Obesity and Oral Diseases in Adult Patients
Obesity and Oral Diseases in Adult Patients
Overweight and obesity are among the major chronic disorders of the 21st century and one of
 the fastest growing health problems worldwide. Obesity is accompanied by a state of low-grade
 inflammation which may contribute to the occurrence of diabetes mellitus, cardiovascular
 disease, hypertension, stroke, and certain cancers. Furthermore, obesity has been associated
 with oral health problems as hyposalivation, dental caries and periodontitis.

 The management and treatment of obesity is outlined in clinical guidelines from American
 Association of Clinical Endocrinologists/American College of Endocrinology and European
 Association for the Study of Obesity. The cornerstone is life-style modification programs
 aiming to reduce energy intake and increase physical activity, referred to as conservative
 treatment. All patients must undergo a thorough systematic work-up. The work-up concludes in
 a final multi-disciplinary meeting with a concrete individualized plan on how sustained
 weight-loss is to be achieved; either by a non-surgical or a surgical approach (Bariatric
 surgery).

 Periodontitis is cited to be the sixth most prevalent chronic condition globally. The
 mechanisms by which obesity affects the periodontal tissues is poorly understood, and the
 understanding of the key role of adipocytes in the inflammatory response to infections is
 crucial in comprehending how periodontal disease susceptibility may be modified in obese
 individuals.

 The main objectives of the present research project are to explore the association between
 obesity and oral diseases and further, to assess how weight changes following non-surgical
 and surgical interventions of obese patients may affect the cariological and periodontal
 health status.

 Four hundred patients referred to the Obesity Centre at Haukeland University Hospital, Norway
 will consecutively be screened and invited to participate in this prospective cohort study.
 At baseline, detailed medical and oral data will be obtained from health forms,
 questionnaires, clinical examinations, and by consulting the patient's care team. Following
 baseline examination, all patients will undergo a thorough systematic work-up consisting av
 interviews and consultations concluding in a final multi-disciplinary individualized
 non-surgical or surgical treatment plan on how sustained weight-loss can be achieved. New
 sets of medical, oral, and molecular data will be collected at 3-, 12- and 18-month following
 non-surgical/surgical interventions.
The management and treatment of obesity is outlined in clinical guidelines from American
 Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE),
 European Association for the Study of Obesity (EASO) and others. The cornerstone is
 life-style modification programs aiming to reduce energy intake and increase physical
 activity, often referred to as conservative treatment. In recent years, pharmacological
 management to achieve weight loss is increasingly used as effective drugs become available.
 Conservative treatment generally targets to induce long-term weight loss of 5-10%. The
 obesity treatment has wider objectives than weight loss alone by also including treatment of
 obesity-related comorbidities like diabetes mellitus, hypertension, dyslipidemia, and
 obstructive sleep apnea with the ultimate goals of improving quality of life, working ability
 and reduce mortality.

 Bariatric surgery is considered an effective and safe intervention for the treatment of
 obesity. Consistent with international consensus gastrointestinal surgery might be
 recommended for patients with extreme obesity (BMI ≥ 40 kg/m2) as well as for those with BMI
 ≥ 35 kg/m2 with significant comorbidities. The surgical procedures are usually performed
 laparoscopically, and includes sleeve gastrectomy, Roux-en-Y gastric bypass and
 biliopancreatic diversion with duodenal switch.

 Benefits of bariatric surgeries include significant weight loss, improved and remission of
 obesity-related comorbidities such as type 2 diabetes, hyperlipidemia, hypertension,
 cardiovascular disease, obstructive sleep apnea, anxiety, depression, and improved quality of
 life. Gastro esophageal reflux and vomiting in addition to increased intake of food and
 drinks have been reported as potential side effects. All these side effects are considered
 risk factors for the occurrence of dental caries and dental erosion, which may lead to
 decreased function and pain. Periodontitis is also reported to be more frequent in
 individuals who have undergone bariatric surgery probably related to nutritional deficiency
 secondary to the surgery.

 Periodontitis is a widespread chronic, inflammatory disease of the gingival tissues and
 alveolar bone triggered by oral biofilms. Since 2010, periodontitis is cited to be the sixth
 most prevalent chronic condition globally. The high prevalence of moderate/severe
 periodontitis may be attributed to multiple factors such as lifestyle, genetics, and medical
 care. Current knowledge recognizes adipose tissue as an endocrine organ in which adipocytes
 play an important role as inflammatory modulators, producing anti- and pro-inflammatory
 cytokines which regulate oral and systemic inflammation. In obese individuals, an imbalance
 may result in an increased expression of pro-inflammatory and reduction of anti-inflammatory
 adipokines, leading to the establishment of a chronic inflammatory status.

 Available data on obesity and oral diseases as well as the influence of non-surgical and
 surgical interventions on oral health are scarce, and several reports have published
 conflicting and inconsistent results. The main objectives of the present research project are
 to explore the association between obesity and oral diseases and assess how weight changes
 following non-surgical and surgical interventions may affect the cariological and periodontal
 health status.

 Pre-study protocols and tests. This cohort study will enroll patients in need for obesity
 therapy at Haukeland University Hospital, Bergen, Norway. The study protocol and informed
 consent, following the Helsinki Declaration of 1975, version 2008, has been submitted to the
 Medical Research Ethics Committee, University of Bergen, Norway (reference 152810). Each
 patient will read and sign the informed consent prior to inclusion in the study.

 Study subjects. Patients referred to the Obesity Centre at Haukeland University Hospital will
 consecutively be screened for eligibility from January 2021 through December 2021. Four
 hundred patients will be invited to participate in this prospective cohort study. At
 baseline, detailed medical and oral data will be obtained from health forms, questionnaires,
 clinical examinations (including weight and height registrations), and by consulting the
 patient's care team. Following baseline examination/registration, the patients will be
 allocated either to non-surgical or surgical interventions according to established medical
 guidelines. At 3-month control post-surgery, periodontal and cariological clinical data
 together with local and systemic molecular data will be obtained from each patient. The
 follow-up controls at 12 and 18 months will contain a complete set of data collection
 including medical, dental, and molecular parameters.

 Treatment. All patients will undergo a thorough systematic work-up. The first interview will
 be conducted by a trained nurse. Data regarding social and occupational situation, social
 network, daily activity levels, weight history, personal resources, and barriers to achieve
 sustained weight loss will be collected. The second consultation will be done by a physician,
 focusing on identifying and optimizing medical and psychiatric disorders. The third interview
 will be done by clinical nutritionist to assess eating habits. If needed, the patient will
 also be evaluated by a physiotherapist, psychologist and/or be referred to further
 investigations at the respiratory, cardiac, and orthopedic departments. The work-up concludes
 in a final multi-disciplinary meeting with a concrete individualized plan on how sustained
 weight-loss is to be achieved.

 Non-surgery group. In this group, included patients will be offered a standardized program
 comprised of individual consultations by a trained nurse every 3 months over 2 years.
 Furthermore, they will participate in a lifestyle course with 13 group sessions focusing on
 healthy diet and activity based on the recommendations of the Norwegian Directorate of
 Health. Other therapeutic options include pharmacotherapy to reduce weight (GLP1 analogues or
 naltrekson/bupropion) as well as treatment of comorbidities (diabetes mellitus, hypertension,
 dyslipidemia, sleep-apnea, etc.).

 Surgery group. After completing the systematic work-up and the lifestyle course, eligible
 subjects will be offered bariatric surgery. The surgical procedure will be chosen at the
 surgeon's discretion taking into consideration the target weight, comorbidities, risk of
 complications, the patient's ability to cope with side effects and complications, and the
 patient's motivation. Generally, sleeve gastrectomy has lower incidence of severe side
 effects compared with gastric bypass (Roux-en-Y gastric bypass) or mini-bypass but are less
 effective in terms of weight loss and amelioration of obesity-related comorbidities. After
 surgery, patients will be followed up at the outpatient clinic 2, 12, 24 months and 5 and 10
 years postoperatively.

 Periodontal diagnosis. Periodontitis will be diagnosed by using the criteria of World
 Workshop on the Classification of Periodontal and Peri-implant Diseases and Conditions.

 Smoking status. Smoking status will be registered as current, former, or never smoker.
 Self-reported smoking experience will be calculated in pack years; the number of cigarettes
 smoked daily multiplied by the number of years divided by 20 (a standard pack of cigarettes).
 In addition, smoking status will be objectively validated by measuring cotinine levels in
 serum.

 Medical examination. Data about current medications, past medical history including
 cardiovascular events, arterial hypertension, BMI, waist-to-hip ratio (WHR) and smoking habit
 will be collected. Glycated hemoglobin (HbA1c) will be measured by standard laboratory
 methods, whereas high-sensitivity C reactive protein (CRP) will be determined in serum by
 particle-enhanced immune-nephelometry (hsCRP kit, Dade Behring, Eschborn, Germany).

 Oral radiographs, and clinical periodontal and cariological examination. Before clinical
 examination, a full mouth series of intraoral radiographs will be taken. The following
 periodontal parameters will be registered at baseline and at 3, 12 and 18 months: PD as the
 distance in mm from the gingival margin to the probable base of the pocket at six sites; CAL
 as the distance in mm from the cementoenamel junction (CEJ) to the probable base of the
 pocket at six sites (PCP, UNC 15, Hu-Friedy, Chicago, IL, USA); full mouth dental plaque
 scores recorded as the percentage of tooth surfaces with visible plaque at the mesial,
 distal, buccal and lingual surfaces following staining with disclosing solution; full mouth
 bleeding on probing (BoP) as the presence of bleeding after gentle probing.

 A full mouth cariological examination including dental caries and dental erosion will be
 performed for the non-surgical and surgical group at baseline and at 12 and 18 months after
 bariatric surgery (matching timepoints for both groups). This will include radiographs
 (bitewings), intraoral photos and cast models made from tooth impressions. In combination
 with established indexes, these data will provide reliable measurements of the cariological
 disease status.

 Gingival crevicular fluid assessments and saliva analysis. Sample sites will be isolated with
 cottons rolls, carefully cleaned for supragingival plaque and air-dried. A perio paper strip
 will then be gently placed one to two mm into the entrance of the pocket and left in place
 for 30 seconds. For quantitative measurements, the perio paper will be inserted into the
 Periotron 8000® (Oraflow Inc, Smithtown, NY, USA), a previously calibrated instrument to
 measure the volume of fluid collected. Gingival crevicular fluid (GCF) volume will be
 measured at baseline and at 3, 12 and 18 months. Strips will be immediately inserted into
 separate and dry microtubes, labelled, and stored at 80°C until further analysis.

 Unstimulated salivary samples (5 mL) will be collected from each patient between 8 am and 10
 am. The patients will rinse their mouth with water 5 minutes before sample collection. The
 first saliva expectoration will be discarded to avoid food and any other substances capable
 of contaminating the sample to interfere with the results of the biochemical analyses. The
 patients will also be instructed to refrain from brushing their teeth and eating or drinking
 60 minutes before sample collection.

 In addition, pH of both unstimulated and paraffin-stimulated saliva samples will be measured,
 and a small aliquot of the stimulated saliva will be used to determine the buffer capacity.
 Saliva samplings and qualitative and quantitative analyzes will be performed at baseline and
 at 3, 12 and, 18 months follow-ups for both groups.

 Questionnaire. At baseline, a questionnaire including 27 multiple-choice questions will be
 distributed to the participants.

 Statistical analysis. The sociodemographic data of the patients will be described using
 descriptive statistics. Age, BMI, medical and oral parameters, and the amount of analyzed
 local and systemic biomarkers will be expressed as median and inter-quartile range (IQR). For
 the cross-sectional analysis, linear regression models and logistic regression models will be
 used to adjust for potential confounding factors. For analysis of differences over time
 between groups (e.g. operated versus non-operated patients) generalized estimation equations
 (linear and logistic models) will be performed, adjusting for potential confounding factors.
 Furthermore, as a causal approach, homogenous groups will be compared using propensity
 matched samples. The standard approach using regression models and the propensity score
 matching will furthermore be compared with analysis using inverse probability weighted
 models. Differences and changes will be considered significant with a two-sided p-value <
 0.05.
Inclusion Criteria:

 -  Obese adult patients.

 -  Patients referred to the Obesity Clinic at the Hospital.

 Exclusion Criteria:

 -  Unwillingness to participate.