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Received: 29 August 2019 Revised: 4 November 2019 Accepted: 17 December 2019

DOI: 10.1111/jerd.12562

REVIEW ARTICLE

Dental caries, diabetes mellitus, metabolic control and diabetes


duration: A systematic review and meta-analysis

Ana Sofia Coelho1,2,3,4,5 | Inês Flores Amaro1 | Francisco Caramelo2,3,4,5,6 |


Anabela Paula1,2,3,4,5 | Carlos Miguel Marto1,2,3,4,5,7 |
Manuel Marques Ferreira2,3,4,5,8 | Maria Filomena Botelho2,3,4,5 |
Eunice Virgínia Carrilho1,2,3,4,5

1
Faculty of Medicine, Institute of Integrated
Clinical Practice, University of Coimbra, Abstract
Coimbra, Portugal Objective: To analyze articles aimed at evaluating the association between diabetes,
2
Faculty of Medicine, Coimbra Institute for
metabolic control, diabetes duration, and dental caries.
Clinical and Biomedical Research (iCBR),
University of Coimbra, Coimbra, Portugal Overview: A systematic search in PubMed, Cochrane Library, Embase, and Web of
3
Center for Innovative Biomedicine and Science was conducted to retrieve papers in English, Portuguese, and Spanish, up to
Biotechnology, University of Coimbra,
Coimbra, Portugal April 2019. The research strategy was constructed considering the “PECO” strategy.
4
Faculty of Medicine, CIMAGO—Center of Only quantitative observational studies were analyzed. The risk of bias was assessed
Investigation on Environment, Genetics and
using the Newcastle-Ottawa Quality Assessment Scale. The meta-analyses were per-
Oncobiology, University of Coimbra, Coimbra,
Portugal formed based on random-effects models using the statistical platform R. A total of
5
CNC.IBILI, University of Coimbra, Coimbra, 69 articles was included in the systematic review and 40 in the meta-analysis. Type
Portugal
6
1 diabetics have a significantly higher DMFT compared to controls. No significant dif-
Faculty of Medicine, Laboratory of
Biostatistics and Medical Informatics, ferences were found between type 2 diabetics and controls and between well-
University of Coimbra, Coimbra, Portugal controlled and poorly controlled diabetics. Concerning diabetes duration, all authors
7
Faculty of Medicine, Experimental Pathology
failed to find differences between groups.
Institute, University of Coimbra, Coimbra,
Portugal Conclusion: Although there is still a need for longitudinal studies, the meta-analysis
8
Faculty of Medicine, Institute of Endodontics, proved that type 1 diabetics have a high dental caries risk.
University of Coimbra, Coimbra, Portugal
Clinical significance: It is necessary to be aware of all risk factors for dental caries
Correspondence that may be associated with these patients, making it possible to include them into
Ana Sofia Coelho, Area de Medicina
Dentária—Av. Bissaya Barreto, Bloco de Celas, an individualized prevention program.
3000-075 Coimbra, Portugal.
Email: anasofiacoelho@gmail.com KEYWORDS

dental caries, diabetes mellitus, oral health

1 | I N T RO DU CT I O N Secondary complications resulting from a fluctuation in the blood


glucose levels are frequent and occur due to vascular degeneration in
Diabetes mellitus is presented as a set of metabolic disorders that are different organs.2 Despite advances in terms of diagnosis, prevention
characterized by hyperglycemia resulting from a deficiency in insulin and treatment, diabetic complications remain a major cause of mor-
production and/or action. Chronic hyperglycemia results in a distur- bidity and mortality.4-6
bance in the metabolism of carbohydrates, lipids, and proteins and in Type 1 diabetes mellitus includes the cases in which there is a
numerous long-term complications that cause damage, dysfunction, destruction of β-pancreatic cells by autoimmune processes (type 1A)
and failure of several organs.1-3 and those in which the etiology and pathogenesis of the destruction is

J Esthet Restor Dent. 2020;1–19. wileyonlinelibrary.com/journal/jerd © 2020 Wiley Periodicals, Inc. 1


2 COELHO ET AL.

idiopathic (type 1B), which occurs less frequently. Type 2 diabetes caries”, “oral health” and “diabetes mellitus.” Furthermore, MeSH syn-
mellitus is characterized by insulin resistance and relative deficiency onyms and related terms were included (Table 1). The reference lists
of its secretion and it is often associated with obesity and metabolic of relevant studies and reviews were manually searched for additional
syndrome.1,2,7-9 reports. Google was used for to search for grey literature. When mul-
In 2013, a study by the International Diabetes Federation esti- tiple articles describing the same population were found, the most
mated the global prevalence of patients with diabetes in 382 million, recent one was reported.
predicting a prevalence of 592 million in 2035. 10
The research strategy was constructed considering the “PECO”
Although there are several oral complications associated with dia- (Patient, Exposure, Comparison, Outcome) method.15 The studies to
betic patients,11,12 periodontal disease is the most frequently studied be included evaluated patients (P) with type 1 or with type 2 diabetes
one, being the other complications not adequately represented in mellitus (E) and a comparison group of non-diabetic healthy individuals
most studies. (C). The outcome (O)—prevalence of dental caries in the permanent or
Regarding dental caries, most studies include type 1 diabetic chil- primary dentition—should be reported according to the decayed, miss-
dren and the results are commonly controversial, which may be ing and filled (DMF/dmf) indices presented as means with SD.
explained by methodological differences between studies and the Regarding the evaluation of the role of metabolic control and dia-
multifactorial etiology associated with the disease. betes duration in dental caries, a comparison group of non-diabetic
The caries detection system proposed by the World Health Orga- individuals was not required.
nization13 remains the most widely used one in epidemiological stud- Only quantitative observational studies on the association
ies aimed at assessing the prevalence of caries in different between diabetes mellitus and dental caries were analyzed. Studies
populations and ages. DMF index is the total number of permanent evaluating patients with type 1 and type 2 diabetes together were
teeth or surfaces that are decayed (D), missing (M), or filled (F) due to excluded, as well as studies whose authors only selected diabetic
caries. When applied to teeth, the index is called DMFT and when patients with other diseases or according to their smoking habits and
applied only to tooth surfaces it is called DMFS. The index can also be articles on dental caries prevalence in newly diagnosed diabetic
applied to the primary dentition (dmft/dmfs, written in lowercase patients. Review articles, nonhuman studies, letters, case reports, con-
letters). ference abstracts and comments were also excluded.
The purpose of this study was to conduct a systematic review The titles and abstracts retrieved were analyzed to identify
and meta-analysis by analyzing articles aimed at evaluating the associ- potentially eligible studies. All titles and abstracts were examined by
ation between diabetes mellitus, metabolic control, diabetes duration, 2 reviewers independently to find relevant studies. The full texts of
and dental caries. To this end, the authors formulated the following the relevant studies were scrutinized by the same two reviewers. Any
questions: disagreement was discussed and the opinion of a third reviewer was
obtained when necessary.
1. When compared to non-diabetic healthy individuals, do patients
with diabetes mellitus have a higher prevalence of dental caries?
TABLE 1 Search strategy for each database
2. Do diabetics with a bad metabolic control have a higher prevalence
Database Search strategy
of dental caries when compared to diabetics with a good metabolic
control? Cochrane #1 MeSH descriptor: [Dental Caries] explode all trees
Library #2 carie*
3. Do diabetics with a longer duration of the disease have a higher
#3 carious
prevalence of dental caries when compared to diabetics with a #4 decay*
shorter duration of the disease? #5 MeSH descriptor: [Oral Health] explode all trees
#6 “oral health”
#7 #1 or #2 or #3 or #4 or #5 or #6
#8 MeSH descriptor: [Diabetes Mellitus] explode all
2 | MATERIALS AND METHODS trees
#9 diabetes
This systematic review and meta-analysis protocol was registered #10 diabetic*
with the International Prospective Register of Systematic Reviews #11 #8 or #9 or #10
#12 #7 and #11
(PROSPERO)—CRD42018092877. The Preferred Reporting Items for
Embase (‘dental caries’/exp OR ‘carie*’ OR decay* OR carious
Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) were
OR ‘oral health’) AND (‘diabetes mellitus’/exp OR
followed.14 ‘diabetes’ OR diabetic*)
An electronic search was performed using Cochrane Library Pubmed (((((((dental caries[MeSH Terms]) OR carie*) OR carious)
(www.cochranelibrary.com), Embase (www.embase.com), PubMed OR decay*) OR oral health[MeSH Terms]))) AND
(www.ncbi.nlm.nih.gov/pubmed) and Web of Science (www. (((diabetes mellitus[MeSH Terms]) OR diabetes) OR
webofscience.com) through April 30, 2019 without any restrictions on diabetic*)

publication type, region or year. The search was limited to articles in Web of TOPIC: (caries OR carious OR decay OR “oral health”)
Science AND TOPIC: (diabetes OR diabetic*)
English, Spanish and Portuguese. The MeSH terms used were “dental
COELHO ET AL. 3

When needed, study authors were contacted in order to request and patients with uncontrolled diabetes a HbA1c cut-off of 7% was
missing data and/or seek clarification. considered since most diabetes mellitus treatment guidelines set a
For each included study, descriptive and quantitative information maximum limit up to 7% for a good metabolic control for most
was collected, including authors, country and year of publication, sam- patients—for this analysis type 1 and type 2 diabetics were separately
ple size, age of participants, diabetes type, criteria adopted to assess evaluated.
the outcome, diabetes duration, metabolic control, results, and The risk of bias of the studies included in the systematic review
limitations. and meta-analysis was assessed using the modified Newcastle-
The meta-analyses, resulting from the systematic review, were Ottawa Quality Assessment Scale for cross-sectional studies16 by two
performed using the “metaphor” package accessible in the statistical independent reviewers. The methodological quality score was calcu-
platform R (v.3.3.2). In order to consider the heterogeneity of the lated based on three domains: Selection (0-4 points), Comparability
2
studies, which was evaluated with the Q test and the I statistic, the (0-2 points), and Exposure (0-3 points). To the assessment of each
meta-analyses were performed based on random-effects models. For domain, a series of multiple choice questions were answered by the
meta-analysis computation the difference in means from each individ- same two independent reviewers based on the reading and under-
ual study were used. Studies evaluating patients with type 1 diabetes standing of each study. A study can be awarded a maximum of one
were analyzed in two groups according to the caries indices used by point for each numbered item within the Selection (four items) and
the authors (dmft/DMFT). Only studies using the DMFT index were Exposure (three items) domains and a maximum of two points can be
included in the meta-analysis regarding type 2 diabetics. For the awarded for Comparability (two items). Therefore, the scores may
meta-analysis of studies evaluating patients with controlled diabetes vary from 1 to a maximum of 9 points.

F I G U R E 1 Flowchart of study
selection process
4

TABLE 2 Dental caries prevalence (Type 1 diabetics)


Authors, year Subject N dmft dmfs dt mt ft dfs DMFT DT MT FT DMFS DFS DS MS FS

Geetha et al,17 2019 DM1 175 *0.26 ± 0.05 *0.39 ± 0.08 *0 ± 0 *0 ± 0 *0.7 ± 0.45 *0.7 ± 0.4 *0.07 ± 0.006 *0.2 ± 0.06

Control 175 0.84 ± 0.2 0.73 ± 0.2 0.07 ± 0.01 0.07 ± 0.01 1.75 ± 0.8 1.46 ± 0.6 0.1 ± 0.01 0.43 ± 0.1

Kamran et al,18 2019 DM1 100 2.6 ± 1.25

Control 100 2.52 ± 1.26

Shakra & Foqaha,19 DM1 60 2.5 ± 3 2.6 ± 3.3


2019
Control 60 3.6 ± 3.4 1.2 ± 1.8

Babu et al,21 2018 DM1 80 0.44 ± 1.28 *1.26 ± 2.49

Control 80 0.88 ± 1.75 0.46 ± 1.02

Coelho et al,22 2018 DM1 60 1.72 ± 2.29 3.73 ± 4.79 *5.15 ± 3.95 *4.77 ± 6.07

Control 60 1.28 ± 1.76 2.9 ± 4.34 3.55 ± 3 2.56 ± 3.89

Coelho et al,23 2018 DM1 36 0.22 ± 0.68 *0.08 ± 0.50 0.97 ± 1.65 1.47 ± 2.021

Control 36 0.36 ± 0.87 0.61 ± 1.18 1.08 ± 1.84 2.11 ± 2.35

Ferizi et al,24 2018 DM1 80 *6.56 ± 3.56 4.78 ± 3.19 0.65 ± 1.42 1.14 ± 1.52

Control 80 4.21 ± 2.63 1.58 ± 1.9 0.75 ± 1.11 1.89 ± 1.65

Ambildhok et al,20 2018 DM1 100 *3.66 ± 4.80 *6.55 ± 5.80

Control 200 1.22 ± 1.09 2.44 ± 2.12

Machado et al,28 2018 DM1 30 3.83 ± 2.6 1.43 ± 4.22 2.73 ± 2.75

Control 30 4.73 ± 2.94 1.57 ± 3.71 2.07 ± 1.93

Techera et al,25 2018 DM1 56 1.23 ± 1.977

Control 30 1.04 ± 1.88

Basir et al,26 2017 DM1 27 *5.68 ± 1.13

Control 27 0.88 ± 0.16

Ismail et al,27 2017 DM1 32 1.09 ± 2.43 0.53 ± 1.85 0.31 ± 1.00 0.25 ± 0.98 1.69 ± 1.75 0.56 ± 0.84 0±0 1.13 ± 1.34

Control 32 1.38 ± 2.71 1.28 ± 2.54 0±0 0.09 ± 0.3 2.03 ± 1.75 0.31 ± 0.59 0±0 1.70 ± 1.46

Sadeghi et al,29 2017 DM1 36 2.5 ± 2

Control 36 2.02 ± 1.7

Fazlic et al,30 2016 DM1 60 *11.49 ± 3.1 *5.27 ± 3.38 *1.47 ± 1.69 *4.75 ± 2.51

Control 30 6.19 ± 2.54 2.63 ± 2.61 0.43 ± 0.86 3.13 ± 2.83

Garcia et al,31 2016 DM1 30 4.6 ± 4.26 4.23 ± 4.28 4.8 ± 3.15

Control 30 4.17 ± 3.09 3.42 ± 4.6 3.77 ± 3.22

Rafatjou et al,32 2016 DM1 73 3.78 ± 3.24

Control 75 3.08 ± 2.74

Rafatjou et al,32 2016 DM1 28 *2.52 ± 3.29

Control 33 5.36 ± 3.21

Busato et al,33 2016 DM1 32 4 ± 0.7

Control 32 1 ± 0.3

(Continues)
COELHO ET AL.
TABLE 2 (Continued)
Authors, year Subject N dmft dmfs dt mt ft dfs DMFT DT MT FT DMFS DFS DS MS FS

Singh-Hüsgen et al,34 DM1 100 *3.86 ± 7.68 3.08 ± 11.38


COELHO ET AL.

2016
Control 100 1.38 ± 5.33 2.57 ± 7.11

Subramaniam et al,35 DM1 30 1.07 ± 2.43


2015
Control 30 0.5 ± 1.14

Arheiam & Omar,36 DM1 70 1.19 ± 1.74 *0.91 ± 1.32 *0.19 ± 0.57 0.09 ± 0.33
2014
Control 70 0.8 ± 1.46 0.57 ± 1.19 0.1 ± 0.35 0.1 ± 0.42

Gupta et al,38 2014 DM1 140 0.59 ± 1.36 0.6 ± 1.63 2.09 ± 2 *1.91 ± 1.94 *0.047 ± 0.21 0.13 ± 0.38 2.25 ± 2.31 2.05 ± 2.18 0.19 ± 0.85 *0.02 ± 0.14

Control 140 0.77 ± 1.37 1.15 ± 1.91 2.25 ± 1.64 2.07 ± 1.6 0.04 ± 0.2 0.14 ± 0.45 2.74 ± 2.11 2.43 ± 1.99 0.16 ± 0.79 0.15 ± 0.47

Bassir et al,37 2014 DM1 31 3.71 ± 2.48 2.41 ± 1.92 0.32 ± 0.54 0.96 ± 1.1

Control 31 4.35 ± 2.74 2.87 ± 1.12 0.32 ± 0.54 1.2 ± 1.13

Alves et al,39 2012 DM1 51 0.64 ± 1.24 1.94 ± 2.84

Control 51 1.27 ± 2.42 1.41 ± 2.34

El-Tekeya et al,41 2012 DM1 50 6.33 ± 4.48 0.82 ± 1.58

Control 50 5.81 ± 5 0.7 ± 1.26

Akpata et al,40 2012 DM1 53 *6.4 ± 4.7 *3.7 ± 3.2 7.3 ± 6.5 1.4 ± 2.8 *3.8 ± 3.3

Control 53 4.7 ± 3.3 1.8 ± 2.3 5.6 ± 4 1 ± 1.5 2.1 ± 2.9

Tagelsir et al,43 2011 DM1 52 2.86 ± 2.52 3.89 ± 3.81 3.84 ± 3.89 5.61 ± 5.97

Control 50 3.51 ± 2.76 7.03 ± 7.33 2.85 ± 2.47 4.46 ± 3.98

del Valle & DM1 25 *1.43 ± 1.8


Oca-sio-Lopez,62
Control 25 0.56 ± 1
2011

Busato et al,45 2010 DM1 51 *3.3 ± 3.7

Control 51 1.5 ± 2.1

Miko et al,44 2010 DM1 259 *11.15 ± 4.2 *3.89 ± 3.64 *3.9 ± 2.3 *3.36 ± 3.48

Control 259 9.56 ± 5.15 6.39 ± 3.95 3.89 ± 3.09 0.89 ± 1.5

Neil et al,46 2009 DM1 63 0.09 ± 0.1

Control 63 0.2 ± 0.15


47
Vaziri et al, 2009 DM1 40 10.16 ± 4.52

Control 20 8.26 ± 3.85

Siudikiene et al,49 2008 DM1 63 0.7 ± 1.9 5.79 ± 6.6 34.5 ± 16.6

Control 63 0.2 ± 1.4 6.2 ± 5.2 37.1 ± 15.1

Orbak et al,48 2008 DM1 50 0.6 ± 1 *1.7 ± 2.1 *1.3 ± 1.9

Control 50 0.7 ± 1.1 5.5 ± 8.3 4.6 ± 7.7

Ilgüy & Bayirli,50 2007 DM1 46 38.17 ± 29.88 4.36 ± 3.95 *23.04 ± 24.86 10.76 ± 12.74

Control 50 21.64 ± 20.36 3.36 ± 3.18 8.04 ± 9 10.24 ± 13.32


51
Amaral et al, 2006 DM1 30 *6.7 ± 5.7

Control 84 10.5 ± 5.8

(Continues)
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TABLE 2 (Continued)
Authors, year Subject N dmft dmfs dt mt ft dfs DMFT DT MT FT DMFS DFS DS MS FS

Siudikiene et al,53 2006 DM1 68 0.29 ± 1.47 3.13 ± 3.74 *23.03 ± 14.54

Control 68 0.07 ± 0.61 3.97 ± 3.93 27.43 ± 16.04

Miralles et al,52 2006 DM1 90 *7.41 ± 4.17

Control 90 5.63 ± 4.04

Edblad et al,54 2001 DM1 41 7.3 ± 4.2 15.4 ± 10.4

Control 41 6.5 ± 4 12.1 ± 10.1

Moore et al,55 2001 DM1 390 *2.51 ± 0.23 *33.7 ± 1.2 21.7 ± 0.8 1 ± 0.1

Control 202 1.44 ± 0.28 26.2 ± 1.7 19.1 ± 1.2 0.9 ± 0.2

Swanljung et al,56 1992 DM1 85 4.3 ± 3.1 5.8 ± 5

Control 85 3.3 ± 2.7 4 ± 3.9

Akyuz & Oktay,57 1990 DM1 42 *4.55 ± 2.45

Control 20 6.4 ± 2.7

Tenovuo et al,59 1986 DM1 35 37.9 ± 25 *8.5 ± 12.4 *23.5 ± 16.1

Control 35 45.7 ± 24.5 3.4 ± 3.2 36.3 ± 15.8

Goteiner et al,58 1986 DM1 169 4.53 ± 3.8

Control 80 4.46 ± 3.22

Bernick et al,60 1975 DM1 50 8.27 ± 1.34

Control 36 8.89 ± 1

Matsson & Koch,61 1975 DM1 33 *13.4 ± 1.6

Control 33 20.5 ± 2.6

Abbreviation: DM1, Type 1 Diabetes mellitus.


Note: Primary dentition—dmft, decayed, missing, and filled teeth; dt, decayed teeth; mt, missing teeth; ft, filled teeth; dmfs, decayed, missing, and filled surfaces; dfs, decayed and filled surfaces. Permanent
dentition—DMFT, decayed, missing, and filled teeth; DT, decayed teeth; MT, missing teeth; FT, filled teeth; DMFS, decayed, missing, and filled surfaces; DFS, decayed and filled surfaces; DS, decayed surfaces;
MS, missing surfaces; FS, filled surfaces.
*Statistically significant difference (P < 0.05).
COELHO ET AL.
TABLE 3 Dental caries prevalence (Type 2 diabetics)
Authors, year Subject N DMFT DT MT FT DMFS DFS DS MS FS DR DRS FRS
Arab & Keshavarzi,63 2018 DM2 50 *32.4 ± 1.5
COELHO ET AL.

Control 50 25.0 ± 1.5


Latti et al,64 2018 DM2 30 *10.67 ± 5.2
Control 30 5.6 ± 2.59
Puttaswamy et al,65 2017 DM2 60 5.75 ± 3.53
Control 40 5.83 ± 4.11
Malvania et al,66 2016 DM2 120 *2.43 ± 2.88 1.06 ± 0.58 *1.24 ± 0.91 0.1 ± 0.47
Control 120 0.74 ± 1.27 0.46 ± 1.03 0.23 ± 0.63 0.07 ± 0.36
Singh et al,67 2016 DM2 30 *14.8 ± 0.59
Control 30 3.75 ± 0.24
Lima et al,68 2014 DM2 50 *30.7 ± 3.6 0.1 ± 0.4 29.8 ± 6.1 0.8 ± 2.7
Control 50 22.3 ± 4.6 1.5 ± 1.6 17.9 ± 6.8 2.9 ± 3.1
Singh et al,69 2014 DM2 60 *12.6 ± 0.48
Control 60 2.67 ± 0.14
Sukminingrum et al,70 2013 DM2 23 *13.52 ± 3.69 *6.7 ± 2.067
Control 26 9.73 ± 2.50 3.81 ± 1.772
Aziz et al,71 2012 DM2 180 14.04 ± 7.06 2.1 ± 1.46 *10.84 ± 7.27 *1.03 ± 1.37
Control 180 12.65 ± 8.22 1.93 ± 1.63 9.17 ± 6.32 1.47 ± 1.56
Vaziri et al,47 2009 DM2 40 13.42 ± 5.09
Control 21 10.55 ± 2.59
Marín et al,72 2008 DM2 35 19.6 ± 3.9 10.5 ± 6 *5.7 ± 3.7 3.4 ± 3.7
Control 35 18.2 ± 3.5 10.9 ± 6.1 3.5 ± 2.9 3.7 ± 3.7
Hintao et al,78 2007 DM2 105 3.8 ± 0.2 8 ± 9.4 *1 ± 0.2 *1.2 ± 0.2
Control 103 3.3 ± 0.3 6.3 ± 7.5 0.4 ± 0.1 0.5 ± 0.1
Ilgüy & Bayirli,50 2007 DM2 40 46.42 ± 32.33 3.35 ± 3.4 *32.4 ± 27.31 10.85 ± 13.56
Control 50 21.64 ± 20.36 3.36 ± 3.18 8.04 ± 9 10.24 ± 13.32
Zielinski et al,74 2002 DM2 32 8.9 ± 6.1 9.2 ± 6.6
Control 40 9.3 ± 6.7 9.1 ± 6.2
Lin et al,75 1999 DM2 24 *41.3 ± 20.9 1.8 ± 2.6 *56 ± 34.1 *39.5 ± 20.5 1.3 ± 1.8 *14.5 ± 15.8
Control 18 54.9 ± 20.3 1±1 38.1 ± 28.1 53.9 ± 20.2 0.6 ± 1 24.1 ± 13.3
Collin et al,76 1998 DM2 25 23.8 ± 6
Control 40 25.1 ± 4.3
Cherry-Peppers & Ship,77 1993 DM2 11 53.8 ± 29.7 *3.8 ± 9.5 20.3 ± 19.6 30 ± 13
Control 43 56.9 ± 33.9 0.7 ± 1.7 16.9 ± 26.8 37 ± 21.6

Abbreviations: DMFT, decayed, missing, and filled teeth; DT, decayed teeth; MT, missing teeth; FT, filled teeth; DMFS, decayed, missing, and filled surfaces; DFS, decayed and filled surfaces; DS, decayed
surfaces; MS, missing surfaces; FS, filled surfaces; DR, decayed roots; DRS, decayed root surfaces; FRS, filled root surfaces; DM2, Type 2 Diabetes mellitus.
*Statistically significant difference (P < .05).
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8

TABLE 4 Dental caries and metabolic control


N

Authors, year DM1 DM2 HbA1c (%) dfs dmft dmfs DMFT DFT DT MT FT DMFS DFS DS MS FS
18
Kamran et al, 2019 30 <7 2.63 ± 1.11
15 ≤7 to <8 2.33 ± 1.11
55 ≥8 2.65 ± 1.27
Vidya et al,80 2018 19 <7 *0.16 ± 0.38
68 >7 1.47 ± 2.77
Sadeghi et al,29 2017 9 ≤7 2.3 ± 0.7 3.1 ± 0.9
21 >7 to ≤8 2.5 ± 0.5 2.7 ± 0.4
20 >8 0.5 ± 0.3 3.2 ± 0.5
Fazlic et al,30 2016 30 ≤7 10.57 ± 3.22
30 >7 12.39 ± 2.97
Kogawa et al,81 2016 32 <7 20.25 ± 6.7
31 >7 18.23 ± 7.31
Malvania et al,66 2016 47 ≤7 *0.62 ± 1.01 0.36 ± 0.79 *0.32 0.04 ± 0.2
± 0.66
73 >7 3.46 ± 3.16 1.51 ± 1.8 1.83 ± 2.2 0.14
± 0.58
Karthikeyan et al,82 25 ≤7 *18.16 ± 9.57 *14.08 1.2 ± 2.61 3.28 ± 3.51
2015 ± 7.59
25 >7 37.76 ± 16.83 31.44 2 ± 4.33 4.32 ± 5.76
± 16.95
Aziz et al,71 2012 119 ≤7 13.92 ± 7.74
61 >7 14.28 ± 5.59
El-Tekeya et al,41 2012 23 <8.5 7.09 0.78 ± 1.52
± 5.09
20 ≥ 9 to 5.63 0.78 ± 1.66
<10.5 ± 3.73
7 ≥ 11 5.86 ± 4.6 1.25 ± 1.89
Tagelsir et al,43 2011 20 <7.5 2.75 3.93 3.16 ± 3.5 5 ± 6.76
± 1.98 ± 3.54
22 ≥ 7.5 to 3.39 5.31 4.18 ± 4.49 6.12 ± 5.94
<8.5 ± 2.88 ± 4.09
10 ≥ 8.5 0.57 0.57 4.75 ± 3.45 6 ± 4.41
± 0.53 ± 0.53
Busato et al,62 2010 17 ≤8 3.6 ± 3.7 0.5 ± 1.2 0.5 ± 1.1 3.3 ± 4
34 >8 3.2 ± 3.7 0.3 ± 1 0.1 ± 0.5 2.9 ± 3.5
Miko et al,44 2010 210 ≤6.5 12.91 ± 5.64 *3.48 4.98 ± 2.23 *4.46
± 2.22 ± 2.1
49 >6.5 13.29 ± 3.25 5.98 ± 4.52 4.86 ± 1.69 2.45
± 1.16

(Continues)
COELHO ET AL.
TABLE 4 (Continued)
N

Authors, year DM1 DM2 HbA1c (%) dfs dmft dmfs DMFT DFT DT MT FT DMFS DFS DS MS FS
COELHO ET AL.

72
Marín et al, 2008 35 ≤7 8.8 ± 4.8 5.5 ± 4.8 1.3 ± 2.2 1.9 ± 4.6
35 >7 8.6 ± 5.9 4.1 ± 4 2 ± 3.2 2.5 ± 3.8
Siudikiene et al,53 2006 39 <9 *19.51 0±0 3.46 ± 4.17
± 12.62
29 ≥9 27.76 ± 15.78 0.69 2.69 ± 3.07
± 2.21
Miralles et al,52 2006 46 ≤7.5 7.84 ± 4.48
44 >7.5 7.47 ± 4.29
Bolgül et al,83 2004 15 <10 *2.2 ± 1.7
30 ≥10 to <13 4.1 ± 1.9
25 ≥13 7.1 ± 2.4
Syrjälä et al,84 2003 69 ≤8.5 6.49 ± 6.25 24.91
± 18.15
59 >8 6.31 ± 6.75 23.05
± 19.92
Twetman et al,85 2002 37 ≤8 0.6 *1.6 ± 2 *1.4 ± 1.9
± 1.1
27 >8 0.8 5.4 ± 8.4 4.8 ± 7.8
± 2.7
Edblad et al,54 2001 26 <8 10.5 7.1 ± 4.1 16 ± 9.8
± 5.1
15 >8 9.6 ± 5 7.6 ± 4.4 14.5
± 11.7
Lin et al,75 1999 9 ≤9 48.8 1.3 ± 2.1 41.6 47.4 ± 16.9
± 17.8 ± 25.9
15 >9 36.9 2.1 ± 2.9 64.7 34.8 ± 21.4
± 21.9 ± 36.3
Karjalainen et al,86 1997 21 <10 *4.1 ± 6.9 0.2 ± 0.6 *3.9 ± 6.9
25 ≥10 to <13 2.3 ± 3.3 0.3 ± 0.7 2 ± 3.1
34 ≥13 7.5 ± 9.2 0.7 ± 1.8 6.9 ± 8.5
Harrison & Bowen,87 14 ≤10 4.8 ± 1.3
1987
16 >10 5.6 ± 1.3

Abbreviations: DM1, Type 1 Diabetes mellitus; DM2, Type 2 Diabetes mellitus.


Note: Primary dentition: dmft, decayed, missing, and filled teeth; dfs, decayed and filled surfaces; dmfs, decayed, missing, and filled surfaces. Permanent dentition: DMFT, decayed, missing, and filled teeth; DFT,
decayed and filled teeth; DT, decayed teeth; MT, missing teeth; FT, filled teeth; DMFS, decayed, missing and filled surfaces; DFS, decayed and filled surfaces; DS, decayed surfaces; MS, missing surfaces; FS,
filled surface.
*Statistically significant difference (P < .05).
9
10 COELHO ET AL.

TABLE 5 Dental caries and diabetes duration

Authors, year DM1 DM2 Duration (years) dmfs DMFT DT MT FT DMFS


Kamran et al,18 2019 48 <6 2.52 ± 1.11
52 ≥6 2.67 ± 1.38
Malvania et al,66 2016 52 <2 2.05 ± 2.94 0.94 ± 1.43 1.02 ± 1.96 0.12 ± 0.58
17 2–5 2.69 ± 1.54 *0.5 ± 0.73 *1 ± 0.55 *0.12 ± 0.5
51 >5 3.01 ± 3.06 1.37 ± 1.87 1.57 ± 1.96 0.08 ± 0.33
Twetman et al,88 1992 26 Onset 3.5 ± 6.1 3.1 ± 3.8
1 4 ± 6.6 4 ± 4.8
2 4 ± 6.6 4.1 ± 5.2
Miralles et al,52 2016 39 <10 6.82 ± 3.9
51 >10 7.87 ± 4.19
Siudikiene et al,49 2008 63 Baseline 0.3 ± 1.5 3.1 ± 4.4 23 ± 15
63 2 0.7 ± 1.9 5.79 ± 6.6 34.5 ± 17

Abbreviations: DM1, Type 1 Diabetes mellitus; DM2, Type 2 Diabetes mellitus.


Note: Primary dentition—dmfs: decayed, missing, and filled surfaces. Permanent dentition—DMFT, decayed, missing and filled teeth; DT, decayed teeth;
MT, missing teeth; FT, filled teeth; DMFS, decayed, missing and filled surfaces.
*Statistically significant difference (P < .05).

T A B L E 6 Risk of bias of the studies included in the systematic review and meta-analysis using the modified Newcastle-Ottawa Quality
Assessment Scale for cross-sectional studies72

Authors, year Selection (0-4) Comparability (0-2) Exposure (0-3) Risk of bias (0–9)
17
Geetha et al, 2019 3 1 3 7
18
Kamran et al, 2019 2 1 3 6
Shakra et al,19 2019 3 1 3 7
Ambildhok et al,20 2018 3 1 3 7
Arab et al,63 2018 2 1 3 6
Babu et al,21 2018 3 1 3 7
Coelho et al,22 2018 4 1 3 8
Coelho et al,23 2018 3 1 3 7
Ferizi et al,24 2018 3 1 3 7
64
Latti et al, 2018 2 2 3 7
Techera et al,25 2018 3 1 3 7
80
Vidya et al, 2018 3 1 3 7
Basir et al,26 2017 4 1 3 8
27
Ismail et al, 2017 3 1 3 7
Machado et al,28 2017 3 1 3 7
65
Puttaswamy et al, 2017 2 2 3 7
Sadeghi et al,29 2017 4 1 3 8
Busato et al,33 2016 4 1 3 8
Fazlic et al,30 2016 3 1 3 7
Garcia et al,31 2016 4 1 3 8
Kogawa et al,81 2016 4 2 3 9
66
Malvania et al, 2016 2 1 3 6
Rafatjou et al,32 2016 4 1 3 8
67
Singh et al, 2016 3 1 3 7
(Continues)
COELHO ET AL. 11

TABLE 6 (Continued)

Authors, year Selection (0-4) Comparability (0-2) Exposure (0-3) Risk of bias (0–9)
34
Singh-Husgen et al, 2016 3 1 3 7
Karthikeyan et al,82 2015 4 1 3 8
35
Subramaniam et al, 2015 4 1 3 8
Arheiam et al,36 2014 3 1 3 7
Bassir et al,37 2014 4 1 3 8
Gupta et al,38 2014 4 2 3 9
Lima et al,68 2014 2 1 3 6
Singh et al,69 2014 3 1 3 7
Sukminingrum et al,70 2013 4 1 3 8
Akpata et al,40 2012 4 2 3 9
39
Alves et al, 2012 2 1 3 6
71
Aziz et al, 2012 3 1 3 7
El-Tekeya et al,41 2012 4 2 3 9
42
López del Valle & Ocasio-Lopez, 2011 3 1 3 7
Tagelsir et al,43 2011 3 1 3 7
Busato et al,45 2010 4 1 3 8
Miko et al,44 2010 2 1 3 6
Neil et al,46 2009 4 1 3 8
Vaziri et al,47 2009 3 2 3 8
Marín et al,72 2008 3 1 3 7
48
Orbak et al, 2008 2 1 3 6
Siudikiene et al,49 2008 4 1 3 8
78
Hintao et al, 2007 3 2 3 8
Ilguy et al,50 2007 3 1 3 7
Amaral et al,51 2006 4 1 3 8
Miralles et al,52 2006 3 1 3 7
53
Siudikiene et al, 2006 4 1 3 8
Bolgul et al,83 2004 3 1 3 7
Syrjala et al,84 2003 3 1 3 7
85
Twetman et al, 2002 3 1 3 7
Zielinski et al,74 2002 3 1 3 7
Edblad et al,54 2001 4 2 3 9
Moore et al,55 2001 3 1 3 7
Lin et al,75 1999 4 1 3 8
Collin et al,76 1998 4 1 3 8
86
Karjalainen et al, 1997 3 2 3 8
Cherry-Peppers et al,77 1993 4 1 3 8
Swanljung et al,56 1992 3 2 3 8
Twetman et al,88 1992 3 2 3 8
Akyuz & Oktay,57 1990 3 1 3 7
87
Harrison et al, 1987 2 1 3 6
Goteiner et al,58 1986 4 2 3 9
Tenovuo et al,59 1986 2 2 3 7
Bernick et al,60 1975 2 1 3 6
Matsson et al,61 1975 3 1 3 7
12 COELHO ET AL.

F I G U R E 2 Forest plot of meta-analysis for studies evaluating the DMFT in permanent dentition comparing patients with type 1 diabetes
mellitus (DM1) and controls

3 | RESULTS duration as a risk factor for dental caries were also analyzed (Tables 4 and
5, respectively).
The flowchart of the study selection process is presented in Figure 1. The earliest studies were published in 1975 (Bernick et al60 and
The literature search resulted in a total of 2744 unique articles, of Matsson & Koch61) and the most recent ones were published in 2019
which 169 proceeded for examination of the full-text (2575 were (Geetha et al,17 Kamran et al,18 and Shakra & Foqaha19).
excluded). Eight additional studies were included for analysis from the Twelve of the studies were conducted in India,17,20,21,35,38,64-67,69,80,82
reference lists and grey literature. A hundred articles were excluded eight in the United States,42,55,58,60,74,75,77,87 six in Brazil,33,39,45,51,68,81 five
since their authors did not report DMF indices, did not mention the in Finland,56,59,76,84,86 four each in Portugal,22,23,28,31 Sweden,54,61,85,88 and
existence of a control group, used a special population (diabetic Turkey,48,50,57,83 two in Lithuania,49,53 one each in Belgium,43 Bosnia and
patients with other diseases, smokers, or newly diagnosed) or did not Herzegovina,30 China,27 Egypt,41 Germany,34 Hungary,44 Iraq,71 Jordan,19
report the data as mean and SD. Republic of Kosovo,24 Kuwait,40 Libya,36 Malaysia,70 Mexico,72 Spain,52
Final analysis was carried out on 69 articles. Forty were pooled Sudan,46 Thailand,73 and Uruguay.25
for meta-analysis. The majority of the studies regarding type 1 diabetes only
Forty-five articles17-61 regarding caries experience among type 1 dia- included children.17-21,23-27,29,30,32-46,48,49,53,56-58,60,61 In most studies,
betics were analyzed (Table 2). Regarding type 2 diabetes 17 stud- the control group was recruited from schools or dental clinics. Dia-
ies47,50,63-77 were included (Table 3). Vaziri et al79 and Ilgüy et al50 betic groups were often recruited from hospitals.
evaluated type 1 and type 2 diabetics but results for each group were Intra-examiner agreement was stated in 15 studies and the kappa co-
separately reported. Twenty-two articles18,29,30,41,43-45,52-54,66,71,72,75,80-87 efficient was between 0.70 and 0.97.17,21,25,27,38,40,43,49,53,56,66,72,82,84,85
regarding metabolic control and five18,49,52,66,88 regarding diabetes The inter-examiner agreement was stated in six studies and the kappa co-
COELHO ET AL. 13

efficient was mainly over 0.80.43,49,53,55,72 The lowest inter-examiner heterogeneity among studies was observed (I2 = 98.5%; Q
agreement was reported by Lin et al75 with a kappa co-efficient of 0.65. [26] = 562.12; P < .001). Regarding dmft index no statistically signifi-
The results of the studies' quality assessment are presented in cant differences between groups were found (mean difference = 0.53;
Table 6. The scores assigned range from 6 points (nine studies), 95% CI: −0.20, 1.26, Figure 3) and a significant heterogeneity among
7 points (31 studies), 8 points (22 studies), and 9 points (six studies). studies was observed (I2 = 97.8%; Q[10] = 489.82; P < .001).

3.1 | Type 1 diabetes 3.2 | Type 2 diabetes

Eleven studies20,21,24,26,30,33,40,44,45,52,55 reported a DMFT/DMFS index Seven studies63,64,66-70 reported a significantly higher DMFT index
17,38,53,57
significantly higher among type 1 diabetics, four found a sig- among type 2 diabetics, while Lin et al75 reported opposite results
18,19,25,27,32,34-37,39,41,43,46,47,49,50,56,58-60
nificantly lower index and 20 regarding DFS. Seven studies47,50,65,71,72,76,77 found no statistically
did not find statistically significant differences between groups. significant differences between groups.
Regarding dmft/dmfs index, Ambildhok et al20 and Singh-Hüsgen Hintao et al78 did not find significant differences between groups
34
et al reported a significantly higher index among type 1 diabetics regarding coronal caries. However, the authors reported a significant
while Geetha et al,17 Rafatjou et al,32 Gupta et al,38 and Amaral et al89 higher prevalence of decayed roots among type 2 diabetics. Lin et al75
19,21,27,29,39,43
reported a significantly lower index. Six studies found reported opposite results regarding filled root surfaces.
no statistically significant differences between groups. No statistically significant differences were found between type 2 dia-
In the meta-analysis, type 1 diabetic patients had a significantly betics and controls regarding DMFT index (mean difference = −5.16;
higher DMFT index than that of non-diabetic individuals (mean differ- 95% CI: −10.62, 0.30, Figure 4). Significant heterogeneity among studies
ence = −0.55; 95% CI: −1.10, −0.01, Figure 2). Significant was observed (I2 = 99.9%; Q[11] = 609.28; P < .001).

F I G U R E 3 Forest plot of meta-analysis for studies evaluating the dmft in temporary dentition comparing patients with type 1 diabetes
mellitus (DM1) and controls
14 COELHO ET AL.

3.3 | Metabolic control Regarding type 2 diabetes mellitus, only five articles66,71,75,81,82
reported results on the influence of metabolic control on dental caries
53
Siudikiene et al found that the mean DMFS index of poorly con- prevalence. Although Malvania et al66 and Karthikeyan et al82
trolled (HbA1c ≥ 9%) type 1 diabetic children was significantly higher reported a significantly higher DMFT/DMFS indices of poorly con-
than that of well-controlled children (HbA1c < 9%). Bolgül et al83 and trolled diabetics (HbA1c ≥ 7%) compared to well-controlled
Karjalainen et al86 reported similar DMFT/DFS results between poorly (HbA1c < 7%) diabetics, the meta-analysis did not find statistically sig-
(HbA1c ≥ 13%), moderately (HbA1c ≥ 10 to <13%) and well-controlled nificant differences between well-controlled and poorly controlled
(HbA1c < 10%) patients. Vidya et al80 also reported a significantly type 2 diabetics (mean difference = −0.30; 95% CI: −1.11, 0.52,
higher mean DMFT/DMFS indices of poorly controlled type 1 dia- Figure 6). No heterogeneity among studies was observed (I2 = 92.3%;
betics (HbA1c ≥ 7%) compared to that of well-controlled patients Q[2] = 24.10; P < .001).
(HbA1c < 7%).
Twetman et al85 observed type 1 diabetic children over a period
of 3 years and reported that HbA1c was higher in children who devel- 3.4 | Diabetes duration
oped dental caries during the study period.
Concerning the meta-analysis only studies considering a HbA1c Although five articles18,49,52,66,88 reported results on diabetes dura-
cut-off of 7% were used. No statistically significant differences were tion, all of them used different cut-off years. Regarding DMFT index,
found between well-controlled and poorly controlled type 1 diabetics all authors failed to find statistically significant differences between
(mean difference = −0.34; 95% CI: −0.74, 0.06, Figure 5). No groups.
2
heterogeneity among studies was observed (I = 47.8%; Q The results regarding the prevalence of dental caries as well as the
[2] = 3.82; P = .15). weight of the different risk factors associated with diabetic patients are

F I G U R E 4 Forest plot of meta-analysis for studies evaluating the DMFT in permanent dentition comparing patients with type 2 diabetes
mellitus (DM1) and controls
COELHO ET AL. 15

F I G U R E 5 Forest plot of meta-analysis for studies evaluating the DMFT in permanent dentition comparing patients with controlled type
1 diabetes (HbA1c ≤ 7) and patients with uncontrolled type 1 diabetes (HbA1c > 7)

F I G U R E 6 Forest plot of meta-analysis for studies evaluating the DMFT in permanent dentition comparing patients with controlled type
2 diabetes (HbA1c ≤ 7) and patients with uncontrolled type 2 diabetes (HbA1c > 7)

controversial. The meta-analysis revealed a statistically significant dif- risk of root caries is described for type 2 diabetics, which may be
ference between type 1 diabetics and control individuals. However, it related to the increasing susceptibility to periodontal disease, but few
failed to prove these differences regarding type 2 diabetics. A higher studies aimed at evaluating this condition.44,76,78,90
16 COELHO ET AL.

4 | DISCUSSION and dental clinics. This might be considered a possible bias since the
individuals selected from these establishments are neither representa-
Studies evaluating patients with type 1 and type 2 diabetes together tive of a randomized group nor of the general community. In addition
were excluded from this review. Although a large number of risk fac- to these studies, 14 others do not make any description about the ori-
tors are common to these two types of patients, the higher prevalence gin of the recruitment of the controls, not providing sufficient infor-
of periodontal disease associated with type 2 diabetics, the differ- mation for the evaluation and validation of these groups.
ences in dietary habits, as well as the different medical complications Regarding the remaining items and domains, all of them presented
associated with them, for example, can make it difficult to interpret a low risk of bias, since all the studies had an adequate definition—
the results.37,89,91 with independent validation—and all individuals of the control groups
Singh-Hüsgen et al34 developed a study that included 100 diabetic had no history of disease (diabetes) in all phases of the studies. All
children and 100 sex-age-matched controls and found no statistically records and results were considered safe and reliable and it is com-
significant differences between groups regarding dental caries. The mon to all studies that the methods used to evaluate the established
authors associated the results with the metabolic control of the dia- study parameters were the same for both test and control groups.
betics, since 88% of the sample was considered to be metabolically Diabetic patients have inherently associated several risk factors
18
well-controlled. However, in cross-sectional studies, Kamran et al, for the development of dental caries. The greater number of daily
Sadeghi et al,29 El-Tekeya et al,41 and Tagelsir et al43 found no signifi- meals to which these patients are subjected, consequently, translates
cant differences regarding dental caries between metabolically well, into a greater daily supply of nutrients that influence the proliferation
moderately, and poorly controlled. The evaluation of the effect of the of microorganisms in the oral cavity as well as the maintenance of a
metabolic control in the development of dental caries may, however, lower salivary pH, a risk factor for the development of dental car-
be better evaluated in longitudinal studies since HbA1c levels fluctu- ies.37,89,96,97 Salivary pH has been studied and proven to reach lower
ates in diabetics. values in diabetic patients compared to healthy individuals.98,99 Sev-
Although in the meta-analysis no statistically significant differ- eral factors contribute to this decrease: the low concentration of
ences were found concerning metabolic control for type 1 and 2 dia- bicarbonate, the greater accumulation of dental plaque and saliva with
betics, it should be taking into account that only a HbA1c cut-off of high cariogenic load and an increased concentration of salivary glu-
7% was considered. The heterogeneity regarding the cut-offs of the cose, possibly related to microvascular complications (damage to the
studies evaluating the metabolic control made it impossible to include basal membrane of salivary glands leads to an endothelial dysfunction
more studies in the meta-analysis. Also, this large variety of cut-offs and the glucose molecule is easily released to the existing
makes it very difficult to interpret the results. saliva).22,100-103
85,92
Twetman et al conducted a longitudinal study and found a Given the heterogeneity of the diabetic population and the differ-
positive correlation between the risk of caries when diabetes was ent risk factors that exist, a dietary assessment is also extremely impor-
diagnosed and metabolic control 3 years after the initial observation. tant as it allows analyzing the frequency of ingestion of cariogenic
However, this correlation may reflect mainly the importance of behav- products—high or low—enabling the identification of this parameter as
ioral factors in the sense that a greater concern for oral health can be a risk or protective factor, respectively. Diabetic patients who present
included in a general health awareness and thus, be associated with a better dietary habits, such as reduced intake of cariogenic products, are
greater commitment to diabetes treatment. those who have a better nutritional control and who are motivated and
The heterogeneity regarding the cut-offs of the studies evaluating willing to cooperate towards a healthier lifestyle.37,89,96,97
the diabetes duration made it impossible to conduct a meta-analysis. The resolution of hypoglycemic episodes using sugar requires the
Although no statistically significant differences between long and diabetic patient to be well informed about procedures for proper oral
short diabetes duration was found, that was expected since there are cavity hygiene, especially when these episodes occur at night.
known biological and behavioral changes over the time. In fact, diabe- Decreased salivary flow is very common in diabetic patients, espe-
tes duration is associated with micro and macrovascular cially at night. This decrease leads to reduced substrate elimination
complications.93-95 and decreased sugar dissolution rates, leading to less effective pH reg-
The highest risk of bias, resulting in the lowest scores, was identi- ulation and antimicrobial mechanisms, promoting bacterial prolifera-
fied in the first domain—Selection—more precisely in items number tion and sugar metabolization by cariogenic bacteria. All this may also
2 (Representativeness of the cases) and 3 (Selection of Controls). In lead to demineralization of the dental structure.98,99
item number 2, 15 studies were identified as having insufficient/non- Dental caries is a multifactorial condition and, as such, implies a
existent description regarding the selection process of the groups, thorough and careful assessment of all its etiological factors so that it
making no reference to possible confounding factors and lacking well- is possible to assess the risk profile of each diabetic patient. Assess-
defined inclusion and exclusion criteria. The non-parametrization of ment of primary—carbohydrate consumption and presence of cario-
the criteria and the insufficient information provided by the studies genic microorganisms—and secondary factors—oral hygiene habits—is
makes it impossible to reproduce them and to confirm the homogene- required.62,104,105
ity of the groups. In item number 3, 18 studies described the selection Most studies do not make this multifactorial assessment, not con-
process of the control group as being from public and private hospitals sidering many other factors, making it very difficult to accurately
COELHO ET AL. 17

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