Effects of a whole diet approach on metabolic flexibility, insulin sensitivity and postprandial glucose responses in overweight and obese adults - A randomized controlled trial

Eva Fechner*, Lena Bilet, Harry P F Peters, Harry Hiemstra, Doris M Jacobs, Cara Op 't Eyndt, Esther Kornips, Ronald P Mensink, Patrick Schrauwen

*Corresponding author for this work

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BACKGROUND & AIMS: Metabolic flexibility is the ability to adapt fuel oxidation to fuel availability. Metabolic inflexibility has been associated with obesity, the metabolic syndrome and insulin resistance, and can be improved by exercise or weight loss. Dietary changes can modulate metabolic flexibility; however, the effect of a whole diet approach on metabolic flexibility has never been studied. Therefore, our objective was to assess the effect of a healthy diet (HD), as compared to a typical Western diet (WD), on several fasting and postprandial markers of metabolic flexibility and insulin sensitivity.

METHODS: In this parallel randomized trial, overweight or obese men and women (50-70 years; BMI 25-35 kg/m2) consumed a healthy diet (HD; high in fruits and vegetables, pulses, fibers, nuts, fatty fish, and low in high-glycemic carbohydrates; n = 19) or a typical Western diet (WD; n = 21) for six weeks, following a two-week run-in period. The change in respiratory quotient upon insulin stimulation (ΔRQ), and insulin sensitivity, expressed as the M-value, were both determined with a hyperinsulinemic euglycemic clamp. Additionally, other fasting and postprandial markers of metabolic flexibility were assessed during a 5-h high-fat high-glycemic mixed meal challenge.

RESULTS: ΔRQ (p = 0.730) and insulin sensitivity (p = 0.802) were not significantly affected by diet. Postprandial RQ did also not show significant differences (p = 0.610), whereas postprandial glucose excursions were significantly higher in the HD group at T30 (p = 0.014) and T45 (p = 0.026) after mixed meal ingestion (p = 0.037). Fasting glucose (p = 0.530) and HbA1c (p = 0.124) remained unchanged, whereas decreases in fasting insulin (p = 0.038) and the HOMA-IR (p = 0.050) were significantly more pronounced with the HD.

CONCLUSION: A healthy diet for six weeks, without further life-style changes, did not improve metabolic flexibility and whole-body insulin sensitivity, when compared to a Western-style diet. It remains to be determined whether the short time increase in postprandial glucose is physiologically relevant or detrimental to metabolic health. This trial was registered at clinicaltrials.gov as NCT02519127.

Original languageEnglish
Pages (from-to)2734-2742
Number of pages9
JournalClinical Nutrition
Issue number9
Early online date17 Dec 2019
Publication statusPublished - Sept 2020


  • Dietary intervention
  • Insulin resistance
  • Hyperinsulinemic euglycemic clamp
  • Mixed meal challenge
  • Postprandial metabolism
  • Obesity

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