Oral Endocannabinoids in People With Prediabetes and Diabetes
- Conditions
- ObesityPreDiabetesDiabetes Mellitus, Type 2Oral DysbiosisMouth Disease
- Interventions
- Other: Observational study
- Registration Number
- NCT06040164
- Lead Sponsor
- Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud
- Brief Summary
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
- Detailed Description
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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 60
- Adults, both sexes (40-65 years)
- With obesity and prediabetes: BMI 30-40 and HbA1c 5.7-6.4
- With obesity and diabetes: BMI 30-40 and previous diagnosis of diabetes
- Pregnant women
- Diagnosis of some type of neoplasia or treated with radiotherapy and/or chemotherapy in the last year.
- Ongoing inflammatory diseases (Crohn's disease, ulcerative colitis, arthritis, etc.) and/or anti-inflammatory treatments
- Presence of systemic diseases of vital organs
- Participants in treatment with drugs that could alter salivary flow
- Smokers
- Participants who have not followed the specifications prior to sampling
- Participants who did not sign the informed consent
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Ob/Diab/OCD Observational study obesity, diabetes and oral cavity disease Ob/Pre/H Observational study obesity, prediabetes and healthy mouth Ob/Pre/OCD Observational study obesity, prediabetes and oral cavity disease Ob/Diab/H Observational study obesity, diabetes and healthy mouth
- Primary Outcome Measures
Name Time Method Change in N-palmitoylethanolamine (PEA) levels in saliva and plasma Basal Measured in pmol/ml
Change in N-palmitoylethanolamine (DHEA) levels in saliva and plasma Basal Measured in pmol/ml
Change in N-oleoylethanolamine (OEA) levels in saliva and plasma Basal Measured in pmol/ml
Change in 2-linoleoyl-glycerol (2-LG) levels in saliva and plasma Basal Measured in pmol/ml
Change in 2-arachidonoyl-glycerol (2-AG) levels in saliva and plasma Basal Measured in pmol/ml
Change in N-arachidonoylethanolamine (AEA) levels in saliva and plasma Basal Measured in pmol/ml
Change in 2-oleoyl-glycerol (2-OG) levels in saliva and plasma Basal Measured in pmol/ml
- Secondary Outcome Measures
Name Time Method Change in interleukin-8 levels in saliva and plasma Basal Measured in pmol/ml
Change in interleukin-10 levels in saliva and plasma Basal Measured in pmol/ml
Change in interleukin-17 levels in saliva and plasma Basal Measured in pmol/ml
Change in Interferon gamma (IFN)-γ levels in saliva and plasma Basal Measured in pmol/ml
Changes from baseline QUICKY levels Basal QUICKY = 1 / (log(fasting insulin μU/mL) + log(fasting glucose mg/dL))
Change in leptin levels in saliva and plasma Basal Measured in pmol/ml
Change in vascular endothelial growth factor (VEGF) levels in saliva and plasma Basal Measured in pmol/ml
Changes in blood pressure Basal Measured in mmHg
Oral health impact profile Basal 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.
Changes in oral bacteriological profile Basal 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.
Changes from baseline HOMA2-IR levels Basal 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.
Changes from baseline HOMA2%S levels Basal Measured in %
Changes in sialometry Basal Measured in mL/min
Changes in waist circumference Basal Measured in cm
Changes in total cholesterol Basal Measured in mg/dL
Changes in LDL cholesterol Basal Measured in mg/dL
Change in interleukin-1β levels in saliva and plasma Basal Measured in pmol/ml
Changes in Fasting glucose levels Basal Measured in mg/dl
BMI (body mass index) changes Basal Calculated as weight ⁄ height (kg/m2)
Changes in waist/height ratio Basal Calculated as waist measurement (cm) divided by height measurement (cm), (W/He)
Changes in triglycerides Basal Measured in mg/dL
Changes in HDL cholesterol Basal Measured in mg/dL
Changes from baseline HbA1c levels Basal Measured in %
Change in interleukin-6 levels in saliva and plasma Basal Measured in pmol/ml
Change in Tumor necrosis factor alpha (TNF)-α levels in saliva and plasma Basal Measured in pmol/ml
Changes in insulin levels Basal Measured in mUI/mL
Changes from baseline HOMA-IR levels Basal HOMA-IR = \[blood insulin (mu/L) × Blood glucose (mmol/L)\]/22.5
Changes from baseline HOMA2%B levels Basal Measured in %
Changes in waist/hip ratio Basal Calculated as waist measurement (cm) divided by hip measurement (cm) (W⁄H)
Changes in salivary viscosity Basal Measured in poise (1 g·(s·cm)-1)
Changes in salivary pH Basal Logarithm of hydrogen ion concentration