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

IMPORTANCE Diabetic retinopathy (DR) is a devastating complication of individuals with type 2 diabetes mellitus. The retina is rich in long-chain omega-3 polyunsaturated fatty acids (LC omega 3PUFAs), which are substrate for oxylipins with anti-inflammatory and antiangiogenic properties. Experimental models support dietary LC omega 3PUFA protection against DR, but clinical data are lacking. OBJECTIVE To determine whether LC omega 3PUFA 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 Prevencion con Dieta Mediterranea (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 LC omega 3PUFA recommendation of at least 500mg/d for primary cardiovascular prevention, as assessed by a validated food-frequency questionnaire. MAIN OUTCOMES AND MEASURES 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 LC omega 3PUFA 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 LC omega 3PUFA 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 LC omega 3PUFA 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 LC omega 3PUFA, 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.