Targeting Risk Factors for Diabetes in Subjects With Normal Blood Cholesterol Using Omega-3 Fatty Acids

What this study is about

Every 3 minutes a new case of diabetes is diagnosed in Canada, mostly type 2 diabetes (T2D) increasing the risk for heart disease. T2D and heart disease share many common risk factors such as aging, obesity and unhealthy lifestyle. Paradoxically however, while lowering blood LDL, commonly known as "bad cholesterol", is protective against heart disease, research over the past 10 years have shown that the lower is blood LDL, the higher is the chance of developing T2D. This phenomena is happening whether blood LDL is lowered by a common drug against heart disease called Statins, or by being born with certain variations in genes, some of which are very common (\~80% of people have them). To date, it is unclear why lowering blood LDL is associated with higher risk for diabetes, and whether this can be treated naturally with certain nutrients. Investigators believe that lowering blood LDL by forcing LDL entry into the body tissue through their receptors promotes T2D. This is because investigators have shown that LDL entry into human fat tissue induces fat tissue dysfunction, which would promote T2D especially in subjects with excess weight. On the other hand, investigators have shown that omega-3 fatty acids (omega-3) can directly treat the same defects induced by LDL entry into fat tissue. Omega-3 is a unique type of fat that is found mostly in fish oil. Thus the objectives of this clinical trial to be conducted in 48 subjects with normal blood LDL are to explore if: 1. Subjects with higher LDL receptors and LDL entry into fat tissue have higher risk factors for T2D compared to subjects with lower LDL receptors and LDL entry into fat tissue 2. 6-month supplementation of omega-3 from fish oil can treat subjects with higher LDL receptors and LDL entry into fat tissue reducing their risk for T2D. This study will thus explore and attempt to treat a new risk factor for T2D using an inexpensive and widely accessible nutraceutical, which would aid in preventing T2D in humans.

Who can join (things the study team will check)

✅ You may be able to join if…

• Having a body mass index (BMI= 25-40 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 be able to join if…

• Plasma LDL cholesterol > 3.5 mmol/L (i.e. > 75th percentile in a Canadian population).
• Elevated risk of cardiovascular disease (≥ 20% of calculated Framingham Risk Score) who would require immediate medical intervention by lipid-lowering agents.
• Prior history of cardiovascular events (like stroke, transient ischemic attack, myocardial infarction, angina, heart failure…)
• Systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg
• Type 1 or 2 diabetes or fasting glucose > 7.0 mmol/L
• Prior history of cancer within the last 3 years
• Thyroid disease - untreated or unstable
• Anemia - Hb < 120 g/L
• Renal dysfunction or plasma creatinine > 100 µmol/L
• Hepatic dysfunction - AST/ALT > 3 times normal limit
• Blood coagulation problems (i.e. bleeding predisposition)
• Autoimmune and chronic inflammatory disease (i.e. celiac, inflammatory bowel, Graves, multiple sclerosis, psoriasis, rheumatoid arthritis, and lupus).Known history of difficulties accessing a vein
• Claustrophobia
• Sleep apnea
• Seizures
• Concomitant medications: Hormone replacement therapy (except thyroid hormone at a stable dose), systemic corticosteroids, anti-psychotic medications and psycho-active medication, anticoagulant or anti-aggregates treatment (Aspirin, NSAIDs, warfarin, coumadin..), adrenergic agonist, anti-hypertensive drugs, weight-loss medication, lipid lowering medication
• Known substance abuse
• Already taking more than 250 mg of omega-3 supplements (EPA/DHA) per day
• Allergy to seafood or fish
• Allergy to Xylocaine

+ 5 more criteria — see the full checklist in the app.

Where this trial is running

• Montreal Clinical Research Institute, Montreal, Quebec, Canada

Who to contact

Justine Fricher, MSc · 514-987-5500 · justine.fricher@ircm.qc.ca

It's completely normal to call and ask questions before deciding anything. Mention the study ID: NCT04485871.