & Knottnerus, 2011; Guyatt et al.,
2008). Studies were independently evaluated by two authors (C.L
and Y.H), and the agreement was reached by discussion, as needed
Supporting Information (Appendix S2: GRADE system assessment).
2.6 | Data extraction and data synthesis
The titles and abstracts of all retrieved articles were independently
screened by two authors (C.L and Y.H). Articles on unrelated top-
ics were excluded. The full texts of potentially qualifying articles
were read to identify qualified studies. Any disagreement between
the two authors was solved by discussion. If the identified studies
had multiple groups of subjects, only the groups fitting the selec-
tion criteria described above were included. If outcomes at multiple
time points were reported, only the outcomes with the longest fol-
low-­up period but within 1 year were included. Data were indepen-
dently extracted by the two authors (C.L and Y.H) with a specially
designed data extraction form and the accuracy of extracted data
was confirmed by another author (M.N). The authors of included ar-
ticles were contacted if there was unclear information that had to
be clarified.
2.7 | Data analysis
The primary outcome was the difference in probing depth (PD)
reduction after non-­surgical treatment between the DM plus peri-
odontitis group (DMP) and the periodontitis group (P). PD was
defined as the distance from the gingival margin to the tip of the
periodontal probe during diagnostic probing. PD reduction was
calculated by subtracting the probing depth at the follow-­up visit
from the probing depth at baseline. Weighted mean difference in
probing depth reduction (WDPD) was calculated by subtracting
the mean PD reduction in the P group from the mean PD reduc-
tion in the DMP group. The difference in PD reduction between
the two groups in each study was pooled based on the assigned
weights. A positive value means the DMP group had more PD re-
duction than the P group, and a negative value means the DMP
group had less PD reduction than the P group. If the study had
multiple DMP groups qualified for data analysis, the data of each
DMP group would be extracted and treated as an independent
data set.
The secondary outcome was the difference in clinical attach-
ment level (CAL) after non-­surgical treatment between the DMP
group and the P group. CAL was defined as the distance from the
cementoenamel junction to the tip of a periodontal probe during
diagnostic probing. CAL gain was calculated by subtracting the
CAL at the follow-­up visit from the CAL at baseline. Weighted
mean difference in CAL gain (WDCAL) was calculated by subtract-
ing the mean CAL gain in the P group from the mean CAL gain
in the DMP group. The difference in CAL gain between the two
groups in each study was pooled based on the assigned weights.
A positive value means the DMP group had more CAL gain than
the control group (P), and a negative value means the DMP group
had less CAL gain than the control group (P). Some studies did
not provide standard deviations of the difference in PD deduction
and/or CAL gain between the DMP group and the P group. The
missing standard deviations were imputed by using an assumptive
correlation coefficient which equals to 0.5 or the known t value
(Follmann, Elliott, Suh, & Cutler, 1992; Higgins & Green, 2011b,c;
Lee, Hum, & Chen, 2016).
Heterogeneity of the data sets for the primary and second-
ary outcomes was tested (chi-­s quare test of homogeneity). If the
heterogeneity was significant (p < 0.05), random effects model
(Dersimonian–Laird test) was chosen to perform the meta-­
analysis. If the heterogeneity was not significant (p ≥ 0.05), fixed
effects model was chosen to perform the meta-­a nalysis (Higgins
& Green, 2011a). Heterogeneity between data sets was also
assessed using I-­s quared (I 2) statistics describing the variation
of each data set (I 2 < 30%: low heterogeneity; I 2 = 30%–60%:
moderate heterogeneity; I 2 > 60%: considerable heterogene-
ity) (Alqaderi, Lee, Borzangy, & Pagonis, 2016; Higgins & Green,
2011d). Forest plots were generated to demonstrate the indi-
vidual and pooled effect estimates, as well as 95% confidence
intervals (CI). Meta-­regression was conducted to evaluate the
correlation between the outcomes of interest and different vari-
ables. In order to evaluate the variables causing heterogeneity or
result bias, subgroup analysis was conducted. Sensitivity analy-
sis was performed to assess the robustness of the results from
meta-­a nalysis by omitting one data set in each step. Publication
bias was evaluated by Egger’s test and funnel plot. All statistical
analysis was performed using STATA® (version 11.2, 2009, Stata
Corp, College Station, TX). Statistical significance was defined as
p-­v alue < 0.05.
3 | R E S U LT S
3.1 | Study selection
Two thousand three hundred and ninety-­eight abstracts and articles
were found in the databases. After checking the titles and abstracts,
only 66 articles potentially qualified. Fifty-­four articles were excluded
HSU et al.
because of no proper control group (periodontitis without DM), no
data of interest (mean PD) or no intervention (non-­surgical periodontal
treatment) (Supporting Information Table S1. excluded articles). Twelve
studies enrolling 491 participants were finally selected (Camargo
et al., 2013; Cirano et al., 2012; da Cruz et al., 2008; Dag, Firat, Arikan,
Kadiroglu, & Kaplan, 2009; Dogan et al., 2016; Kara, Cifcibasi, Karsidag,
& Cintan, 2015; Kardesler, Buduneli, Cetinkalp, & Kinane, 2010; Mirnic
et al., 2013; Navarro-­Sanchez, Faria-­Almeida, & Bascones-­Martinez,
2007; Shen, Yin, & Shu, 2008; Silva-­Boghossian, Orrico, Goncalves,
Correa, & Colombo, 2014; Wei, Chang, Pan, Yu, & Zhao, 2011) and fif-
teen data sets were included in the analyses because three studies had
groups of patients with DM at different levels of glycaemic control (Dag
et al., 2009; Kardesler et al., 2010; Mirnic et al., 2013).
3.2 | Study characteristics
All selected studies were prospective cohort studies. Randomized
controlled trial design was not possible for these studies since nei-
ther disease status nor treatment could be randomized. Four out of
twelve studies had included less than 30% smokers; whereas the
rest of the selected articles either did not include smokers or did not
F I G U R E   1   Pooled difference of probing depth (PD) reduction between the diabetes and periodontitis (DMP) group and the periodontitis
(P) group
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      211
mention in the study. (Kara et al., 2015; Kardesler et al., 2010; Mirnic
et al., 2013; Navarro-­Sanchez et al., 2007; Wei et al., 2011). (Table 1).
Smoking history was not considered in the analyses due to limited in-
formation. Generally, mean PD or mean CAL was calculated by using
the sum of all sites divided by the number of sites; however, one
study used the mean number of Ramfjord index teeth instead (Shen
et al., 2008). All selected patients had chronic periodontitis, but the
extent and severity of the disease were not consistent.
3.3 | Quality assessment and
heterogeneity evaluation
These studies had NOS scores ranging from 7 to 9 and the mean
score was 7.83 ± 0.72 (Supporting Information Table S2). The
evidence level of each study following the Oxford Centre for
Evidence-­B ased Medicine recommendation was either 2b or 3b.
The kappa coefficients for the agreement in these two assess-
ments between the two authors (C.L and Y.H) were 0.88 and 1.0,
respectively.
The data sets for WDPD had considerable heterogeneity (het-
erogeneity chi-­squared p-­value<0.001, I2 = 70.9%), and the data
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212       HSU et al.
F I G U R E   2   Pooled difference of clinical attachment level (CAL) gain between the diabetes and periodontitis (DMP) group and the
periodontitis (P) group
sets of WDCAL analyses had low heterogeneity (heterogeneity chi-­
squared p-­value= 0.308, I2 = 13.0%) (Higgins & Green, 2011a).
3.4 | Synthesis of results
Both DMP and P groups showed significant PD reduction and CAL
gain in response to treatment compared to baseline (p < 0.05). The
differences in PD reduction and CAL gain after non-­surgical treat-
ment between the DMP group and the P group were pooled, and
estimates were calculated. The PD reduction in the DMP group
was not significantly different from the P group (WDPD: −0.03 (CI:
[−0.15, 0.08]), p = 0.546) (Figure 1). The CAL gain in the DMP group
was not significantly different from the P group (WDPD: −0.02 (CI:
[−0.10, 0.06]), p = 0.654) (Figure 2).
3.5 | Meta-­regression analysis
Several clinical variables (follow-­up period, age, HBA1c level and
mean PD difference at baseline/mean CAL difference at base-
line) were evaluated in the meta-­regression analysis. Mean age of
two groups and mean PD difference at baseline were significantly
associated with the difference in PD reduction between two groups
(p = 0.041 and p = 0.027, respectively). The results demonstrated
that increased mean age of two groups favoured PD reduction in the
P group. Also, when the mean baseline PD in the DMP group was
higher than the P group, the DMP group had more PD reduction than
the P group after non-­surgical treatment (Table 2). None of the vari-
ables was significantly related to the difference in CAL gain between
two groups (Table 2).
3.6 | Subgroup analysis and sensitivity analysis
Since the difference in mean baseline PD between the two groups
was significantly associated with mean PD reduction after non-­
surgical treatment, these data sets were categorized into mean base-
line PD difference ≥0 (mean baseline PD in the DMP group is higher
than the P group) or <0 (mean baseline PD in the DMP group is lower
than the P group). The mean baseline PD difference ≥0 group ap-
peared to favour PD reduction in the DMP group (0.06 (CI: [−0.06,
0.18])) and the mean baseline PD difference <0 group appeared
to favour PD reduction in the P group (−0.26 (CI: [−0.34, −0.17]))
(Figure 3).
HSU et al. |
      213

TA B L E   2   The association between

Parameters Variables (95% confidence interval) p-­value
patient-­related variables and the
difference in probing depth reduction Probing depth Follow-­up period −0.050 (−0.170, 0.069) 0.380
(WDPD), and clinical attachment level reduction Age −0.031 (−0.061, −0.001) 0.041
gain (WDCAL) between the two groups (WDPD)
HbA1c level 0.045 (−0.064, 0.153) 0.391
(diabetes and periodontitis (DMP) and
periodontitis (P)) Probing depth difference at 0.285 (0.038, 0.532) 0.027
baseline
Clinical Follow-­up period 0.034 (−0.051, 0.119) 0.405
attachment Age −0.018 (−0.043, 0.008) 0.151
level gain
(WDCAL) HbA1c level 0.035 (−0.061, 0.132) 0.443
Clinical attachment level −0.018 (−0.043, 0.008) 0.804
difference at baseline

Notes. Follow-­up period: the time period in months between the baseline measurement and the last
post-­treatment measurement.
Age of patients: mean age of patients in the DMP and the P groups.
HbA1c level: mean HbA1c level in DMP patients.
Probing depth difference at baseline: the difference in baseline mean probing depth between the
DMP group and the P group.
Clinical attachment level difference at baseline: the difference in baseline mean clinical attachment
level between the DMP group and the P group.
Bold text indicates a statistically significant association with a p-value less than 0.05.

In the sensitivity analysis of assessing the impact of each data
set, WDPD was the lowest while Camargo et al. (2013) was omitted
(−0.077, CI: [−0.170, 0.015]) (Camargo et al., 2013). WDPD was the
highest while Cirano et al. (2012) was omitted (−0.013, CI: [−0.125,
0.100]) (Cirano et al., 2012). WDCAL was the lowest while one study,
Navarro-­Sanchez et al. (2007), was omitted (−0.047, CI: [−0.133,
0.040]) (Navarro-­Sanchez et al., 2007). WDCAL was the highest
while the data set of Mirnic et al. (2013), a well-­controlled DMP
group, was omitted (0.014, CI: [−0.07, 0.099]) (Mirnic et al., 2013).
No individual data set appeared to significantly affect the outcomes.
3.7 | Publication bias
The results of Egger’s test showed no significance in WDPD and
WDCAL (p = 0.08 and p = 0.94, respectively). The funnel plots gener-
ally demonstrated symmetric distribution of the data sets (Supporting
Information Figures S1 and S2). Due to the limited number of included
studies, publication bias could not be completely ruled out.
3.8 | Quality of evidence
Based on GRADE guidelines (Guyatt et al., 2008), the effect of DM
combined with periodontitis on PD reduction or CAL gain after
non-­
surgical periodontal treatment had “low” evidence quality
(Supporting Information Table S2).
4 | D I S CU S S I O N
Diabetes mellitus is known to be associated with periodontitis, but
the response of patients with DM to periodontal therapy is not clear.
To the best of the authors’ knowledge, this meta-­analysis is the first
attempting to investigate the impact of DM on clinical periodontal
outcomes following non-­surgical periodontal therapy. Our results
suggest that DM does not significantly affect PD and CAL improve-
ment after non-­surgical periodontal therapy.
Non-­surgical periodontal therapy using mechanical debridement
aims to eliminate the bacterial biofilm and control tissue inflamma-
tion. Scaling and root planing removes plaque, bacterial endotoxins,
calculus and other plaque-­retaining factors. Abundant evidence has
shown the positive impact of non-­surgical periodontal treatment on
clinical periodontal variables (Pihlstrom, McHugh, Oliphant, & Ortiz-­
Campos, 1983; Ramfjord, Knowles, Nissle, Burgett, & Shick, 1975).
Interestingly, the current results also revealed that, among older
subjects, those with periodontitis alone had greater PD reduction
following non-­surgical therapy compared to those with periodontitis
and DM. A negative impact of older age on DM outcomes has been
previously reported. An animal study showed a significant reduc-
tion in gene expression of hypoxia-­inducible factor 1α and angio-
genic growth factors, such as vascular endothelial growth factor, in
aged DM mice. The synergistic activities of reduced expression of
these factors may further impair the tissue and vascular responses
to injury, which are highly associated with morbidity and mortality in
older people with DM (Liu et al., 2008). With regard to oral health,
adverse effects could be seen in this population because they may
also have reduced capability for effective plaque removal and self-­
performed care (Lamster, Asadourian, Del Carmen, & Friedman,
2016). Additionally, older patients with DM may have a longer dura-
tion of DM than younger patients. An increased period of compro-
mised host responses caused by both DM and periodontitis could
worsen the response to periodontal treatment (Iacopino, 2001).
More evidence is needed to support these speculations.
The current results showed that the HbA1C level may not have a
significant influence on PD reduction and CAL gain after non-­surgical
 |
214       HSU et al.

F I G U R E   3   Pooled difference of probing depth (PD) reduction between the diabetes and periodontitis (DMP) group and the periodontitis
(P) group in subgroup analysis (Group 0 = mean baseline probing depth DMP<P; Group 1 = mean baseline probing depth DMP>P)

treatment. Two reasons could be ascribed to explain the absence of
a significant impact on treatment outcomes: (a) Bias of patient se-
lection: The baseline HbA1C value among DM patients in this meta-­
analysis was relatively low (<8%), indicating overall good glycaemic
control (Table 1). Even though poorly controlled patients (HbA1c: 9%–
10%) were included, these accounted for only 11.6% (57 patients out
of 491) of the total population in the current meta-­analysis. Studies
have reported similar levels of periodontal health in DM patients with
good or moderate glycaemic control compared to non-­DM controls
(Tervonen & Karjalainen, 1997). (b) Bias from the pooled data: The
data were pooled and analysed for the average PD reduction and CAL
gain from sites with both shallow and deep baseline PD. Thus, a po-
tentially negative effect of hyperglycaemia on treatment outcomes
could be masked by the uneven baseline disease severity and distri-
bution in the included population (Costa et al., 2013).
The meta-­regression analysis and the further subgroup analy-
sis suggested that the amount of PD reduction after treatment was
highly associated with the baseline PD, in favour of the group with
greater baseline PD. This finding further suggests that the severity
of periodontitis affects treatment outcomes following non-­surgical
periodontal therapy regardless of the patient’s glycaemic status. As
PD increases, it is true that the elimination of the biofilm and residual
calculus becomes more challenging. However, previous studies have
also reported a significant PD reduction in the sites with initial deep
PD compared to those sites with initial shallow PD (Hill et al., 1981;
Pihlstrom et al., 1983). In the DM population, a similar trend was
also mentioned in a study enrolling a total of 85 Pima Indians (Grossi
et al., 1996): The treatment outcomes became significant (1.29 mm
of PD reduction and 1.63 mm of CAL gain) when examining sites
with initially deep PD (≥5 mm) only (Grossi et al., 1996) although the
overall changes were insignificant compared to the baseline. Due to
the limitations of patient inclusion criteria and diagnosis criteria in
the selected studies, periodontitis could be diagnosed based on the
presence of some sites with initial deep PD while most sites were
shallow. In other words, the patient population selected in these
studies may not represent the general population with generalized
HSU et al.
and severe periodontitis, leading to an underestimation of the bene-
fits of periodontal therapy in the DM population.
Adjunctive antibiotics have been used to improve clinical out-
comes of periodontal treatment. However, some investigators
have reported that the adjunctive use of antibiotics may have
limited benefit for periodontal treatment outcomes (Lira Junior,
Santos, Oliveira, Fischer, & Santos, 2017) in patients with DM and
that it does not enhance HbA1C reduction beyond scaling and
root planing alone (Santos, Lira-­J unior, Fischer, Santos, & Oliveira,
2015). In the present review, the effect of antibiotics on treat-
ment outcomes in DM subjects could not be determined because
only one of the selected studies (Shen et al., 2008) included use of
antibiotics (patients received cephalexin 500 mg, b.i.d and metro-
nidazole 200 mg, q.i.d 3 days before and 3 days after scaling and
root planing).
In addition to experimental heterogeneity, it is acknowledged that
there were certain inherent limitations in the current meta-­analysis
and, therefore, results should be interpreted with caution: (a) The data
among smokers, former smokers and non-­smokers were all pooled
together. Smoking is a major risk indicator for periodontal disease
and significantly impairs periodontal treatment outcomes (Renvert,
Dahlen, & Wikstrom, 1998). Four included studies enrolled smokers,
but failed to provide separate treatment outcomes. Thus, it is diffi-
cult to distinguish the potential impact of smoking on periodontal
treatment outcomes in DMP vs P patients. The influence of smoking
on treatment outcomes cannot be ruled out given statistical analysis
could not be performed due to insufficient information reported in
these studies; (b) the inconsistent severity and extent of periodontitis
in the included articles may have contributed to a variety of clinical
outcomes. As mentioned earlier, the severity of periodontitis is asso-
ciated with PD and glycaemic control and may affect response to non-­
surgical periodontal therapy; (c) the majority of the selected studies
only reported short-­term clinical outcomes up to 6 months (Table 1).
The long-­
term effects of non-­
surgical periodontal therapy in DM
groups are important since the healing process could be consistently
impaired in patients with poorly controlled DM (Costa et al., 2013).
However, it should also be noted that long-­term outcomes might be
significantly influenced by other factors, including changes in medica-
tions, patient compliance with oral hygiene and periodontal mainte-
nance visits (Costa et al., 2014). Other study limitations include small
sample size and various examination protocols of the selected studies.
5 | CO N C LU S I O N S
It is acknowledged that the present meta-­analysis has several limita-
tions, and thus, the present results must be interpreted with caution.
The current findings suggest that periodontitis patients with mostly
well-­controlled DM respond similarly to non-­surgical periodontal
therapy, in terms of PD reduction and CAL gain, to periodontitis pa-
tients without DM. Baseline PD and age were two variables found to
play a significant role in PD reduction following treatment. The influ-
ence of poorly controlled DM and smoking could not be determined.
|
      215
Outcomes over longer observation periods (i.e., over 6 months post-­
treatment) could also not be determined.
AC K N OW L E D G E M E N T S
The authors express sincere appreciation to Ms. Amy Taylor, liaison
librarian, Texas Medical Center Library, for her valuable contribution
in the search strategy for this article. The authors would also like to
thank Dr. Nurcan Buduneli for generously sharing the raw data of his
study (Kardesler et al., 2010).
C O N FL I C T O F I N T E R E S T
The authors do not have any financial interests, either directly or
indirectly, in the products or information included in this paper. The
authors declare that there are no conflicts of interest in this study.
ORCID
Chun-Teh Lee  https://orcid.org/0000-0001-7812-5637
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S U P P O R T I N G I N FO R M AT I O N
Additional supporting information may be found online in the
Supporting Information section at the end of the article. 
How to cite this article: Hsu Y-T, Nair M, Angelov N, Lalla E,
Lee C-T. Impact of diabetes on clinical periodontal outcomes
following non-­surgical periodontal therapy. J Clin Periodontol.
2019;46:206–217. https://doi.org/10.1111/jcpe.13044