Omega-3 to Reduce Diabetes Risk in Subjects With High Number of Particles That Carry "Bad Cholesterol" in the Blood

NCT04496154 | Completed

• 2 other identifiers: 2013-14 and 2014-756NUT273741
• Study Type: interventional
• Target: 41
• Locations: 0 countries
• Sites: N/A

Brief Summary

In this project, investigators explored the role of the particles that carry "bad cholesterol" in the blood (termed LDL) that are known to promote heart disease, in the promotion of type 2 diabetes (T2D) in humans. In specific, they investigated how these particles may induce the activation of an immune pathway in human fat tissue leading to multiple anomalies that favors T2D. They also explored whether omega-3 fatty acids, which are the type of fat found in fish oils can counterbalance the negative effects of LDL in fat tissue, thus providing a natural way to help reduce the risk for T2D in subjects with elevated blood LDL. To do so, 41 subjects who were free of disease or medication affecting metabolism were enrolled at the Montreal Clinical Research Institute between 2013 and 2019 and were placed on an intervention with omega-3 fatty acids supplementation for 12 weeks (2.7 g/day, Triple Strength Omega-3 from Webbers Naturals). Investigators examined the effects of LDL and omega-3 on risk factors for T2D before and after the intervention in the whole body and specifically in fat tissue biopsies taken from the hip region. Eighty percent of the subjects who were enrolled into the study completed the intervention.

Conditions

Type 2 Diabetes; Insulin Sensitivity/Resistance; Inflammatory Response; Fatty Acids, Omega-3

Keywords

HyperapoB; ApoB-lipoproteins; White adipose tissue; NLRP3 inflammasome; Fat metabolism; Insulin sensitivity and secretion; Systemic inflammation; Eicosapentaenoic acid (EPA); Docosahexaenoic acid (DHA)

Outcome Measures

Primary Outcomes (2)

• Fasting WAT IL-1β secretion

  Accumulation of IL-1β in WAT medium ex vivo (by AlphaLISA)

  Baseline

• Fasting WAT IL-1β secretion

  Accumulation of IL-1β in WAT medium ex vivo (by AlphaLISA)

  At 12-weeks post-intervention

Secondary Outcomes (8)

• WAT function and inflammation

  Baseline

• WAT function and inflammation

  Change at 12 weeks from baseline

• Postprandial fat metabolism

  Baseline

• Postprandial fat metabolism

  Change at 12 weeks from baseline

• Systemic inflammation

  Baseline

Other Outcomes (5)

• Plasma and red blood cells phospholipid fatty acid profile to assess compliance

  Baseline

• Plasma and red blood cells phospholipid fatty acid profile to assess compliance

  Change at 12 weeks from baseline

• Subject phenotyping

  Baseline

Study Arms (1)

Omega-3 fatty acids

EXPERIMENTAL

3 oral softgels (600 mg EPA and 300 mg DHA / softgel), Triple Strength Omega-3 from Webber Naturals

Dietary Supplement: Omega-3 fatty acids (2.7 g/d, EPA:DHA, 2:1)

Interventions

Omega-3 fatty acids (2.7 g/d, EPA:DHA, 2:1) DIETARY_SUPPLEMENT

Triple Strength Omega-3 from Webber Naturals

Omega-3 fatty acids

Eligibility Criteria

• Age: 45 Years - 74 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and post-menopausal women:
• Having a body mass index (BMI) \> 20 kg/m2
• Aged between 45 and 74 years
• Having confirmed menopausal status (FSH ≥ 30 U/l)
• Non-smoker
• Sedentary (less than 2 hours of structured physical exercise (ex: sports club) per week)
• Low alcohol consumption: less than 2 alcoholic drinks/day

You may not qualify if:

• Subjects with elevated risk of cardiovascular disease (≥ 20% of calculated Framingham Risk Score) who require immediate medical intervention by lipid-lowering agents OR who cannot be placed on a 4 weeks wash-out period from their lipid-lowering medication at screening (i.e. upon admission to IRCM clinic).
• Subjects with systolic blood pressure \> 160 mmHg or diastolic blood pressure \> 100 mmHg
• Prior history of cardiovascular events (like stroke, transient ischemic attack, myocardial infarction, angina, heart failure...)
• Prior history of cancer within the last 3 years
• Thyroid disease - untreated
• Type 1 or 2 diabetes or fasting glucose \> 7.0 mmol/L
• Claustrophobia
• Anemia - Hb \< 120 g/L
• Creatinine \> 100 μmol/L
• Hepatic dysfunction - AST/ALT \> 3 times normal limit
• Blood coagulation problems (i.e. bleeding predisposition)
• Autoimmune diseases
• Chronic inflammatory diseases
• Concomitant medications
• Hormone replacement therapy (except thyroid hormone at a stable dose)

Sponsors & Collaborators

• May Faraj, PDt, PhD: lead
• Canadian Institutes of Health Research (CIHR): collaborator

Related Publications (8)

• Lamantia V, Bissonnette S, Wassef H, Cyr Y, Baass A, Dufour R, Rabasa-Lhoret R, Faraj M. ApoB-lipoproteins and dysfunctional white adipose tissue: Relation to risk factors for type 2 diabetes in humans. J Clin Lipidol. 2017 Jan-Feb;11(1):34-45.e2. doi: 10.1016/j.jacl.2016.09.013. Epub 2016 Oct 3.

  PMID: 28391908 BACKGROUND

• Bissonnette S, Saint-Pierre N, Lamantia V, Cyr Y, Wassef H, Faraj M. Plasma IL-1Ra: linking hyperapoB to risk factors for type 2 diabetes independent of obesity in humans. Nutr Diabetes. 2015 Sep 28;5(9):e180. doi: 10.1038/nutd.2015.30.

  PMID: 26417659 BACKGROUND

• Lamantia V, Bissonnette S, Provost V, Devaux M, Cyr Y, Daneault C, Rosiers CD, Faraj M. The Association of Polyunsaturated Fatty Acid delta-5-Desaturase Activity with Risk Factors for Type 2 Diabetes Is Dependent on Plasma ApoB-Lipoproteins in Overweight and Obese Adults. J Nutr. 2019 Jan 1;149(1):57-67. doi: 10.1093/jn/nxy238.

  PMID: 30535058 BACKGROUND

• Skeldon AM, Faraj M, Saleh M. Caspases and inflammasomes in metabolic inflammation. Immunol Cell Biol. 2014 Apr;92(4):304-13. doi: 10.1038/icb.2014.5. Epub 2014 Feb 11.

  PMID: 24518981 BACKGROUND

• Lamantia V, Sniderman A, Faraj M. Nutritional management of hyperapoB. Nutr Res Rev. 2016 Dec;29(2):202-233. doi: 10.1017/S0954422416000147. Epub 2016 Nov 8.

  PMID: 27821191 BACKGROUND

• Faraj M. LDL, LDL receptors, and PCSK9 as modulators of the risk for type 2 diabetes: a focus on white adipose tissue. J Biomed Res. 2020 Mar 12;34(4):251-259. doi: 10.7555/JBR.34.20190124.

  PMID: 32701068 BACKGROUND

• Bissonnette S, Lamantia V, Ouimet B, Cyr Y, Devaux M, Rabasa-Lhoret R, Chretien M, Saleh M, Faraj M. Native low-density lipoproteins are priming signals of the NLRP3 inflammasome/interleukin-1beta pathway in human adipose tissue and macrophages. Sci Rep. 2023 Nov 1;13(1):18848. doi: 10.1038/s41598-023-45870-1.

  PMID: 37914804 RESULT

• Lamantia V, Bissonnette S, Beaudry M, Cyr Y, Rosiers CD, Baass A, Faraj M. EPA and DHA inhibit LDL-induced upregulation of human adipose tissue NLRP3 inflammasome/IL-1beta pathway and its association with diabetes risk factors. Sci Rep. 2024 Nov 7;14(1):27146. doi: 10.1038/s41598-024-73672-6.

  PMID: 39511203 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Insulin Resistance

Interventions

Fatty Acids, Omega-3

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Dietary Fats, Unsaturated; Dietary Fats; Fats; Lipids; Fatty Acids, Unsaturated; Fatty Acids; Fish Oils; Oils

Study Officials

• May Faraj, PDt, PhD

  Montreal Clinical Research Institute/ University of Montreal

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 29, 2020
• First Posted: August 3, 2020
• Study Start: September 5, 2013
• Primary Completion: January 22, 2020
• Study Completion: February 24, 2020
• Last Updated: February 11, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share