Cardiometabolic health improvements upon dietary intervention are driven by tissue-specific insulin resistance phenotype: A precision nutrition trial

Inez Trouwborst, Anouk Gijbels, Kelly M. Jardon, Els Siebelink, Gabby B. Hul, Lisa Wanders, Balázs Erdos, Szabolcs Péter, Cécile M. Singh-Povel, Johan de Vogel-van den Bosch, Michiel E. Adriaens, Ilja C.W. Arts, Dick H.J. Thijssen, Edith J.M. Feskens, Gijs H. Goossens, Lydia A. Afman, Ellen E. Blaak*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Summary Precision nutrition based on metabolic phenotype may increase the effectiveness of interventions. In this proof-of-concept study, we investigated the effect of modulating dietary macronutrient composition according to muscle insulin-resistant (MIR) or liver insulin-resistant (LIR) phenotypes on cardiometabolic health. Women and men with MIR or LIR (n = 242, body mass index [BMI] 25–40 kg/m2, 40–75 years) were randomized to phenotype diet (PhenoDiet) group A or B and followed a 12-week high-monounsaturated fatty acid (HMUFA) diet or low-fat, high-protein, and high-fiber diet (LFHP) (PhenoDiet group A, MIR/HMUFA and LIR/LFHP; PhenoDiet group B, MIR/LFHP and LIR/HMUFA). PhenoDiet group B showed no significant improvements in the primary outcome disposition index, but greater improvements in insulin sensitivity, glucose homeostasis, serum triacylglycerol, and C-reactive protein compared with PhenoDiet group A were observed. We demonstrate that modulating macronutrient composition within the dietary guidelines based on tissue-specific insulin resistance (IR) phenotype enhances cardiometabolic health improvements. registration: NCT03708419, CCMO registration NL63768.068.17.
Original languageEnglish
Pages (from-to)71-83.e5
Number of pages19
JournalCell Metabolism
Issue number1
Publication statusPublished - 3 Jan 2023


  • precision nutrition
  • dietary intervention trial
  • tissue-specific insulin resistance
  • metabotyping
  • glucose homeostasis
  • cardiometabolic health

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