Correspondence to Dr Kohei Hasegawa; [email protected]
STRENGTHS AND LIMITATIONS OF THIS STUDY
This study utilised a national health claims database in Japan, which allowed for analysis at a nationwide level.
Vital covariates, including health behaviours, educational level, household income and family history of diabetes, were not provided in the employed database.
The follow-up period was limited to 2 years, and the generalisability of our results to longer-term associations was therefore limited.
Due to the significant limitations of the study, it was impossible to determine causality for the observed associations.
Introduction
Diabetes is a chronic condition that profoundly impacts health and well-being, and its prevalence is increasing rapidly worldwide.1 In addition to diabetes, pre-diabetes, a condition in which glucose levels are elevated but do not reach the diagnostic criteria for diabetes, has been receiving more attention in recent years. Pre-diabetes not only is a predictor of future diabetes but also is already associated with several health outcomes.2 3
The number of teeth serves as a straightforward and widely used measure of oral health status and is particularly suitable for large-scale studies.4 Previous research indicates that a lower number of teeth is associated with increased mortality and morbidity,5–9 including diabetes onset.7 10–12 The number of teeth could indicate exposure to periodontal disease,5–7 a chronic inflammatory oral disease that can destroy supporting periodontal tissues,13 and is the primary cause of adult tooth loss.14 The low-grade systemic inflammation triggered by this disease may be one explanation for the association between the number of teeth and diabetes.15 On the other hand, changes in dietary habits related to a decline in masticatory function due to tooth loss might also explain the association.16 17 However, the potential association between number of teeth and pre-diabetes, rather than diabetes, remains unclear due to limited studies.18 19 Furthermore, while several studies have been conducted on the association between periodontal disease and pre-diabetes, their results are inconsistent.20–22
In Japan, nearly all dental claims for periodontal disease include information on the number of teeth. Using these data, examinations of the associations between the number of teeth and subsequent health outcomes at a nationwide level are feasible.19 23 In this study, we analysed data from Japanese oral health claims combined with annual check-up data to examine the association between the number of teeth and the onset of pre-diabetes using one of the largest sample sizes reported.
Methods
Study design
This retrospective cohort study used the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), which comprised the information on all of the country’s health insurance claims and Specific Health Checkup results.24 The Ministry of Health, Labour and Welfare of Japan (MHLW) owns and manages this database. The claims data in the database include clinical details such as age group, sex, diagnosis codes from the 10th edition of the International Classification of Disease (ICD-10), dental formula information and codes for procedures and prescriptions. The NDB has documented nearly all claims for medical and dental treatments received under Japan’s universal health insurance coverage, which provides coverage to most of Japan’s residents. As a result, the database provides near-complete coverage of the healthcare utilisation data in Japan.
In 2008, the MHLW introduced an annual health screening programme called the Specific Health Checkups. Health insurance providers have been mandated to offer this programme to all members aged 40–74 years. This check-up programme consists of anthropometry, laboratory tests and a self-administered questionnaire regarding health and lifestyle. Details of the programme, including the specific measurements used, are provided elsewhere.25 The results of Specific Health Checkups are stored in the NDB, which includes information including age, sex, current smoking status, frequency of alcohol consumption, amount of alcohol consumption, exercise habit, self-reported medical history (cardiovascular disease, cerebrovascular disease and renal disease), self-reported medication (hypertension, lipidaemia and diabetes), body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), haemoglobin A1c (HbA1c) and fasting blood glucose (FBG).
We obtained de-identified extracted NDB data consisting of dental claims data and Specific Health Checkup records from the MHLW. To link dental claims and Specific Health Checkup data, we used an anonymised identifier called ID1N, which was generated by combining the individual’s date of birth, sex, the insurer’s identification number and the identification number within the insurer’s system.
Subjects
Figure 1 is the flow chart of the subjects enrolled in this study. We initially included subjects who met the following criteria: those who (1) participated in the Specific Health Checkup programme every year from fiscal year (FY) 2015 to FY 2018 and (2) had dental insurance claims data with a diagnosis of periodontal disease (ICD-10 code: K05.3) during the baseline year (FY 2016). We then excluded subjects who met any of the following exclusion criteria: those (1) with a self-reported medical history of cardiovascular disease, cerebrovascular disease or anaemia or missing data related to these conditions at the Specific Health Checkups at the baseline year (FY 2016); (2) with missing data regarding the number of teeth or were edentulous; (3) with no records for HbA1c, FBG or self-reported medication for diabetes in the records of Specific Health Checkups during the year before the baseline year (FY 2015), the baseline year (FY 2016) or the follow-up year (FY 2018); (4) who were classified as having pre-diabetes or diabetes in the Specific Health Checkup during the baseline year (FY 2016) or 1 year prior (FY 2015); or (5) with missing covariate data.
Figure 1. Selection of study participants. FBG, fasting blood glucose; FY, fiscal year; HbA1c: haemoglobin A1c.
Exposures, outcomes and covariates
We used the number of teeth, excluding third molars, derived from the dental claims during the baseline year as the exposure. We determined the number of teeth by using the dental formula data for periodontal disease diagnoses, as in studies that used Japanese dental claims data.19 23 Given the skewed distribution of the number of teeth among the participants, we categorised the number of teeth into four groups (26–28, 20–25, 15–19 and 1–14) as previously described,6 with the modifications of excluding third molars and edentate status. We assigned the ordinal numbers 4–1 to the above categories, respectively, and calculated estimates per decrease in tooth category in regression models. Concurrently, we treated the number of teeth as a continuous variable without categorisation, presenting the estimates corresponding to every five fewer teeth.
The outcome was pre-diabetes or diabetes observed at the Specific Health Checkup during the follow-up year. Pre-diabetes was defined as an HbA1c value 5.7%–6.4% or FBG of 100–125 mg/dL, and diabetes was defined as HbA1c ≥6.5%, FBG ≥126 mg/dL or self-reported diabetes medication, in accord with the criteria described by the American Diabetes Association (ADA).26
We selected the following covariates based on previous studies11 20 27: age, sex, BMI, current smoking, excessive alcohol drinking, regular exercise, hypertension, dyslipidaemia and baseline HbA1c level. We used the results of the subjects’ Specific Health Checkups during the baseline year to define all these variables. Age was divided into the following categories: <45, 45–54, 55–64 and ≥65. BMI (kg/m2) was classified into distinct categories as follows: underweight (<18.5), normal (18.5–24.9), overweight (25.0–29.9) and obese (≥30.0). Excessive alcohol drinking and regular exercise were defined as described.28 Hypertension was defined as SBP ≥140 mm Hg, DBP ≥90 mm Hg or self-reported medication for hypertension. Dyslipidaemia was defined as TG ≥150 mg/dL, LDL-C ≥140 mg/dL, HDL-C <40 mg/dL or self-reported medication for dyslipidaemia. We also included changes in BMI (defined as a difference in the subject’s BMI between the follow-up and baseline) as a covariate to examine the mediational role of weight changes in the association.
Statistical analyses
We used a multivariate logistic regression to estimate the ORs and their 95% CIs for the onset of pre-diabetes or diabetes at the follow-up examination. We began with crude models, followed by adjustments for age and sex, and we further adjusted for BMI, current smoking, excessive alcohol drinking, regular exercise, hypertension, dyslipidaemia and baseline HbA1c level. We also used a model that additionally included changes in BMI to examine its mediational role. To explore potential heterogeneity, we performed a subgroup analysis by fitting models for each subgroup according to age group, sex, current smoking and BMI. The statistical significance of differences between estimates was obtained as described.29 For sensitivity analysis, we used the WHO/Information, Education & Communication (WHO/IEC) criteria, which define pre-diabetes as an HbA1c value of 6.0%–6.4% or an FBG of 110–125 mg/dL,30 31 and we repeated the entire analysis. We further incorporated the criteria used in the National Health and Nutrition Survey in Japan.32 According to this survey, ‘individuals strongly suspected of having diabetes’ (diabetes) were defined as having an HbA1c value of ≥6.5% or self-reported medication for diabetes, and ‘individuals who cannot deny the possibility of diabetes’ (pre-diabetes) were defined as having an HbA1c value of 6.0%–6.4%. Additionally, we treated age and BMI as continuous variables and applied natural spline functions with 5 df to account for potential non-linear relationships. We defined statistical significance using a two-tailed p value threshold of <0.05. Python 3 (ver. 3.8.5) and R (ver. 4.0.5) were used for the data handling and statistical analyses.
Patient and public involvement
Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Results
Descriptive analysis
The final sample consisted of 1 098 371 subjects who were followed for a median follow-up of 2 years. Of the included subjects, 177 908 had developed pre-diabetes, and 579 had developed diabetes at the Specific Health Checkup during the follow-up year. The median number of teeth was 28, with 75th and 25th percentiles at 28 and 27, respectively. Figure 2 illustrates the distribution of the subjects’ number of teeth. Table 1 presents the distribution of the baseline characteristics stratified by the subjects’ number of teeth. We observed that the subjects with greater tooth loss tended to be older and current smokers.
Table 1Baseline characteristics of the subjects by the number of teeth
No. of teeth | ||||
Characteristic | 26–28 | 20–25 | 15–19 | 1–14 |
n | 788 341 | 233 988 | 40 579 | 35 463 |
Age, years, n (%) | ||||
232 996 (29.6) | 26 872 (11.5) | 1222 (3.0) | 1041 (2.9) | |
362 666 (46.0) | 74 137 (31.7) | 6435 (15.9) | 4686 (13.2) | |
119 288 (15.1) | 62 491 (26.7) | 11 769 (29.0) | 9439 (26.6) | |
73 391 (9.3) | 70 488 (30.1) | 21 153 (52.1) | 20 297 (57.2) | |
Sex, female, n (%) | 375 594 (47.6) | 126 581 (54.1) | 23 158 (57.1) | 18 981 (53.5) |
BMI at baseline, kg/m2, n (%) | ||||
72 419 (9.2) | 22 192 (9.5) | 3731 (9.2) | 3380 (9.5) | |
588 292 (74.6) | 172 581 (73.8) | 29 661 (73.1) | 25 931 (73.1) | |
114 515 (14.5) | 35 511 (15.2) | 6592 (16.2) | 5614 (15.8) | |
13 115 (1.7) | 3704 (1.6) | 595 (1.5) | 538 (1.5) | |
Current smoking, yes, n (%) | 134 541 (17.1) | 46 499 (19.9) | 8836 (21.8) | 8780 (24.8) |
Excessive alcohol drinking, yes, n (%) | 292 559 (37.1) | 81 452 (34.8) | 12 848 (31.7) | 11 631 (32.8) |
Regular exercise, no, n (%) | 651 921 (82.7) | 177 826 (76.0) | 28 701 (70.7) | 25 177 (71.0) |
Hypertension, yes, n (%) | 133 495 (16.9) | 63 939 (27.3) | 14 752 (36.4) | 13 777 (38.8) |
Dyslipidaemia, yes, n (%) | 297 493 (37.7) | 105 462 (45.1) | 20 514 (50.6) | 17 606 (49.6) |
HbA1c at baseline, %, mean (SD) | 5.30 (0.21) | 5.32 (0.21) | 5.34 (0.20) | 5.34 (0.20) |
FBG at baseline, mg/dL, mean (SD) | 88.23 (6.23) | 88.34 (6.21) | 88.33 (6.20) | 88.37 (6.21) |
Pre-diabetes at follow-up, n (%) | 122 515 (15.5) | 40 899 (17.5) | 7678 (18.9) | 6816 (19.2) |
Diabetes at follow-up, n (%) | 329 (0.0) | 183 (0.1) | 34 (0.1) | 33 (0.1) |
Changes in BMI, kg/m2, mean (SD) | 0.21 (0.98) | 0.18 (1.00) | 0.14 (0.97) | 0.16 (1.05) |
BMI, body mass index; FBG, fasting blood glucose; HbA1c, haemoglobin A1c.
Regression analysis
The results of the logistic regression analysis are presented in table 2. After adjusting for potential covariates, our analysis revealed that a lower number of teeth were positively associated with incident pre-diabetes or diabetes, and the ORs increased as the number of teeth decreased. These associations were almost unchanged after the adjustment for BMI changes between the baseline and follow-up.
Table 2ORs for pre-diabetes or diabetes based on the number of teeth
Exposure | Crude | Model 1* | Model 2† | Model 3‡ |
OR (95% CI) | OR (95% CI) | OR (95% CI) | OR (95% CI) | |
No. of teeth | ||||
Ref. | Ref. | Ref. | Ref. | |
1.15 (1.14 to 1.17) | 1.06 (1.04 to 1.07) | 1.03 (1.02 to 1.05) | 1.03 (1.02 to 1.04) | |
1.27 (1.24 to 1.30) | 1.10 (1.07 to 1.13) | 1.06 (1.03 to 1.09) | 1.06 (1.03 to 1.09) | |
1.30 (1.26 to 1.33) | 1.11 (1.08 to 1.14) | 1.07 (1.04 to 1.11) | 1.07 (1.04 to 1.10) | |
Per decrease in tooth category | 1.11 (1.11 to 1.12) | 1.04 (1.03 to 1.05) | 1.03 (1.02 to 1.03) | 1.03 (1.02 to 1.03) |
Per five fewer teeth | 1.10 (1.09 to 1.11) | 1.04 (1.03 to 1.05) | 1.03 (1.02 to 1.03) | 1.03 (1.02 to 1.03) |
*Adjusted for age and sex.
†Additionally adjusted for body mass index (BMI), current smoking, excessive alcohol drinking, regular exercise, hypertension, dyslipidaemia and baseline haemoglobin A1c level.
‡Additionally adjusted for changes in BMI.
Tables 3 and 4 display the results of the stratification analysis by age group, sex, BMI and current smoking status. The observed associations were found to be stronger in younger age groups, and there was no evidence of effect modifications by sex, BMI or current smoking.
Table 3ORs for pre-diabetes or diabetes based on the number of teeth category stratified by baseline characteristics
Subgroup | No. of teeth | |||
26–28 | 20–25 | 15–19 | 1–14 | |
— | OR* (95% CI) | OR* (95% CI) | OR* (95% CI) | |
Age, years | ||||
Ref. | 1.08 (1.04 to 1.12) | 1.11 (0.95 to 1.31) | 1.09 (0.90 to 1.31) | |
Ref. | 1.05 (1.03 to 1.07) | 1.11 (1.04 to 1.19) | 1.09 (1.01 to 1.18) | |
Ref. | 1.03 (1.00 to 1.05) | 1.05 (1.00 to 1.11) | 1.08 (1.02 to 1.14) | |
Ref. | 0.99 (0.96 to 1.02) | 1.03 (0.99 to 1.07) | 1.06 (1.02 to 1.10) | |
Sex | ||||
Ref. | 1.04 (1.02 to 1.06) | 1.06 (1.02 to 1.11) | 1.09 (1.05 to 1.14) | |
Ref. | 1.02 (1.00 to 1.04) | 1.05 (1.01 to 1.09) | 1.05 (1.01 to 1.10) | |
BMI, kg/m2 | ||||
Ref. | 1.03 (1.01 to 1.05) | 1.06 (1.02 to 1.09) | 1.07 (1.04 to 1.11) | |
Ref. | 1.06 (1.01 to 1.12) | 1.08 (0.98 to 1.20) | 1.16 (1.05 to 1.29) | |
Ref. | 1.02 (0.99 to 1.05) | 1.08 (1.01 to 1.15) | 1.04 (0.97 to 1.12) | |
Ref. | 1.09 (1.00 to 1.19) | 0.94 (0.77 to 1.16) | 1.11 (0.89 to 1.37) | |
Current smoking | ||||
Ref. | 1.03 (1.01 to 1.04) | 1.06 (1.03 to 1.09) | 1.08 (1.04 to 1.12) | |
Ref. | 1.04 (1.01 to 1.07) | 1.08 (1.01 to 1.14) | 1.08 (1.02 to 1.14) |
*Adjusted for age, sex, body mass index (BMI), current smoking, excessive alcohol drinking, regular exercise, hypertension, dyslipidaemia and baseline haemoglobin A1c level. The variable used for stratification was excluded from the covariate set.
Table 4ORs per decrease in tooth category or per five fewer teeth for pre-diabetes or diabetes stratified by baseline characteristics
Subgroup | Per decrease in tooth category | Per five fewer teeth | ||
OR* (95% CI) | pdiff | OR* (95% CI) | pdiff | |
Age, years | ||||
1.06 (1.03 to 1.09) | Ref. | 1.06 (1.03 to 1.09) | Ref. | |
1.04 (1.03 to 1.06) | 0.333 | 1.04 (1.03 to 1.06) | 0.361 | |
1.03 (1.01 to 1.04) | 0.052 | 1.02 (1.01 to 1.04) | 0.054 | |
1.02 (1.00 to 1.03) | 0.014 | 1.02 (1.01 to 1.03) | 0.022 | |
Sex | ||||
1.03 (1.02 to 1.04) | Ref. | 1.03 (1.02 to 1.04) | Ref. | |
1.02 (1.01 to 1.03) | 0.109 | 1.02 (1.01 to 1.03) | 0.121 | |
BMI, kg/m2 | ||||
1.05 (1.02 to 1.08) | 0.099 | 1.05 (1.02 to 1.07) | 0.098 | |
1.03 (1.02 to 1.04) | Ref. | 1.02 (1.02 to 1.03) | Ref. | |
1.02 (1.00 to 1.04) | 0.665 | 1.02 (1.01 to 1.04) | 0.892 | |
1.04 (0.98 to 1.09) | 0.742 | 1.04 (0.99 to 1.09) | 0.451 | |
Current smoking | ||||
1.03 (1.02 to 1.04) | Ref. | 1.03 (1.02 to 1.03) | Ref. | |
1.03 (1.01 to 1.05) | 0.701 | 1.03 (1.01 to 1.04) | 0.877 |
*Adjusted for age, sex, body mass index (BMI), current smoking, excessive alcohol drinking, regular exercise, hypertension, dyslipidaemia and baseline haemoglobin A1c level. The variable used for stratification was excluded from the covariate set.
Sensitivity analysis
Online supplemental figure S1 and tables S1–S4 display the results obtained using the WHO/IEC criteria in place of the ADA criteria, and the results for the entire sample were virtually identical to those obtained using the ADA criteria. However, the results of the stratification analysis were sensitive to the change in criteria. Online supplemental figure S2 and tables S5–S8 show the results obtained by employing the criteria of the National Health and Nutrition Survey in Japan. These results were almost comparable to those obtained using the WHO/IEC criteria. Online supplemental table S9 shows the results of the logistic regression analyses using continuous age and BMI instead of categorised variables. The results were nearly unchanged compared with those of the main analysis.
Discussion
This nationwide retrospective cohort study examined the association between the number of teeth and the occurrence of pre-diabetes or diabetes 2 years later among middle-aged Japanese adults. Our findings indicate that a lower number of teeth were associated with an increased incidence of pre-diabetes or diabetes, and the estimated ORs increased monotonically as the number of teeth decreased.
Several studies have found an association between a decreased number of teeth and diabetes incidence,7 10–12 which is consistent with our findings. For instance, a longitudinal study from Finland reported that having ≥9 missing teeth, in comparison with 0–1 missing teeth, was associated with incident diabetes.7 Likewise, a study from the USA found an increased incidence of diabetes among subjects missing ≥25 teeth compared with those missing 0–8.10 Additionally, a recent study from Korea reported that an increased number of missing teeth was associated with a new onset of diabetes.11 Using periodontal disease as an exposure yielded similar results,10 11 33 34 though there are some exceptions.35 36
In contrast, studies that explore the association between the number of teeth and pre-diabetes are scarce, and their results are inconclusive. A cross-sectional study from Korea reported that a decreased number of teeth was associated with increased pre-diabetes prevalence; however, the results were insignificant except for a linear trend.18 Another cross-sectional study from Japan reported that pre-diabetes was associated with a decreased number of remaining teeth.19 Several other studies have examined periodontal disease and the new onset of pre-diabetes, with varied conclusions.20–22 For example, a study conducted in Taiwan revealed that periodontal disease was linked to incident pre-diabetes in participants who were normoglycaemic at baseline.20 However, a study of Hispanic/Latino adults in the USA found no such association.22 The precise explanations for these conflicting results are unclear, but differences in the study populations, the definitions of exposure and outcome, the study designs, and the employed statistical models may have contributed.
One potential explanation for the observed association between the number of teeth and pre-diabetes could be periodontal disease, the primary reason for tooth loss among adults.14 Numerous longitudinal studies have reported an association between periodontal disease exposure and the onset of pre-diabetes or diabetes.10 11 20 33 34 Periodontal disease may cause low-grade systemic inflammation through persistent bacteraemia and/or the dissemination of periodontal inflammation mediators into the bloodstream.15 This systemic inflammation may then impair insulin signalling and resistance,37 resulting in elevated glycaemic levels.
Another possible explanation could relate to altered masticatory performance due to tooth loss. Having fewer teeth impairs masticatory performance, which may lead to a shift in diet selection toward fewer vegetables and fibres,16 17 subsequently increasing the incidence of diabetes.38 39 Additionally, impaired masticatory performance can reduce satiety, leading to increased food intake.40 We considered BMI changes as a critical mediator of these pathways and tested models with BMI change between baseline and follow-up as an additional covariate. However, the estimates remained essentially consistent whether or not the model included BMI changes, suggesting that these hypothesised pathways may not explain the observed association. Nevertheless, the follow-up duration in the present study was limited to 2 years, and future research with a longer study period is required to obtain a clearer picture.
Our stratification analysis did not reveal any clear association modification by age, sex, BMI or current smoking habit. Although a few of these tested modifications showed statistical significance, the differences in the magnitude of the associations were negligible and not robust. Similar to our present findings, previous results on the association between periodontal disease and diabetes did not discern consistent patterns.10 11 33 35 Our results suggest that these factors may not modify the association between the number of teeth and the incidence of pre-diabetes or diabetes. However, further studies are necessary to thoroughly test this possibility.
This study has several important limitations. First, due to the lack of data, it was not possible to consider certain vital covariates, such as health behaviours, educational level, household income, family history of diabetes or any other unmeasured confounders. This limitation prevented any definitive inference of causality for the observed associations. Additionally, this may have introduced bias in either direction into our estimations. Second, we used the number of teeth exclusively as the exposure definition, but the specific reasons for tooth loss were not considered as they were not available in the employed database. While periodontal disease is the primary reason for tooth loss in the studied population,14 other causes, such as dental caries or injury, may have contributed to tooth loss. Moreover, detailed timings of tooth loss were also unavailable, limiting the exploration of temporal relationships. And finally, other oral health information, including periodontal disease status and masticatory function, was also not provided in the database. Third, the follow-up period was limited to 2 years, which may limit the generalisability of our results to longer-term associations. Fourth, our study lacked information regarding the specific subtypes of diabetes, although it is known that type 2 diabetes is dominant among Japanese patients.41 Fifth, our sample was restricted to individuals who had undergone a dental visit with a diagnosis of periodontal disease and who regularly participated in Specific Health Checkups. It has been suggested that the characteristics of individuals who undergo Specific Health Checkups may differ from those of the general population.42 Additionally, an investigation of Japanese subjects revealed that having a family dentist was associated with socioeconomic status.43 Our present findings may thus have been affected by selection bias, and their generalisability is therefore limited. Notably, however, the Specific Health Checkup introduced a new questionnaire item in 2018 about chewing ability.44 Using the responses to this questionnaire item might help to mitigate some of the selection bias.
Conclusions
Having fewer teeth was found to be associated with a higher incidence of pre-diabetes. However, due to the significant limitations of this study, particularly the absence of vital covariates, causality remains undetermined.
Data availability statement
No data are available.
Data availability statement
The dataset used in this study is not publicly available due to the data protection requirement imposed by Japan’s MHLW.
Ethics statements
Patient consent for publication
Not applicable.
Ethics approval
This study was conducted according to the guidelines of the Declaration of Helsinki. The Committee for Medical Ethics of Shinshu University School of Medicine gave approval for the study on 2 September 2019 (protocol code: 4484). The Committee waived the requirement for obtaining informed consent from subjects in light of the study’s retrospective nature and use of anonymised data.
Contributors KH: conceptualisation, methodology, software, formal analysis, resources, writing—original draft, writing—review and editing, guarantor. AS: conceptualisation, methodology, writing—review and editing. MM: writing—review and editing. HK: conceptualisation, methodology, writing—review and editing, supervision. TT: conceptualisation, validation, writing—review and editing. TN: conceptualisation, resources, writing—review and editing, project administration.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient and public involvement statement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.
1 Saeedi P, Petersohn I, Salpea P, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: results from the international diabetes federation diabetes Atlas, 9th edition. Diabetes Res Clin Pract 2019; 157: 107843. doi:10.1016/j.diabres.2019.107843
2 Islam Z, Akter S, Inoue Y, et al. Prediabetes, diabetes, and the risk of all-cause and cause-specific mortality in a Japanese working population: Japan epidemiology collaboration on occupational health study. Diabetes Care 2021; 44: 757–64. doi:10.2337/dc20-1213
3 Schlesinger S, Neuenschwander M, Barbaresko J, et al. Prediabetes and risk of mortality, diabetes-related complications and comorbidities: umbrella review of meta-analyses of prospective studies. Diabetologia 2022; 65: 275–85. doi:10.1007/s00125-021-05592-3
4 Haworth S, Shungin D, Kwak SY, et al. Tooth loss is a complex measure of oral disease: determinants and methodological considerations. Community Dent Oral Epidemiol 2018; 46: 555–62. doi:10.1111/cdoe.12391
5 Jimenez M, Krall EA, Garcia RI, et al. Periodontitis and incidence of cerebrovascular disease in men. Ann Neurol 2009; 66: 505–12. doi:10.1002/ana.21742
6 Vedin O, Hagström E, Budaj A, et al. Tooth loss is independently associated with poor outcomes in stable coronary heart disease. Eur J Prev Cardiol 2016; 23: 839–46. doi:10.1177/2047487315621978
7 Liljestrand JM, Havulinna AS, Paju S, et al. Missing teeth predict incident cardiovascular events, diabetes, and death. J Dent Res 2015; 94: 1055–62. doi:10.1177/0022034515586352
8 Goto Y, Wada K, Uji T, et al. Number of teeth and all-cause and cancer mortality in a Japanese community: the Takayama study. J Epidemiol 2020; 30: 213–8. doi:10.2188/jea.JE20180243
9 Yu Y-H, Cheung WS, Steffensen B, et al. Number of teeth is associated with all-cause and disease-specific mortality. BMC Oral Health 2021; 21: 568. doi:10.1186/s12903-021-01934-0
10 Demmer RT, Jacobs DR, Desvarieux M. Periodontal disease and incident type 2 diabetes: results from the First National Health and Nutrition Examination Survey and its epidemiologic follow-up study. Diabetes Care 2008; 31: 1373–9. doi:10.2337/dc08-0026
11 Chang Y, Lee JS, Lee K-J, et al. Improved oral hygiene is associated with decreased risk of new-onset diabetes: a nationwide population-based cohort study. Diabetologia 2020; 63: 924–33. doi:10.1007/s00125-020-05112-9
12 Raju K, Taylor GW, Tahir P, et al. Association of tooth loss with morbidity and mortality by diabetes status in older adults: a systematic review. BMC Endocr Disord 2021; 21: 205. doi:10.1186/s12902-021-00830-6
13 Kinane DF, Stathopoulou PG, Papapanou PN. Periodontal diseases. Nat Rev Dis Primers 2017; 3: 17038. doi:10.1038/nrdp.2017.38
14 Suzuki S, Sugihara N, Kamijo H, et al. Reasons for tooth extractions in Japan: the second nationwide survey. Int Dent J 2022; 72: 366–72. doi:10.1016/j.identj.2021.05.008
15 Polak D, Shapira L. An update on the evidence for pathogenic mechanisms that may link periodontitis and diabetes. J Clin Periodontol 2018; 45: 150–66. doi:10.1111/jcpe.12803
16 Hung H-C, Colditz G, Joshipura KJ. The association between tooth loss and the self-reported intake of selected CVD-related nutrients and foods among US women. Community Dent Oral Epidemiol 2005; 33: 167–73. doi:10.1111/j.1600-0528.2005.00200.x
17 Wakai K, Naito M, Naito T, et al. Tooth loss and intakes of nutrients and foods: a nationwide survey of Japanese dentists. Community Dent Oral Epidemiol 2010; 38: 43–9. doi:10.1111/j.1600-0528.2009.00512.x
18 Jung Y-S, Shin M-H, Kweon S-S, et al. Periodontal disease associated with blood glucose levels in urban Koreans aged 50 years and older: the Dong-gu study. Gerodontology 2015; 32: 267–73. doi:10.1111/ger.12107
19 Harada K, Morino K, Ishikawa M, et al. Glycemic control and number of natural teeth: analysis of cross-sectional Japanese employment-based dental insurance claims and medical check-up data. Diabetol Int 2022; 13: 244–52. doi:10.1007/s13340-021-00533-2
20 Chiu SY-H, Lai H, Yen AM-F, et al. Temporal sequence of the bidirectional relationship between hyperglycemia and periodontal disease: a community-based study of 5,885 Taiwanese aged 35–44 years (KCIS No.32). Acta Diabetol 2015; 52: 123–31. doi:10.1007/s00592-014-0612-0
21 Joshipura KJ, Muñoz-Torres FJ, Dye BA, et al. Longitudinal association between periodontitis and development of diabetes. Diabetes Res Clin Pract 2018; 141: 284–93. doi:10.1016/j.diabres.2018.04.028
22 Laniado N, Khambaty T, Hua S, et al. Periodontal disease and incident prediabetes and diabetes: the Hispanic Community Health Study/Study of Latinos. J Clin Periodontol 2022; 49: 313–21. doi:10.1111/jcpe.13599
23 Tsuneishi M, Yamamoto T, Yamaguchi T, et al. Use of the dental formula from the national database of health insurance claims and specific health checkups of Japan. Jpn Dent Sci Rev 2022; 58: 52–8. doi:10.1016/j.jdsr.2021.11.003
24 Hirose N, Ishimaru M, Morita K, et al. A review of studies using the Japanese national database of health insurance claims and specific health checkups. ACE 2020; 2: 13–26. doi:10.37737/ace.2.1_13
25 Ministry of Health, Labour and Welfare. Operational guide to specific health checkups and specific health guidance. 2013. Available: https://www.mhlw.go.jp/bunya/shakaihosho/iryouseido01/info03d.html
26 American Diabetes Association. Classification and diagnosis of diabetes: standards of medical care in diabetes—2019. Diabetes Care 2019; 42: S13–28. doi:10.2337/dc19-S002
27 Miyawaki A, Toyokawa S, Inoue K, et al. Self-reported periodontitis and incident type 2 diabetes among male workers from a 5-year follow-up to MY health up study. PLOS ONE 2016; 11: e0153464. doi:10.1371/journal.pone.0153464
28 Wakasugi M, Kazama JJ, Narita I, et al. Association between combined lifestyle factors and non-restorative sleep in Japan: a cross-sectional study based on a Japanese health database. PLoS One 2014; 9: e108718. doi:10.1371/journal.pone.0108718
29 Altman DG, Bland JM. Interaction Revisited: the difference between two estimates. BMJ 2003; 326: 219. doi:10.1136/bmj.326.7382.219
30 The International Expert Committee. International expert committee. International expert committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care 2009; 32: 1327–34. doi:10.2337/dc09-9033
31 Kawata I, Koshi T, Hirabayashi K, et al. Prediabetes defined by the international expert committee as a risk for development of glomerular hyperfiltration. Acta Diabetol 2019; 56: 525–9. doi:10.1007/s00592-019-01287-9
32 Ministry of Health, Labour and Welfare. The national health and nutrition survey in Japan 2016. 2017. Available: https://www.mhlw.go.jp/bunya/kenkou/eiyou/dl/h28-houkoku.pdf
33 Zhang S, Philips KH, Moss K, et al. Periodontitis and risk of diabetes in the atherosclerosis risk in communities (ARIC) study: a BMI-modified association. J Clin Endocrinol Metab 2021; 106: e3546–58. doi:10.1210/clinem/dgab337
34 Wu C-Z, Yuan Y-H, Liu H-H, et al. Epidemiologic relationship between periodontitis and type 2 diabetes mellitus. BMC Oral Health 2020; 20: 204. doi:10.1186/s12903-020-01180-w
35 Ide R, Hoshuyama T, Wilson D, et al. Periodontal disease and incident diabetes: a seven-year study. J Dent Res 2011; 90: 41–6. doi:10.1177/0022034510381902
36 Kebede TG, Pink C, Rathmann W, et al. Does periodontitis affect diabetes incidence and haemoglobin A1C change? An 11-year follow-up study. Diabetes Metab 2018; 44: 243–9. doi:10.1016/j.diabet.2017.11.003
37 Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest 2006; 116: 1793–801. doi:10.1172/JCI29069
38 Kimura Y, Yoshida D, Hirakawa Y, et al. Dietary fiber intake and risk of type 2 diabetes in a general Japanese population: the Hisayama Study. J Diabetes Investig 2021; 12: 527–36. doi:10.1111/jdi.13377
39 Pokharel P, Kyrø C, Olsen A, et al. Vegetable, but not potato, intake is associated with a lower risk of type 2 diabetes in the Danish Diet, Cancer and Health cohort. Diabetes Care 2023; 46: 286–96. doi:10.2337/dc22-0974
40 Nakata M. Masticatory function and its effects on general health. Int Dent J 1998; 48: 540–8. doi:10.1111/j.1875-595x.1998.tb00489.x
41 Neville SE, Boye KS, Montgomery WS, et al. Diabetes in Japan: a review of disease burden and approaches to treatment. Diabetes Metab Res Rev 2009; 25: 705–16. doi:10.1002/dmrr.1012
42 Fukasawa T, Tanemura N, Kimura S, et al. Utility of a specific health checkup database containing lifestyle behaviors and lifestyle diseases for employee health insurance in Japan. J Epidemiol 2020; 30: 57–66. doi:10.2188/jea.JE20180192
43 Oshima K, Miura H, Tano R, et al. Characteristics of individuals in Japan who regularly manage their oral health by having a family dentist: a nationwide cross-sectional web-based survey. Int J Environ Res Public Health 2022; 19: 10479. doi:10.3390/ijerph191710479
44 Saito M, Shimazaki Y, Yoshii S, et al. Association of self-rated chewing function and oral health status with metabolic syndrome. J Oral Sci 2023; 65: 29–33. doi:10.2334/josnusd.22-0229
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Abstract
Objectives
To investigate the association between the number of teeth and the new onset of pre-diabetes.
Design
Retrospective cohort study.
Setting
The National Database of Health Insurance Claims and Specific Health Checkups of Japan, which holds information from both the yearly health check-up programme known as the ‘Specific Health Checkup’ and health insurance claims data.
Participants
1 098 371 normoglycaemic subjects who participated in the Specific Health Checkup programme every year from fiscal year (FY) 2015 to FY 2018 and had dental insurance claims data with a diagnosis of periodontal disease during FY 2016.
Outcome measures
Incidence of pre-diabetes or diabetes observed at the Specific Health Checkup during FY 2018.
Results
Among the participants, 1 77 908 subjects developed pre-diabetes, and 579 developed diabetes at the check-up during the subsequent follow-up year. Compared with the subjects with 26–28 teeth, those with 20–25, 15–19 or 1–14 teeth were associated with an increased likelihood of developing pre-diabetes or diabetes onset with adjusted ORs of 1.03 (95% CI: 1.02 to 1.05), 1.06 (1.03 to 1.09) and 1.07 (1.04 to 1.11), respectively. No clear modifications were observed for age, sex, body mass index or current smoking.
Conclusions
Having fewer teeth was associated with a higher incidence of pre-diabetes. Due to the limitations of this study, however, causality remains undetermined.
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Details

1 Department of Preventive Medicine and Public Health, Shinshu University School of Medicine, Matsumoto, Nagano, Japan
2 Department of Dentistry and Oral Surgery, Shinshu University School of Medicine, Matsumoto, Nagano, Japan
3 Center for Perinatal, Pediatric, and Environmental Epidemiology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan
4 Department of Dentistry and Oral Surgery, Shinshu University School of Medicine, Matsumoto, Nagano, Japan; Center for Perinatal, Pediatric, and Environmental Epidemiology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan
5 Department of Preventive Medicine and Public Health, Shinshu University School of Medicine, Matsumoto, Nagano, Japan; Center for Perinatal, Pediatric, and Environmental Epidemiology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan; Department of Occupational Medicine, Shinshu University School of Medicine, Matsumoto, Nagano, Japan