title: The insulin resistance phenotype (muscle or liver) interacts with the type of diet to determine changes in disposition index after 2 years of intervention: the CORDIOPREV-DIAB randomised clinical trial.
abstract: OBJECTIVE
  The aim of the study was to determine whether basal insulin resistance (IR) phenotype (muscle and/or liver) determines the effect of long-term consumption of a Mediterranean diet or a low-fat diet on tissue-specific IR and beta cell function.
  
  
  METHODS
  The study was performed in 642 patients included in The effect of an olive oil rich Mediterranean diet on type 2 diabetes mellitus risk and incidence study (CORDIOPREV-DIAB). A total of 327 patients were randomised to a Mediterranean diet (35% fat; 22% from monounsaturated fatty acids) and 315 to a low-fat diet (<28% fat). At baseline, the patients were classified into four phenotypes according to the type of IR: (1) no IR; (2) muscle IR; (3) liver IR; (4) muscle + liver IR. The hepatic insulin resistance index (HIRI), muscular insulin sensitivity index (MISI) and disposition index were analysed at baseline and after 2 years of follow-up.
  
  
  RESULTS
  At baseline, 322 patients presented no IR, 106 presented muscle IR, 109 presented liver IR, and 105 presented muscle + liver IR. With both dietary interventions, HIRI decreased in all patients (p < 0.001) and MISI increased in muscle IR and muscle + liver IR patients (p < 0.01). Long-term intake of the Mediterranean diet increased the disposition index and insulinogenic index in the muscle IR patients (p = 0.042 and p = 0.044, respectively) and the disposition index in the muscle + liver IR patients (p = 0.048), whereas the low-fat diet increased the disposition index in the liver IR patients (p = 0.017).
  
  
  CONCLUSIONS
  Although both diets improve insulin sensitivity, there are differences based on basal IR phenotypes. Moreover, according to insulinogenic and disposition index data, a low-fat diet might be more beneficial to patients with liver IR, whereas patients with muscle IR and muscle + liver IR might benefit more from a Mediterranean diet. Trial registration ClinicalTrials.gov NCT00924937 FUNDING: The study was supported by the Ministerio de Economia y Competitividad (AGL2012/39615) and by the Ministerio de Ciencia e Innovacion (PIE14/00005 and PI13/00023).
authors.affiliation: Lipids and Atherosclerosis Research Unit, Reina Sofia University Hospital, Avda Menendez Pidal, s/n, 14004, Cordoba, Spain.|Nutrigenomics and Metabolic Syndrome, Maimonides Institute for Biomedical Research at Cordoba (IMIBIC), Cordoba, Spain.|Department of Medicine, University of Cordoba, Cordoba, Spain.|CIBER Fisiopatología Obesidad y Nutrición (CIBEROBN).
authors.forename: Ruth
authors.initials: R
authors.lastname: Blanco-Rojo
authors.affiliation: Lipids and Atherosclerosis Research Unit, Reina Sofia University Hospital, Avda Menendez Pidal, s/n, 14004, Cordoba, Spain.|Nutrigenomics and Metabolic Syndrome, Maimonides Institute for Biomedical Research at Cordoba (IMIBIC), Cordoba, Spain.|Department of Medicine, University of Cordoba, Cordoba, Spain.|CIBER Fisiopatología Obesidad y Nutrición (CIBEROBN).
authors.forename: Juan F
authors.initials: JF
authors.lastname: Alcala-Diaz
authors.affiliation: TNO, Zeist, the Netherlands.
authors.forename: Suzan
authors.initials: S
authors.lastname: Wopereis
authors.affiliation: Lipids and Atherosclerosis Research Unit, Reina Sofia University Hospital, Avda Menendez Pidal, s/n, 14004, Cordoba, Spain.|Nutrigenomics and Metabolic Syndrome, Maimonides Institute for Biomedical Research at Cordoba (IMIBIC), Cordoba, Spain.|Department of Medicine, University of Cordoba, Cordoba, Spain.|CIBER Fisiopatología Obesidad y Nutrición (CIBEROBN).
authors.forename: Pablo
authors.initials: P
authors.lastname: Perez-Martinez
authors.affiliation: Lipids and Atherosclerosis Research Unit, Reina Sofia University Hospital, Avda Menendez Pidal, s/n, 14004, Cordoba, Spain.|Nutrigenomics and Metabolic Syndrome, Maimonides Institute for Biomedical Research at Cordoba (IMIBIC), Cordoba, Spain.|Department of Medicine, University of Cordoba, Cordoba, Spain.|CIBER Fisiopatología Obesidad y Nutrición (CIBEROBN).
authors.forename: Gracia M
authors.initials: GM
authors.lastname: Quintana-Navarro
authors.affiliation: Lipids and Atherosclerosis Research Unit, Reina Sofia University Hospital, Avda Menendez Pidal, s/n, 14004, Cordoba, Spain.|Nutrigenomics and Metabolic Syndrome, Maimonides Institute for Biomedical Research at Cordoba (IMIBIC), Cordoba, Spain.|Department of Medicine, University of Cordoba, Cordoba, Spain.|CIBER Fisiopatología Obesidad y Nutrición (CIBEROBN).
authors.forename: Carmen
authors.initials: C
authors.lastname: Marin
authors.affiliation: Nutrition and Genomics Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.|IMDEA Food Institute, Madrid, Spain.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Ordovas
authors.affiliation: TNO, Zeist, the Netherlands.
authors.forename: Ben
authors.initials: B
authors.lastname: van Ommen
authors.affiliation: Lipids and Atherosclerosis Research Unit, Reina Sofia University Hospital, Avda Menendez Pidal, s/n, 14004, Cordoba, Spain.|Nutrigenomics and Metabolic Syndrome, Maimonides Institute for Biomedical Research at Cordoba (IMIBIC), Cordoba, Spain.|Department of Medicine, University of Cordoba, Cordoba, Spain.|CIBER Fisiopatología Obesidad y Nutrición (CIBEROBN).
authors.forename: Francisco
authors.initials: F
authors.lastname: Perez-Jimenez
authors.affiliation: Lipids and Atherosclerosis Research Unit, Reina Sofia University Hospital, Avda Menendez Pidal, s/n, 14004, Cordoba, Spain.|Nutrigenomics and Metabolic Syndrome, Maimonides Institute for Biomedical Research at Cordoba (IMIBIC), Cordoba, Spain.|Department of Medicine, University of Cordoba, Cordoba, Spain.|CIBER Fisiopatología Obesidad y Nutrición (CIBEROBN).
authors.forename: Javier
authors.initials: J
authors.lastname: Delgado-Lista
authors.affiliation: Lipids and Atherosclerosis Research Unit, Reina Sofia University Hospital, Avda Menendez Pidal, s/n, 14004, Cordoba, Spain. jlopezmir@uco.es.|Nutrigenomics and Metabolic Syndrome, Maimonides Institute for Biomedical Research at Cordoba (IMIBIC), Cordoba, Spain. jlopezmir@uco.es.|Department of Medicine, University of Cordoba, Cordoba, Spain. jlopezmir@uco.es.|CIBER Fisiopatología Obesidad y Nutrición (CIBEROBN), . jlopezmir@uco.es.
authors.forename: Jose
authors.initials: J
authors.lastname: Lopez-Miranda
keywords: Beta cell function; Dietary intervention; Insulin resistance; Low-fat diet; Mediterranean diet