Omega-3 Fatty Acids and Insulin Sensitivity

Mayo Clinic

Status and phase: Completed; Phase 3

Conditions: Insulin Resistance

Treatments: Drug: placebo; Drug: Omega-3

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01686568

DK50456 (Other Grant/Funding Number)

12-004590

DK40484 (Other Grant/Funding Number)

U24DK100469 (U.S. NIH Grant/Contract)

5T32DK007352 (U.S. NIH Grant/Contract)

KL2TR000136 (U.S. NIH Grant/Contract)

5UL1TR000135 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

This study is being done to understand the effects of dietary omega-3 fats on insulin sensitivity in adult men and women.

Full description

Dietary omega-3 polyunsaturated fatty acids (n-3 PUFA), which include eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish oil, prevent insulin resistance in rodents, but data in humans is ambiguous. No existing studies have systematically evaluated the influence of n-3 PUFAs on insulin sensitivity and beta cell function in insulin resistant, non-diabetic humans. The Investigators hypothesize that 6 months of oral supplementation of purified EPA/DHA (3.9g/day) will significantly improve hepatic and peripheral insulin sensitivity and beta cell responsiveness in insulin-resistant, non-diabetic individuals. Based on recent work in mice, the investigators also hypothesize that EPA/DHA will increase the content and function of mitochondria in skeletal muscle, measured using a combination of in vivo and in vitro methods. Overall, the investigators hypothesize that EPA+DHA supplementation will improve hepatic and peripheral insulin sensitivity in insulin resistant humans, and this improvement will be associated with mitochondrial biogenesis and attenuated lipid accumulation in skeletal muscle and liver.

A sub-study was added in which participants receiving dietary omega-3 fatty acids or placebo supplements underwent abdominal subcutaneous adipose tissue biopsies to measure the content of total, pro- (M1) and anti- (M2) inflammatory macrophages (immunohistochemistry), crown-like structures (immunohistochemistry), and senescent cells (β-galactosidase staining), as well as a two-step euglycemic, pancreatic clamp with a stable-isotope labeled precursor ((U-13C)palmitate) infusion to determine the insulin concentration needed to suppress palmitate flux by 50% (IC50(palmitate)f).

Enrollment: 31 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Age 18-65 years
2. Insulin resistant (Homeostasis Model Assessment (HOMA) Insulin Resistance (IR) ≥2.6)

Exclusion criteria

1. Current use of omega-3 nutritional supplements
2. Fasting plasma glucose ≥126 mg/dL
3. Active coronary artery disease
4. Participation in structured exercise (>2 times per week for 30 minutes or longer)
5. Smoking
6. Medications known to affect muscle metabolism (e.g., beta blockers, corticosteroids, tricyclic-antidepressants, benzodiazepines, opiates, barbiturates, anticoagulants)
7. Renal failure (serum creatinine > 1.5mg/dl)
8. Chronic active liver disease (AST>144 IU/L and alanine transaminase (ALT)>165 IU/L)
9. Anti-coagulant therapy (warfarin/heparin)
10. International normalized ratio (INR) >3
11. Use of systemic glucocorticoids
12. Chronic use of NSAIDS or aspirin
13. Pregnancy or breastfeeding
14. Alcohol consumption greater than 2 glasses/day
15. Hypothyroidism
16. Fish or shellfish allergy

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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31 participants in 2 patient groups, including a placebo group

Omega-3

Experimental group

Description:

Patients in this group will receive oral supplementation with EPA+DHA (3.9grams/day) for 6 months.

Treatment:

Drug: Omega-3

Placebo

Placebo Comparator group

Description:

Patients in this group will be supplemented with placebo capsules containing ethyl oleate.

Treatment:

Drug: placebo