Impact of a 12-week personalized dietary intervention on vascular function and cardiovascular risk factors.

Individuals with liver insulin-resistant (LIR) or muscle insulin-resistant (MIR) phenotypes may respond differently to dietary interventions. Given the interaction between insulin resistance and cardiovascular risk, this sub-analysis of the PERSON study examined whether a personalized diet according to MIR or LIR phenotypes improves vascular function and cardiovascular disease risk factors. We randomized 119 participants to a 12-week low-fat, high-protein, high-fibre diet (LFHP; may be optimal for LIR) or Mediterranean diet (high in monounsaturated fat, HMUFA; may be optimal for MIR). Randomization linked the insulin-resistant (IR) phenotype to the proposed optimal diet, leading to PhenoDiet A (MIR-HMUFA and LIR-LFHP) and PhenoDiet B (MIR-LFHP and LIR-HMUFA). Before and after the intervention, vascular function (carotid artery reactivity) and cardiovascular risk factors (blood pressure, total cholesterol, HDL-cholesterol and Framingham risk score) were examined. A 7-point oral glucose tolerance test was performed to determine insulin resistance (Matsuda index and HOMA-IR) and disposition index. Following drop-out (n = 18), 101 participants finished the intervention (54 women, 61 ± 7 years, 27.6 [26.4;30.0] kg/m2), with n = 80 available for the primary outcome of vascular function. Overall, the dietary interventions significantly decreased blood pressure, total cholesterol, HDL-cholesterol and the Framingham risk score (all p < 0.05), while vascular function was not affected (p = 0.485). Insulin resistance (p ≤ 0.001), but not disposition index (p = 0.362), was significantly improved after intervention. The Matsuda index (p = 0.078) tended to increase more and total cholesterol (p = 0.052) tended to decrease more in PhenoDiet group B than A, but other changes in outcome parameters were not significantly different between PhenoDiet groups. The LFHP diet resulted in more pronounced improvements in cholesterol, diastolic blood pressure (DBP) and insulin resistance compared with the HMUFA diet (all p < 0.05). A 12-week diet improves metabolic and cardiovascular outcomes, but not vascular function in insulin-resistant adults with overweight or obesity. Whilst the LFHP diet resulted in greater improvements in cardiometabolic risk markers than the HMUFA diet, we found no significant differences between the PhenoDiet groups.

Wanders L ，Gijbels A ，Hul GB ，Feskens EJM ，Afman LA ，Blaak EE ，Hopman MTE ，Goossens GH ，Thijssen DHJ ... -  《-》

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

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. Clinicaltrials.gov registration: NCT03708419, CCMO registration NL63768.068.17.

Trouwborst I ，Gijbels A ，Jardon KM ，Siebelink E ，Hul GB ，Wanders L ，Erdos B ，Péter S ，Singh-Povel CM ，de Vogel-van den Bosch J ，Adriaens ME ，Arts ICW ，Thijssen DHJ ，Feskens EJM ，Goossens GH ，Afman LA ，Blaak EE ... -  《-》

Fasting and postprandial plasma metabolite responses to a 12-wk dietary intervention in tissue-specific insulin resistance: a secondary analysis of the PERSonalized glucose Optimization through Nutritional intervention (PERSON) randomized trial.

We previously showed that dietary intervention effects on cardiometabolic health were driven by tissue-specific insulin resistance (IR) phenotype: individuals with predominant muscle IR (MIR) benefited more from a low-fat, high-protein, and high-fiber (LFHP) diet, whereas individuals with predominant liver insulin resistance (LIR) benefited more from a high-monounsaturated fatty acid (HMUFA) diet. To further characterize the effects of LFHP and HMUFA diets and their interaction with tissue-specific IR, we investigated dietary intervention effects on fasting and postprandial plasma metabolite profile. Adults with MIR or LIR (40-75 y, BMI 25-40 kg/m2) were randomly assigned to a 12-wk HMUFA or LFHP diet (n = 242). After the exclusion of statin use, 214 participants were included in this prespecified secondary analysis. Plasma samples were collected before (T = 0) and after (T = 30, 60, 120, and 240 min) a high-fat mixed meal for quantification of 247 metabolite measures using nuclear magnetic resonance spectroscopy. A larger reduction in fasting VLDL-triacylglycerol (TAG) and VLDL particle size was observed in individuals with MIR following the LFHP diet and those with LIR following the HMUFA diet, although no longer statistically significant after false discovery rate (FDR) adjustment. No IR phenotype-by-diet interactions were found for postprandial plasma metabolites assessed as total area under the curve (tAUC). Irrespective of IR phenotype, the LFHP diet induced greater reductions in postprandial plasma tAUC of the larger VLDL particles and small HDL particles, and TAG content in most VLDL subclasses and the smaller LDL and HDL subclasses (for example, VLDL-TAG tAUC standardized mean change [95% CI] LFHP = -0.29 [-0.43, -0.16] compared with HMUFA = -0.04 [-0.16, 0.09]; FDR-adjusted P for diet × time = 0.041). Diet effects on plasma metabolite profiles were more pronounced than phenotype-by-diet interactions. An LFHP diet may be more effective than an HMUFA diet for reducing cardiometabolic risk in individuals with tissue-specific IR, irrespective of IR phenotype. Am J Clin Nutr 20xx;x:xx. This trial was registered at the clinicaltrials.gov registration (https://clinicaltrials.gov/study/NCT03708419?term=NCT03708419&rank=1) as NCT03708419 and CCMO registration (https://www.toetsingonline.nl/to/ccmo_search.nsf/fABRpop?readform&unids=3969AABCD9BA27FEC12587F1001BCC65) as NL63768.068.17.

Gijbels A ，Jardon KM ，Trouwborst I ，Manusama KC ，Goossens GH ，Blaak EE ，Feskens EJ ，Afman LA ... -  《-》

Insulin resistance determines a differential response to changes in dietary fat modification on metabolic syndrome risk factors: the LIPGENE study.

Previous data support the benefits of reducing dietary saturated fatty acids (SFAs) on insulin resistance (IR) and other metabolic risk factors. However, whether the IR status of those suffering from metabolic syndrome (MetS) affects this response is not established. Our objective was to determine whether the degree of IR influences the effect of substituting high-saturated fatty acid (HSFA) diets by isoenergetic alterations in the quality and quantity of dietary fat on MetS risk factors. In this single-blind, parallel, controlled, dietary intervention study, MetS subjects (n = 472) from 8 European countries classified by different IR levels according to homeostasis model assessment of insulin resistance (HOMA-IR) were randomly assigned to 4 diets: an HSFA diet; a high-monounsaturated fatty acid (HMUFA) diet; a low-fat, high-complex carbohydrate (LFHCC) diet supplemented with long-chain n-3 polyunsaturated fatty acids (1.2 g/d); or an LFHCC diet supplemented with placebo for 12 wk (control). Anthropometric, lipid, inflammatory, and IR markers were determined. Insulin-resistant MetS subjects with the highest HOMA-IR improved IR, with reduced insulin and HOMA-IR concentrations after consumption of the HMUFA and LFHCC n-3 diets (P < 0.05). In contrast, subjects with lower HOMA-IR showed reduced body mass index and waist circumference after consumption of the LFHCC control and LFHCC n-3 diets and increased HDL cholesterol concentrations after consumption of the HMUFA and HSFA diets (P < 0.05). MetS subjects with a low to medium HOMA-IR exhibited reduced blood pressure, triglyceride, and LDL cholesterol levels after the LFHCC n-3 diet and increased apolipoprotein A-I concentrations after consumption of the HMUFA and HSFA diets (all P < 0.05). Insulin-resistant MetS subjects with more metabolic complications responded differently to dietary fat modification, being more susceptible to a health effect from the substitution of SFAs in the HMUFA and LFHCC n-3 diets. Conversely, MetS subjects without IR may be more sensitive to the detrimental effects of HSFA intake. The metabolic phenotype of subjects clearly determines response to the quantity and quality of dietary fat on MetS risk factors, which suggests that targeted and personalized dietary therapies may be of value for its different metabolic features. This study was registered at clinicaltrials.gov as NCT00429195.

Yubero-Serrano EM ，Delgado-Lista J ，Tierney AC ，Perez-Martinez P ，Garcia-Rios A ，Alcala-Diaz JF ，Castaño JP ，Tinahones FJ ，Drevon CA ，Defoort C ，Blaak EE ，Dembinska-Kieć A ，Risérus U ，Lovegrove JA ，Perez-Jimenez F ，Roche HM ，Lopez-Miranda J ... -  《-》

Body composition and body fat distribution in tissue-specific insulin resistance and in response to a 12-week isocaloric dietary macronutrient intervention.

Body composition and body fat distribution are important predictors of cardiometabolic diseases. The etiology of cardiometabolic diseases is heterogenous, and partly driven by inter-individual differences in tissue-specific insulin sensitivity. To investigate (1) the associations between body composition and whole-body, liver and muscle insulin sensitivity, and (2) changes in body composition and insulin sensitivity and their relationship after a 12-week isocaloric diet high in mono-unsaturated fatty acids (HMUFA) or a low-fat, high-protein, high-fiber (LFHP) diet. This subcohort analysis of the PERSON study includes 93 individuals (53% women, BMI 25-40 kg/m2, 40-75 years) who participated in this randomized intervention study. At baseline and after 12 weeks of following the LFHP, or HMUFA diet, we performed a 7-point oral glucose tolerance test to assess whole-body, liver, and muscle insulin sensitivity, and whole-body magnetic resonance imaging to determine body composition and body fat distribution. Both diets are within the guidelines of healthy nutrition. At baseline, liver fat content was associated with worse liver insulin sensitivity (β [95%CI]; 0.12 [0.01; 0.22]). Only in women, thigh muscle fat content was inversely related to muscle insulin sensitivity (-0.27 [-0.48; -0.05]). Visceral adipose tissue (VAT) was inversely associated with whole-body, liver, and muscle insulin sensitivity. Both diets decreased VAT, abdominal subcutaneous adipose tissue (aSAT), and liver fat, but not whole-body and tissue-specific insulin sensitivity with no differences between diets. Waist circumference, however, decreased more following the LFHP diet as compared to the HMUFA diet (-3.0 vs. -0.5 cm, respectively). After the LFHP but not HMUFA diet, improvements in body composition were positively associated with improvements in whole-body and liver insulin sensitivity. Liver and muscle insulin sensitivity are distinctly associated with liver and muscle fat accumulation. Although both LFHP and HMUFA diets improved in body fat, VAT, aSAT, and liver fat, only LFHP-induced improvements in body composition are associated with improved insulin sensitivity. NCT03708419 (clinicaltrials.gov).

Trouwborst I ，Jardon KM ，Gijbels A ，Hul G ，Feskens EJM ，Afman LA ，Linge J ，Goossens GH ，Blaak EE ... -  《Nutrition & Metabolism》