Aus der Klinik und Poliklinik für Zahnerhaltung, Parodontologie und Endodontogie (Direktor: Univ.- Prof. Dr. Dr. h.c. G. Meyer) Funktionsbereich Parodontologie (Leiter: Univ.-Prof. Dr.T. Kocher) im Zentrum für Zahn-, Mund- und Kieferheilkunde (Geschäftsführender Direktor: Univ.- Prof. Dr. Dr. h.c. G. Meyer) der Medizinischen Fakultät der Ernst-Moritz-Arndt-Universität Greifswald Association between Type 1 and Type 2 Diabetes with Periodontal disease and Tooth loss in the Study of Health in Pomerania (SHIP) Inaugural - Dissertation zur Erlangung des akademischen Grades Doktor der Zahnmedizin (Dr. med. dent.) der Medizinischen Fakultät der Ernst-Moritz-Arndt-Universität Greifswald 2009 vorgelegt von: Gaganpreet kaur geb. am: 03.09.1981 in: Ludhiana, India
64
Embed
Aus der Klinik und Poliklinik für Zahnerhaltung ... · Aus der Klinik und Poliklinik für Zahnerhaltung, Parodontologie und Endodontogie (Direktor: Univ.- Prof. Dr. Dr. h.c. G. Meyer)
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Aus der Klinik und Poliklinik für Zahnerhaltung, Parodontologie und Endodontogie
(Direktor: Univ.- Prof. Dr. Dr. h.c. G. Meyer)
Funktionsbereich Parodontologie
(Leiter: Univ.-Prof. Dr.T. Kocher)
im Zentrum für Zahn-, Mund- und Kieferheilkunde
(Geschäftsführender Direktor: Univ.- Prof. Dr. Dr. h.c. G. Meyer)
der Medizinischen Fakultät der Ernst-Moritz-Arndt-Universität Greifswald
Association between Type 1 and Type 2 Diabetes with Periodontal disease
and Tooth loss in the Study of Health in Pomerania (SHIP)
Inaugural - Dissertation
zur
Erlangung des akademischen Grades
Doktor der Zahnmedizin
(Dr. med. dent.)
der
Medizinischen Fakultät
der
Ernst-Moritz-Arndt-Universität
Greifswald
2009
vorgelegt von: Gaganpreet kaur
geb. am: 03.09.1981
in: Ludhiana, India
Dekan: Dekan: Prof. Dr. rer. nat. Heyo K. Kroemer
1. Gutachter: Prof. Dr. med. dent. Thomas Kocher
2. Gutachter: Prof. Dr. med. dent. Dr. med. Sören Jepsen
Ort, Raum: Greifswald, Hörsaal neue Zahnklinik, Walther-Rathenau-Straße 42
Tag der Disputation: 28.01.2010
‘For science is more than the search for truth, more than a challenging game, more than a
profession. It is a life that a diversity of people leads together, in the closest proximity, a
school for social living. We are members one of another.’
A.G.Ogston, Australian Biochem. Soc. Annual Lecture,
Search, Vol.1, No.2, August, 1970.
Table of contents
1 Introduction……………………………………………………………………... 1
2 Periodontal disease……………………………………………………………… 2
2.1 Definition and classification ……………………………………………… 2
2.2 Epidemiological assessment of periodontal disease………………………. 2
2.3 Prevalence of periodontal disease…………………………………………. 3
2.4 Risk factors for periodontal disease……………………………………….. 4
3 Diabetes mellitus………………………………………………………………... 8
3.1 Definition and classification………………………………………………. 8
3.2 Type 1 Diabetes mellitus………………………………………………….. 8
3.3 Type 2 Diabetes mellitus………………………………………………….. 9
3.4 Prevalence of Diabetes mellitus…………………………………………… 9
4 Aim of the study………………………………………………………………... 11
5 The Study of Health in Pomerania: Materials and Methods……………………. 12
5.1 Study population…………………………………………………………... 13
5.2 Oral health examination…………………………………………………… 14
Treasure, E., Kelly, M., Nuttall, N., Nunn, J., Bradnock, G. & White, D.
(2001). Factors associated with oral health: a multivariate analysis
of results from the 1998 Adult Dental Health survey. Br Dent J
190, 60-68.
Tsai, C., Hayes, C. & Taylor, G. W. (2002). Glycemic control of type 2
diabetes and severe periodontal disease in the US adult population.
Community Dent Oral Epidemiol 30, 182-192.
Vozarova, B., Weyer, C., Lindsay, R. S., Pratley, R. E., Bogardus, C. &
Tataranni, P. A. (2002). High white blood cell count is associated
with a worsening of insulin sensitivity and predicts the
development of type 2 diabetes. Diabetes 51, 455-461.
Wild, S., Roglic, G., Green, A., Sicree, R. & King, H. (2004). Global
prevalence of diabetes: estimates for the year 2000 and projections
for 2030. Diabetes Care 27, 1047-1053.
Wimmer, G., Janda, M., Wieselmann-Penkner, K., Jakse, N., Polansky, R.
& Pertl, C. (2002). Coping with stress: its influence on periodontal
disease. J Periodontol 73, 1343-1351.
Winocour, P. H. (2002). Effective diabetes care: a need for realistic
targets. BMJ 324, 1577-1580.
Yalda, B., Offenbacher, S. & Collins, J. G. (1994). Diabetes as a modifier
of periodontal disease expression. Periodontol 2000 6, 37-49.
Association between type 1 andtype 2 diabetes with periodontaldisease and tooth loss
Kaur G, Holtfreter B, Rathmann W, Schwahn C, Wallaschofski H, Schipf S, Nauck M,Kocher T. Association between type 1 and type 2 diabetes with periodontal disease and toothloss. J Clin Periodontol 2009; 36: 765–774. doi: 10.1111/j.1600-051X.2009.01445.x.
AbstractAim: The aim of this study was to determine whether both type 1 (T1DM) and type 2diabetes mellitus (T2DM) are associated with increased prevalence and extent ofperiodontal disease and tooth loss compared with non-diabetic subjects within ahomogeneous adult study population.
Material and Methods: T1DM, T2DM and non-diabetic subjects were recruitedfrom the population-based Study of Health in Pomerania. Additionally, T1DMsubjects were retrieved from a Diabetes Centre. The total study population comprised145 T1DM and 2647 non-diabetic subjects aged 20–59 years, and 182 T2DM and 1314non-diabetic subjects aged 50–81 years. Periodontal disease was assessed byattachment loss (AL) and the number of missing teeth.
Results: Multivariable regression revealed an association between T1DM (po0.001)and T2DM (po0.01) with mean AL after full adjustment. After age stratification(p 5 0.04 for interaction), the effect of T2DM was only statistically significant in the60–69-year-old subjects (B 5 0.90 (95% confidence intervals [95% CI]; 0.49, 1.31).T1DM was positively associated with tooth loss (adjusted, po0.001). The associationbetween T2DM and tooth loss was statistically significant only for females (oddsratios 5 1.60 [95% CI: 1.10, 2.33]).
Conclusions: Our study confirmed an association between both T1DM and T2DMwith periodontitis and tooth loss. Therefore, oral health education should be promotedin diabetic subjects.
Key words: attachment loss; epidemiology;periodontal disease; study of health inPomerania; tooth loss; type 1 diabetes; type 2diabetes
Accepted for publication 31 May 2009
Gaganpreet Kaur1, Birte Holtfreter1,Wolfgan G. Rathmann2, ChristianSchwahn1, Henry Wallaschofski3,Sabine Schipf4, Matthias Nauck3 andThomas Kocher1
1Unit of Periodontology, Department of
Restorative Dentistry, Periodontology, and
Endodontology, Dental school, University of
Greifswald, Greifswald, Germany; 2German
Diabetes Center, Institute of Biometrics and
Epidemiology, Leibniz Center for Diabetes
Research at Heinrich Heine University,
Dusseldorf, Germany; 3Institute for Clinical
Chemistry and Laboratory Medicine,
University of Greifswald, Greifswald,
Germany; 4Department of Community
Medicine, University of Greifswald,
Greifswald, Germany
Conflict of interest and source offunding statement
There are no conflicts of interest associatedwith this work.This research is supported by SHIP, which ispart of the Community Medicine Researchnet (http://www.medizin.uni-greifswald.de/cm) of the University of Greifswald, Ger-many, which is funded by the GermanFederal Ministry of Education and Research(BMBF-01-ZZ-9603/0), the Ministry forEducation, Research and Cultural Affairsas well as the Ministry of Social Affairs ofthe Federal State of Mecklenburg-WestPomerania. G. Kaur was supported by aneducational grant by Gaba, Switzerland.
Diabetes mellitus comprises a group ofmetabolic diseases characterized byhyperglycaemia resulting from defectsin insulin secretion, insulin action orboth (American Diabetes Association2007). It is an evolving disease withchanging patterns in both type 1 dia-betes mellitus (T1DM) and type 2 dia-betes mellitus (T2DM). Unlike T2DM,T1DM is well defined, usually diag-nosed at a young age, has a rapid onsetof symptoms and is rarely undiagnosed(American Diabetes Association 2007).
Periodontal disease is an inflamma-tory disease caused by infection of thesupporting tissue around the teeth and
may subsequently lead to tooth loss ifleft untreated (Listgarten 1986, Burt2005). Different studies have supportedthe existence, strength and effect of bothtype 1 and type 2 diabetes on periodontaldisease (Emrich et al. 1991, AmericanAcademy of Periodontology 2000, Ryanet al. 2003, Borrell & Papapanou 2005,Lalla et al. 2006a). Differences in thereported prevalence of periodontal dis-ease in T1DM and T2DM subjects mayrelate to the specific pathogenesis of thetwo types of diabetes, as well as utiliza-tion of dental care, ethnic disparities instudy populations, disparities in con-founder distributions and differences in
the study design and methodology.Further, most studies were too small toadjust for confounders, resulting in pos-sibly biased results.
Some studies evaluating the relation-ship between diabetes mellitus andperiodontal disease failed to distinguishbetween both types of diabetes (Sznaj-der et al. 1978, Tervonen & Knuuttila1986, Bridges et al. 1996), while othersincluded T1DM or T2DM subjects only(Hugoson et al. 1989, Emrich et al.1991, Mattout et al. 2006, Lalla et al.2006a, b). A few studies were evenconducted without a reference group(Furukawa et al. 2007, Lalla et al.2007a). Moreover, studies on perio-dontal disease in T1DM and T2DMsubjects did not use comparable defini-tion criteria.
Our knowledge of the relationshipbetween T1DM and periodontal diseasehas emerged from studies in youngindividuals (o18 years) (Lalla et al.2007a, b). The role of T1DM as a riskfactor for periodontal disease has not yetbeen investigated systematically in alarge homogeneous adult cohort. Inaddition, a limited number of popula-tion-based studies have investigated theassociation between both types of dia-betes and tooth loss (Kapp et al. 2007).Thus, our understanding of the evolvingrole of T1DM as a risk factor forperiodontal disease is limited.
The aim of this study was to deter-mine whether both T1DM and T2DMare associated with increased prevalenceand extent of periodontal disease andtooth loss compared with non-diabeticsubjects in a homogeneous adult studypopulation.
Material and Methods
Study population
The Study of Health in Pomerania(SHIP) is a population-based survey,including a medical and dental exami-nation of the adult population in a north-east region of Germany. Details aboutthe study population, recruitment andexaminations have been published else-where (John et al. 2001). From the entireregional population of 212,157 inhabi-tants, a representative sample of 7008subjects with German citizenship aged20–79 years was selected from thepopulation registration offices. A two-stage cluster sampling method wasadopted from the World Health Organi-zation Monitoring Trends and Deter-
minants in Cardiovascular Disease(MONICA) Study, yielding 12 5-yearage strata (20–79 years) for both gen-ders, each including 292 individuals.Between October 1997 and May 2001,a total of 4310 individuals (response68.8%) participated in this study.
The T1DM cohort (233 subjects aged20–81 years) was recruited from theCentre of Cardiology and Diabetes,Karlsburg, and the surrounding practicingdiabetologists. These subjects lived in thesame geographical region as the subjectsrecruited for SHIP. Data collection forT1DM subjects was performed betweenDecember 1997 and December 2000from the diabetic registries of the Centreof Cardiology and Diabetes, Karlsburg.The study methods for these subjectswere identical to the SHIP methods. Allparticipants gave informed written con-sent. Both the studies were approved bythe local ethics committee a priori.
Periodontal measurements
Data collection comprised oral and med-ical examinations, health-related inter-views and risk-related questionnaires.Periodontal status was registered accord-ing to the half-mouth method on theright or the left side in alternate subjectsusing a periodontal probe (PCP 11, Hu-Friedy, Chicago, IL, USA) at four sitesper tooth (mesiobuccal, midbuccal, dis-tobuccal and midlingual) (Hensel et al.2003). Periodontal assessment includedattachment loss (AL) and probing depth(PD) measurements. AL represents thedistance from the cemento-enamel junc-tion to the bottom of the periodontalpocket. PD represents the distance fromthe gingival margin to the base of theperiodontal pocket. All fully eruptedteeth, except the third molars, wereassessed, resulting in a maximum of 14teeth per subject. The number of teethwas determined full mouth on a max-imum of 28 teeth. The frequency ofdental visits in the last 12 months wasalso recorded. Similar periodontal exam-inations were performed in T1DM sub-jects recruited from the Centre ofCardiology and Diabetes.
Calibrated licensed dentists per-formed all the examinations. Every6–12 months, calibration exercises wereperformed on a subset of persons notconnected to the study, yielding anintra-class correlation of 0.82–0.91 perexaminer, and an inter-rater correlationof 0.84 relative to AL (Hensel et al.2003).
Definition of diabetes
The T1DM cohort (233 subjects aged20–81 years) was recruited from theCentre of Cardiology and Diabetes.The diagnosis of T1DM in these sub-jects was confirmed by the physician.
In SHIP, diabetes was assessed byself-reported physician diagnosis as wellas use of anti-diabetic drugs. To ascer-tain the use of anti-diabetic drugs, pre-scriptions or medications brought duringhealth-related interviews were categor-ized according to the Anatomical Ther-apeutic Chemical (ATC) classificationsystem. Diabetes duration, and durationand mode of anti-diabetic therapy wereassessed by self-reports.
In SHIP, subjects were defined as hav-ing T1DM if the onset of disease wasbefore the age of 30 years or if adminis-tration of insulin started less than one yearafter the onset of the disease. Eight sub-jects (prevalence 0.2%) were identifiedas having T1DM. In SHIP, subjects weredefined as having T2DM if the onsetof disease was after the age of 29 or ifthe administration of insulin started 41year after disease onset in subjects youn-ger than 30 years. In addition, subjectswith T2DM were identified via a self-administered questionnaire, diet recom-mendations or oral anti-diabetic drugsaccording to the ATC codes. In SHIP,339 subjects (prevalence 7.9%) wereidentified as having T2DM. A total of241 T1DM (eight from SHIP and 233from the Centre of Cardiology and Dia-betes) and 339 T2DM subjects wereexamined (Fig. 1). Non-diabetic subjectsfrom SHIP served as the reference group.
Assessment of confounders
A computer-aided personal interview wasused to gain information on medical anddental history, behavioural and socio-demographic characteristics. School edu-cation level was categorized based on theeastern German three-level school systemas low (o10 years), medium (10 years)and high (410 years). Height and weightwere determined using calibrated scales.The measurement of waist circumference(WC) (in centimetres) was based on thenarrowest place between the last rib andthe highest part of the abdomen and wascategorized into normal (WC4102 cmin males, WC488 cm in females) andincreased (WC4102 cm in males,WC488 cm in females). Cigarette smok-ing was categorized as never, former andcurrent smoking. Non-fasting venous
766 Kaur et al.
r 2009 John Wiley & Sons A/S
blood samples were collected. Glycosy-lated haemoglobin (HbA1c) was measuredby high-performance liquid chromato-graphy (HPLC) (ClinRep HbA1c, Re-cipe chemicals and Instruments GmbH,Munich, Germany). HbA1c was categor-ized into three levels (o6.0 and 6.0–6.9,X7.0%). White blood cell (WBC) countwas measured using the impedance mea-surement method (CoultersMaxMt,Coulter Electronics, Miami, FL, USA).
Analyses were conducted separatelyfor T1DM and T2DM. As the prevalenceof T1DM and T2DM differs consider-ably with age (American Diabetes Asso-ciation 2007), analyses on T1DM versusnon-diabetic subjects were restricted tosubjects aged 20–59 years. Analyses onT2DM versus non-diabetic subjects werelimited to subjects aged 50–81 years.Subjects without oral examinations,missing AL measurements or missingdata for potential confounders (age,gender, school education, smoking,WC and the frequency of dental visitsin the last 12 months) were excluded(see Fig. 1). Finally, 145 T1DM (sevenfrom SHIP and 138 from the Centre ofCardiology and Diabetes) and 2647 non-diabetic subjects aged 20–59 years, and182 T2DM and 1314 non-diabetic sub-jects aged 50–81 years were availablefor analyses.
Statistical analysis
Continuous data were expressed as meanand standard deviation. Nominal datawere presented as absolute numbers andper cent values. For continuous data,
comparisons between groups were per-formed using the Mann–Whitney U-test.For nominal data, the w2 test was applied.
Linear regression models were fittedto assess the association between T1DMas well as T2DM and mean AL as thedependent variable. The final model wasadjusted for age, gender, school educa-tion, smoking, WC and the frequency ofdental visits (in the last 12 months).Linear regression coefficients (B) withtheir 95% confidence intervals (95% CI)and p values were reported.
To evaluate the association betweenT1DM or T2DM and the number ofmissing teeth multivariable logisticregression analyses were performed.Because of a bimodal and skewed dis-tribution of number of missing teeth, thevariable was dichotomized. Cases with ahigh number of missing teeth wereassessed in relation to their age andgender. Thus, 25% of females and males(separately) with the highest number ofmissing teeth in each 5-year age groupwere considered as cases. The referencegroup included the remaining 75% offemales and males (separately) withineach 5-year age group. This dichoto-mous variable was used to estimate theassociation between both types of dia-betes and a high number of missingteeth. The final model was adjusted forage, gender, school education, smoking,WC and the frequency of dental visits.Odds ratios (OR) with 95% CI andp values are listed in the tables.
Effect modifications were assessedincluding interaction terms between con-founders and the exposure variable in the
multivariable models. The statistical sig-nificance of interactions was assessedusing likelihood ratio tests. In case of astatistically significant interaction (po0.1for interaction), stratified analyses wererun, and the results are presented inTables 2–4 and Fig. 2.
Sensitivity analyses were run to assessthe association between T1DM, T2DMand periodontal disease by changingdisease definition to verify the stabilityof findings regarding the associationbetween both diabetes types and perio-dontitis. We replaced the mean AL bythe square-rooted mean AL as it betterfulfils the model assumptions, the meanPD (log-transformed to fulfil the modelassumptions) and different extent mea-sures (ALX4 mm and PDX4 mm, dichot-omized). Additionally, analyses wererestricted to subjects with at least 12sites with valid AL measurements.
A value of po0.05 was considered tobe statistically significant for all ana-lyses. Analyses were performed usingSTATA 10.0 (Stata Corporation LP,College Station, TX, USA) and R 2.7.1(free statistical shareware).
Results
General characteristics
T1DM subjects were younger, but did notdiffer considerably with regard to educa-tion and smoking habits compared withnon-diabetic subjects (Table 1). No differ-ences were observed between T1DMand non-diabetic subjects with respect toperiodontal variables. The mean age of
-50 aged ≥ 60 years -1160 aged ≥ 60 years -28 aged <50 years -2077 aged <50 years
-46 excluded for missing data (1 without oralexamination + 20 no AL measurements + 25 missing confounder data)
-156 excluded for missingdata (14 without oral examination + 130 no AL measurements + 12 missing confounder data)
-129 excluded for missing data (1 withoutoral examination + 128no AL measurements)
-572 excluded for missingdata (6 without oralexamination + 553 noAL measurements + 13missing confounder data)
145Type 1 diabetes
2647Non-diabetic
1886 Non-diabeticaged 50-81 years
311 Type 2 diabetesaged 50-81 years
2803 Non-diabetic aged 20-59 years
191 Type 1 diabetesaged 20-59 years
182Type 2 diabetes
1314Non-diabetic
241Type 1 diabetes
3963Non-diabetic
339Type 2 diabetes
3963Non-diabetic
233Type 1 diabetes
4310subjects in SHIP
4310subjects in SHIP
Fig. 1. Description of the study population. AL, attachment loss.
Diabetes and periodontal disease 767
r 2009 John Wiley & Sons A/S
diagnosis and the mean duration of T1DMwas 20.5 � 11.6 and 17 � 11.0 years, re-spectively. Sixty-three per cent of T1DMsubjects had HbA1c levels above 7%.
T2DM subjects were less educated,more obese and more frequently formersmokers than non-diabetic subjects(Table 1). Also, T2DM subjects had asubstantially higher mean AL, mean PDand a higher number of missing teeththan non-diabetic subjects (po0.01).Furthermore, the percentage of siteswith ALX4 mm was significantly high-er in T2DM (59.3 versus 46.4%,po0.001). As expected, T2DM subjectswere older at the age of diagnosis(54.6 � 9.5 years) and had a shorterduration of diabetes (10.0 � 7.6 years)compared with T1DM subjects. Forty-eight per cent of T2DM subjects hadHbA1c levels above 7%. Moreover,T2DM and non-diabetic subjects dif-fered significantly in the WBC count(po0.001).
Multivariate analyses
T1DM and mean attachment loss
A statistically significant associationwas observed between T1DM andmean AL after adjusting for confoun-ders (B 5 0.40 [95% CI: 0.19, 0.61])compared with non-diabetic subjects(Table 2). To check whether HbA1c orWBC may act as an intermediatorbetween diabetes and periodontal dis-ease, we stepwise included both vari-ables in the fully adjusted linear models.For T1DM, inclusion of HbA1c consid-erably reduced the coefficient for T1DMfrom 0.40 to 0.08 (p 5 0.55). Inclusionof the WBC count did not materiallyaffect the regression coefficient forT1DM.
Considering interactions betweenT1DM with age group (Fig. 2a), gender,smoking status or high WC, none ofthem revealed statistical significance.
T2DM and mean attachment loss
Subjects with T2DM had a significantlyhigher mean AL compared with non-diabetic subjects after adjusting for con-founders (B 5 0.47 [95% CI: 0.21,0.73]). As for the T1DM model, inclu-sion of HbA1c reduced the coefficientfor the fully adjusted T2DM model from0.47 to 0.27 (p 5 0.09). Inclusion of theWBC count did not relevantly affect theregression coefficient for T2DM.
Examination of interaction terms withT2DM in the fully adjusted modelrevealed an effect modification by agegroup (p 5 0.04 for interaction).According to age-stratified analyses,the statistically significant effect ofT2DM on the mean AL was observedin the 60–69-year-old age group(B 5 0.90 [95% CI: 0.49, 1.31], seeTable 2 and Fig. 2b). The effect ofT2DM on the mean AL was not statis-tically significant in subjects aged 50–
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
Mea
n at
tach
men
t los
s, m
m
Non−diabetica
3.0
3.5
4.0
4.5
5.0
Mea
n at
tach
men
t los
s, m
m
Non−diabeticb
0.1
0.2
0.3
0.4
0.5
0.6
Pro
babi
lity
of h
igh
toot
h lo
ss
Non−diabeticc
0.1
0.2
0.3
0.4
0.5
Pro
babi
lity
of h
igh
toot
h lo
ss
Non−diabeticd
20−29 years 30−39 years
40−49 years 50−59 years
50−59 years 60−69 years
70−81 years
T1DM T2DM
T1DM T2DM
Fig. 2. Mean attachment loss across age groups: (a) among type 1 diabetes mellitus (T1DM) and non-diabetic subjects (p 5 0.55 for ageinteraction) and (b) among type 2 diabetes mellitus (T2DM) and non-diabetic subjects (p 5 0.04 for age interaction). Probability of high toothloss (dependent variable: age- and gender-specific highest quartile versus three lower quartiles for the number of missing teeth) by age groups:(c) among T1DM and non-diabetic subjects (p 5 0.02 for age interaction) and (d) among T2DM and non-diabetic subjects (p 5 0.69 for ageinteraction). All models were adjusted for age, gender, school education, smoking, waist circumference and frequency of dental visits.
768 Kaur et al.
r 2009 John Wiley & Sons A/S
59 years (B 5 0.20 [95% CI: � 0.24,0.64]) and subjects aged 70–81 years(B 5 0.13 [95% CI: � 0.45, 0.72]).There was no statistically significantinteraction of T2DM with gender, smok-ing status or high WC.
T1DM and the number of missing teeth
In agreement with the results for AL,logistic regression analyses revealedtwofold higher odds for increased num-ber of missing teeth for T1DM subjectscompared with non-diabetic subjectsafter adjustment for confounders (OR 51.93 [95% CI: 1.37, 2.71]).
The interaction between T1DM andage groups was statistically significantwhen it was added to the fully adjustedmodel (Table 3). Stratifying accordingto age groups revealed that the associa-tion between T1DM and tooth loss wasstatistically significant in subjects aged40–49 years (OR 5 3.49 [95% CI: 1.92,6.36]) and 50–59 years (OR 5 4.54[95% CI: 1.70, 12.10]), while it wasnot statistically significant in subjectsaged 20–29 years (OR 5 0.86 [95% CI:0.41, 1.82]) or 30–39 years (OR 5 1.28[95% CI: 0.67, 2.46]); see Table 3 andFig. 2c. No statistically significant inter-
action was observed between T1DMand gender, smoking status or high WC.
T2DM and the number of missing teeth
For T2DM, a statistically significantassociation between T2DM and thenumber of missing teeth was onlyobserved in the crude model(OR 5 1.38 [95% CI: 1.07, 1.77]), butnot in the fully adjusted model(OR 5 1.17 [95% CI: 0.90, 1.52]).
A statistically significant effect mod-ification was found for gender (p 5 0. 01for interaction, Table 4). In gender-stratified analyses, the associationbetween T2DM and tooth loss wasstatistically significant only in females(OR 5 1.60 [95% CI: 1.10, 2.33], Table4). There was no effect modification byage group, smoking status or high WC.
Sensitivity analyses
The statistically significant associationbetween T1DM and periodontal diseasewas confirmed for the square-root trans-formed mean AL, the extent of ALX4 mm and the extent of PDX4 mm. ForT2DM the association with periodontaldisease was confirmed by replacing the
mean AL by the square-rooted meanAL, mean PD (log transformed) andthe extent of PDX4 mm. For a moreprecise definition of the periodontalstatus, the main and sensitivity analyseswith mean AL as the dependent variablewere restricted to subjects with a mini-mum of 12 sites with valid AL measure-ments. Restrictions did not alter thestatistically significant association bet-ween both diabetes types and mean AL.
Further, to increase the homogeneityof non-diabetic subjects, additional ana-lyses were run excluding non-diabeticsubjects with HbA1c levelsX7%. Over-all, sensitivity analyses confirmed theassociation between both diabetes typesand periodontal disease. None of therestrictions substantially changed theeffect estimates for T1DM or T2DMon periodontal disease.
Discussion
This population-based study confirmedan association between both T1DM andT2DM with periodontal disease andtooth loss within a homogeneous studypopulation. This association was per-sistent using various definitions for
Table 1. Demographic, medical, and dental characteristics of the study population in T1DM versus non-diabetic subjects aged 20–59 years andT2DM versus non-diabetic subjects aged 50–81 years
T1DM Non-diabetic p valuen T2DM Non-diabetic p valuen
Data shown as mean � SD or number (percentages).nw2 test (nominal data); Mann–Whitney U-test (continuous data).
T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus; N, number of subjects; HbA1c, glycosylated haemoglobin; AL, attachment loss; PD,
probing depth; NS, not significant; SD, standard deviation.
Diabetes and periodontal disease 769
r 2009 John Wiley & Sons A/S
Table
2.
Lin
ear
regre
ssio
nm
odel
sfo
rm
ean
atta
chm
ent
loss
inT
1D
M(N
5145)
vers
us
non-d
iabet
icsu
bje
cts
(N5
2647)
aged
20–59
yea
rs,an
dre
gre
ssio
nm
odel
inT
2D
M(N
5182)
vers
us
non-d
iabet
icsu
bje
cts
(N5
1314)
aged
50–81
yea
rsin
cludin
gth
est
atis
tica
lly
signifi
cant
inte
ract
ion
term
for
age
gro
up
Model
T1D
Mve
rsus
non-d
iabet
icO
ver
all
T2D
Mve
rsus
non-d
iabet
icag
eca
tegori
esz
over
all
50–59
yea
rs60–69
yea
rs70–81
yea
rs
Unadju
sted
Dia
bet
esm
elli
tus
0.0
3(0
.05,
0.5
4)n
0.7
9(0
.50,
1.0
7)n
n
Adju
sted
Dia
bet
esm
elli
tus
0.4
0(0
.19,
0.6
1)n
n0.1
9(�
0.2
8,
0.6
5)
0.2
0(�
0.2
4,
0.6
4)
0.9
0(0
.49,
1.3
1)n
n0.1
3(�
0.4
5,
0.7
2)
Age
(yea
rs)
20–29
030–39
0.7
9(0
.66,
0.9
2)n
n
40–49
1.8
0(1
.66,
1.9
3)n
n
50–59
2.3
2(2
.17,
2.4
6)n
n0
60–69
0.7
0(0
.49,
0.9
1)n
n
70–81
1.3
8(1
.11,
1.6
5)n
n
60–69
yea
rs�
T2D
M0.6
9(0
.07,
1.3
0)w
70–81
yea
rs�
T2D
M0.0
1(�
0.6
8,
0.6
9)
Gen
der
(ref
eren
ce:
fem
ales
)0.2
7(0
.16,
0.3
7)n
n0.6
7(0
.46,
0.8
9)n
n0.5
5(0
.27,
0.8
3)n
n0.6
8(0
.31,
1.0
6)n
n1.1
0(0
.47,
1.7
3)n
n
Sch
ool
educa
tion
(ref
eren
ce:o
10
yea
rs)
10
yea
rs�
0.4
3(�
0.5
6,�
0.3
0)n
n�
0.4
3(�
0.6
4,�
0.2
2)n
n�
0.5
0(�
0.7
5,�
0.2
4)n
n�
0.5
0(�
0.9
0,�
0.1
0)w
0.1
4(�
0.5
2,
0.8
0)
410
yea
rs�
0.6
3(�
0.7
9,�
0.4
8)n
n�
0.8
2(�
1.0
7,�
0.5
7)n
n�
0.6
5(�
0.9
9,�
0.3
1)n
n�
1.0
2(�
1.4
3,�
0.6
0)n
n�
0.9
9(�
1.7
7,�
0.2
2)w
Sm
okin
g(r
efer
ence
:nev
ersm
oker
s)F
orm
ersm
oker
s0.1
4(0
.02,
0.2
6)w
0.2
3(0
.03,
0.4
4)w
0.3
1(0
.02,
0.6
0)w
0.2
2(�
0.1
3,
0.5
7)
0.0
9(�
0.4
8,
0.6
6)
Curr
ent
smoker
s0.6
3(0
.51,
0.7
4)n
n1.0
2(0
.77,
1.2
7)n
n1.0
1(0
.70,
1.3
1)n
n1.2
5(0
.78,
1.7
3)n
n0.5
2(�
0.5
2,
1.5
5)
Hig
hW
C(r
efer
ence
:lo
wW
C)
0.1
0(�
0.0
5,
0.2
5)
0.2
2(�
0.0
1,
0.4
6)
0.1
5(�
0.1
8,
0.4
7)
0.0
04
(�0.3
8,
0.3
9)
0.9
7(0
.30,
1.6
4)n
Fre
quen
cyof
den
tal
vis
its
0.0
1(�
0.0
1,
0.0
2)
�0.0
3(�
0.0
7,�
0.0
02)w
�0.0
04
(�0.0
5,
0.0
4)
�0.0
5(�
0.1
0,
0.0
04)
�0.1
5(�
0.2
6,�
0.0
3)w
Mo
del
sfo
rT
2D
Man
dm
ean
atta
chm
ent
loss
stra
tifi
edb
yag
eg
rou
par
ep
rese
nte
d.
Lin
ear
regre
ssio
nco
effi
cien
tsw
ith
thei
r9
5%
con
fid
ence
inte
rval
sar
ep
rese
nte
d.
nnp4
0.0
01
,np4
0.0
1,w p4
0.0
5.
z Adju
sted
for
gen
der
,sc
hool
educa
tion,
smokin
g,
WC
and
freq
uen
cyof
den
tal
vis
its
(in
last
12
month
s).
T1
DM
,ty
pe
1d
iab
etes
mel
litu
s;T
2D
M,
type
2d
iabet
esm
elli
tus;
N,
num
ber
of
subje
cts;
WC
,w
aist
circ
um
fere
nce
.
770 Kaur et al.
r 2009 John Wiley & Sons A/S
severity and extent of AL and PD.Considering the fact that T1DM andT2DM occur predominantly at differentages, the present analyses were per-formed in different age groups. Thisenabled a valid evaluation of the asso-ciation between periodontal disease andT1DM as well as T2DM compared withnon-diabetic subjects. Moreover, ana-lyses were performed excluding non-diabetic subjects with HbA1c levelsX7%, because undiagnosed diabeteswas found to be highly frequent in thegeneral population (Rohlfing et al. 2000,Rathmann et al. 2003). None of therestrictions substantially changed theeffect estimates.
Previous studies reported comparableresults regarding the association betweenT1DM or T2DM and periodontal dis-eases (Ryan et al. 2003, Mealey & Oates2006). Both types of diabetes mellituswere seldom reported together in a largeadult population. A statistically signifi-cant association was found betweenT1DM and mean AL compared withnon-diabetic subjects aged 20–59 years.However, most studies on periodontalhealth in T1DM subjects were carriedout in children, reporting significantlymore plaque (Lalla et al. 2006a) andincreased clinical AL in T1DM subjects
compared with non-diabetic subjects(Lalla et al. 2007b).
The results from the present studydemonstrated a statistically significantassociation between T2DM and meanAL compared with non-diabetic subjectsaged 50–81 years. Importantly, theeffect of T2DM on the mean AL wassignificantly pronounced in 60–69-year-old subjects. An epidemiological studyconducted among the Pima Indiansreported significantly poorer periodontalhealth in T2DM subjects, with odds ofdestructive AL being about three timeshigher than among non-diabetic subjects(Emrich et al. 1991). Similarly, otherstudies confirmed the significant asso-ciation between diabetes and extent ofPD (Oliver & Tervonen 1993, Tervonen& Karjalainen 1997) and AL (Mooreet al. 1999).
Tooth loss can be a consequence ofsevere periodontal disease. In the presentstudy, a strong association was observedbetween T1DM and the number of miss-ing teeth after adjusting for confounders.Stratified analyses revealed that theeffect was restricted to 40–49- and 50–59-year-old subjects. The presence andseverity of diabetes-related periodontaldisease might have led to an increasednumber of missing teeth in T1DM
subjects. However, in other studies anassociation between T1DM and toothloss was not concordantly reported(Hugoson et al. 1989, Thorstensson &Hugoson 1993). A recent study compar-ing T1DM with non-diabetic subjectsaged 18–70 years reported more severeperiodontal disease in the younger agegroups (Lalla et al. 2006b), supportingthe findings of more pronounced toothloss in T1DM subjects. These resultsconcur with our results for T1DM sub-jects, suggesting poor oral health careamong T1DM subjects. In the presentstudy, T1DM subjects had fewer teethalthough they more frequently visitedthe dentist compared with non-diabeticsubjects. This finding may indicate alack of skilled dental services.
The relationship between T2DM andtooth loss is also complicated by the factthat disease onset generally occurs inmiddle and late age, coinciding with thetime point when periodontal diseasebecomes more prevalent. In this study,the association between T2DM and thenumber of missing teeth was not main-tained after adjusting for age and otherconfounders. The dilution of the effectof T2DM on the number of teeth inolder subjects could be explained bythe presence of primary confounders
Table 3. Overall and age stratified logistic regression models in increased tooth loss (dependent variable: age- and gender-specific highest quartileversus three lower quartiles for the number of missing teeth) in T1DM (N 5 161) versus non-diabetic subjects (N 5 2777) aged 20–59 years
Model Overall T1DM versus non-diabeticage group categoriesz
Frequency of dental visits 1.04 (1.02, 1.07)nn 1.08 (1.03, 1.14)n 1.09 (1.04, 1.15)nn 1.02 (0.96, 1.07) 0.98 (0.93, 1.04)
Odds ratios with their 95% confidence intervals are presented.nnp40.001, np40.01, wp40.05.zAge stratified models were adjusted for gender, school education, smoking, WC and frequency of dental visits (in the last 12 months).
T1DM, type 1 diabetes mellitus; N, number of subjects; WC, waist circumference.
Diabetes and periodontal disease 771
r 2009 John Wiley & Sons A/S
such as age, smoking and co-morbid-ities. Moreover, in older subjects toothloss is not only a consequence of perio-dontal disease, but occurs also due toendodontic infections, a lack of preven-tive methods or prosthetic treatmentdecisions. Previous studies have reportedsignificantly more tooth loss in subjectswith diabetes compared with non-dia-betic subjects (Bridges et al. 1996), espe-cially in younger age groups (Kapp et al.2007). In contrast, Oliver & Tervonen(1994) reported that tooth loss wassimilar in Minnesota diabetic subjectsand US employed adults. In this study,we investigated the effect of gender onthe association between T2DM and thenumber of missing teeth. The associa-tion was stronger among females withT2DM possibly due to differences inhealth awareness between males andfemales.
The aetiopathogenesis of periodontaldisease is complex. Several factors areprobably responsible for the increasedrisk of periodontal disease in diabeticsubjects. Systemic inflammation andhyperglycaemia are thought to play animportant role in the pathogenesis ofperiodontal disease in diabetic subjects.Elevated numbers of WBC in diabetesand periodontal diseases have been
reported previously (Loos et al. 2000,Vozarova et al. 2002). In the presentstudy, no change in the coefficients forboth diabetes types was observed whenthe WBC count was entered into themodel. From these findings we maytentatively conclude that inflammationdoes not mediate the associationbetween diabetes and periodontal dis-ease, although it has been reportedpreviously that elevated systemicinflammation plays an important rolein the interaction between diabetes andperiodontal disease (Lim et al. 2007).Further studies are needed to investigatethe role of inflammation in diabetes-associated periodontitis.
The present data demonstrated thatthe association between T1DM orT2DM and periodontal disease may bemediated by HbA1c levels. Most pre-vious studies favour a direct causalassociation, which would implicate thathyperglycaemia is directly involved inthe aetiology of periodontal diseases(Tervonen & Knuuttila 1986, Seppala& Ainamo 1994, Engebretson et al.2004). Several mechanisms explaininghow diabetes leads to an alteration indifferent tissues and organs, includingthe periodontium, have been proposed(Soskolne & Klinger 2001, Mealey &
Oates 2006). Earlier studies havedemonstrated that Advanced GlycationEndproducts (AGE) formed by hyper-glycaemia can transform macrophagesinto cells with a destructive phenotypeproducing high levels of interleukin(IL)-1, IL-6 and TNF-a (Hudson et al.2003). Furthermore, AGE is able torender the endothelium hyperpermeableand to express high levels of adhesionmolecule references. These changescause an increased susceptibility toinfections and an impaired healing pro-cess in diabetic patients. Therefore,achieving good glycaemic controlappears to be a realistic approach toimprove the periodontal condition indiabetic subjects.
The major strength of this study is thelarge sample size comprising a wide agerange of social and medical data, per-mitting the estimation of the associationbetween T1DM and T2DM with perio-dontal disease with good statistical pre-cision. To reduce the misclassificationof diabetes type, T1DM and T2DMsubjects were clearly defined. One lim-itation may exist due to missing evalua-tion of the oral glucose tolerance testand non-fasting glucose values. Becauseof the cross-sectional design, there wasno detailed information on the reasonsfor and the timing of tooth loss, previousperiodontal treatment and previous gly-caemic control. Furthermore, teeth withworse periodontal disease might havebeen extracted; hence the remainingteeth may not represent the long-termperiodontal status. Thus, the associationbetween periodontal disease and dia-betes may be underestimated, especiallyfor older T2DM subjects.
In conclusion, the present studydemonstrated an association betweenboth T1DM and T2DM and an increasedseverity of periodontal disease and toothloss compared with non-diabetic subjectsin a large homogeneous study population.However, T2DM was positively asso-ciated with mean AL in 60–69-year-oldsubjects. In T1DM, tooth loss was pro-minent in 40–49- and 50–59-year-oldsubjects, whereas in T2DM tooth losswas only significantly increased infemale diabetic subjects compared withnon-diabetic female subjects.
References
American Academy of Periodontology. (2000)
Diabetes and periodontal diseases. Committee
on Research, Science and Therapy. American
Table 4. Overall and gender-stratified multivariable logistic regression analyses for increasedtooth loss (dependent variable: age- and gender-specific highest quartile versus three lowerquartiles for the number of missing teeth) in T2DM (N 5 310) versus non-diabetic subjects(N 5 1858) aged 50–81
Odds ratios with their 95% confidence intervals are presented.nnp40.001, np40.01, wp40.05.zGender-stratified models were adjusted for age (reference: 50–59 years), school education,
smoking, WC and frequency of dental visits (in last 12 months).
T2DM, type 2 diabetes mellitus; N, number of subjects; WC, waist circumference.
Scientific rationale for the study: Theassociation between both types ofdiabetes with periodontal diseaseand tooth loss was assessed within ahomogeneous adult study populationin West Pomerania.
Principal findings: Subjects with type1 and type 2 diabetes are at a high riskof having periodontal disease andtooth loss compared with non-diabeticsubjects. The effect of T2DM on meanAL was only statistically significantwithin the 60–69-year-old age group.
Practical implications: The resultshighlight the need to increase thefocus on maintaining good oralhygiene and metabolic control insubjects with diabetes.
774 Kaur et al.
r 2009 John Wiley & Sons A/S
Eidesstattliche Erklärung
Hiermit erkläre ich, daß ich die vorliegende Dissertation selbständig verfaßt und keine
anderen als die angegebenen Hilfsmittel benutzt habe.
Die Dissertation ist bisher keiner anderen Fakultät vorgelegt worden.
Ich erkläre, daß ich bisher kein Promotionsverfahren erfolglos beendet habe und daß eine
Aberkennung eines bereits erworbenen Doktorgrades nicht vorliegt.
Datum Unterschrift
Curriculum Vitae
Personal
Name: Gaganpreet kaur
Date of birth: 03.09.1981
Nationality: Indian
Academic Credentials
1985- 1999: Primary and secondary education, Ludhiana, Punjab, India
2000- 2005: Bachelors of Dental Surgery, Bhojia Dental College &
Hospital, Himachal Pradesh University, Shimla, India
2006-2007: Masters of Science (Clinical Epidemiology), Erasmus
University, Rotterdam, The Netherlands
2007-present: PhD student in Department of Periodontology, School of
Dentistry, Ernst-Moritz-Arndt-University of Greifswald,
Germany
Work experience
2005- 2006: Worked as a Dental surgeon in a Dental clinic, Ludhiana,
Punjab, India
Relevant experience
Research experiences: Association between calcium channel blockers and gingival
Hyperplasia (Nested case control study), Erasmus University,
Rotterdam, The Netherlands (2007)
Conference presentations
2008: Oral presentation, The International Society for
Pharmacoepidemiology, Copenhagen, Denmark
2009: Poster presentation, Europerio6, Stockholm, Sweden
Acknowledgements
This work has been carried out at the Department of Periodontology, School of Dentistry,
Ernst-Moritz-Arndt-University of Greifswald, Germany.
I owe my sincere thanks to my supervisor, Prof. Dr. Thomas Kocher, for instilling in me
a spirit of scientific knowledge, for his expert advice, for sharing his wisdom and
knowledge, for constructive and inspiring discussions, for his endless assurance, never
ending enthusiasm. I am filled with gratitude for this.
I am very grateful to Dr. Birte Holtfreter for her support, brilliant guidance and valuable
advice in my professional and personal matters.
I also want to convey my thanks to Dr. Wolfgang Rathmann for his great scientific
guidance and encouragement. I was honored to receive such supportive criticism and
valuable advice, which enormously helped me to finalize this work.
I am deeply grateful to all co-authors Dr. Christian Schwahn, Dr. Henri Wallaschofski,
Prof. Dr. Matthias Nauck and Mrs. Sabine Schipf for their critical comments and reviews
of my work. A warm thanks to Prof. Dr. Peter Meisel for helping me when ever required.
I am also thankful to all the faculty and staff members in the Department of
Periodontolgy especially Mrs. Kerstin Scholz for all the timely help and support.
My special thank to my parents and my brothers for providing me with their immense
love, constant support, and invaluable encouragement. I express my heartfelt thanks to
my fiancé for his everlasting love and support. Last but not the least, I thank God