title: Effects of sardine-enriched diet on metabolic control, inflammation and gut microbiota in drug-naïve patients with type 2 diabetes: a pilot randomized trial.
abstract: BACKGROUND
  Nutrition therapy is the cornerstone of treating diabetes mellitus. The inclusion of fish (particularly oily fish) at least two times per week is recommended by current international dietary guidelines for type 2 diabetes. In contrast to a large number of human studies examining the effects of oily fish on different cardiovascular risk factors, little research on this topic is available in patients with type 2 diabetes. The aims of this pilot study were to investigate the effects of a sardine-enriched diet on metabolic control, adiponectin, inflammatory markers, erythrocyte membrane fatty acid (EMFA) composition, and gut microbiota in drug-naïve patients with type 2 diabetes.
  
  
  METHODS
  35 drug-naïve patients with type 2 diabetes were randomized to follow either a type 2 diabetes standard diet (control group: CG), or a standard diet enriched with 100 g of sardines 5 days a week (sardine group: SG) for 6 months. Anthropometric, dietary information, fasting glycated hemoglobin, glucose, insulin, adiponectin, inflammatory markers, EMFA and specific bacterial strains were determined before and after intervention.
  
  
  RESULTS
  There were no significant differences in glycemic control between groups at the end of the study. Both groups decreased plasma insulin (SG: -35.3%, P = 0.01, CG: -22.6%, P = 0.02) and homeostasis model of assessment--insulin resistance (HOMA-IR) (SG: -39.2%, P = 0.007, CG: -21.8%, P = 0.04) at 6-months from baseline. However only SG increased adiponectin in plasma compared to baseline level (+40.7%, P = 0.04). The omega-3 index increased 2.6% in the SG compared to 0.6% in the CG (P = 0.001). Both dietary interventions decreased phylum Firmicutes (SG and CG: P = 0.04) and increased E. coli concentrations (SG: P = 0.01, CG: P = 0.03) at the end of the study from baseline, whereas SG decreased Firmicutes/Bacteroidetes ratio (P = 0.04) and increased Bacteroides-Prevotella (P = 0.004) compared to baseline.
  
  
  CONCLUSIONS
  Although enriching diet with 100 g of sardines 5 days a week during 6 months to a type 2 diabetes standard diet seems to have neutral effects on glycemic control in drug-naïve patients with type 2 diabetes, this nutritional intervention could have beneficial effects on cardiovascular risk. Furthermore, both dietary interventions decreased HOMA-IR and altered gut microbiota composition of drug-naïve patients with type 2 diabetes.
  
  
  BACKGROUND
  Trial number and name of the registry: NCT02294526, ClinicalTrials.gov.
authors.affiliation: CIBER in Diabetes and Associated Metabolic Disorders (CIBERDEM), c/ Monforte de Lemos 3-5 Pabellón 11 planta 0, 28029, Madrid, Spain. mbalfego@clinic.ub.es.|Diabetes and Obesity Research Laboratory, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), c/ Roselló 149 planta 5, 08036, Barcelona, Spain. mbalfego@clinic.ub.es.
authors.forename: Mariona
authors.initials: M
authors.lastname: Balfegó
authors.affiliation: Diabetes and Obesity Research Laboratory, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), c/ Roselló 149 planta 5, 08036, Barcelona, Spain.|Les Corts Primary Health Care Center, Tranverse Group for Research in Primary Care, IDIBAPS, c/ Mejia Lequerica s/n, 08028, Barcelona, Spain.|Present address: Centre Hospitalier Universitaire Vaudois (CHUV), Departement de Endocrinologie, Rue Saint-Martin 3, CH-1003, Lausanne, Switzerland.
authors.forename: Silvia
authors.initials: S
authors.lastname: Canivell
authors.affiliation: CIBER in Diabetes and Associated Metabolic Disorders (CIBERDEM), c/ Monforte de Lemos 3-5 Pabellón 11 planta 0, 28029, Madrid, Spain.|Department of Endocrinology and Nutrition, Hospital Clínic of Barcelona, c/Villarroel 170 Escala 11 planta 2, 08036, Barcelona, Spain.|University of Barcelona, Facultat de Medicina, c/ Casanova 143, 08036, Barcelona, Spain.
authors.forename: Felicia A
authors.initials: FA
authors.lastname: Hanzu
authors.affiliation: CIBER in Physiopathology of Obesity and Nutrition (CIBERobn), c/Villarroel 170, Edifici Helios, 08036, Barcelona, Spain.
authors.forename: Aleix
authors.initials: A
authors.lastname: Sala-Vila
authors.affiliation: Laboratory of Molecular Microbiology, Biology Department, University of Girona, Av. Montilivi s/n, E-17071, Girona, Spain.
authors.forename: Margarita
authors.initials: M
authors.lastname: Martínez-Medina
authors.affiliation: CIBER in Diabetes and Associated Metabolic Disorders (CIBERDEM), c/ Monforte de Lemos 3-5 Pabellón 11 planta 0, 28029, Madrid, Spain.|Diabetes and Obesity Research Laboratory, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), c/ Roselló 149 planta 5, 08036, Barcelona, Spain.
authors.forename: Serafín
authors.initials: S
authors.lastname: Murillo
authors.affiliation: Terrassa Sud Primary Health Care Center, Mútua de Terrassa, Av. Santa Eulàlia s/n, 08223, Terrassa, Barcelona, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Mur
authors.affiliation: CIBER in Diabetes and Associated Metabolic Disorders (CIBERDEM), c/ Monforte de Lemos 3-5 Pabellón 11 planta 0, 28029, Madrid, Spain.|Diabetes and Obesity Research Laboratory, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), c/ Roselló 149 planta 5, 08036, Barcelona, Spain.
authors.forename: Elena G
authors.initials: EG
authors.lastname: Ruano
authors.affiliation: CIBER in Diabetes and Associated Metabolic Disorders (CIBERDEM), c/ Monforte de Lemos 3-5 Pabellón 11 planta 0, 28029, Madrid, Spain.|Endocrinology and Nutrition Department, Hospital Carlos Haya, Biomedical Research Institute of Málaga (IBIMA), Plaza Hospital Civil s/n Sótano Pabellón 1, 29009, Málaga, Spain.
authors.forename: Francisca
authors.initials: F
authors.lastname: Linares
authors.affiliation: CIBER in Diabetes and Associated Metabolic Disorders (CIBERDEM), c/ Monforte de Lemos 3-5 Pabellón 11 planta 0, 28029, Madrid, Spain.|Endocrinology and Nutrition Department, Hospital Carlos Haya, Biomedical Research Institute of Málaga (IBIMA), Plaza Hospital Civil s/n Sótano Pabellón 1, 29009, Málaga, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Porras
authors.affiliation: CIBER in Diabetes and Associated Metabolic Disorders (CIBERDEM), c/ Monforte de Lemos 3-5 Pabellón 11 planta 0, 28029, Madrid, Spain.|Vall d'Hebrón Research Institute and Autonomous University of Barcelona, Pg. de la Vall d'Hebrón 119-129 planta 8, Barcelona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Valladares
authors.affiliation: CIBER in Diabetes and Associated Metabolic Disorders (CIBERDEM), c/ Monforte de Lemos 3-5 Pabellón 11 planta 0, 28029, Madrid, Spain.|Endocrinology and Nutrition Department, Hospital Carlos Haya, Biomedical Research Institute of Málaga (IBIMA), Plaza Hospital Civil s/n Sótano Pabellón 1, 29009, Málaga, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Fontalba
authors.affiliation: Alicia Foundation, Camí Sant Benet, 08272 Sant Fruitós de Bages, Barcelona, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Roura
authors.affiliation: CIBER in Diabetes and Associated Metabolic Disorders (CIBERDEM), c/ Monforte de Lemos 3-5 Pabellón 11 planta 0, 28029, Madrid, Spain.|Diabetes and Obesity Research Laboratory, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), c/ Roselló 149 planta 5, 08036, Barcelona, Spain.|Department of Endocrinology and Nutrition, Hospital Clínic of Barcelona, c/Villarroel 170 Escala 11 planta 2, 08036, Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Novials
authors.affiliation: CIBER in Diabetes and Associated Metabolic Disorders (CIBERDEM), c/ Monforte de Lemos 3-5 Pabellón 11 planta 0, 28029, Madrid, Spain.|Vall d'Hebrón Research Institute and Autonomous University of Barcelona, Pg. de la Vall d'Hebrón 119-129 planta 8, Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Hernández
authors.affiliation: Department of Endocrinology and Nutrition, Hospital Clínic of Barcelona, c/Villarroel 170 Escala 11 planta 2, 08036, Barcelona, Spain.
authors.forename: Gloria
authors.initials: G
authors.lastname: Aranda
authors.affiliation: Les Corts Primary Health Care Center, Tranverse Group for Research in Primary Care, IDIBAPS, c/ Mejia Lequerica s/n, 08028, Barcelona, Spain.|University of Barcelona, Facultat de Medicina, c/ Casanova 143, 08036, Barcelona, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Sisó-Almirall
authors.affiliation: CIBER in Diabetes and Associated Metabolic Disorders (CIBERDEM), c/ Monforte de Lemos 3-5 Pabellón 11 planta 0, 28029, Madrid, Spain.|Endocrinology and Nutrition Department, Hospital Carlos Haya, Biomedical Research Institute of Málaga (IBIMA), Plaza Hospital Civil s/n Sótano Pabellón 1, 29009, Málaga, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Rojo-Martínez
authors.affiliation: CIBER in Diabetes and Associated Metabolic Disorders (CIBERDEM), c/ Monforte de Lemos 3-5 Pabellón 11 planta 0, 28029, Madrid, Spain.|Vall d'Hebrón Research Institute and Autonomous University of Barcelona, Pg. de la Vall d'Hebrón 119-129 planta 8, Barcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Simó
authors.affiliation: CIBER in Diabetes and Associated Metabolic Disorders (CIBERDEM), c/ Monforte de Lemos 3-5 Pabellón 11 planta 0, 28029, Madrid, Spain.|Diabetes and Obesity Research Laboratory, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), c/ Roselló 149 planta 5, 08036, Barcelona, Spain.|Department of Endocrinology and Nutrition, Hospital Clínic of Barcelona, c/Villarroel 170 Escala 11 planta 2, 08036, Barcelona, Spain.|University of Barcelona, Facultat de Medicina, c/ Casanova 143, 08036, Barcelona, Spain.
authors.forename: Ramon
authors.initials: R
authors.lastname: Gomis
mesh_terms: D052242:Adiponectin / Q000097:blood; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001823:Body Composition / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000178:diet therapy* / Q000382:microbiology*; D004910:Erythrocyte Membrane / Q000737:chemistry / Q000187:drug effects; D005227:Fatty Acids / Q000032:analysis / Q000097:blood; D015525:Fatty Acids, Omega-3 / Q000097:blood; D005260:Female; D005396:Fish Products; D005399:Fishes; D000069196:Gastrointestinal Microbiome; D006801:Humans; D007249:Inflammation / Q000097:blood; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D015415:Biomarkers; D005227:Fatty Acids; D015525:Fatty Acids, Omega-3
keywords: Nutrition therapy; Oily fish; Pilot trial; Sardine; Type 2 diabetes