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  • Risk of diabetes associated with fatty acids in the de novo lipogenesis pathway is independent of insulin sensitivity and response: the Insulin Resistance Atherosclerosis Study (IRAS)

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Epidemiology/Health Services Research
Risk of diabetes associated with fatty acids in the de novo lipogenesis pathway is independent of insulin sensitivity and response: the Insulin Resistance Atherosclerosis Study (IRAS)
  1. Waqas Qureshi1,
  2. Ingrid D Santaren2,
  3. Anthony J Hanley2,
  4. Steven M Watkins3,
  5. Carlos Lorenzo4,
  6. Lynne E Wagenknecht5
  1. 1Department of Internal Medicine, Wake Forest University, Winston Salem, North Carolina, USA
  2. 2Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada
  3. 3Department of Lipomics, Metabolon Inc, West Sacramento, North Carolina, USA
  4. 4Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
  5. 5Department of Public Health Sciences, Wake Forest University, Winston-Salem, North Carolina, USA
  1. Correspondence to Dr Anthony J Hanley; anthony.hanley{at}utoronto.ca

Abstract

Objective To examine the associations of fatty acids in the de novo lipogenesis (DNL) pathway, specifically myristic acid (14:0), palmitic acid (16:0), cis-palmitoleic acid (c16:1 n-7), cis-myristoleic acid (c14:1n5), stearic acid (18:0) and cis-oleic acid (c18:1 n-9), with 5-year risk of type 2 diabetes. We hypothesized that DNL fatty acids are associated with risk of type 2 diabetes independent of insulin sensitivity.

Research design and methods We evaluated 719 (mean age 55.1±8.5 years, 44.2% men, 42.3% Caucasians) participants from the Insulin Resistance Atherosclerosis Study. Multivariable logistic regression models with and without adjustment of insulin sensitivity were used to assess prospective associations of DNL fatty acids with incident type 2 diabetes.

Results Type 2 diabetes incidence was 20.3% over 5 years. In multivariable regression models, palmitic, palmitoleic, myristic, myristoleic and oleic acids were associated with increased risk of type 2 diabetes (p<0.05). Palmitic acid had the strongest association (OR per standard unit of palmitic acid 1.46; 95% CI 1.23 to 1.76; p<0.001), which remained similar with addition of insulin sensitivity and acute insulin response (AIR) to the model (OR 1.36; 95% CI 1.09 to 1.70, p=0.01). Oleic and palmitoleic acids were also independently associated with incident type 2 diabetes. In multivariable models, ratios of fatty acids corresponding to stearoyl CoA desaturase-1 and Elovl6 enzymatic activity were significantly associated with risk of type 2 diabetes independent of insulin sensitivity and AIR.

Conclusions We observed associations of DNL fatty acids with type 2 diabetes incidence independent of insulin sensitivity.

  • Diabetes mellitus
  • ethnicity
  • fatty acid metabolism
  • insulin sensitivity
  • acute insulin response

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/bmjdrc-2019-000691

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    Footnotes

    • WQ and IDS contributed equally.

    • Contributors WQ wrote the manuscript and researched data. IDS wrote/reviewed/edited the manuscript and revisions. AH reviewed/edited manuscript. SKW researched data and reviewed/edited manuscript. CL reviewed/edited manuscript. LEW reviewed/edited and wrote the manuscript. AH is the guarantor of this work and, as such, had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

    • Funding This work was supported by grants U01-HL-47892, U01-HL-47902, DK-29867, R01-58329 and DK-079888 from the National Heart, Lung, and Blood Institute and grant M01-RR-43 from the National Institutes of Health. AJH holds a Tier II Canada Research Chair in the Epidemiology of Type 2 Diabetes. Waqas Qureshi reports receiving Ruth L Kirschstein NRSA Institutional Training Grant 5T32HL076132-10.

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement No data are available.