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Background

The transcription factor 7-like 2 (TCF7L2) gene confers one of the strongest genetic predispositions to type 2 diabetes, but diabetes development can be modified by diet.

Objective

The aim of our study was to evaluate postprandial metabolic alterations in healthy men with a high genetic risk of diabetes, after two meals with varying macronutrient content.

Methods

The study was conducted in 21 homozygous nondiabetic men carrying the high-risk (HR, n = 8, age: 31.2 ± 6.3 y, body mass index (BMI, kg/m2) 28.5 ± 8.1) or low-risk (LR, n = 13, age: 35.2 ± 10.3 y, BMI: 28.1 ± 6.4) genotypes at the rs7901695 locus. During two meal challenge test visits subjects received standardized isocaloric (450 kcal) liquid meals: high-carbohydrate (HC, carbohydrates: 89% of energy) and normo-carbohydrate (NC, carbohydrates: 45% of energy). Fasting (0 min) and postprandial (30, 60, 120, 180 min) plasma samples were analyzed for metabolite profiles through untargeted metabolomics. Metabolic fingerprinting was performed on an ultra-high-performance liquid chromatography (UHPLC) system connected to an iFunnel quadrupole-time-of-flight (Q-TOF) mass spectrometer.

Results

In HR-genotype men, after the intake of an HC-meal, we noted a significantly lower area under the curves (AUCs) of postprandial plasma concentrations of most of the phospholipids (-37% to -53%, variable importance in the projection (VIP) = 1.2-1.5), lysophospholipids (-29% to -86%, VIP = 1.1-2.6), sphingolipids (-32% to -47%, VIP = 1.1-1.3), as well as arachidonic (-36%, VIP = 1.4) and oleic (-63%, VIP = 1.3) acids, their metabolites: keto- and hydoxy-fatty acids (-38% to -78%, VIP = 1.3-2.5), leukotrienes (-65% to -83%, VIP = 1.4-2.2), uric acid (-59%, VIP = 1.5), and pyroglutamic acid (-65%, VIP = 1.8). The AUCs of postprandial sphingosine concentrations were higher (125-832%, VIP = 1.9-3.2) after the NC-meal, AUCs of acylcarnitines were lower (-21% to -61%, VIP = 1.1-2.4), and AUCs of fatty acid amides were higher (51-508%, VIP = 1.7-3.1) after the intake of both meals.

Conclusions

In nondiabetic men carrying the TCF7L2 HR genotype, subtle but detectable modifications in intermediate lipid metabolism are induced by an HC-meal. This trial was registered at www.clinicaltrials.gov as NCT03792685."xsd:string
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http://purl.uniprot.org/citations/31049566http://purl.uniprot.org/core/author"Bauer W."xsd:string
http://purl.uniprot.org/citations/31049566http://purl.uniprot.org/core/author"Barbas C."xsd:string
http://purl.uniprot.org/citations/31049566http://purl.uniprot.org/core/author"Gorska M."xsd:string
http://purl.uniprot.org/citations/31049566http://purl.uniprot.org/core/author"Kretowski A."xsd:string
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http://purl.uniprot.org/citations/31049566http://purl.uniprot.org/core/author"Godzien J."xsd:string
http://purl.uniprot.org/citations/31049566http://purl.uniprot.org/core/author"Samczuk P."xsd:string
http://purl.uniprot.org/citations/31049566http://purl.uniprot.org/core/author"Pietrowska K."xsd:string
http://purl.uniprot.org/citations/31049566http://purl.uniprot.org/core/date"2019"xsd:gYear
http://purl.uniprot.org/citations/31049566http://purl.uniprot.org/core/name"J Nutr"xsd:string
http://purl.uniprot.org/citations/31049566http://purl.uniprot.org/core/pages"915-922"xsd:string
http://purl.uniprot.org/citations/31049566http://purl.uniprot.org/core/title"Metabolomics Reveal Altered Postprandial Lipid Metabolism After a High-Carbohydrate Meal in Men at High Genetic Risk of Diabetes."xsd:string
http://purl.uniprot.org/citations/31049566http://purl.uniprot.org/core/volume"149"xsd:string
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