Associations between omega-6 polyunsaturated fatty acids, hyperinsulinemia and incident diabetes by race/ethnicity: The Multi-Ethnic Study of Atherosclerosis

Natalie L. Weir, Sarah O. Nomura, Brian T. Steffen, Weihua Guan, Amy B. Karger, Ronald Klein, Barbara E.K. Klein, Mary Frances Cotch, Michael Y. Tsai

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24 Scopus citations


Background & aims: Omega-6 polyunsaturated fatty acids (PUFAs) have been shown to relate to insulin resistance and type 2 diabetes (T2D), but influence of race/ethnicity has not been investigated. The aim of this study was to determine whether omega-6 PUFAs, and estimated desaturase enzyme activity, are associated with fasting glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and incident T2D, and whether associations differ by race/ethnicity. Methods: This study was conducted in the Multi-Ethnic Study of Atherosclerosis (MESA) (N = 6282). Associations between baseline plasma phospholipid fatty acids (LA, Linoleic Acid; GLA, γ-linoleic acid; DGLA, Dihomo-γ-linolenic acid; AA, arachidonic acid; D5D, delta-5 desaturase; D6D, delta-6 desaturase), fasting glucose, insulin, and HOMA-IR [(fasting insulin – fasting glucose)/22.5] were evaluated using linear regression. Associations between omega-6 PUFAs (N = 5508 after excluding diabetics at baseline) and T2D incidence were assessed using Cox proportional hazards regression. Analyses were replicated/stratified by race/ethnicity (White, Black, Chinese, Hispanic) and tests for interaction were assessed by inclusion of a cross-product term in models. Results: In fully adjusted models, insulin and HOMA-IR were positively associated with LA (insulin: 0.213 per SD, p = 0.01; HOMA-IR: 0.252 per SD, p < 0.001), GLA (insulin: 0.010 per SD, p < 0.001; HOMA-IR: 0.006 per SD, p < 0.001), DGLA (insulin: 0.279 per SD, p < 0.001; HOMA-IR: 0.175 per SD, p < 0.001) and D6D activity (insulin: 0.001 per SD, p < 0.001; HOMA-IR: 0.006 per SD, p < 0.001), and inversely associated with AA (insulin −0.272 per SD, p < 0.001; HOMA-IR: −0.125 per SD, p = 0.03) and D5D activity (insulin: −0.530 per SD, p < 0.001; HOMA-IR: −0.322 per SD, p < 0.001), while weak or no associations were observed with fasting glucose, and associations appeared to differ by race/ethnicity. After accounting for HOMA-IR at baseline, LA was inversely (HR: 0.87, p = 0.003) and DGLA (HR: 1.17, p < 0.001) and AA (HR: 1.15, p = 0.001) were positively associated with T2D in the overall population, but associations were attenuated or no longer present when stratified by race/ethnicity (P-interaction >0.05). Conclusions: Results confirm previous reports that omega-6 PUFAs are associated with hyperinsulinemia. Findings suggest omega-6 PUFAs are more likely markers of hyperinsulinemia rather than a protective/risk factor for T2D and indicate racial/ethnic differences in associations, but further research is needed to confirm findings.

Original languageEnglish (US)
Pages (from-to)3031-3041
Number of pages11
JournalClinical Nutrition
Issue number10
StatePublished - Oct 2020

Bibliographical note

Funding Information:
We would like to especially acknowledge the contribution and advice of Dr. Ronald Klein prior to his death on August 31, 2019. The authors thank the other investigators, the staff, and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at . This research was supported by contracts HHSN268201500003I , N01-HC-95159 , N01-HC-95160 , N01-HC-95161 , N01-HC-95162 , N01-HC-95163 , N01-HC-95164 , N01-HC-95165 , N01-HC-95166 , N01-HC-95167 , N01-HC-95168 and N01-HC-95169 from the National Heart, Lung, and Blood Institute , and by grants UL1-TR-000040 , UL1-TR-001079 , and UL1-TR-001420 from NCATS .

Publisher Copyright:
© 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism


  • Fatty acids
  • Hyperinsulinemia
  • Omega-6
  • Race/ethnicity
  • Type 2 diabetes


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