Periodontitis as a potential early risk indicator for diabetes mellitus, atherosclerotic cardiovascular disease, metabolic syndrome and obstructive sleep apnea syndrome

Diabetes Mellitus (DM), Atherosclerotic Cardiovascular Disease (ASCVD),
Metabolic Syndrome (MetS) and Obstructive Sleep Apnea Syndrome (OSAS) are major
health problems. However due to absence of symptoms and/or lack of knowledge,
people are often unaware of having DM, ASCVD, MetS or OSAS while early
treatment could prevent or stop the progression of these diseases. Therefore
risk indicators for early detection of DM, ASCVD, MetS and OSAS are needed and
proposed.

Many studies demonstrate the association between oral diseases and DM and/or
ASCVD. The most observed chronic oral disease is periodontitis. Periodontitis
is a common chronic multifactorial inflammatory disease of the supporting
structures of the teeth. DM and ASCVD might, due to their pro-inflammatory
state and alteration of the immune system, contribute to the onset and/or
progression of periodontitis. Therefore periodontitis could be considered as an
early sign of an underlying vascular and/or metabolic pathology.

Some studies have also reported a positive association between periodontitis
and MetS. The MetS prevalence in patients with periodontitis was shown to be
higher than controls and MetS showed to be associated with severe
periodontitis. The association between periodontitis and OSAS is less
established, however there is some evidence to a plausible association between
periodontal disease and Obstructive Sleep Apnea (OSA).

Due to the broad overlap of objective biomarkers, in this study, subjects with
or without periodontitis will be screened for determining the prevalence of
(pre)DM, the 10-year-risk of ASCVD, the prevalence of MetS and the risk of
OSAS. The screening will be based on clinical measures, specific blood markers
determined by venipuncture or finger stick procedure and two questionnaires.

Notably, a recently published pilot paper from our research group presents the
feasibility and preliminary results of proposed screening for (pre)DM; we found
18.1% new DM cases among subjects with severe periodontitis compared to 9.9% in
mild/moderate periodontitis and 8.5% in controls.

Besides blood, also a 30 seconds mouth rinse can be used to measure for DM,
ASCVD and MetS biomarkers in patients with periodontitis and controls. Because
the majority of dental offices may not be keen on applying the finger stick,
the use of biochemical markers in a simple, non-invasive, rapid (30-sec) mouth
rinse may be an alternative and feasible approach for screening of biochemical
markers during a dental visit.

From the same mouth rinse also the oral microbiome can be assessed. The
microbial composition in various ecological niches of the body is now regarded
indicative for the functioning of the individual*s health. If the oral
microbiome reflects a disease pattern or *finger print*, it can be very useful
to make a distinction between normal and diseased oral microbiomes. The focus
of our study is the early detection of DM and ASCVD, and therefore, also
knowledge about the oral microbiome is an essential research target. In this
study, we can assess the oral microbiome relatively simple from the mouth rinse
and we will correlate this to clinical and biochemical measurements. New
knowledge obtained will help in designing further steps to obtain a normal and
functional oral microbiome in relation to the important systemic diseases such
as DM, ASCVD and MetS.

After screening for above mentioned diseases, the periodontitis patients will
be approached again during a follow-up to investigate whether they indeed
visited their general practitioner if they were advised to do so. Also we will
explore the variation in periodontal treatment outcomes and whether or not
these are affected by the obtained patterns of biochemical markers (from blood
analyses and oral rinse samples) and oral microbiome signatures (from oral
rinse samples).

The aim of the proposed study is to screen for (pre)DM, an increased
10-year-risk of ASCVD, MetS and a high risk of OSAS in subjects with and
without periodontitis. Consequently, the dental office will be evaluated as a
suitable location for early detection of these diseases.

Cross-sectional and follow-up study

- The extra burden for the patients and control subjects will be two
questionnaires, measurement of blood pressure, weight, waist and neck
circumference, venipuncture or finger stick procedure and an oral rinse of 30
seconds.
- The risks associated with participation are negligible.
- Possible benefit of participation will be early detection of health risks
such as (pre)DM, ASCVD, MetS, OSAS and possibly a referral for further
diagnosis and/or treatment at the family physician.