Omega-3 Fatty Acids for Type 2 Diabetes Risk Factors
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Institut de Recherches Cliniques de Montreal
Must not be taking: Hormone therapy, Corticosteroids, Antipsychotics, others
Disqualifiers: Cardiovascular disease, Diabetes, Cancer, others
No Placebo Group
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?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.
Will I have to stop taking my current medications?
Yes, you may need to stop taking certain medications. The trial excludes participants on hormone replacement therapy (except stable thyroid hormone), systemic corticosteroids, anti-psychotic medications, psycho-active medication, anticoagulant or anti-aggregates treatment, adrenergic agonist, anti-hypertensive drugs, weight-loss medication, and lipid-lowering medication.
What data supports the effectiveness of the treatment Omega-3 fatty acids for type 2 diabetes risk factors?
Research shows that omega-3 fatty acids can lower triglycerides (a type of fat in the blood) and may improve blood flow, which could be beneficial for heart health in people with type 2 diabetes. However, their direct effect on blood sugar levels and diabetes risk is still unclear.
12345Is it safe to take omega-3 fatty acids for type 2 diabetes risk factors?
Omega-3 fatty acids, found in supplements like fish oil and krill oil, are generally considered safe for most people and have been shown to have heart health benefits. However, high doses can sometimes cause side effects like upset stomach or bleeding, so it's important to follow recommended dosages and consult with a healthcare provider.
12467How does the treatment of omega-3 fatty acids differ from other treatments for type 2 diabetes?
Omega-3 fatty acids, such as EPA and DHA, are unique because they are natural compounds found in fish oil and are being studied for their potential to lower the risk of type 2 diabetes by affecting lipid (fat) levels in the blood. Unlike standard diabetes medications that directly lower blood sugar, omega-3s may offer cardiovascular benefits, although their exact role in diabetes prevention is still being researched.
12589Eligibility Criteria
This trial is for sedentary adults aged 45-74 with a BMI of 25-40 who are non-smokers, drink little alcohol, and have normal blood LDL cholesterol. It's not for those allergic to seafood or fish, with recent cancer history, high cardiovascular risk needing immediate treatment, diabetes, severe hypertension, renal or liver dysfunction, certain medication use or other medical conditions that the physician finds unsuitable.Inclusion Criteria
You do not exercise regularly (less than 2 hours of structured physical activity per week).
I am a man or post-menopausal woman with a BMI between 25-40.
You are confirmed to have reached menopause based on a hormone test result.
+3 more
Exclusion Criteria
You are allergic to seafood or fish.
I have diabetes or my fasting blood sugar is high.
I have a condition that makes me bleed easily.
+23 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Weight Stabilization
Participants undergo weight stabilization with a +/- 2 kg change over 4 weeks and confirmation of eligibility after a medical examination
4 weeks
1 visit (in-person)
Baseline Testing
Baseline testing to assess participants' risk factors for T2D, including white adipose tissue NLRP3 inflammasome activity, systemic inflammation, and insulin secretion and sensitivity
1-4 weeks
2 visits (in-person)
Treatment
24-week intervention with omega-3 fatty acid supplementation (3.6 g EPA and DHA, 2:1 ratio)
24 weeks
Regular check-ins (frequency not specified)
Post Intervention Testing
Post intervention testing to assess risk factors for T2D that were measured at baseline
1-4 weeks
2 visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study tests if omega-3 fatty acids from fish oil can reduce the risk of type 2 diabetes in people with higher LDL receptors and fat tissue entry. Participants will take omega-3 supplements for six months to see if it treats defects caused by LDL entering fat tissue.
1Treatment groups
Experimental Treatment
Group I: Omega-3 fatty acidsExperimental Treatment1 Intervention
3.6 g EPA:DHA / day (2:1)
Omega-3 fatty acids is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Omega-3 fatty acids for:
- Hypertriglyceridemia
- Cardiovascular health
🇪🇺 Approved in European Union as Omega-3 fatty acids for:
- Hypertriglyceridemia
- Cardiovascular health
🇨🇦 Approved in Canada as Omega-3 fatty acids for:
- Hypertriglyceridemia
- Cardiovascular health
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Montreal Clinical Research InstituteMontréal, Canada
Loading ...
Who Is Running the Clinical Trial?
Institut de Recherches Cliniques de MontrealLead Sponsor
Canadian Institutes of Health Research (CIHR)Collaborator
References
The effects of omega-3 fatty acids in type 2 diabetes: A systematic review and meta-analysis. [2022]The effect of omega-3 polyunsaturated fatty acids (n-3 PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on cardiovascular risk modification in type 2 diabetes and related complications remain unclear. We aim to assess the published effects of n-3 PUFA interventions on lipid risk factors in type 2 diabetes.
Omega-3 fatty acids and incident type 2 diabetes: the Singapore Chinese Health Study. [2023]The role of omega-3 (n-3) fatty acids (FAs) in the development of type 2 diabetes is uncertain, especially with regard to any differential influence of α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA).
(n-3) Fatty Acids: Clinical Trials in People with Type 2 Diabetes. [2023]Recent human clinical trials of the effects of (n-3) fatty acids on participants with type 2 diabetes (T2D) were reviewed, focusing on 11 clinical trials conducted within the past 4 y, and subsequent to a Cochrane Database meta-analysis of this topic. Doses of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in these studies were mostly in the range of ∼2 g/d provided for 6 wk to 6 mo. Summarizing across these studies, there were no changes in fasting glucose or insulin compared with baseline or placebo. (n-3) Fatty acids generally decreased serum triglycerides but had varying effects on serum cholesterol, LDL cholesterol, and HDL cholesterol. A few studies indicated beneficial effects of (n-3) fatty acids on arterial blood flow. The effects of EPA and/or DHA have not yet been studied in clinical trials in participants at risk for T2D; the prevention or exacerbation of T2D by fish oil or EPA and DHA supplements of amounts >0.5 g/d deserves study. The prevention of adverse vascular effects of T2D by (n-3) fatty acids may be a promising direction for further study.
N-3 fatty acids in glucose metabolism and insulin sensitivity. [2022]Polyunsaturated fatty acids (PUFA) of the n-3 series are essential for normal growth and development. The health effects of these fatty acids include reduction of cardiovascular risk due to antiarrhythmic, antiinflammatory, anti-thrombotic and lipid lowering actions. An increase in unsaturation of the muscle membrane fatty acids is associated with improved insulin sensitivity. Higher proportion of n-3 fatty acids may have beneficial roles, such as antiobesity effects and protection against the metabolic syndrome and type 2 diabetes mellitus through a number of metabolic effects. However, controversy exists on the different effects of n-6 and n-3 polyunsaturated fatty acids as well as on the interacting effect of dietary saturated and monounsaturated fat. In addition, some adverse effects have been described concerning the use of fish oil supplements containing high doses of n-3 fatty acids. Several studies show Eskimos diabetes risk, while results of nutritional interventions on the influence of consuming diets rich in oily fish or other food rich in n-3 fatty acids is very limited. This article reviews the possible mechanisms through which n-3 PUFA are involved in glucose level control and insulin sensitivity. Intervention and epidemiological studies together with recent findings on the nutrigenomic field related with this subject are also briefly reviewed.
Omega-3 fatty acids and incident type 2 diabetes: a systematic review and meta-analysis. [2022]The relationship between omega-3 polyunsaturated fatty acids (n-3 PUFA) from seafood sources (eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA) or plant sources (alpha-linolenic acid, ALA) and risk of type 2 diabetes mellitus (DM) remains unclear. We systematically searched multiple literature databases through June 2011 to identify prospective studies examining relations of dietary n-3 PUFA, dietary fish and/or seafood, and circulating n-3 PUFA biomarkers with incidence of DM. Data were independently extracted in duplicate by 2 investigators, including multivariate-adjusted relative risk (RR) estimates and corresponding 95 % CI. Generalized least-squares trend estimation was used to assess dose-response relationships, with pooled summary estimates calculated by both fixed-effect and random-effect models. From 288 identified abstracts, 16 studies met inclusion criteria, including 18 separate cohorts comprising 540,184 individuals and 25,670 cases of incident DM. Consumption of fish and/or seafood was not significantly associated with DM (n = 13 studies; RR per 100 g/d = 1·12, 95 % CI = 0·94, 1·34); nor were consumption of EPA+DHA (n = 16 cohorts; RR per 250 mg/d = 1·04, 95 % CI = 0·97, 1·10) nor circulating levels of EPA+DHA biomarkers (n = 5 cohorts; RR per 3 % of total fatty acids = 0·94, 95 % CI = 0·75, 1·17). Both dietary ALA (n = 7 studies; RR per 0·5 g/d = 0·93, 95 % CI = 0·83, 1·04) and circulating ALA biomarker levels (n = 6 studies; RR per 0·1 % of total fatty acid = 0·90, 95 % CI = 0·80, 1·00, P = 0·06) were associated with non-significant trend towards lower risk of DM. Substantial heterogeneity (I²~80 %) was observed among studies of fish/seafood or EPA+DHA and DM; moderate heterogeneity (
Effects of krill oil on endothelial function and other cardiovascular risk factors in participants with type 2 diabetes, a randomized controlled trial. [2019]The purpose of this trial was to evaluate the effect of krill oil supplementation, a source of ω-3 fatty acids, on cardiovascular disease risk factors and blood glucose control among participants with type 2 diabetes.
Increased plasma levels of palmitoleic acid may contribute to beneficial effects of Krill oil on glucose homeostasis in dietary obese mice. [2020]Omega-3 polyunsatuarted fatty acids (PUFA) are associated with hypolipidemic and anti-inflammatory effects. However, omega-3 PUFA, usually administered as triacylglycerols or ethyl esters, could also compromise glucose metabolism, especially in obese type 2 diabetics. Phospholipids represent an alternative source of omega-3 PUFA, but their impact on glucose homeostasis is poorly explored. Male C57BL/6N mice were fed for 8 weeks a corn oil-based high-fat diet (cHF) alone or cHF-based diets containing eicosapentaenoic acid and docosahexaenoic acid (~3%; wt/wt), admixed either as a concentrate of re-esterified triacylglycerols (ω3TG) or Krill oil containing mainly phospholipids (ω3PL). Lean controls were fed a low-fat diet. Insulin sensitivity (hyperinsulinemic-euglycemic clamps), parameters of glucose homeostasis, adipose tissue function, and plasma levels of N-acylethanolamines, monoacylglycerols and fatty acids were determined. Feeding cHF induced obesity and worsened (~4.3-fold) insulin sensitivity as determined by clamp. Insulin sensitivity was almost preserved in ω3PL but not ω3TG mice. Compared with cHF mice, endogenous glucose production was reduced to 47%, whereas whole-body and muscle glycogen synthesis increased ~3-fold in ω3PL mice that showed improved adipose tissue function and elevated plasma adiponectin levels. Besides eicosapentaenoic and docosapentaenoic acids, principal component analysis of plasma fatty acids identified palmitoleic acid (C16:1n-7) as the most discriminating analyte whose levels were increased in ω3PL mice and correlated negatively with the degree of cHF-induced glucose intolerance. While palmitoleic acid from Krill oil may help improve glucose homeostasis, our findings provide a general rationale for using omega-3 PUFA-containing phospholipids as nutritional supplements with potent insulin-sensitizing effects.
Serum omega-3 polyunsaturated fatty acids and risk of incident type 2 diabetes in men: the Kuopio Ischemic Heart Disease Risk Factor study. [2018]OBJECTIVE The relationship between fish or omega-3 polyunsaturated fatty acids (PUFAs) and type 2 diabetes is inconclusive. Even contaminants in fish, such as mercury, may modify the effects. We investigated the associations between serum omega-3 PUFAs eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), α-linolenic acid (ALA), hair mercury, and risk of incident type 2 diabetes in middle-aged and older Finnish men. RESEARCH DESIGN AND METHODS A total of 2,212 men from the prospective, population-based Kuopio Ischemic Heart Disease Risk Factor study, aged 42-60 years and free of type 2 diabetes at baseline in 1984-1989, were investigated. Serum PUFA and hair mercury were used as biomarkers for exposure. Dietary intakes were assessed with 4-day food recording. Type 2 diabetes was assessed by self-administered questionnaires and fasting and 2-h oral glucose tolerance test blood glucose measurement at re-examination rounds 4, 11, and 20 years after the baseline and by record linkage to hospital discharge registry and reimbursement register on diabetes medication expenses. Cox proportional hazards models were used to analyze associations. RESULTS During the average follow-up of 19.3 years, 422 men developed type 2 diabetes. Men in the highest versus the lowest serum EPA + DPA + DHA quartile had 33% lower multivariate-adjusted risk for type 2 diabetes (95% CI 13-49; P trend 0.01). No statistically significant associations were observed with serum or dietary ALA, dietary fish or EPA + DHA, or hair mercury. CONCLUSIONS Serum long-chain omega-3 PUFA concentration, an objective biomarker for fish intake, was associated with long-term lower risk of type 2 diabetes.
n-3 Fatty Acid Biomarkers and Incident Type 2 Diabetes: An Individual Participant-Level Pooling Project of 20 Prospective Cohort Studies. [2022]Prospective associations between n-3 fatty acid biomarkers and type 2 diabetes (T2D) risk are not consistent in individual studies. We aimed to summarize the prospective associations of biomarkers of α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with T2D risk through an individual participant-level pooled analysis.