A human model of dietary saturated fatty acid induced insulin resistance

Metabolism. 2016 Nov;65(11):1621-1628. doi: 10.1016/j.metabol.2016.07.015. Epub 2016 Aug 5.

Abstract

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 30min 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 24h 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.

Keywords: Diet; Glucose; Insulin resistance; Octreotide; Saturated fatty acids.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Blood Glucose / analysis
  • Blood Glucose / metabolism
  • Breakfast
  • Cross-Over Studies
  • Dietary Carbohydrates / pharmacology
  • Dietary Fats / adverse effects*
  • Energy Intake
  • Fatty Acids / adverse effects*
  • Female
  • Glucose Intolerance / chemically induced
  • Humans
  • Insulin / blood
  • Insulin Resistance*
  • Lipids / blood
  • Male
  • Middle Aged
  • Models, Biological

Substances

  • Blood Glucose
  • Dietary Carbohydrates
  • Dietary Fats
  • Fatty Acids
  • Insulin
  • Lipids