Oral Endocannabinoids in People With Prediabetes and Diabetes

NCT06040164 | Unknown

• 1 other identifier: SMILE
• Study Type: observational
• Target: 60
• Locations: 0 countries
• Sites: N/A

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

Conditions

PreDiabetes; Diabetes Mellitus, Type 2; Obesity; Oral Dysbiosis; Mouth Disease

Keywords

Endocannabinoids; Prediabetes; Diabetes Mellitus Type 2; Obesity; Oral Dysbiosis; Oral Disease; Cannabinoids

Outcome Measures

Primary Outcomes (7)

• 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

Secondary Outcomes (31)

• Change in interleukin-1β levels in saliva and plasma

  Basal

• Change in interleukin-6 levels in saliva and plasma

  Basal

• Change in interleukin-8 levels in saliva and plasma

  Basal

• Change in interleukin-10 levels in saliva and plasma

  Basal

• Change in interleukin-17 levels in saliva and plasma

  Basal

Study Arms (4)

Ob/Pre/H

obesity, prediabetes and healthy mouth

Other: Observational study

Ob/Pre/OCD

obesity, prediabetes and oral cavity disease

Other: Observational study

Ob/Diab/H

obesity, diabetes and healthy mouth

Other: Observational study

Ob/Diab/OCD

obesity, diabetes and oral cavity disease

Other: Observational study

Interventions

Observational study OTHER

No intervention will be performed

Ob/Diab/H; Ob/Diab/OCD; Ob/Pre/H; Ob/Pre/OCD

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

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.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud: lead

Related Publications (30)

• 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

  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.

  PMID: 3056758 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.

  PMID: 23418299 BACKGROUND

• Tavares RDCR, Ortigara GB, Tatsch KF, Ferreira CM, Boligon J, Moreira CHC. Association between periodontitis and glycated hemoglobin levels in individuals living in rural Southern Brazil. Clin Oral Investig. 2021 Dec;25(12):6901-6907. doi: 10.1007/s00784-021-03980-y. Epub 2021 May 31.

  PMID: 34059955 BACKGROUND

• Kriebel K, Hieke C, Muller-Hilke B, Nakata M, Kreikemeyer B. Oral Biofilms from Symbiotic to Pathogenic Interactions and Associated Disease -Connection of Periodontitis and Rheumatic Arthritis by Peptidylarginine Deiminase. Front Microbiol. 2018 Jan 30;9:53. doi: 10.3389/fmicb.2018.00053. eCollection 2018.

  PMID: 29441048 BACKGROUND

• Canepari P, Zerman N, Cavalleri G. Lack of correlation between salivary Streptococcus mutans and lactobacilli counts and caries in IDDM children. Minerva Stomatol. 1994 Nov;43(11):501-5.

  PMID: 7739481 BACKGROUND

• Estrich CG, Araujo MWB, Lipman RD. Prediabetes and Diabetes Screening in Dental Care Settings: NHANES 2013 to 2016. JDR Clin Trans Res. 2019 Jan;4(1):76-85. doi: 10.1177/2380084418798818. Epub 2018 Sep 6.

  PMID: 30596147 BACKGROUND

• Kocher T, Holtfreter B, Petersmann A, Eickholz P, Hoffmann T, Kaner D, Kim TS, Meyle J, Schlagenhauf U, Doering S, Gravemeier M, Prior K, Rathmann W, Harks I, Ehmke B, Koch R. Effect of Periodontal Treatment on HbA1c among Patients with Prediabetes. J Dent Res. 2019 Feb;98(2):171-179. doi: 10.1177/0022034518804185. Epub 2018 Oct 16.

  PMID: 30326764 BACKGROUND

• Artur C, Otto-Buczkowska E (2014) Oral Health Problems among Diabetic Patients - Part of Dental Professionals in Diagnostic and Therapy. J Oral Hyg Health 2:167. doi:10.4172/2332-0702.1000167

  BACKGROUND

• Di Marzo V, Silvestri C. Lifestyle and Metabolic Syndrome: Contribution of the Endocannabinoidome. Nutrients. 2019 Aug 20;11(8):1956. doi: 10.3390/nu11081956.

  PMID: 31434293 BACKGROUND

• Gatta-Cherifi B, Cota D. New insights on the role of the endocannabinoid system in the regulation of energy balance. Int J Obes (Lond). 2016 Feb;40(2):210-9. doi: 10.1038/ijo.2015.179. Epub 2015 Sep 16.

  PMID: 26374449 BACKGROUND

• Bermudez-Silva FJ, Cardinal P, Cota D. The role of the endocannabinoid system in the neuroendocrine regulation of energy balance. J Psychopharmacol. 2012 Jan;26(1):114-24. doi: 10.1177/0269881111408458. Epub 2011 Aug 8.

  PMID: 21824982 BACKGROUND

• Di Marzo V. New approaches and challenges to targeting the endocannabinoid system. Nat Rev Drug Discov. 2018 Sep;17(9):623-639. doi: 10.1038/nrd.2018.115. Epub 2018 Aug 17.

  PMID: 30116049 BACKGROUND

• Hillard CJ. Circulating Endocannabinoids: From Whence Do They Come and Where are They Going? Neuropsychopharmacology. 2018 Jan;43(1):155-172. doi: 10.1038/npp.2017.130. Epub 2017 Jun 27.

  PMID: 28653665 BACKGROUND

• Fabio Arturo, Iannotti and Fabiana, Piscitelli (November 2018)Endocannabinoidome. In: eLS. John Wiley & Sons, Ltd:Chichester.DOI: 10.1002/9780470015902.a0028301

  BACKGROUND

• Davis, M.P. (2022). Overview of the Endocannabinoid System and Endocannabinoidome. In: Cannabis and Cannabinoid-Based Medicines in Cancer Care. Springer, Cham. https://doi.org/10.1007/978-3-030-89918-9_1

  BACKGROUND

• Cani PD, Plovier H, Van Hul M, Geurts L, Delzenne NM, Druart C, Everard A. Endocannabinoids--at the crossroads between the gut microbiota and host metabolism. Nat Rev Endocrinol. 2016 Mar;12(3):133-43. doi: 10.1038/nrendo.2015.211. Epub 2015 Dec 18.

  PMID: 26678807 BACKGROUND

• Romero-Zerbo SY, Bermudez-Silva FJ. Cannabinoids, eating behaviour, and energy homeostasis. Drug Test Anal. 2014 Jan-Feb;6(1-2):52-8. doi: 10.1002/dta.1594. Epub 2013 Dec 26.

  PMID: 24375977 BACKGROUND

• Lalla E, Papapanou PN. Diabetes mellitus and periodontitis: a tale of two common interrelated diseases. Nat Rev Endocrinol. 2011 Jun 28;7(12):738-48. doi: 10.1038/nrendo.2011.106.

  PMID: 21709707 BACKGROUND

• Sanz M, Ceriello A, Buysschaert M, Chapple I, Demmer RT, Graziani F, Herrera D, Jepsen S, Lione L, Madianos P, Mathur M, Montanya E, Shapira L, Tonetti M, Vegh D. Scientific evidence on the links between periodontal diseases and diabetes: Consensus report and guidelines of the joint workshop on periodontal diseases and diabetes by the International Diabetes Federation and the European Federation of Periodontology. J Clin Periodontol. 2018 Feb;45(2):138-149. doi: 10.1111/jcpe.12808. Epub 2017 Dec 26.

  PMID: 29280174 BACKGROUND

• Rohani B. Oral manifestations in patients with diabetes mellitus. World J Diabetes. 2019 Sep 15;10(9):485-489. doi: 10.4239/wjd.v10.i9.485.

  PMID: 31558983 BACKGROUND

• Thorstensson H, Dahlen G, Hugoson A. Some suspected periodontopathogens and serum antibody response in adult long-duration insulin-dependent diabetics. J Clin Periodontol. 1995 Jun;22(6):449-58. doi: 10.1111/j.1600-051x.1995.tb00176.x.

  PMID: 7560223 BACKGROUND

• Takahashi K, Nishimura F, Kurihara M, Iwamoto Y, Takashiba S, Miyata T, Murayama Y. Subgingival microflora and antibody responses against periodontal bacteria of young Japanese patients with type 1 diabetes mellitus. J Int Acad Periodontol. 2001 Oct;3(4):104-11.

  PMID: 12666949 BACKGROUND

• Prestifilippo JP, Fernandez-Solari J, de la Cal C, Iribarne M, Suburo AM, Rettori V, McCann SM, Elverdin JC. Inhibition of salivary secretion by activation of cannabinoid receptors. Exp Biol Med (Maywood). 2006 Sep;231(8):1421-9. doi: 10.1177/153537020623100816.

  PMID: 16946411 BACKGROUND

• Matias I, Gatta-Cherifi B, Tabarin A, Clark S, Leste-Lasserre T, Marsicano G, Piazza PV, Cota D. Endocannabinoids measurement in human saliva as potential biomarker of obesity. PLoS One. 2012;7(7):e42399. doi: 10.1371/journal.pone.0042399. Epub 2012 Jul 31.

  PMID: 22860123 BACKGROUND

• Piscitelli F, Di Marzo V. "Redundancy" of endocannabinoid inactivation: new challenges and opportunities for pain control. ACS Chem Neurosci. 2012 May 16;3(5):356-63. doi: 10.1021/cn300015x. Epub 2012 Feb 27.

  PMID: 22860203 BACKGROUND

• Andreis K, Billingsley J, Naimi Shirazi K, Wager-Miller J, Johnson C, Bradshaw H, Straiker A. Cannabinoid CB1 receptors regulate salivation. Sci Rep. 2022 Aug 19;12(1):14182. doi: 10.1038/s41598-022-17987-2.

  PMID: 35986066 BACKGROUND

• Oral health. Global Burden of Disease Study 2019. Published 2019. Accessed September 30, 2022. https://www.who.int/news-room/fact-sheets/detail/oral-health

  BACKGROUND

• Ramfjord SP. The Periodontal Disease Index (PDI). J Periodontol. 1967 Nov-Dec;38(6):Suppl:602-10. doi: 10.1902/jop.1967.38.6.602. No abstract available.

  PMID: 5237683 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

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.

MeSH Terms

Conditions

Prediabetic State; Diabetes Mellitus, Type 2; Obesity; Mouth Diseases

Interventions

Observation

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Stomatognathic Diseases

Intervention Hierarchy (Ancestors)

Methods; Investigative Techniques

Study Officials

• Francisco J Bermúdez-Silva, PhD

  Hospital Regional Universitario de Málaga - FIMABIS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

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

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2023
• First Posted: September 15, 2023
• Study Start: October 1, 2023
• Primary Completion: June 30, 2024
• Study Completion: December 31, 2024
• Last Updated: September 15, 2023

Record last verified: 2023-03