Mediterranean Diet, Glucose Homeostasis, and Inflammasome Genetic Variants: The CORDIOPREV Study

• Published in: Molecular nutrition & food research 2018-05, Vol.62 (9), p.e1700960-n/a
• Main Authors: Roncero‐Ramos, Irene, Rangel‐Zuñiga, Oriol A., Lopez‐Moreno, Javier, Alcala‐Diaz, Juan F., Perez‐Martinez, Pablo, Jimenez‐Lucena, Rosa, Castaño, Justo P., Roche, Helen M., Delgado‐Lista, Javier, Ordovas, Jose M., Camargo, Antonio, Lopez‐Miranda, Jose
• Format: Article
• Language: English
• Subjects: Cardiovascular disease; Cardiovascular diseases; CORDIOPREV; Coronary artery disease; Coronary Disease - complications; Coronary Disease - genetics; Coronary Disease - metabolism; Coronary Disease - prevention & control; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - diet therapy; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - metabolism; Diabetic Angiopathies - genetics; Diabetic Angiopathies - immunology; Diabetic Angiopathies - metabolism; Diabetic Angiopathies - prevention & control; Diabetic Cardiomyopathies - genetics; Diabetic Cardiomyopathies - immunology; Diabetic Cardiomyopathies - metabolism; Diabetic Cardiomyopathies - prevention & control; Diet; Diet, Fat-Restricted; Diet, Mediterranean; Female; Follow-Up Studies; Genetic Association Studies; Genetic diversity; Genetic Predisposition to Disease; Genetic variance; Genetics; Glucose; Heart diseases; Heterozygote; Homeostasis; Humans; Immunity; Inflammasomes; Inflammasomes - immunology; Inflammasomes - metabolism; Innate immunity; Insulin; Insulin Resistance; insulin sensitivity; Intervention; Low fat; Low fat diet; Male; Mediterranean diet; Middle Aged; NLR Family, Pyrin Domain-Containing 3 Protein - genetics; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; NLRP3 inflammasome; Nutrient deficiency; Nutrigenomics - methods; Patients; Polymorphism, Single Nucleotide; Pyrin protein; Secondary Prevention; single nucleotide polymorphisms; Single-nucleotide polymorphism; Spain
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.201700960

Scope Insulin resistance (IR) and chronic low‐grade inflammation are hallmarks of type 2 diabetes mellitus (T2DM). The “NOD‐like receptor pyrin domain containing‐3” (NLRP3) inflammasome component of innate immunity is a metabolic stress sensor modulated by dietary and genetics factors. The aim of this study was to evaluate the effects of the consumption of two diets for 3 years, Mediterranean (Med) and low fat, on glucose homeostasis in the 1002 coronary heart disease patients of the CORDIOPREV study, according to a genetic variant of NLRP3 inflammasome. Methods and results The study was conducted in the framework of the CORDIOPREV study, a randomized dietary intervention with Med and low‐fat diets. Single nucleotide polymorphisms (SNPs) located at inflammasome NLRP3 gene were genotyped by OpenArray platform. Nondiabetic CT+TT carriers of the rs4612666 SNP and AG+AA carriers of the rs10733113 SNP increased insulin sensitivity index (ISI) after 3 years of dietary intervention, whereas no effect was observed in diabetic patients. Further analysis by diet showed that the improvement of the ISI in nondiabetic rs10733113 AG+AA carriers was specific to the consumption of the Med diet. Conclusion Our results show that the benefits associated with a Med diet regarding glucose homeostasis in non‐T2DM patients depend on genetic variation in the inflammasome. NLRP3 inflammasome activation specifically induces IL‐1β inflammation, which in turn leads to insulin resistance and progression of type 2 diabetes. It is shown that rs10733113 A allele carriers improve the insulin sensitivity after 3 years of Mediterranean (Med) diet consumption, presumably by dietary MUFA‐inflammasome gene variant interaction. Thus, the beneficial properties associated with Med diet in terms of glucose homeostasis may depend on an individual's genetic background.