The Associations of Dietary Intake of Polyunsaturated Fatty Acids With Diabetic Retinopathy in Well-Controlled Diabetes

Sasaki, Mariko; Kawasaki, Ryo; Rogers, Sophie; Man, Ryan Eyn Kidd; Itakura, Kiho; Xie, Jing; Flood, Victoria M; Tsubota, Kazuo; Lamoureux, Ecosse L.; Wang, Jie Jin

doi:10.1167/iovs.15-17485

Cited by 63 publications

(86 citation statements)

References 33 publications

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“…Actually, a small cross-sectional study reported that increased PUFA intake (although not distinguishing between ω-3 or ω-6 fatty acids) was associated with reduced odds of prevalent DR and lesser DR severity in patients with well-controlled diabetes, while no associations were found for those poorly controlled. 22 Suprisingly, neither epidemiologic studies nor clinical trials focused on dietary LCω3PUFA and DR, although the link has repeatedly been proven in experimental models. [8][9][10][11] By reporting that regular LCω3PUFA intake seems to reduce the risk of the most severe form of DR, particularly in patients with hypertension or advanced diabetes, we reinforce the benefits of these particular fatty acid species in a critical population group.…”

Section: Discussionmentioning

confidence: 99%

Dietary Marine ω-3 Fatty Acids and Incident Sight-Threatening Retinopathy in Middle-Aged and Older Individuals With Type 2 Diabetes

et al. 2016

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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 500 mg/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 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 (Ն500 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 AND RELEVANCE 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. TRIAL REGISTRATION clinicaltrials.gov Identifier: http://www.controlled-trials.com /ISRCTN35739639

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Section: Discussionmentioning

confidence: 99%

Dietary Marine ω-3 Fatty Acids and Incident Sight-Threatening Retinopathy in Middle-Aged and Older Individuals With Type 2 Diabetes

et al. 2016

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“…Based on the retrospective analysis of this study, patients with T1D were advised to reduce their total dietary fat to ,30% and the saturated fat to ,10%, as was formerly recommended by the American Diabetes Association. To this day, the evidence for the effect of dietary fat intake on DR incidence and progression remains inconclusive, and a potential positive effect of specific saturated fatty acids (SFAs) and unsaturated fatty acids has been raised (15)(16)(17)(18).…”

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confidence: 99%

In contrast to Western diet, a plant‐based, high‐fat, low‐sugar diet does not exacerbate retinal endothelial injury in streptozotocin‐induced diabetes

et al. 2019

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Controversy remains about how diet affects the vascular endothelial dysfunction associated with disordered insulin‐glucose homeostasis. It is postulated that the type and level of certain macronutrients contribute to endothelial dysfunction in vascular diabetes complications. However, it is not well understood how specific macronutrients affect the molecular inflammatory response under conditions of hyperglycemia. Here, we examined retinal microvascular endothelial injury in streptozotocin (STZ)‐diabetic rats fed a laboratory Western diet (WD). WD, characterized by its high content of saturated fat, cholesterol, and sugar, significantly increased retinal leukocyte accumulation and endothelial injury in the STZ‐diabetic rats. Suppression of endothelial NF‐κB signaling in the STZ model reduced the WD‐induced increase in leukocyte accumulation. To isolate the effect of dietary fat, we generated high‐fat diets with varying fatty acid balance and type. These diets contained moderate amounts of carbohydrates but no sugar. We found that neither high levels of saturated or unsaturated fats per se increased retinal leukocyte accumulation and endothelial injury in the STZ‐diabetic rat model but that the combination of high levels of dietary cholesterol with specific saturated fatty acids that are abundant in WD exacerbated leukocyte accumulation and endothelial injury in the retinas of STZ‐diabetic rats.—Barakat, A., Nakao, S., Zandi, S., Sun, D., Schmidt‐Ullrich, R., Hayes, K. C., Hafezi‐Moghadam, A. In contrast to Western diet, a plant‐based, high‐fat, low‐sugar diet does not exacerbate retinal endothelial injury in streptozotocin‐induced diabetes. FASEB J. 33, 10327–10338 (2019). http://www.fasebj.org

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“…Similarly, DR was not associated with omega-3 or −6 PUFA levels in our cohort. This is different from saturated fatty acids, for which a positive association with the presence and severity of DR was described [21]. …”

Section: Discussionmentioning

confidence: 97%

Systemic confounders affecting serum measurements of omega-3 and -6 polyunsaturated fatty acids in patients with retinal disease

et al. 2016

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BackgroundOmega-3 polyunsaturated fatty acids (PUFAs) have a highly anti-angiogenic effect in animal models. However, the clinical relevance of omega-3PUFAs in human retinal pathologies remains unclear. The ARED 2 study found no effect of omega-3 PUFA supplementation on progression of age related macular degeneration (AMD). The aim of this study was to compare serum levels of omega-3- and omega-6 PUFAs between patients with diabetic retinopathy (DR), AMD and retinal vein occlusion (RVO), and to identify potential confounders of serum level measurements.MethodsVenous blood samples were collected from 44 patients with DR, 25 with AMD, 12 with RVO and 27 controls. The lipid phase was extracted and analyzed using mass spectrometry. Retinal disease staging was done by indirect funduscopy and FAG where appropriate. Patient demographics and medical history including current medication and fasting state were acquired. Tukey contrasts for multiple comparisons of the mean and linear regression analysis were used for statistical analysis.ResultsOur data revealed no significant differences in omega-6 PUFA serum levels between patients with AMD, DR, RVO and controls (p > 0.858). Uncorrected omega-3 PUFA levels were significantly higher in patients with AMD compared to DR but not compared to controls (p = 0.004). However, after correcting for possible confounders such as body mass index (BMI), age, sex, fasting and use of statins, no statistically significant difference remained for serum omega-3 PUFA levels. Fasting was identified as an independent confounder of total omega-6 PUFAs, three individual omega-6 PUFAs and one omega-3 PUFA(p < 0.0427). Statin use was identified as an independent confounder of α-linolenic acid (an omega-3PUFA; p = 0.0210).ConclusionIn this pilot study with relatively low patient numbers, we report significant differences in serum levels of omega-3PUFAs among patients with different types of retinal diseases. However, these differences were not robust for disease specificity after correction for possible confounders in our cohort. Our results demonstrate that serum lipid profiles need to be interpreted with caution since they are significantly altered by variables like fasting and medication use independent from the underlying disease. Correcting for respective confounders is thus necessary to compare serum lipid profiles in clinical studies.Electronic supplementary materialThe online version of this article (doi:10.1186/s12886-016-0335-9) contains supplementary material, which is available to authorized users.

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The Associations of Dietary Intake of Polyunsaturated Fatty Acids With Diabetic Retinopathy in Well-Controlled Diabetes

Cited by 63 publications

References 33 publications

Dietary Marine ω-3 Fatty Acids and Incident Sight-Threatening Retinopathy in Middle-Aged and Older Individuals With Type 2 Diabetes

Dietary Marine ω-3 Fatty Acids and Incident Sight-Threatening Retinopathy in Middle-Aged and Older Individuals With Type 2 Diabetes

In contrast to Western diet, a plant‐based, high‐fat, low‐sugar diet does not exacerbate retinal endothelial injury in streptozotocin‐induced diabetes

Systemic confounders affecting serum measurements of omega-3 and -6 polyunsaturated fatty acids in patients with retinal disease

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