SMILE: Oral Endocannabinoids in People With Prediabetes and Diabetes

Sponsor

Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06040164

Collaborator

(none)

Enrollment

Anticipated Duration (Months)

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
PreDiabetes Diabetes Mellitus, Type 2 Obesity Oral Dysbiosis Mouth Disease	Other: Observational study

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

60 participants

Observational Model:

Case-Only

Time Perspective:

Cross-Sectional

Official Title:

Molecular Study of Oral Dysbacteriosis in People With Prediabetes and Diabetes

Anticipated Study Start Date :

Oct 1, 2023

Anticipated Primary Completion Date :

Jun 30, 2024

Anticipated Study Completion Date :

Dec 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Ob/Pre/H obesity, prediabetes and healthy mouth	Other: Observational study No intervention will be performed
Ob/Pre/OCD obesity, prediabetes and oral cavity disease	Other: Observational study No intervention will be performed
Ob/Diab/H obesity, diabetes and healthy mouth	Other: Observational study No intervention will be performed
Ob/Diab/OCD obesity, diabetes and oral cavity disease	Other: Observational study No intervention will be performed

Outcome Measures

Primary Outcome Measures

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 N-palmitoylethanolamine (PEA) 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 N-palmitoylethanolamine (DHEA) 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-oleoyl-glycerol (2-OG) levels in saliva and plasma [Basal]
Measured in pmol/ml

Secondary Outcome Measures

Change in interleukin-1β levels in saliva and plasma [Basal]
Measured in pmol/ml
Change in interleukin-6 levels in saliva and plasma [Basal]
Measured in pmol/ml
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 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
Change in Interferon gamma (IFN)-γ 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 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 in Fasting glucose levels [Basal]
Measured in mg/dl
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-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 from baseline HOMA2%B levels [Basal]
Measured in %
Changes from baseline QUICKY levels [Basal]
QUICKY = 1 / (log(fasting insulin μU/mL) + log(fasting glucose mg/dL))
Changes from baseline HbA1c levels [Basal]
Measured in %
BMI (body mass index) changes [Basal]
Calculated as weight ⁄ height (kg/m2)
Changes in waist circumference [Basal]
Measured in cm
Changes in waist/hip ratio [Basal]
Calculated as waist measurement (cm) divided by hip measurement (cm) (W⁄H)
Changes in waist/height ratio [Basal]
Calculated as waist measurement (cm) divided by height measurement (cm), (W/He)
Changes in blood pressure [Basal]
Measured in mmHg
Changes in triglycerides [Basal]
Measured in mg/dL
Changes in total cholesterol [Basal]
Measured in mg/dL
Changes in HDL cholesterol [Basal]
Measured in mg/dL
Changes in LDL cholesterol [Basal]
Measured in mg/dL
Changes in sialometry [Basal]
Measured in mL/min
Changes in salivary viscosity [Basal]
Measured in poise (1 g·(s·cm)-1)
Changes in salivary pH [Basal]
Logarithm of hydrogen ion concentration
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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