Obesity and Oral Diseases in Adult Patients

Overview

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.