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)

Waqas Qureshi, Ingrid D. Santaren, Anthony J. Hanley, Steven M. Watkins, Carlos Lorenzo, Lynne E. Wagenknecht

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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.

Original languageEnglish (US)
Article numbere00691
JournalBMJ Open Diabetes Research and Care
Volume7
Issue number1
DOIs
StatePublished - Sep 1 2019

Keywords

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

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

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