title: Insulin resistance determines a differential response to changes in dietary fat modification on metabolic syndrome risk factors: the LIPGENE study.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Lipids and Atherosclerosis Unit, Maimonides Institute for Biomedical Research in Cordoba, Reina Sofia University Hospital, University of Córdoba, Córdoba, Spain; CIBER Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Spain;
authors.forename: Elena M
authors.identifier: http://orcid.org/0000-0002-2733-5359
authors.initials: EM
authors.lastname: Yubero-Serrano
authors.affiliation: Lipids and Atherosclerosis Unit, Maimonides Institute for Biomedical Research in Cordoba, Reina Sofia University Hospital, University of Córdoba, Córdoba, Spain; CIBER Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Spain;
authors.forename: Javier
authors.initials: J
authors.lastname: Delgado-Lista
authors.affiliation: Nutrigenomics Research Group, University College Dublin Conway Institute, School of Public Health, University College Dublin, Dublin, Ireland;
authors.forename: Audrey C
authors.initials: AC
authors.lastname: Tierney
authors.affiliation: Lipids and Atherosclerosis Unit, Maimonides Institute for Biomedical Research in Cordoba, Reina Sofia University Hospital, University of Córdoba, Córdoba, Spain; CIBER Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Spain;
authors.forename: Pablo
authors.initials: P
authors.lastname: Perez-Martinez
authors.affiliation: Lipids and Atherosclerosis Unit, Maimonides Institute for Biomedical Research in Cordoba, Reina Sofia University Hospital, University of Córdoba, Córdoba, Spain; CIBER Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Spain;
authors.forename: Antonio
authors.initials: A
authors.lastname: Garcia-Rios
authors.affiliation: Lipids and Atherosclerosis Unit, Maimonides Institute for Biomedical Research in Cordoba, Reina Sofia University Hospital, University of Córdoba, Córdoba, Spain; CIBER Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Spain;
authors.forename: Juan F
authors.initials: JF
authors.lastname: Alcala-Diaz
authors.affiliation: Department of Cell Biology, Physiology and Immunology, University of Córdoba, Maimonides Institute for Biomedical Research in Cordoba/Reina Sofia University, CIBER Maimonides Institute for Biomedical Research in Cordoba, Córdoba, Spain;
authors.forename: Justo P
authors.identifier: http://orcid.org/0000-0002-3145-7287
authors.initials: JP
authors.lastname: Castaño
authors.affiliation: Biomedical Research Institute of Málaga, Virgen de la Victoria Hospital, University of Málaga, Málaga, Spain;
authors.forename: Francisco J
authors.identifier: http://orcid.org/0000-0001-7662-7772
authors.initials: FJ
authors.lastname: Tinahones
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway;
authors.forename: Christian A
authors.initials: CA
authors.lastname: Drevon
authors.affiliation: NRA-Joint Research Unit, UMR1260, and French National Institute of Health and Medical Research ERL1025 Lipid Nutrients and the Prevention of Metabolic Diseases, Faculty of Medicine, Marseille, France;
authors.forename: Catherine
authors.initials: C
authors.lastname: Defoort
authors.affiliation: Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center, Maastricht, Netherlands;
authors.forename: Ellen E
authors.initials: EE
authors.lastname: Blaak
authors.affiliation: Department of Clinical Biochemistry, Jagiellonian University, Collegium Medicum, Kraków, Poland;
authors.forename: Aldona
authors.initials: A
authors.lastname: Dembinska-Kieć
authors.affiliation: Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden; and.
authors.forename: Ulf
authors.initials: U
authors.lastname: Risérus
authors.affiliation: Hugh Sinclair Unit of Human Nutrition and Institute for Cardiovascular and Metabolic Research, Department of Food and Nutritional Sciences, University of Reading, Reading, United Kingdom.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Lovegrove
authors.affiliation: Lipids and Atherosclerosis Unit, Maimonides Institute for Biomedical Research in Cordoba, Reina Sofia University Hospital, University of Córdoba, Córdoba, Spain; CIBER Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Spain;
authors.forename: Francisco
authors.initials: F
authors.lastname: Perez-Jimenez
authors.affiliation: Nutrigenomics Research Group, University College Dublin Conway Institute, School of Public Health, University College Dublin, Dublin, Ireland;
authors.forename: Helen M
authors.initials: HM
authors.lastname: Roche
authors.affiliation: Lipids and Atherosclerosis Unit, Maimonides Institute for Biomedical Research in Cordoba, Reina Sofia University Hospital, University of Córdoba, Córdoba, Spain; CIBER Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Spain; jlopezmir@uco.es.
authors.forename: Jose
authors.initials: J
authors.lastname: Lopez-Miranda
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D015331:Cohort Studies; D018752:Diet, Fat-Restricted; D004042:Dietary Fats, Unsaturated / Q000627:therapeutic use*; D019587:Dietary Supplements; D005060:Europe / Q000453:epidemiology; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use*; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006949:Hyperlipidemias / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D006973:Hypertension / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D007333:Insulin Resistance; D008297:Male; D024821:Metabolic Syndrome / Q000178:diet therapy* / Q000453:epidemiology / Q000378:metabolism / Q000503:physiopathology; D008875:Middle Aged; D012307:Risk Factors; D016037:Single-Blind Method; D055105:Waist Circumference
chemical_list: D015415:Biomarkers; D004042:Dietary Fats, Unsaturated; D005229:Fatty Acids, Monounsaturated; D015525:Fatty Acids, Omega-3
keywords: dietary fat modification; insulin resistance; metabolic syndrome; monounsaturated fat; polyunsaturated fat