Effect of Fish Oil on Insulin Sensitivity

Study Overview
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Brief Summary
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The purpose of this study is to determine whether a prolonged (9 month) high (6g/d) of marine oil improves insulin sensitivity and glucose control in subjects with impaired glucose regulation.

Detailed Description
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The incidence of Type 2 diabetes is related both to age and obesity. The disease impacts on quality of life and treatments represent a major health cost. Prevention or delayed onset of the disease remains a key target. Animal studies have shown that provision of high amounts of fish oil in the diet improves insulin sensitivity but human trials have proved equivocal. Recent dose-response trials in animals have shown the improved insulin sensitivity only occurs when the proportion of n-3 long chain polyunsaturated fatty acids (n-3 PUFA), docosahexaenoic acid and eicosapentaenoic acid, exceeds 14% of the total phospholipid fraction within tissue cell membranes. To achieve such values in humans would require a high dose of n-3 PUFA supplied over a prolonged period of time. This is tested within the current study where a daily dose of 6 g day of fish oil (containing a total of 3g docosahexaenoic acid plus eicosapentaenoic acid) is supplied for 9 months. As well as improving control of glycemia increased insulin sensitivity may also enhance protein metabolism and reduce the impact of frailty in older subjects.

Official Title
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Chronic Long-chain n-3 PUFA Supplement and Insulin Action in Human Subjects With Impaired Glucose Regulation

Conditions
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Metabolic Syndrome X, Type 2 Diabetes Mellitus, Sarcopenia

Intervention / Treatment
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* Dietary Supplement: EPAX 6000 (marine omega 3 EPA/DHA fatty acid concentrates
* Dietary Supplement: Maize (corn) oil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and post-menopausal women aged 40-65 years Recruited from the surrounding community of Aberdeen Insulin resistance with either venous plasma fasting glucose > 5.0, < 7.0 mmo/l, venous plasma 2-h 75-g OGTT > 5.0, < 11.1 mmol/l newly diagnosed with type 2 diabetes; must be asymptomatic and detected during our screenings and not require oral hypoglycemic or insulin therapy, HbA1c < 7.0% Exclusion Criteria: Diabetes requiring oral hypoglycemic therapy or insulin Treatment with anticoagulants, regular steroids or non-steroidal anti-inflammatory drug treatment, tricyclic antidepressants, anti-arrhythmics Hepatic failure Renal failure Significant respiratory disease Anaemia Cardiovascular disease Malignancy Thromboembolic or coagulation disorders Alcoholism or other substance misuse Eating disorders or significant psychiatric disorders

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 69 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fish oil<br> | Dietary Supplement: EPAX 6000 (marine omega 3 EPA/DHA fatty acid concentrates<br>* 6 x 1g capsules per day of marine oil (contains 3g/d docosahexaenoic acid plus eicosapentaenoic acid) for a 9 month period<br>* Other names: EPAX 6000TG code F0-5222/XT;|
| Placebo Comparator: Maize (corn) oil<br> | Dietary Supplement: Maize (corn) oil<br>* 6 x 1g capsules per day for 9 months<br>* Other names: Banner chemicals product GL-518/XT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in insulin sensitivity assessed by hyperinsulinemic-euglycemic-eu-aminoacidemic clamp |  | 0 months and 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in amount of docosahexaenoic acid and eicosapentaenoic acid incorporated into phospholipid fraction of red blood cell membranes |  | at monthly intervals between 0 and 9 months | 
| Change in plasma inflammatory markers |  | 0, 4 and 9 months |