title: Dietary Marine ω-3 Fatty Acids and Incident Sight-Threatening Retinopathy in Middle-Aged and Older Individuals With Type 2 Diabetes: Prospective Investigation From the PREDIMED Trial.
abstract: OBJECTIVE
  Diabetic retinopathy (DR) is a devastating complication of individuals with type 2 diabetes mellitus. The retina is rich in long-chain ω-3 polyunsaturated fatty acids (LCω3PUFAs), which are substrate for oxylipins with anti-inflammatory and antiangiogenic properties. Experimental models support dietary LCω3PUFA protection against DR, but clinical data are lacking.
  
  
  OBJECTIVE
  To determine whether LCω3PUFA intake relates to a decreased incidence of sight-threatening DR in individuals with type 2 diabetes older than 55 years.
  
  
  METHODS
  In late 2015, we conceived a prospective study within the randomized clinical trial Prevención con Dieta Mediterránea (PREDIMED), testing Mediterranean diets supplemented with extra virgin olive oil or nuts vs a control diet for primary cardiovascular prevention. The trial was conducted in primary health care centers in Spain. From 2003 to 2009, 3614 individuals aged 55 to 80 years with a previous diagnosis of type 2 diabetes were recruited. Full data were available for 3482 participants (48% men; mean age 67 years).
  
  
  METHODS
  Meeting the dietary LCω3PUFA recommendation of at least 500 mg/d for primary cardiovascular prevention, as assessed by a validated food-frequency questionnaire.
  
  
  METHODS
  The main outcome was incident DR requiring laser photocoagulation, vitrectomy, and/or antiangiogenic therapy confirmed by an external adjudication committee.
  
  
  RESULTS
  Of the 3482 participants, 48% were men and the mean age was 67 years. A total of 2611 participants (75%) met target LCω3PUFA recommendation. During a median follow-up of 6 years, we documented 69 new events. After adjusting for age, sex, intervention group, and lifestyle and clinical variables, participants meeting the LCω3PUFA recommendation at baseline (≥500 mg/d) compared with those not fulfilling this recommendation (<500 mg/d) showed a 48% relatively reduced risk of incident sight-threatening DR, with a hazard ratio of 0.52 (95% CI, 0.31-0.88; P = .001). This association was slightly stronger for yearly updated LCω3PUFA intake (relative risk, 0.48; 95% CI, 0.28-0.82; P = .007).
  
  
  CONCLUSIONS
  In middle-aged and older individuals with type 2 diabetes, intake of at least 500 mg/d of dietary LCω3PUFA, easily achievable with 2 weekly servings of oily fish, is associated with a decreased risk of sight-threatening DR. Our results concur with findings from experimental models and the current model of DR pathogenesis.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: http://www.controlled-trials.com/ISRCTN35739639.
authors.affiliation: Lipid Clinic, Endocrinology and Nutrition Service, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain2CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Aleix
authors.initials: A
authors.lastname: Sala-Vila
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain3Human Nutrition Unit, Biochemistry and Biotechnology Department, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, Reus, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Díaz-López
authors.affiliation: Lipid Clinic, Endocrinology and Nutrition Service, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain2CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Cinta
authors.initials: C
authors.lastname: Valls-Pedret
authors.affiliation: Lipid Clinic, Endocrinology and Nutrition Service, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain2CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Cofán
authors.affiliation: Department of Ophthalmology, University of Navarra, Pamplona, Spain.
authors.forename: Alfredo
authors.initials: A
authors.lastname: García-Layana
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain5Department of Nutrition and Food Science, School of Pharmacy, University of Barcelona, Barcelona, Spain.
authors.forename: Rosa-María
authors.initials: RM
authors.lastname: Lamuela-Raventós
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain6Cardiovascular Risk and Nutrition Research Group, Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona Biomedical Research Park, Barcelona, Spain.
authors.forename: Olga
authors.initials: O
authors.lastname: Castañer
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain7Department of Preventive Medicine, University of Valencia, Valencia, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Zanon-Moreno
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain8Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Martinez-Gonzalez
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain8Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain.
authors.forename: Estefanía
authors.initials: E
authors.lastname: Toledo
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain3Human Nutrition Unit, Biochemistry and Biotechnology Department, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, Reus, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Basora
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain3Human Nutrition Unit, Biochemistry and Biotechnology Department, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, Reus, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Salas-Salvadó
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain7Department of Preventive Medicine, University of Valencia, Valencia, Spain.
authors.forename: Dolores
authors.initials: D
authors.lastname: Corella
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain9Department of Preventive Medicine, University of Malaga, Malaga, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Gómez-Gracia
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain10Institute of Health Sciences, Instituto de Investigación Sanitaria de Palma, Palma de Mallorca, Spain.
authors.forename: Miquel
authors.initials: M
authors.lastname: Fiol
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain11Department of Internal Medicine, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: Estruch
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain12Department of Family Medicine, Primary Care Division of Sevilla, San Pablo Health Center, Sevilla, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Lapetra
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain6Cardiovascular Risk and Nutrition Research Group, Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona Biomedical Research Park, Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Fitó
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain13Department of Cardiology, University Hospital of Alava, Vitoria, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Arós
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain14Research Institute of Biomedical and Health Sciences, University of Las Palmas de Gran Canaria, Las Palmas, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Serra-Majem
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain15Department of Internal Medicine, Bellvitge Biomedical Research Institute-Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, FIPEC (Research Foundation for Cardiovascular Disease Prevention), Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Pintó
authors.affiliation: Lipid Clinic, Endocrinology and Nutrition Service, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain2CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Emilio
authors.initials: E
authors.lastname: Ros
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000178:diet therapy; D003930:Diabetic Retinopathy / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D019587:Dietary Supplements; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D017747:Seafood; D013030:Spain / Q000453:epidemiology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015525:Fatty Acids, Omega-3