A human model of dietary saturated fatty acid induced insulin resistance

Juraj Koska, Marlies K. Ozias, James Deer, Julie Kurtz, Arline D. Salbe, S. Mitchell Harman, Peter D. Reaven

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


Background Increased consumption of high-fat diets is associated with the development of insulin resistance and type 2 diabetes. Current models to study the mechanisms of high-fat diet-induced IR in humans are limited by their long duration or low efficacy. In the present study we developed and characterized an acute dietary model of saturated fatty acid-enriched diet induced insulin resistance. Methods High caloric diets enriched with saturated fatty acids (SFA) or carbohydrates (CARB) were evaluated in subjects with normal and impaired glucose tolerance (NGT or IGT). Both diets were compared to a standard eucaloric American Heart Association (AHA) control diet in a series of crossover studies. Whole body insulin resistance was estimated as steady state plasma glucose (SSPG) concentrations during the last 30 min of a 3-h insulin suppression test. Results SSPG was increased after a 24-h SFA diet (by 83 ± 74% vs. control, n = 38) in the entire cohort, which was comprised of participants with NGT (92 ± 82%, n = 22) or IGT (65 ± 55%, n = 16) (all p < 0.001). SSPG was also increased after a single SFA breakfast (55 ± 32%, p = 0.008, n = 7). The increase in SSPG was less pronounced after an overnight fast following a daylong SFA diet (24 ± 31%, p = 0.04, n = 10), and further attenuated 24 h after returning to the control diet (19 ± 35%, p = 0.09, n = 11). SSPG was not increased after a 24-h CARB diet (26 ± 50%, p = 0.11, n = 12). Conclusions A short-term SFA-enriched diet induced whole body insulin resistance in both NGT and IGT subjects. Insulin resistance persisted overnight after the last SFA meal and was attenuated by one day of a healthy diet. This model offers opportunities for identifying early mechanisms and potential treatments of dietary saturated fat induced insulin resistance.

Original languageEnglish (US)
Pages (from-to)1621-1628
Number of pages8
JournalMetabolism: Clinical and Experimental
Issue number11
StatePublished - Nov 1 2016
Externally publishedYes


  • Diet
  • Glucose
  • Insulin resistance
  • Octreotide
  • Saturated fatty acids

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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