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

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


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.