related to DM.
1.2.2.3 Association between periodontitis and DM
The relationship between periodontitis and diabetes has been a subject of several longitudinal and interventional studies and it has been suggested that their relationship is bidirectional in both T1DM and T2DM and periodontal diseases62. For example, in diabetes, local inflammatory reactions within the periodontal tissues are modulated by the associated metabolic dysregulation (i.e. tissue responses to inflammatory stimuli are enhanced in poorly controlled diabetes)63, which is explained in further detail in Section 1.3 ‘Cellular and molecular mechanisms’.
Epidemiological studies
Diabetes and periodontitis are chronic inflammatory diseases that have been considered to be biologically linked. Diabetes is known to be a primary risk factor for periodontitis, and periodontitis is considered as the sixth complication of DM25. Evidence linking periodontitis and diabetes began to emerge in the 1990s from several studies conducted in the Pima Indian population in the United States64. Cross-sectional studies showing the prevalence and longitudinal studies showing the incidence of diabetes, demonstrate that periodontitis is significantly more abundant in subjects who have T1DM65 or T2DM66 diabetes, with a higher risk of having the severe forms of periodontitis. The risk of periodontitis is approximately three to four times higher in people with T2DM than in non-diabetes subjects67. The direct relationship between the glucose level and the severity of periodontitis has been demonstrated, with the ORs in T2DM patients of periodontal destruction being 1.97 in well, 2.10 in moderately, and 2.42 in people with poorly controlled diabetes68. In addition, data from the NHANES show that individuals with diabetes are at greater risk for incident and prevalent periodontitis and have more severe periodontitis than individuals without diabetes, after controlling for age, education, smoking status and calculus69. These data were also supported by a recent meta-regression analysis of longitudinal studies, which included 13 studies. The authors reported that diabetic subjects present a 70% higher incidence or progression risk of periodontitis than non-diabetics (relative risk [RR] 1.86, 95% CI 1.3 to 2.8), despite of high heterogeneity between studies70. Similarly, a 2019 Taiwanese large-scale cohort study, including 39,384 patients with new-onset diabetes and 39,384 subjects without periodontitis, found that patients with diabetes had a higher risk for periodontitis compared with the patients without diabetes (adjusted hazard ratio 1.04, 95% CI 1.01 to 1.08). As a major shortcoming, however, periodontitis was poorly defined, using ICD-9-CM (International Classification of Diseases, Ninth Revision, Clinical Modification) codes only71. Conversely, a systematic review and meta-analysis of 12 intervention studies (follow-up period: 6 months) published in the same year, stated that there was no significant difference in pocket reduction or clinical attachment gain between periodontitis patients and those with both diabetes and periodontitis. Furthermore the level of HbA1c at baseline did not affect the difference in pocket reduction. However, this study pooled data from smokers and non-smokers, which is likely to have affected treatment outcomes and therefore the results of this meta-analysis. Furthermore, heterogeneity of the included studies with regard to periodontal diagnosing as well as the relatively short follow-up period may have impacted the results72.
SUMMARY
● In 2015, it was estimated that 415 million people worldwide have diabetes.
● By 2040, an increase to 642 million is expected.
● The estimated costs associated with diabetes in the United States in 2002 were US $132 billion.
● Intense glycaemic control in both T1DM and T2DM can decrease the morbidity and mortality.
● For every percentage point decrease in HbA1c, there are:
– 35% reduction in the risk of microvascular complications,
– 25% reduction in diabetes-related deaths,
– 7% reduction in all-cause mortality,
– 18% reduction in combined fatal and nonfatal myocardial infarction.
On the other hand, there is evidence for periodontitis promoting the development of diabetes. Overall, six studies with a total sample of 77,716 participants from the United States, Japan and Taiwan demonstrated that patients with periodontitis exhibit a higher chance of developing pre-diabetes and diabetes2. One of these studies demonstrated that systemically healthy subjects with probing depths equal to or greater than 6 mm have a 3.45 times higher risk of developing diabetes than those without periodontitis73. Another study demonstrated that subjects with gingivitis have a 40% elevated risk, subjects with periodontitis a 50% elevated risk, and subjects who are partially edentulous a 70% elevated risk of developing T2DM. It is important to mention that this association was observed in non-smoking subjects with normal weight74. This association can also be seen for gestational DM75. Furthermore, a recent (2019) study was conducted in 139 periodontitis patients, which employed chair-side screening for HbA1c levels and considered BMI, waist circumference and periodontal parameters. It was found that almost 25% of the subjects had unknown hyperglycaemia and those with HbA1c ≥ 5.7% displayed higher proportions of sites with clinical attachment loss > 5 mm76.
One recently published longitudinal study followed 2047 subjects aged 20 to 81 years from the Study of Health in Pomerania cohort over a period of 11 years. Although the study was well conducted and excluded many potential biases, it reported no association between periodontal parameters and either diabetes incidence or long-term changes in HbA1c. One shortcoming of this study may be, however, that diabetes was assessed by different methods (self-reporting or antidiabetic medication intake or HbA1c levels or fasting blood glucose)77.
Moreover, the majority of the studies report an association between worse periodontal conditions and diabetes complications. For example, Shultis et al78 observed that moderate and severe periodontitis, as well as edentulousness, significantly predicted both macroalbuminuria (2.0, 2.1 and 2.6 times higher, respectively) and end-stage renal disease in a dose-dependent manner among Pima Indians with T2DM. In this population, as shown by another study, those with severe periodontitis had a 3.5 times higher risk for cardiorenal death; moreover, nephropathy and death from ischaemic heart disease were significantly predicted by periodontitis79. In a systematic review and meta-analysis of 27 epidemiological studies, Ziukaite et al80 observed that the prevalence of diabetes was 13.1% among subjects with periodontitis and 9.6% among subjects without periodontitis. Interestingly, for subjects with periodontitis, the prevalence of diabetes was 6.2% when diabetes was self-reported, compared to 17.3% when diabetes was clinically assessed. According to this study, the highest prevalence of diabetes among subjects with periodontitis was observed in studies originating from Asian countries (17.2%) and the lowest in studies describing