Clinical trial NCT01686568: Omega-3 Fatty Acids and Insulin Sensitivity
Official title: Dietary Omega-3 Fatty Acids as a Therapeutic Strategy in Insulin Resistant Humans
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Insulin Resistance
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Center for Advancing Translational Sciences (NCATS)
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Building Interdisciplinary Research Careers in Women's Health
First posted: 2012-09-18
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed 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).

Eligibility criteria: 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

Primary outcomes:
measure: Insulin Sensitivity by Hyperinsulinemic-euglycemic Clamp at Baseline and 6 Month Follow up
timeFrame: Baseline, after 6 months of treatment
Secondary outcomes:
measure: Beta Cell Function From Insulin Secretion Following Ingestion of a Mixed Meal at Baseline and 6 Month Follow up
timeFrame: baseline, after 6 months of treatment
measure: Mitochondrial Function Determined by Muscle Biopsy at Baseline and 6 Month Follow up
timeFrame: Baseline, after 6 months of treatment
measure: Insulin Concentration Needed to Suppress Palmitate Appearance Rates (IC50(Palmitate)f)
timeFrame: approximately after 6 months of treatment
measure: Senescent Cells
timeFrame: approximately after 6 months of treatment
measure: Immunohistochemistry Assessments of Macrophage Burden
timeFrame: approximately after 6 months of treatment
measure: Macrophage Crown-like Structures
timeFrame: approximately after 6 months of treatment
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Ian Lanza, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lalia AZ, Johnson ML, Jensen MD, Hames KC, Port JD, Lanza IR. Effects of Dietary n-3 Fatty Acids on Hepatic and Peripheral Insulin Sensitivity in Insulin-Resistant Humans. Diabetes Care. 2015 Jul;38(7):1228-37. doi: 10.2337/dc14-3101. Epub 2015 Apr 7.
citation: Hames KC, Morgan-Bathke M, Harteneck DA, Zhou L, Port JD, Lanza IR, Jensen MD. Very-long-chain omega-3 fatty acid supplements and adipose tissue functions: a randomized controlled trial. Am J Clin Nutr. 2017 Jun;105(6):1552-1558. doi: 10.3945/ajcn.116.148114. Epub 2017 Apr 19.