Effect of Fish Oil on Insulin Sensitivity

• Change in amount of docosahexaenoic acid and eicosapentaenoic acid incorporated into phospholipid fraction of red blood cell membranes [ Time Frame: at monthly intervals between 0 and 9 months ] [ Designated as safety issue: No ]
• Change in plasma inflammatory markers [ Time Frame: 0, 4 and 9 months ] [ Designated as safety issue: No ]

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.

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.

• Metabolic Syndrome X
• Type 2 Diabetes Mellitus
• Sarcopenia

• Dietary Supplement: EPAX 6000 (marine omega 3 EPA/DHA fatty acid concentrates
  6 x 1g capsules per day of marine oil (contains 3g/d docosahexaenoic acid plus eicosapentaenoic acid) for a 9 month period
  Other Name: EPAX 6000TG code F0-5222/XT
• Dietary Supplement: Maize (corn) oil
  6 x 1g capsules per day for 9 months
  Other Name: Banner chemicals product GL-518/XT

• Experimental: Fish oil
  Intervention: Dietary Supplement: EPAX 6000 (marine omega 3 EPA/DHA fatty acid concentrates
• Placebo Comparator: Maize (corn) oil
  Intervention: Dietary Supplement: Maize (corn) oil

Inclusion Criteria:

• Men and post-menopausal women aged 40-65 years
• Recruited from the surrounding community of Aberdeen

• Insulin resistance with either

  1. venous plasma fasting glucose > 5.0, < 7.0 mmo/l,
  2. venous plasma 2-h 75-g OGTT > 5.0, < 11.1 mmol/l
  3. 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