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This study evaluates the relationship of endocannabinoids in saliva with inflammation and oral dysbacteriosis present in people with periodontal disease and prediabetes/type 2 diabetes
Diabetes is a disease that affects millions of people worldwide, and the number of cases is expected to continue to increase in the coming years. Type 2 diabetes (T2D) is the most common form of diabetes and is closely related to prediabetes, a condition in which blood glucose levels are high but not high enough to be diagnosed as diabetes. Both prediabetes and T2D increase the risk of cardiovascular disease and are also associated with diseases of the oral cavity, such as dental caries and periodontal disease. The presence of pathogenic bacteria in the mouth has been linked to these diseases. The endocannabinoid system, a signaling system in the body that regulates various biological processes, has been found to play an important role in energy homeostasis and is implicated in obesity, prediabetes, and T2D. This study seeks to investigate the role of endocannabinoids and related lipids in diseases of the oral cavity in the context of prediabetes and T2D. A bidirectional relationship has been observed between periodontitis and T2D, with inflammation playing a central role in both diseases. Although subtle differences in the microbial composition of the mouth have been identified in people with diabetes, the exact mechanisms remain unclear. Our findings could open up a promising line of research on the therapeutic potential of cannabinoid drugs for the treatment of this type of complications in people with prediabetes/T2D.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ob/Pre/H | obesity, prediabetes and healthy mouth |
| |
| Ob/Pre/OCD | obesity, prediabetes and oral cavity disease |
| |
| Ob/Diab/H | obesity, diabetes and healthy mouth |
| |
| Ob/Diab/OCD | obesity, diabetes and oral cavity disease |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Observational study | Other | No intervention will be performed |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in 2-arachidonoyl-glycerol (2-AG) levels in saliva and plasma | Measured in pmol/ml | Basal |
| Change in N-arachidonoylethanolamine (AEA) levels in saliva and plasma | Measured in pmol/ml | Basal |
| Change in N-palmitoylethanolamine (PEA) levels in saliva and plasma | Measured in pmol/ml | Basal |
| Change in N-oleoylethanolamine (OEA) levels in saliva and plasma | Measured in pmol/ml | Basal |
| Change in N-palmitoylethanolamine (DHEA) levels in saliva and plasma | Measured in pmol/ml | Basal |
| Change in 2-linoleoyl-glycerol (2-LG) levels in saliva and plasma | Measured in pmol/ml | Basal |
| Change in 2-oleoyl-glycerol (2-OG) levels in saliva and plasma | Measured in pmol/ml | Basal |
| Measure | Description | Time Frame |
|---|---|---|
| Change in interleukin-1β levels in saliva and plasma | Measured in pmol/ml | Basal |
| Change in interleukin-6 levels in saliva and plasma | Measured in pmol/ml |
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Inclusion Criteria:
Exclusion Criteria:
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The patients to enroll will come from three clinical studies led by our unit: The Pizarra study, an epidemiological study of the Endocrinology and Nutrition unit of the Regional Hospital of Malaga that has provided detailed information on anthropometric and biochemical parameters, eating habits and lifestyle in a cohort of about 1700 subjects; the di@bet.es study, a national epidemiological study carried out on a sample of more than 5,000 people; and the April study, a nutritional intervention study in people with obesity and prediabetes. In addition, the obesity databases of the Endocrinology and Nutrition unit of the Regional Hospital of Malaga will also be used.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Rodolfo M Ortiz Flores, PhD | Contact | 951 29 03 43 / 951 03 01 17 | rodolfo.ortiz@ibima.eu | |
| Francisco J Bermúdez-Silva, PhD | Contact | 951 29 03 43 / 951 03 01 17 | javier.bermudez@ibima.eu |
| Name | Affiliation | Role |
|---|---|---|
| Francisco J Bermúdez-Silva, PhD | Hospital Regional Universitario de Málaga - FIMABIS | Principal Investigator |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| Background | IDF Diabetes Atlas 10th edition. Accessed September 29, 2022. www.diabetesatlas.org | ||
| Background | Aleixandre MA, Miguel M. Síndrome metabólico. Endocrinologia y Nutricion. 2007;54(9). doi:10.1016/S1575-0922(07)71487-0 | ||
| 3056758 | Background | Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988 Dec;37(12):1595-607. doi: 10.2337/diab.37.12.1595. | |
| 23418299 |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 29, 2023 | Sep 7, 2023 | Prot_000.pdf |
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| ID | Term |
|---|---|
| D011236 | Prediabetic State |
| D003924 | Diabetes Mellitus, Type 2 |
| D009765 | Obesity |
| D009059 | Mouth Diseases |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D019370 | Observation |
| ID | Term |
|---|---|
| D008722 | Methods |
| D008919 | Investigative Techniques |
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Saliva samples will be collected under resting conditions using the passive drooling method, in 15 mL tubes, every 1 min, for 5 min in the same tube. Along with the saliva samples, trained personnel will collect 9 ml of blood samples, under resting conditions, in ethylenediaminetetraacetic acid (EDTA) tubes.
| Basal |
| Change in interleukin-8 levels in saliva and plasma | Measured in pmol/ml | Basal |
| Change in interleukin-10 levels in saliva and plasma | Measured in pmol/ml | Basal |
| Change in interleukin-17 levels in saliva and plasma | Measured in pmol/ml | Basal |
| Change in leptin levels in saliva and plasma | Measured in pmol/ml | Basal |
| Change in vascular endothelial growth factor (VEGF) levels in saliva and plasma | Measured in pmol/ml | Basal |
| Change in Interferon gamma (IFN)-γ levels in saliva and plasma | Measured in pmol/ml | Basal |
| Change in Tumor necrosis factor alpha (TNF)-α levels in saliva and plasma | Measured in pmol/ml | Basal |
| Changes in oral bacteriological profile | Bacterial 16S rRNA amplicon of the following bacterial strains: Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Prevotella intermedia, Fusobacterium nucleatum, Parvimonas micra, Campylobacter rectus, Eikenella corroe, Veillonella parvula and Actinomyces naeslundii for periodontal disease; and Streptococcus mutans, S. sanguis, S. mitior, S. salivarius and S. milleri for dental caries. Unit of Measurement: Fold-increase over reference genes, delta-delta Ct method. | Basal |
| Changes in Fasting glucose levels | Measured in mg/dl | Basal |
| Changes in insulin levels | Measured in mUI/mL | Basal |
| Changes from baseline HOMA-IR levels | HOMA-IR = [blood insulin (mu/L) × Blood glucose (mmol/L)]/22.5 | Basal |
| Changes from baseline HOMA2-IR levels | The homeostasis model assessment computational method is used to estimate insulin resistance (HOMA2-IR) from fasting plasma glucose and insulin. The HOMA2-IR is the reciprocal of insulin sensitivity (%S), as a percentage of a normal reference population (normal young adult). A higher score indicates a lower insulin sensitivity. | Basal |
| Changes from baseline HOMA2%S levels | Measured in % | Basal |
| Changes from baseline HOMA2%B levels | Measured in % | Basal |
| Changes from baseline QUICKY levels | QUICKY = 1 / (log(fasting insulin μU/mL) + log(fasting glucose mg/dL)) | Basal |
| Changes from baseline HbA1c levels | Measured in % | Basal |
| BMI (body mass index) changes | Calculated as weight ⁄ height (kg/m2) | Basal |
| Changes in waist circumference | Measured in cm | Basal |
| Changes in waist/hip ratio | Calculated as waist measurement (cm) divided by hip measurement (cm) (W⁄H) | Basal |
| Changes in waist/height ratio | Calculated as waist measurement (cm) divided by height measurement (cm), (W/He) | Basal |
| Changes in blood pressure | Measured in mmHg | Basal |
| Changes in triglycerides | Measured in mg/dL | Basal |
| Changes in total cholesterol | Measured in mg/dL | Basal |
| Changes in HDL cholesterol | Measured in mg/dL | Basal |
| Changes in LDL cholesterol | Measured in mg/dL | Basal |
| Changes in sialometry | Measured in mL/min | Basal |
| Changes in salivary viscosity | Measured in poise (1 g·(s·cm)-1) | Basal |
| Changes in salivary pH | Logarithm of hydrogen ion concentration | Basal |
| Oral health impact profile | The Oral Health Impact Profile will be assessed by using the OHIP-14sp questionnaire, which is one of the most internationally spread indicators of oral health-related quality of life and it is used to measure the impact of oral conditions on quality of life to complement clinical data in cross-sectional and longitudinal studies. The OHIP-14 is a self-filled questionnaire that focuses on seven dimensions of impact (functional limitation, pain, psychological discomfort, physical disability, psychological disability, social disability and handicap) with participants being asked to respond according to frequency of impact on a 5-point Likert scale coded never (score 0), hardly ever (score 1), occasionally (score2), fairly often (score 3) and very often (score 4) using a twelve-months recall period. | Basal |
| Background |
| Bissett SM, Stone KM, Rapley T, Preshaw PM. An exploratory qualitative interview study about collaboration between medicine and dentistry in relation to diabetes management. BMJ Open. 2013 Feb 14;3(2):e002192. doi: 10.1136/bmjopen-2012-002192. Print 2013. |
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| D004700 | Endocrine System Diseases |
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009057 | Stomatognathic Diseases |