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

Importance: 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. Design, Setting, and Participants: 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). Exposures: Meeting the dietary LCω3PUFA recommendation of at least 500mg/d for primary cardiovascular prevention, as assessed by a validated food-frequency questionnaire. Main Outcomes and Measures: The main outcomewas 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 (≥500mg/d) compared with those not fulfilling this recommendation (<500mg/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 and Relevance: In middle-aged and older individuals with type 2 diabetes, intake of at least 500mg/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.