Abstract
Aim:
To assess the role of periodontal disease (PD) as a predictor of coronary artery disease (CAD) and mortality in a prospective type 1 diabetes (T1D) cohort and to evaluate the role of smoking in this relationship.
Methods:
Data were based on 320 participants of the Pittsburgh Epidemiology of Diabetes Complications study of T1D who, during 1992-94, received a partial mouth periodontal exam, and who were followed for up to 19 years to ascertain complication incidence. PD was defined as clinical attachment loss of ≥4 mm for at least 10% of the examined sites. Predictors of all-cause mortality; Hard CAD (CAD death, myocardial infarction or revascularization), and Total CAD (Hard CAD, angina, ischemic ECG) were assessed using Cox models.
Results:
During 19 years of follow-up, 33.7% (97/288) developed CAD, 27.3% (83/304) developed Hard CAD, and 16.9% (54/320) died. Among current smokers, 46.4% (26/56) developed CAD, 42.7% (24/56) developed Hard CAD and 29.5% (18/61) died. PD was not associated with all-cause mortality, although it was a significant predictor of both CAD (HR=1.12, CI=1.01-1.23) and Hard CAD (HR=1.30, CI=1.11-1.51). As smoking modified the PD-CAD and PD-Hard CAD associations, analyses were stratified by smoking status. PD was associated with an increased risk of CAD (HR=1.25, CI= 1.03-1.50) and Hard CAD (HR=1.85, CI=1.17-2.93) only among smokers.
Conclusion:
PD was a significant predictor of CAD and Hard CAD among current smokers with T1D.
Keywords: type 1 diabetes, periodontal disease, coronary artery disease, smoking, diabetes complications
1. Introduction
Type 1 diabetes (T1D) is one of the most common chronic diseases of childhood. Recent data from the U.S. suggest that the incidence of T1D among youth has increased by 1.8% annually from 2001 to 2012.1 T1D is associated with increased morbidity and mortality with an associated cost of $14.4 billion per year in direct medical expenses and indirect costs.2 Periodontal disease (PD) is one of the main oral manifestations of T1D .3
PD is a chronic inflammatory disease of the surrounding tooth structure caused by pathogens, leading to tissue destruction and tooth loss. It is estimated that 47.2% of US adults have some form of PD, based on data from NHANES 2009-2012.4 Smoking and hyperglycemia are two modifying risk factors for PD.5 Smoking leads to a strong inflammatory reaction that has detrimental effects on the periodontium and can increase the risk of periodontitis 2-5 times.5,6 Hyperglycemia in patients with diabetes leads to oxidative stress and the formation of advanced glycation end products (AGE) that activate various proinflammatory mediator cascades leading to periodontal tissue damage.7,8
PD has been linked to systemic diseases such as cardiovascular disease (CVD), diabetes and chronic kidney disease.9-11 Although studies have found a strong association between PD and CVD, a large NHANES study suggested that smoking plays a significant role in the PD-CVD relationship as an effect modifier12, while others have found the relationship to be independent of smoking.13 Both diabetes and PD have been individually identified as risk factors for CVD. The combined effect of PD and diabetes on the development of CVD has been studied widely in type 2 diabetes.14 Thus, individuals with type 2 diabetes and PD were shown to have a higher incidence of coronary artery disease 15, carotid atherosclerosis 16 and myocardial infarction.17 Findings from the Study of Health in Pomerania further suggested that although measures of PD were independently associated with all cause and CVD mortality, there was no evidence of interaction between diabetes and periodontitis.18 A single study in individuals with T1D suggested that PD was significantly associated with coronary artery calcium progression, a marker of subclinical atherosclerosis.19 The aim of this study was therefore to assess the role of PD as a predictor of documented cardiovascular complications and mortality in a cohort of individuals with childhood-onset T1D and to evaluate the effect of smoking on this relationship.
2. Materials and Methods
2.1. Study population
The Pittsburgh Epidemiology of Diabetes Complications (EDC) study is a prospective cohort study of childhood-onset (<17 years) T1D. All participants of the EDC study were diagnosed, or seen within 1 year of diagnosis, at Children’s Hospital of Pittsburgh between 1950 and 1980. The cohort has been described in detail elsewhere.20,21 In brief, participants (n=658) have been followed with biennial surveys since study initiation (1986-1988). Clinical examinations occurred biennially for the first 10 years and thereafter at 18- and 25-years post baseline. Between March 1992 and August 1994, of 412 participants scheduled for an EDC clinic visit, 406 enrolled in a dental study. Of these, 16 were missing all their teeth, two had scheduling conflicts that prevented complete oral health assessments, and 68 were excluded for possible risk of bacteremia, leaving 320 eligible to receive a comprehensive oral health assessment, including a periodontal examination. The methodology of the oral health assessment is described in detail elsewhere.22 Briefly, a periodontal examination was conducted following the National Institute of Dental Research (NIDR) adult survey methodology.23 Three facial sites (mesial, mid-cervical and distal) of the right maxillary/left mandibular or left maxillary/right mandibular quadrants were probed, excluding third molars. Clinical attachment loss and pocket depths were measured using a standard WHO Community Periodontal Index of Treatment Needs (CPITN) pressure-controlled probe by one of two calibrated dentist examiners. Bleeding on probing and visual assessment of supragingival calculus was assessed as present or absent on each tooth examined. In addition, all missing teeth excluding the third molar were recorded using modified criteria from the NIDR adult survey to determine the cause of extraction (disease or orthodontic treatment).
2.2. Assessment of PD
Participants who had clinical attachment loss of ≥ 4 mm in more than 10% of periodontal sites examined were defined as having PD. This definition reflects the Healthy People 2000 and 2010 definition of PD24,25. This parameter was selected to describe a clinically significant amount of disease, include an ample sample size for analysis and minimize misclassification of cases due to measurement error.22
2.3. Assessment of covariates
Covariates of interest were selected for analysis from the time of the oral health exam. The number of missing teeth was assessed clinically during the oral health exam. Demographic data, including age, sex, educational status (used as an indicator of socioeconomic status), and alcohol consumption were assessed via survey. Smoking status was assessed by self-report to the question “Have you smoked at least 100 cigarettes in your lifetime?” Participants who responded in the affirmative were asked if they currently smoke in a follow-up question. Those who responded positively were classified as current smokers, while all others, including former smokers, were considered non-smokers.
Fasting blood samples were taken to measure HbA1, lipids, lipoproteins, serum creatinine and serum albumin. HbA1 values were converted to DCCT (Diabetes Control and Complications Trial)-aligned values HbA1c using a regression equation derived from duplicate assays [DCCT HbA1c = 0.14 + 0.83 (EDC HbA1 )].26 Total cholesterol and triglycerides were determined enzymatically.27,28 High density lipoprotein (HDL) cholesterol was determined using a modified precipitation technique.29 Non-HDL cholesterol (non-HDLc) was calculated by subtracting HDL from total cholesterol. Blood pressure was measured according to the Hypertension Detection and Follow-Up protocol with a random-zero sphygmomanometer.30 Hypertension was defined as blood pressure >140/90 mm/Hg or use of blood pressure-lowering medications.
Serum and urinary albumin were measured by immunonephelometry 31,32 and creatinine was assayed by an Ectachem 400 Analyzer (Eastman Kodak Co., Rochester, NY). Albumin excretion rate (AER) was calculated for each of three timed urine samples (24-hr, overnight and 4-hr collections obtained over a 2-week period); the median of the three AERs was used in analyses and was natural logarithm transformed due to its skewed distribution. White blood cell (WBC) count and hemoglobin were measured using a Coulter Counter S-Plus IV. Height and weight were measured using standard methods to calculate body mass index (BMI).
2.4. Assessment of outcomes
Participants were followed until October 31, 2014 to ascertain complication status (median follow-up time, 19 years). Three main outcomes were assessed for this analysis. All-cause mortality; Hard Coronary Artery Disease (Hard CAD; CAD death, myocardial infarction confirmed by Q-waves on electrocardiogram (Minnesota codes 1.1 or 1.2) or hospital records, or revascularization); and total Coronary Artery Disease (CAD; Hard CAD but also including angina, determined by the EDC study physician, and ischemic electrocardiogram changes (Minnesota codes 1.3, 4.1-4.3, 5.1-5.3, 7.1)). In the EDC study, mortality was ascertained using medical records, death certificates, autopsy reports, and/or interview with next of kin.
2.5. Statistical analysis
Differences in baseline characteristics were evaluated between PD cases and non-PD cases using the Student’s t-test for normally distributed continuous variables, the Wilcoxon rank sum (Mann-Whitney U) test for non-normally distributed continuous variables and the chi-square or Fischer’s exact test for categorical variables. The Cochran–Armitage test for trend was used for ordinal variables.
Kaplan Meier curves were used to assess survival probabilities between PD cases and non-PD cases for each of the outcomes. Predictors of CAD, Hard CAD and all-cause mortality were assessed using Cox models, excluding prevalent cases of CAD or Hard CAD, as appropriate, at the time of the oral health exam. Survival time was defined as the time in years from the oral health exam to the date of the first event for each outcome studied or censorship. The proportional hazards assumption was assessed visually and confirmed by testing time-dependent PD interaction variables. PD violated the proportional hazard assumption for both CAD and Hard CAD and was therefore added to models relating to these two outcomes as a time-varying covariate.
We assessed the role of current smoking as an effect modifier by including an interaction term between PD and current smoking in the models along with the lower order terms. Stratified analyses by current smoking status were conducted when effect modification was observed. Cox proportional hazards models stratifying by current smoking status were first constructed assessing the association between each potential risk factor and the outcome of interest, allowing only for diabetes duration. Variables that were significantly associated with the outcome were subsequently included in separate multivariable Cox models for current smokers and non-smokers. Backward elimination with a significance level of 0.05 was used to retain significant covariates in the models. All analyses were repeated replacing the dichotomous covariate for hypertension status with a continuous variable for systolic blood pressure. All statistical analyses were conducted using SAS® 9.4 software (SAS Institute Inc., Cary, NC, USA.)
3. Results
Participants with prevalent CAD at the time of the oral health exam (n=32) were excluded from analyses. The prevalence of PD in this cohort was 10.6%. Table 1 describes the baseline characteristics of the study population based on PD status. PD cases were significantly older, with a later age at the onset of T1D, more likely to have less than a high school education as well as more likely to have more missing teeth compared with non-PD cases. The prevalence of current smoking was significantly higher among PD cases compared with non-PD cases (current smoker 61.8% vs 14.0%). WBC count was also significantly higher among cases, although there were no differences in other biological markers by PD status. PD cases had a higher incidence of CAD, Hard CAD and all-cause mortality.
Table 1:
Baseline characteristics of EDC participants who received an oral health exam (1992-1994) by periodontal disease (PD)
| Non-PD cases (n=286) | PD cases (n=34) | p-value | |
|---|---|---|---|
| Age (years) | 31.47 (7.67) | 37.61 (6.06) | <0.0001 |
| Age at onset (years) | 8.09 (4.08) | 10.71 (3.75) | 0.0004 |
| Duration of diabetes (years) | 23.38 (7.34) | 26.90 (7.47) | 0.009 |
| Female sex | 130 (45.45) | 12 (35.29) | 0.26 |
| More than high school education | 208 (72.73) | 18 (52.94) | 0.02 |
| ≥7 ounces alcohol/wk (n=282,33) | 199 (70.57) | 20 (60.61) | 0.24 |
| Current smoker | 40 (13.99) | 21 (61.76) | <0.0001 |
| Number of missing teeth | |||
| None | 161 (56.29) | 6 (17.65) | |
| 1-4 | 97 (33.92) | 10 (29.41) | <0.0001 |
| ≥5 | 28 (9.79) | 18 (52.94) | |
| White blood cell count (×103/μL, n=283,34) | 7.11 (1.97) | 8.80 (2.92) | <0.0001 |
| BMI (kg/m2 n=284,33) | 24.66 (3.35) | 23.90 (3.26) | 0.22 |
| Hypertension | 50 (17.48) | 10 (29.41) | 0.09 |
| HDL cholesterol (mg/dL, n=285,34) | 52.07 (12.40) | 53.01 (14.03) | 0.68 |
| Non-HDL cholesterol (mg/dL, n=285,34) | 134.2 (37.07) | 145.3 (39.19) | 0.10 |
| Albumin excretion rate (μg/min) | 14.74 (5.18-69.07) | 23.82 (6.27-143.33) | 0.44 |
| HbA1c (%, n= 284,34) | 9.25 (1.41) | 9.40 (1.36) | 0.53 |
| CAD incidence (n=259,29) | 79 (30.50) | 18 (62.07) | 0.0006 |
| Hard CAD incidence (n=273,31) | 68 (24.91) | 15 (48.39) | 0.005 |
| All-cause mortality | 43 (15.03) | 11 (32.35) | 0.01 |
Data are means (SD), medians (interquartile range) or n (%)
During 19 years of follow-up, 33.7% (97/288) developed CAD, 27.3% (83/304) developed Hard CAD, and 16.9% (54/320) died. Among current smokers, 46.4% (26/56) developed CAD, 42.7% (24/56) developed Hard CAD and 29.5% (18/61) died. Table 2 shows the characteristics of the study population at the time of the oral health exam by the follow-up status of each of the three outcomes of interest. Regardless of outcome studied, participants who experienced an event were older, with a longer duration of diabetes, more likely to be hypertensive, with higher levels of HbA1c, white blood cell count, non-HDL cholesterol and albumin excretion rate. Incident cases were also more likely to be missing a larger number of teeth and a greater proportion of incident cases had PD. Figure 1 shows a clear separation of the Kaplan Meier survival curves according to PD status for all outcomes studied: CAD (Figure 1a), hard CAD (Figure 1b) and Mortality (Figure 1c).
Table 2:
Baseline characteristics for all EDC participants who received an oral health exam by incident outcome of interest
| CAD (N=288) | Hard CAD (N=304) | All- Cause Mortality (N=320) | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Participant characteristics | No (n=191) |
Yes (n=97) |
p-value | No (n=221) |
Yes (n=83) |
p-value | No (n=266) |
Yes (n=54) |
p-value |
| Age (years) | 29.73 (7.44) | 35.33 (6.38) | <0.0001 | 30.38 (7.54) | 35.78 (6.40) | <0.0001 | 31.19 (7.51) | 36.67 (7.26) | <0.0001 |
| Age at onset (years) | 8.38 (4.18) | 8.21 (4.01) | 0.67 | 8.46 (4.05) | 8.34 (4.31) | 0.83 | 8.41 (4.09) | 8.15 (4.29) | 0.67 |
| Duration of diabetes (years) | 21.35 (6.65) | 27.11 (7.20) | <0.0001 | 21.93 (6.86) | 27.43 (7.03) | <0.0001 | 22.79(6.98) | 28.53 (7.74) | <0.0001 |
| Female sex | 87 (45.55) | 44 (45.36) | 0.23 | 99 (44.80) | 38 (45.78) | 0.88 | 122 (45.86) | 20 (37.04) | 0.23 |
| More than high school education | 139 (72.77) | 65 (67.01) | 0.78 | 157 (71.04) | 57 (68.67) | 0.69 | 187 (70.30) | 39 (72.22) | 0.78 |
| Alcohol consumption | N=187 | N=96 | N=217 | N=82 | N=261 | N=54 | |||
| >=7ounces/week | 130 (69.52) | 67 (69.79) | 0.96 | 149 (68.66) | 60 (73.17) | 0.45 | 186 (71.26) | 33 (61.11) | 0.14 |
| Current smoker | 30 (15.71) | 26 (26.80) | 0.02 | 32 (14.48) | 24 (28.92) | 0.01 | 43 (16.17) | 18 (33.33) | 0.017 |
| Periodontal disease | 11 (5.76) | 18 (18.56) | 0.01 | 16 (7.24) | 15 (18.07) | 0.005 | 23 (8.64) | 11 (20.37) | 0.011 |
| Number of missing teeth | |||||||||
| None | 114 (59.69) | 40 (41.24) | <0.0001 | 129 (58.37) | 31 (37.35) | 0.0004 | 154 (57.89) | 13 (24.07) | <0.0001 |
| 1-4 | 55 (28.80) | 40 (41.24) | 68 (30.77) | 33 (39.76) | 82 (30.83) | 25 (46.30) | |||
| ≥5 | 22 (11.52) | 17 (17.53) | 24 (10.86) | 19 (22.89) | 30 (11.28) | 16 (29.63) | |||
| HbA1c (%) | N=190 | N=96 | N=220 | N=82 | N=266 | N=52 | |||
| 9.11 (1.42) | 9.58 (1.27) | 0.0065 | 9.12 (1.35) | 9.63 (1.35) | 0.0031 | 9.14 (1.33) | 9.90 (1.60) | 0.0003 | |
| White blood cell count (×103/μL) | N=190 | N=95 | N=220 | N=81 | N=264 | N=53 | |||
| 7.021 (1.98) | 7.78 (2.39) | <0.0001 | 6.98 (1.98) | 7.74 (2.10) | 0.004 | 7.06 (2.03) | 8.42 (2.40) | <0.0001 | |
| BMI (kg/m2) | N=189 | N=96 | N=219 | N=82 | N=263 | N=54 | |||
| 24.14 (3.02) | 25.20 (3.70) | 0.94 | 24.42 (3.19) | 24.96 (3.69) | 0.21 | 24.58 (3.35) | 24.61 (3.30) | 0.94 | |
| Hypertension | 18 (9.42) | 27 (27.84) | <0.0001 | 25 (11.31) | 27 (32.53) | <0.0001 | 35 (13.16) | 25 (46.30) | <0.0001 |
| N=196 | N=96 | N=221 | N=82 | N=266 | N=53 | ||||
| HDL cholesterol (mg/dL) | 52.49 (12.49) | 52.05 (12.73) | 0.79 | 52.31 (12.50) | 52.36 (12.81) | 0.98 | 52.26 (12.46) | 51.74 (13.17) | 0.79 |
| Non-HDL cholesterol (mg/dL) | N=191 | N=96 | N=221 | N=82 | N=266 | N=53 | |||
| 126.7 (34.02) | 150.6 (38.56) | <0.0001 | 128.6 (33.74) | 151.2 (41.13) | <0.0001 | 130.9 (33.50) | 158.1 (46.91) | <0.0001 | |
| Albumin excretion rate (μg/min) | N=190 | N=97 | N=220 | N=83 | N=265 | N=54 | |||
| 11.04 (4.36-37.33) | 21.30 (6.79-146.54) | <0.0001 | 11.04 (4.36-42.30) | 39.54 (9.33-366.43) | <0.0001 | 11.50 (4.42-44.27) | 107.03 (21.15-1209.51) | <0.0001 | |
Data are means (SD), medians (interquartile range) or n (%).
Figure 1:
Kaplan Meier Survival Curves Stratified by Periodontal Disease (PD)
a. CAD
b. Hard CAD.
c. All-cause mortality (0=non-PD cases, 1=PD cases)
Results from Cox proportional hazard models for the risk of CAD and Hard CAD are displayed in Tables 3 and 4, respectively. In unadjusted Cox models, PD was significantly associated with a greater risk of CAD (HR=1.11, CI=1.01-1.23), Hard CAD (HR=1.24, CI=1.08-1.43) and all-cause mortality (HR=2.41, CI=1.24-4.7). However, after allowing for covariates, PD was no longer a significant predictor of all-cause mortality (HR=0.87, CI=0.41-1.83), although it remained significantly associated with both CAD (HR=1.12, CI=1.01-1.23) and Hard CAD (HR=1.30, CI=1.11-1.51) (not shown).
Table 3:
Cox proportional hazard models for the prediction of CAD
| Crude model (n=283, 95 events) |
Model with interaction term for PD*smoking |
Crude model for smokers (n=55, 25 events) |
Crude model for non-smokers (n=228, 70 events) |
Adjusted model for smokers (n=55, 25 events) |
Adjusted model for non-smokers (n=228, 70 events) a |
|
|---|---|---|---|---|---|---|
| PD (time-dependent) | 1.10 (1.002-1.21)b | 1.15 (1.04-1.28) c | 1.29 (1.07-1.56)c | 1.10 (0.85-1.42) | 1.25 (1.03-1.50) b | 1.09 (0.84-1.40) |
| PD*smoking | 9.45 (1.80-49.74)c | |||||
| Diabetes duration | 1.08 (1.01-1.54) b | 1.09 (1.05-1.12)d | ||||
| HbA1c | Not allowed | 1.20 (1.01-1.42) b | ||||
| Non-HDL cholesterol | Not allowed | 1.02 (1.01-1.02) d | ||||
| WBC | Not allowed | 1.16 (1.01-1.33) b |
Data are HR (95%CI)
Multivariable models allowed for univariate predictors of CAD.
The model also allowed for log Albumin Excretion Rate and hypertension.
p-value <0.05
p-value <0.01
p-value <0.001
Table 4:
Cox proportional hazard models for the prediction of Hard CAD
| Crude model (n=299, 81 events) |
Model with interaction term for PD*smoking |
Crude model for smokers (n=55, 23 events) |
Crude model for non-smokers (n=244, 58 events) |
Adjusted model for smokers (n=55, 23 events) |
Adjusted model for non-smokers (n=244, 58 events) a |
|
|---|---|---|---|---|---|---|
| PD (time-dependent) | 1.26 (1.09-1.46) c | 1.35 (1.15-1.58) d | 1.93 (1.23-3.05) c | 1.19 (0.84-1.68) | 1.85 (1.17-2.93) c | 1.18 (0.83-1.70) |
| PD*smoking | 7.02 (1.31-37.59) b | |||||
| Diabetes duration | 1.13 (1.05-1.21) d | 1.09 (1.05-1.13) d | ||||
| HbA1c | Not allowed | 1.32 (1.10-1.60) c | ||||
| Non-HDL cholesterol | Not allowed | 1.01 (1.002-1.02) c | ||||
| Log Albumin excretion rate | Not allowed | 1.20 (1.05-1.38) c | ||||
| WBC | Not allowed | 1.17 (1.01-1.35) b |
Data are HR (95%CI)
Multivariable models allowed for univariate predictors of CAD.
The model also allowed for hypertension.
p-value <0.05
p-value <0.01
p-value <0.001
Significant effect modification of PD by current smoking status was observed for both CAD (p-interaction <0.01) and Hard CAD (p-interaction <0.001) but not for mortality (p-interaction = 0.65). Indeed, in unadjusted analyses stratifying by current smoking status, PD significantly predicted the development of CAD and Hard CAD among current smokers (HRCAD=1.29, CI= 1.07-1.56 and HR Hard CAD =1.93, CI=1.23-3.05) but not among those not currently smoking (HRCAD = 1.10, CI=0.85-1.42 and HRHard CAD = 1.19, CI=0.84-1.68). Adjusting for covariates did not alter these findings (Tables 3 and 4). When analyses were repeated replacing the categorical covariate for hypertension with a continuous variable for systolic blood pressure, similar results were obtained.
4. Discussion
In this prospective cohort study of individuals with childhood-onset T1D, we observed that PD significantly increased the risk of both CAD and Hard CAD among current smokers only. This is similar to the finding from the Coronary Artery Calcification in Type 1 Diabetes study, where self-reported PD was significantly associated with CAC progression at 6 years follow-up.19 Our study presents stronger evidence of this association as we have verified measure of periodontal disease, a longer follow up time and verified clinical outcomes. A recent meta-analysis also showed that PD was associated with cardiovascular mortality and coronary heart disease among patients with type 2 diabetes, however there was not enough evidence for this association in T1D.14 Studies in the general population found that PD was associated with all-cause mortality and was an independent risk factor for CVD, after adjusting for traditional risk factors including smoking and diabetes.33,34 We observed a significant association between PD and all-cause mortality in the unadjusted models, although this association was no longer significant after adjusting for confounders. This different finding could be due to a smaller sample size and our study focusing on T1D patients only.
Because smoking is a major risk factor for PD and CVD6 and based on findings from previous studies12, we tested for effect modification by current smoking status. We found current smoking to be an effect modifier as the PD – CAD / Hard CAD association was restricted to current smokers only. Both smoking and diabetes are known risk factors for periodontal disease.35 Although it is known that compared to controls, T1D patients have elevated periodontal pro-inflammatory factors, different periodontal pathogen composition36 and lower salivary flow rates37-39, further research is required to investigate how these factors, in addition to genetics, differ in T1D by smoking status. Among the type 2 diabetes population, a study found that two inhibitors of the osteoblastogenesis pathway, Sclerostin and Dickkopf, were upregulated in patients with chronic periodontitis and type 2 diabetes and/or smoking.40 Joaquim et al41, found no difference in key periodontal pathogens between smoking and non-smoking patients with type 2 diabetes compared to smoking and non-smoking non-diabetic patients who had generalized chronic periodontitis. In addition, there is no direct mechanism for how periodontitis affects diabetic complications; suggested pathways include oxidative stress, dyslipidemia, endothelial dysfunction and elevated CRP.42 There is evidence that periodontal treatment improves short-term glycemic control and circulating levels of markers of inflammation in type 2 diabetes.14 However, there is insufficient evidence on the effect of PD therapy on HBA1c levels in T1D.14
As the risk of CVD associated with PD among patients with diabetes is significant, screening for PD may provide a cost-effective modality for identifying patients at high CVD risk. A recent systematic review showed that most patients with diabetes were unaware of the PD-diabetes connection; they were not aware of their risk of PD and did not receive information about their oral health risk or advice about oral healthcare from their diabetes care provider.43 This issue has been addressed in the recent guidelines developed by the International Diabetes Federation and the European Federation of Periodontology to integrate the health care, including oral health care, of patients with diabetes between physicians and dentists.11 The guidelines state that children and adolescents with type 1 diabetes should be placed on annual oral screenings as soon as possible.11 It is important to note that although smoking is a significant risk factor for periodontal disease, bleeding on probing, which is one of the classical signs of active periodontal disease, is usually masked in smokers due to the vasoconstrictive effect of nicotine on blood vessels.44,45 Consequently, patients can be unaware of periodontal problems until the disease progresses to an advanced stage, which could increase their risk of CAD. Therefore, patients with T1D should be advised by their healthcare providers that PD, in addition to smoking, places them at increased risk of CVD complications beyond the traditional risk factors. These patients should be referred to a periodontist and placed on a periodontal treatment regimen.
4.1. Strengths and Limitations
Our study has some limitations. The use of partial mouth measure with three facial sites only could have underestimated the prevalence of PD.46 Partial mouth measures have been shown to bias epidemiological measures of association between PD and smoking, alcohol, obesity and diabetes.47 However, when the EDC oral health exam took place in 1992-94, this partial mouth exam was commonly used as an acceptable measure of the prevalence of periodontal disease. In addition, we used a definition of periodontal disease (>=4mm of attachment loss in >=10% of examined sites). Research shows that the association of PD with systemic diseases differs according to the classification or definition of PD used.48 Data for this cohort were collected to reflect the Healthy People 2000 and 2010 definition of PD24,25 and do not allow the application of different definitions of PD. However, our main conclusion is that patients with T1D who have clinically verified PD and who currently smoke might be at increased risk of developing CVD complications. Moreover, oral health measures were assessed at one point and we cannot account for changes in PD over time. Smoking status was based on self-report and could be subject to reporting bias. Inflammation is suspected to play a role in the restriction of PD-CAD/HCAD association to smokers. However, we were unable to adjust for markers of inflammation beyond WBC count, as they were not collected for this sample. Adding markers of inflammation such as IL-8, TNF and CRP would help further understand the relationship between PD and smoking in the development of CVD complications of T1D. Despite these limitations, this study is unique in that it uses longitudinal data from a prospective study with 19 years of follow up with verified CVD events. This enables us to establish a strong association with the exposure (PD) proceeding the outcome (CVD complications) in T1D, a topic that is understudied.
4.2. Conclusion
PD could be used as an early clinical predictor of CAD complications in TID patients who smoke. In addition, T1D patients who smoke should receive coordinated care from both a periodontist and their usual healthcare provider to ensure optimal treatment of both their periodontal disease and CAD risk. Studies that investigate complications of diabetes should examine PD to further aid our understanding of the PD-diabetes complications association. Clinical trials to evaluate the effect of periodontal treatment on outcomes in patients with T1D are warranted.
Highlights.
Little is known about the possible role of periodontal disease in the development of cardiovascular complications in individuals with type 1 diabetes
In our cohort with childhood onset type 1 diabetes, periodontal disease was associated with increased risk of coronary artery disease among smokers
Assessment of periodontal disease could be used as an early clinical predictor of CVD complications among individuals with type 1 diabetes who smoke.
Acknowledgments
Funding
This research was funded by NIH grant DK34818 and the Rossi Memorial Fund.
Footnotes
Declarations of interest
None
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