title: n-3 Fatty acids attenuate the risk of diabetes associated with elevated serum nonesterified fatty acids: the multi-ethnic study of atherosclerosis.
abstract: OBJECTIVE
  Chronically high nonesterified fatty acids (NEFAs) are a marker of metabolic dysfunction and likely increase risk of type 2 diabetes. By comparison, n-3 fatty acids (FAs) have been shown to have various health benefits and may protect against disease development. In 5,697 participants of the Multi-Ethnic Study of Atherosclerosis (MESA), we examined whether serum levels of NEFAs relate to risk of incident type 2 diabetes and further tested whether plasma n-3 FA levels may interact with this relation.
  
  
  METHODS
  NEFAs were measured in fasting serum using an enzymatic colorimetric assay and phospholipid n-3 FAs eicosapentaenoic and docosahexaenoic acids were determined in plasma through gas chromatography-flame ionization detection in 5,697 MESA participants. Cox proportional hazards regression evaluated the association between NEFA levels and incident type 2 diabetes and whether plasma n-3 FAs modified this association adjusting for age, sex, race, education, field center, smoking, and alcohol use.
  
  
  RESULTS
  Over a mean 11.4 years of the study period, higher diabetes incidence was found across successive NEFA quartiles (Q) (hazard ratio [95% CI]): Q1, 1.0; Q2, 1.35 (1.07, 1.71); Q3, 1.58 (1.24, 2.00); and Q4, 1.86 (1.45, 2.38) (P(trend) < 0.001). A significant interaction of n-3 FAs on the relation between NEFAs and type 2 diabetes was also observed (P(interaction) = 0.03). For individuals with lower n-3 levels (<75th percentile), a higher risk of type 2 diabetes was observed across quartiles of NEFAs: Q1, 1.0; Q2, 1.41 (1.07, 1.84); Q3, 1.77 (1.35, 2.31); and Q4, 2.18 (1.65, 2.88) (P(trend) < 0.001). No significant associations were observed in those with n-3 FAs ≥ 75th percentile (P(trend) = 0.54).
  
  
  CONCLUSIONS
  NEFAs are a marker of type 2 diabetes and may have clinical utility for detecting risk of its development. The modifying influence of n-3 FAs suggests a protective effect against disease and/or metabolic dysfunction related to NEFAs and requires further study.
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Steffen
authors.affiliation: Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN.
authors.forename: Lyn M
authors.initials: LM
authors.lastname: Steffen
authors.affiliation: Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Medicine, Johns Hopkins University, Baltimore, MD.
authors.forename: Pamela
authors.initials: P
authors.lastname: Ouyang
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN.
authors.forename: Natalie L
authors.initials: NL
authors.lastname: Weir
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN tsaix001@umn.edu.
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Tsai
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000097:blood / Q000208:ethnology; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology / Q000209:etiology*; D004281:Docosahexaenoic Acids / Q000097:blood; D005006:Ethnicity; D005215:Fasting; D005230:Fatty Acids, Nonesterified / Q000009:adverse effects* / Q000097:blood*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010743:Phospholipids / Q000097:blood; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D005230:Fatty Acids, Nonesterified; D015525:Fatty Acids, Omega-3; D010743:Phospholipids; D004281:Docosahexaenoic Acids