Periodontal health in a cohort of subjects with type 1 diabetes mellitus

Abstract To evaluate periodontal health and oral health behaviors in a cohort of subjects with type 1 diabetes (T1D), 50 persons with T1D (30 males and 20 females; mean age: 35.2 years) were recruited from the Diabetology Unit of the Geneva University Hospitals; 50 nondiabetic persons matched for gender, age, and smoking status comprised the control group. We assessed periodontal health using the gingival index (GI), plaque index, probing depth (PD), bleeding on probing (BOP), and clinical attachment level (CAL) and recorded self‐reported attitudes and behaviors regarding dental care. The two groups were compared using conditional logistic regression. With respect to the mean PD, CAL, and the mean number of sites with PD >4 mm that bled upon probing, there were no significant differences between the groups. However, subjects with diabetes had significantly more plaque and gingival inflammation and presented more sites with BOP compared with control subjects. Further analysis of the subjects in younger (<40 years) and older (>40 years) cohorts revealed a marked difference in GI between younger healthy and controls, which was also present in older patients and controls but much reduced in magnitude and significance. This marked difference in the gingival health of young versus old diabetic patients to matched controls may provide diagnostic advantages and screening and prevention opportunities to exploit. In spite of similar self‐reported oral hygiene habits and frequency of dental visits, patients with T1D presented more plaque and more inflammation than healthy controls, particularly in the younger subjects. Gingivitis in young T1D patients may be an early indicator for more complicated diabetes and periodontitis in the future. Thus, patients with T1D mellitus should be screened for signs of periodontal disease early and should be motivated and instructed in good oral hygiene practices.

periodontal conditions in children with T1D, as compared with systemically healthy children, notably with regards to greater plaque accumulation and higher levels of inflammation (Ismail, McGrath, & Yiu, 2015).
For caries experience, the evidence was inconclusive. A populationbased prospective cohort study in East Germany examined the influence of T1D and T2D on periodontal disease progression over 5 years (Demmer et al., 2012). T1D subjects were from 20 to 81 years of age.
The authors reported a direct influence of uncontrolled diabetic status on progression of attachment loss for both disease types.
The prognostic value of various clinical parameters to indicate disease progression has been evaluated in clinical studies (Gonzalez et al., 2015;Lang, Schatzle, & Loe, 2009;Schatzle et al., 2003). Among these, bleeding on probing (BOP) has been associated to higher risk for future attachment loss: Sites that repeatedly bled on probing had a significantly higher risk for attachment loss compared with sites with no BOP (Schatzle et al., 2003). These studies showed that periodontitis only occurs in areas of long-standing gingivitis, suggesting that gingivitis is an obligatory precursor of periodontitis.
The accumulation of bacterial biofilms in T1D subjects may lead to more severe gingivitis, which in turn may increase the risk to develop periodontitis. In the present case-control study, we assessed the periodontal conditions and oral health behaviors of a cohort of subjects with T1D and compared them with those of a group of age-and gender-matched nondiabetic individuals. In the T1D group, we further analyzed the impact of diabetes-related factors, such as the duration of the diabetes and the number of complications on the periodontal conditions.

| Periodontal examination
Before the periodontal examination, information regarding dental history was obtained by questionnaire and included oral hygiene habits, frequency of dental appointments, smoking habits, and previous den- The severity of periodontitis was graded according to the CDC/AAP classification (Albandar, 2007)  For subjects of the control group, absence of diabetes was confirmed by an HbA1c test. The system used (A1C Now+, pts Diagnostics) provided the results in a few minutes using blood, sampled with a fingerstick.

| Statistical analysis
Diabetic and nondiabetic participants were described using frequencies and percentages for categorical variables and mean and standard deviations for continuous variables. The two groups were compared using conditional logistic regression. We used the same tests for comparisons when each group (diabetic and nondiabetic) was further divided in younger (<40 years old) and older (≥40 years old) subjects.
Prediction of periodontal status was done using mixed effects logistic regression to account for the matched structure of the data. All analyses were conducted using R v3.5.1, with a significance threshold set at P < 0.05.

| RESULTS
Fifty subjects with T1DM and 50 nondiabetic subjects matched for gender, age, and smoking status participated in the study. The mean age was 35 years; and approximately 40% of the subjects of both groups were females. As shown in Table 1, the 3-year mean HbA1c in the diabetic group was 8.3% and for the nondiabetic group 5.2%, the difference being statistically significant (P < 0.001). The overall characteristics of the diabetic population are shown in Table 2. The mean time since diagnosis of diabetes was 13.3 years (±11.9), and T1D subjects had a mean body mass index of 24.5 (±3.8). The Sudoscan measurements showed that only one among the 28 subjects presented severe dysfunction in the right hand.   The oral health behavior of the study populations is shown in  Table 4 shows the clinical characteristics of the study populations.
The number of teeth present, the mean PD, REC, AL, and the mean number of sites with a plaque index score of ≥1 and the mean number of sites with PD > 4 mm that bled upon probing did not differ between the groups. All the other clinical parameters, including the mean presence of plaque, GI, BOP, and the mean number of sites with GI score ≥ 1, were significantly higher in the diabetic as compared with nondiabetic group.
Concerning the diagnosis of periodontal disease, no significant differences were observed between the groups. As shown in Table 5, gingivitis was present in 68% of the diabetics and 60% of the nondiabetics. Fifteen diabetic subjects (30%) and 14 (35%) nondiabetics had a diagnosis of periodontitis according to the CDC/AAP classification. We further compared periodontal parameters between controls and diabetics in younger (<40 years old) and older (>40 years old) subjects. As shown in Table 6, diabetics <40 years old had significantly more plaque (P = 0.004) and more inflammation (GI; P < 0.001) compared with their matched controls. In the older group (>40 years old), only gingival inflammation was significantly higher in diabetics compared with controls (P = 0.003). The associations among several measured parameters that affect the periodontal condition are shown in Table 7A. The only variables identified as determinants of the periodontal conditions in the whole group (both diabetic and control) were age (P < 0.001), BOP (P = 0.009), and smoking (P = 0.01). However, when considering these three factors together, only age and BOP remained significantly associated with periodontitis (Table 7A). Finally, when examining the associations of the parameters with periodontitis only among diabetic patients, age, HbA1c, BOP, and smoking were significantly associated with periodontitis (Table 7B).

| DISCUSSION
The aim of the present cross-sectional, case-control study was to evaluate the periodontal clinical conditions and oral health behavior in a cohort of subjects with T1D and in a control group matched for age, sex, and smoking status. Results showed that T1DM subjects presented significantly more plaque and more inflammation as compared with the control group in spite of similar self-reported oral hygiene habits and frequency of dental visits. However, the prevalence of     periodontitis did not differ between the two groups. Multivariable logistic regression showed that periodontitis was related mainly to age and BOP index. Our hypothesis was based on the findings of the longitudinal studies of Lang et al. (2009) and Schatzle et al. (2003), who reported that gingivitis precedes the established periodontal lesion and thus can be considered as a risk factor in periodontal disease. In their studies, teeth scored GI = 0 had a mean cumulative attachment loss (LA) of <2 mm over 60 years life span, teeth with slight inflammation (GI = 1) had a mean LA of >2 mm, and those who consistently bled on probing (GI = 2), the mean LA was >3 mm.
In the present study, the higher inflammation, in terms of GI and BOP scores found in the diabetic group, suggests that these subjects will be more susceptible in developing periodontitis in the future. Furthermore, the high oral hygiene level of the individuals further confirms that the higher inflammation is not related to simply poor oral hygiene habits but is an innate susceptibility feature of the patient.
An interesting finding in the present study was the marked difference in GI for the younger cohort, supporting a preventive approach with good diagnostic differentiation possibilities and strong treatment opportunities in the younger age group. The reduction in differences between older diabetic and matched nondiabetic subjects may reflect a plateauing of the inflammatory burden on the gingiva with aging.
The association between T1DM and oral health conditions and the assumption that T1DM is a risk factor for periodontitis has been the subject of several investigations.
Two previously published systematic reviews and meta-analysis concluded that the evidence of a link between T1DM and periodontitis is not sufficient (Chavarry et al., 2009;Khader, Dauod, El-Qaderi, Alkafajei, & Batayha, 2006). However, the studies included in these reviews had several important drawbacks, such as small sample size, control group not matched for age, gender, or other parameters, periodontal measures recorded to half of the mouth, lack of the examiners' calibration, and lack of taking in consideration potential confounding factors.
More recently, two cross-sectional studies, including subjects from five hospitals in Glasgow, reported that the prevalence of severe   periodontitis, in terms of clinical attachment loss and radiographic bone loss, was significantly higher in both well-controlled and poorly controlled subjects with T1DM as compared with nondiabetic subjects (Hodge et al., 2012;Plessas, Robertson, & Hodge, 2018). In a cohort of subjects with T1DM, the bacterial profile based on 12 species was examined and was compared with that from a control group matched for age, gender, and level of periodontitis. No significant difference was observed between the two groups, suggesting that it is the host response to the bacterial challenge that drives the enhanced susceptibility to periodontal disease in diabetes (Lalla et al., 2006).
The majority of the studies emphasized that the duration of diabetes, poor metabolic control, and other existing complications of diabetes are important factors to take into consideration in the evaluation of diabetes as a risk factor for periodontal disease. In our study, the prevalence of periodontitis-mild, moderate, or severe-did not differ between the diabetic and nondiabetic population. It should be emphasized, however, that the majority of the participants were nonsmokers or former smokers (53% and 20%, respectively) and did not have any severe complications related to their diabetes status.
Indeed, only one subject out of 50 diabetics had a major complication affecting the microvasculature (cardiovascular disease), seven suffered from neuropathy, seven others from nephropathy, and 11 subjects from retinopathy. In addition, the majority of subjects reported having annual dental appointment. More specifically, subjects in the control group were recruited among patients of the dental school who regularly see the students and receive repeatedly oral hygiene instructions.
In Switzerland, a population-based cross-sectional survey was conducted in the canton de Vaud in order to assess the quality of care provided to patients with diabetes. Based on self-administered paper questionnaires, among the 406 participants, 18.2% had T1DM, 68.5% had T2DM, and for 20% of the subjects, the diabetes type remained undetermined. Although routine clinical and laboratory tests were performed annually in most of the subjects, several risk screenings related to diabetes were less often reported. For example, feet examination, microalbuminuria, and physical activity and dietary recommendations were reported only by a minority of the subjects (Peytremann-Bridevaux, Bordet, & Burnand, 2013). Subjects had received no recommendation for dental examination.
In conclusion, the results of this study add to the body of literature supporting the observation that there is a high prevalence of plaque and gingival inflammation in subjects with T1DM. Whether these subjects are more susceptible to develop severe forms of periodontal disease in the future remains to be elucidated longitudinally. Our further analysis of the subjects in younger (<40 years) and older (>40 years) T1DM cohorts revealed a marked difference in GI between younger healthy and controls, which was less pronounced in older patients.
This marked difference in the gingival health of young versus old diabetic patients to matched controls may provide diagnostic advantages and screening and prevention opportunities to exploit. We suggest that periodontal health, particularly gingivitis in younger patients, may be an early indicator for both more complicated diabetes and periodontitis, and thus, oral health education and early diagnosis and treatment of periodontal disease should be recommended by both physicians and dentists to T1DM subjects.